Search

Background: Papillary thyroid carcinoma occasionally presents with concomitant hyperparathyroidism; however, the clinical significance has not been well established. This study aimed to evaluate the long-term cancer prognosis following a multimodality therapy. Methods: We conducted a case-control study using prospectively maintained data from a medical center thyroid cancer database between 1980 and 2013. The study cohort comprised patients with concomitant papillary thyroid carcinoma and hyperparathyroidism. Patients with papillary thyroid carcinoma only were matched using the propensity score method. Therapeutic outcomes, including the non-remission rate of papillary thyroid carcinoma and patient mortality, were compared. Results: We identified 27 study participants from 2537 patients with papillary thyroid carcinoma, with 10 patients having primary hyperparathyroidism and 17 having renal hyperparathyroidism. Eighty-five percent of the cohort was found to have tumor–node–metastasis stage I disease. During a mean follow-up of 7.7 years, we identified 3 disease non-remission and 4 mortality events. The non-remission risk did not increase (hazard ratio [HR], 1.66; 95% confidence interval [CI], 0.43–6.40; p = 0.47); however, the overall mortality risk significantly increased (HR, 4.43; 95% CI, 1.11–17.75; p = 0.04). All mortality events were not thyroid cancer related, including two identified cardiovascular diseases. Conclusions: Patients with papillary thyroid carcinoma who present with concomitant hyperparathyroidism are usually diagnosed at an early cancer stage with compatible therapeutic outcomes. However, hyperparathyroidism-related comorbidity may decrease long-term survival. Keywords: Papillary thyroid carcinoma, Hyperparathyroidism, Therapeutic outcomes

Background/Purpose: The objectives of this study were to evaluate the associations between clinical parameters and quality of life (QOL) of patients with acromegaly in Taiwan and to identify the impacts of hormone control, regimens, or co-morbidities on acromegalic patients' daily life. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. Clinical data were recorded. The QOL of enrolled patients were assessed by using Acromegaly Quality of Life Questionnaire (AcroQoL). Results: This study enrolled 272 acromegalic subjects (117 males, 155 females). Remission, defined by normalization of IGF-1, had significant positive association with QOL scores in psychological/appearance (PSY/APP) dimension (β = 6.760, p = 0.023). Somatostatin analogues therapy had negative associations with total score and score in psychological (PSY) dimension (β = −4.720, p = 0.046 and β = −5.388, p = 0.035, respectively). Diabetes mellitus had negative associations with score in PSY dimension and psychological/personal relations (PSY/PER) dimensions (β = −5.839, p = 0.034 and β = −7.516, p = 0.013, respectively). Cerebral vascular accident (CVA) had significant negative associations with total score and scores in physical (PHY), PSY, and PSY/PER dimensions (β = −26.632, p = 0.013; β = −28.353, p = 0.024; β = −25.648, p = 0.026; and β = −34.586, p = 0.006, respectively). All these associations remained significant even after adjusted with sex and age. Conclusion: Our analysis suggested that not only hormone control but also therapeutic regimens and presence of co-morbidities might affect QOL of patients with acromegaly in some dimensions. Keywords: Taiwan acromegaly registry, Quality of life, Clinical parameters

Background/purpose: The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. Results: The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4 ± 12.9 years. Their mean age at diagnosis was 41.8 ± 12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7 ± 9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9 ± 8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and the insulin-like growth factor 1 levels were 2.7 ± 4.9 μg/L, 2.4 ± 6.1 μg/L, and 291.5 ± 162.4 ng/mL, respectively. The remission rate assessed by random GH level (≦2 μg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0 ± 19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. Conclusion: This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly. Keywords: Acromegaly, Patient registry, Taiwan, Health outcome, Quality of life

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. Keywords: Total thyroidectomy, Thyroglobulin, Radioactive iodide, Cancer-specific mortality

Background: Subclinical hypothyroidism (SCH) is defined as elevation in serum thyroid-stimulating hormone (TSH) levels despite normal serum levels of free thyroxine. It remains controversial whether people with SCH have higher total cholesterol and low-density lipoprotein cholesterol levels compared to normal-thyroid subjects. The aim of this study was to assess the metabolic risk factors for SCH. Methods: Subjects were recruited from the health examination center of Chang Gung Memorial Hospital, Linkou, from January 1, 2010 to December 31, 2011. This was a cross-sectional review of medical records. The subjects were ethnic Taiwanese residents without known thyroid disease at baseline. Results: A total of 22,324 subjects received annual health examination at Chang Gung Memorial Hospital from 2010 to 2011. Among them, 15,943 subjects were included as the normal thyroid group (NG), and 203 subjects (101 men and 102 women) met the criteria for SCH. The prevalence of metabolic syndrome (MetS) in the NG was 26.2% in men and 18.7% in women, whereas that in the SCH group was 39.6% in men and 29.4% in women. Women in the SCH group showed significantly higher cholesterol, triglyceride, non-high density lipoprotein (HDL) and cholesterol/HDL levels than those in the NG (p

Background/Objective: To investigate the influence of serum anti-thyroglobulin antibody (TgAb) on the prognosis in papillary thyroid cancer (PTC) patients. Methods: In this retrospective study, the participants were enrolled from 1206 PTC patients (927 women, 279 men; mean age, 42.2 years) with T2 and higher, or N1 or M1 classifications in tumor–node–metastasis staging after total thyroidectomy. We recorded the final serum TgAb data (on thyroxin therapy) at the end of follow-up in 2012. Patients were classified as negative TgAb or positive TgAb groups on the basis of their serum TgAb levels (< 70 IU/mL or ≥ 70 IU/mL). Results: Among the 1206 patients, after mean follow-up for 11.6 ± 6.1 years (range, 2.0–29.2 years), there were 75 with positive TgAb and 1131 with negative TgAb. Patient categorization depending on the follow-up time (2–5 years after surgery, 5–10 years after surgery, and 10–30 years after surgery) was performed. In comparison to traditional risk factors, such as age, tumor size, and sex, which were important prognostic factors for cancer recurrence and mortality in PTC patients, there was no significant difference in the prognosis between positive TgAb patients and negative TgAb patients by the multivariate analyses (cancer recurrence, p = 0.164, p = 0.112, p = 0.202, respectively; cancer mortality, p = 0.181, p = 0.646, p = 0.656, respectively) based on the different follow-up times. Conclusion: Positive serum TgAb was not a risk factor, and was not associated with the prognosis of PTC patients.

The follicular variant of papillary thyroid carcinoma (FVPTC) is the most common variant of papillary thyroid carcinoma (PTC). A previous population-based study revealed its clinical behavior as a mix of classic papillary thyroid carcinoma (C-PTC) and follicular thyroid carcinoma. Whereas locoregional extension was lower in FVPTC than in C-PTC, the distant metastasis rate was higher in FVPTC than in C-PTC. The aim of this study was to evaluate the risk factors of distant metastasis in FVPTC postoperatively. Methods: A retrospective review of 359 patients with final pathological diagnosis of FVPTC treated at Chang Gung Memorial Hospital between January 2000 and January 2014 was performed. After excluding patients who had inadequate pathological data for analysis or did not attend regular follow up for >1 year, 346 patients were included in this study. Univariate and multivariate statistical analyses were performed to determine the significance of various factors. Results: Of the 346 patients with FVPTC, 19 (5.5%) had lymph node metastases and 32 (9.2%) had distant metastases. Two positive and one negative risk factors were predictive for distant metastasis using multivariate analysis: angiolymphatic invasion [odds ratio (OR), 3.085; 95% confidence interval (CI), 1.008–9.442], extrathyroidal extension (OR, 3.929; 95% CI, 1.330–11.602), and encapsulation (OR, 0.361; 95% CI, 0.154–0.850). Conclusion: The presence of angiolymphatic invasion, extrathyroidal extension, or nonencapsulation was associated with distant metastasis in FVPTC in this study. In FVPTC patients, postoperative investigation for distant metastasis may be warranted by the presence of these two positive risk factors or the absence of the one negative risk factor.

The most common diagnostic finding of autoimmune thyroid disease (AITD) is the presence of antithyroid antibodies. While autoimmune thyroiditis (AT) is a common AITD, aspiration cytology is one of the important diagnostic tools of AT. Methods: We evaluated 116 AT patients with ultrasound-guided aspiration cytology and then analyzed the correlation between thyroid hormone status and thyroid autoantibodies. This was a retrospective analysis with prospective collection of data with a mean follow-up period of 68.8 ± 37.8 months. The patients were classified as either euthyroid, hypothyroid, or hyperthyroid (HT). Of the 116 patients, 22 were hypothyroid, 37 were euthyroid, and 57 were HT. Results: During the follow-up period, 95.5% of the hypothyroid group remained hypothyroid and only one patient improved to euthyroid. In the euthyroid group, 16.2% progressed to hypothyroid and 83.8% remained euthyroid. In the HT group, 8.7% progressed to hypothyroid, 70.2% progressed to euthyroid, and 21.1% remained HT. Most patients with a high titer of thyroglobulin antibody (TgAb) will progress to hypothyroid, and patients with a high titer of thyroid stimulating hormone (TSH) receptor antibody (TRAb) will remain HT. Strong correlations between thyroid functional status and positive number of thyroid autoantibodies were seen in this study. Patients with all the three antibodies positive had a high prevalence of hyperthyroidism. Conclusion: In our study, most patients were HT; this may be because of the early diagnosis and treatment of AT in our clinic. Although antithyroperoxidase antibody (TPOAb) is a hallmark antibody of HT, it cannot predict the initial presentation and clinical outcome.

The aims of this study were to investigate papillary and follicular thyroid carcinomas with bone metastasis in various clinical presentations and to determine the prognostic factors after multimodality treatment. A retrospective analysis was performed of 3,120 patients with papillary and follicular thyroid carcinoma. Of these patients, 131 (including 97 women, 71.8%) were diagnosed with bone metastasis and underwent follow-up at the Chang Gung Medical Center. Patients with bone metastasis were categorized into two groups. Group A was comprised of patients who were diagnosed with bone metastasis either before thyroidectomy or within 6 months of the initial thyroidectomy (90 patients, 68.7%). Group B was comprised of patients with bone metastasis who received a diagnosis 6 months post-thyroidectomy in the follow-up period (41 patients, 31.3%). After a mean follow-up period of 8.4 ± 7.0 years, there were 88 deaths (67.2%) attributed to thyroid cancer and 13 patients (9.9%) achieved disease-free status. A multivariate analysis showed that older age, early diagnosis, and brain metastasis were each associated with a poor prognosis. The difference in disease-specific mortality rates between groups A and B was significant (p < 0.0001). In conclusion, papillary and follicular thyroid cancers with bone metastasis have a high rate of mortality. Despite this high mortality, 9.9% patients still had an excellent response to treatment.

We explored the therapeutic effects of dinaciclib, a cyclin-dependent kinase (CDK) inhibitor, in the treatment of thyroid cancer.Seven cell lines originating from three pathologic types of thyroid cancer (papillary, follicular and anaplastic) were studied. The cytotoxicity of dinaciclib was measured using a lactate dehydrogenase assay. The expression of proteins associated with cell cycle and apoptosis was assessed using Western blot analysis and immunofluorescence microscopy. Cell cycle distribution was measured by flow cytometry and immunofluorescence microscopy. Apoptosis and caspase-3 activity were measured by flow cytometry and fluorometric assay. Mice bearing flank anaplastic thyroid cancer (ATC) were treated with intraperitoneal injections of dinaciclib.Dinaciclib inhibited thyroid cancer cell proliferation in a dose-dependent manner. Dinaciclib had a low median-effect dose (≤ 16.0 nM) to inhibit cell proliferation in seven thyroid cancer cell lines. Dinaciclib decreased CDK1, cyclin B1, and Aurora A expression, induced cell cycle arrest in the G2/M phase, and induced accumulation of prophase mitotic cells. Dinaciclib decreased Mcl-1, Bcl-xL and survivin expression, activated caspase-3 and induced apoptosis. In vivo, the growth of ATC xenograft tumors was retarded in a dose-dependent fashion with daily dinaciclib treatment. Higher-dose dinaciclib (50 mg/kg) caused slight, but significant weight loss, which was absent with lower-dose dinaciclib (40 mg/kg) treatment.Dinaciclib inhibited thyroid cancer proliferation both in vitro and in vivo. These findings support dinaciclib as a potential drug for further studies in clinical trials for the treatment of patients with refractory thyroid cancer.

A retrospective review of 626 patients with multifocal papillary thyroid carcinoma (PTC) including 147 patients (23.5%) with multifocal papillary thyroid microcarcinoma (PTMC) from a total of 2,536 patients with PTC who visited the Chang Gung Medical Center in Linkou, Taiwan, was performed. A comparison of the clinical features between 626 multifocal and 1,910 solitary PTC cases showed that patients in the multifocal PTC group were older and had a smaller mean tumor size, a more advanced tumor-node-metastasis (TNM) stage, and a higher percentage of nonremission status compared to patients in the solitary PTC group. Of the 626 patients with multifocal PTC, the group with larger tumors showed a more advanced TNM stage, a higher percentage of lymph node metastasis and soft tissue invasion, and a higher nonremission rate compared to the multifocal PTMC group. Of the 626 patients with multifocal PTC, 25 patients (4%) died during a mean follow-up period of 7.1 ± 5.3 years. Kaplan-Meier survival curves showed a significantly lower survival rate associated with multifocal PTMC compared to that with solitary PTMC.

Radiotherapy is a crucial treatment for acromegalic patients with growth hormone (GH)-secreting pituitary tumors. However, its effect takes time. We retrospectively reviewed the long-term outcome of linear accelerator stereotactic radiosurgery (LINAC SRS) for patients with acromegaly from the perspective of biochemical remission and associated factors. Methods: Twenty-two patients presenting with residual or recurrent (GH)-secreting functional pituitary tumor between 1994 and 2004 who received LINAC SRS were enrolled and followed up for at least 3 years. Residual or recurrent tumor was defined as persistent elevated GH or insulin-like growth factor-1 (IGF-1) level and image-confirmed tumor after previous surgical treatment. Biochemical remission was defined as fasting GH less than 2.5 ng/mL with normal sex-and-age adjusted IGF-1. Results: The mean follow-up period was 94.7 months (range 36–161 months). Overall mean biochemical remission time was 53 months (median 30 months). Biochemical control was achieved in 15 patients (68.2%) over the follow up period. One patient experienced recurrence after SRS and underwent another operation. Initial GH at diagnosis and pre-SRS GH correlated with biochemical control (p = 0.005 and p

Background. The aims of this study were to analyze the clinical characteristics of SPM in patients with well-differentiated thyroid cancer and to determine the long-term prognosis in patients with double malignancies. Materials and Methods. We retrospectively analyzed 2,864 patients with well-differentiated thyroid cancer and a mean age of 44.0±14.4 years. Of these, 200 (7.0%) were diagnosed with SPM, 115 of which were diagnosed with metachronous SPM. Results. Of 2,864 patients, 163 (5.7%) patients died of thyroid cancer and 301 (10.5%) died of any cause by the end of the follow-up period. Multivariate analysis identified age, SPM, external radiotherapy, TNM stage, and postoperative serum Tg level to be factors independently associated with decreased survival. Of 200 patients with SPM, 74 (37.0%) died. In comparison to the anachronous and synchronous groups, the metachronous SPM group had a higher mean age; more advanced tumor, node, and metastasis stage; lower remission rate; higher postoperative radioactive iodide (131I) accumulated dose; a higher proportion of patients who underwent external radiotherapy; and higher thyroid cancer and total mortality rates. Conclusions. Patients with well-differentiated thyroid carcinoma and metachronous SPM had worse prognoses compared to patients without SPM.

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.

This study was to investigate the clinical features and therapeutic outcomes of multifocal papillary thyroid microcarcinoma (PTMC). A total of 2,418 papillary thyroid carcinoma (PTC) patients had undergone thyroidectomy in one medical center between 1977 and 2010. There were 483 (20.0%) diagnosed with multifocal PTC. The percentage of multifocal PTC was higher in PTMC patients (22.0%) than in non-PTMC patients (19.5%). Demographic and clinical characteristics of PTMC and multifocal PTC in PTC patients were traced. Multifocal PTC patients presented with smaller tumors at an older age, and a higher percentage underwent total or complete thyroidectomy. These patients also showed a higher incidence of postoperative disease progression than did unifocal PTC patients. Comparison of 483 patients with multifocal PTMC and non-PTMC tumors showed a higher incidence of postoperative disease progression in patients with non-PTMC; otherwise, there was no statistical difference in disease-specific and total mortality between these two groups. In conclusion, the incidence of multifocal PTMC was not lower than that of non-PTMC, and postoperative therapies were necessary for both multifocal PTMC and non-PTMC patients.

BACKGROUND: Increased body mass index is related to the incidence of thyroid cancer. However, the presentation and therapeutic outcomes of different thyroid cancers and type 2 diabetes mellitus (DM) have not been studied. This study investigated the effect of type 2 DM on the clinical presentations and therapeutic outcome of well-differentiated thyroid cancer. METHODS AND FINDINGS: A retrospective analysis of adult thyroid cancer patients with or without type 2 DM admitted between January 2001 and December 2010 was performed at an institution. A total of 1,687 well-differentiated thyroid cancer patients with different histological patterns were enrolled. Among these subjects, 122 were type 2 DM patients. Patients with thyroid cancer and type 2 DM were significantly older than non-DM patients. After a mean follow-up period of 5.6±0.1 years, patients with thyroid cancer and type 2 DM showed a higher percentage of disease progression than non-DM patients (24.6% vs. 17.4%). In addition, disease-specific mortality was higher in the type 2 DM group (10.7% vs. 3.8%). Thyroid cancer patients with type 2 DM showed a higher percentage of secondary primary cancers than those without DM (10.7% vs. 4.9%). Thyroid cancer-specific survival rates in the type 2 DM and non-DM groups were 82.2% and 94.9% at 5 years, 72.9% and 91.4% at 10 years, and 36.5% and 61.3% at 20 years, respectively. Multivariate analysis showed that type 2 DM was independent of thyroid cancer-specific mortality. CONCLUSION: Patients with type 2 DM and well-differentiated thyroid cancer had an advanced tumor-node-metastasis stage at the time of diagnosis and an increased disease-specific mortality. Aggressive surgical procedures and close follow-up for well-differentiated thyroid cancer patients with type 2 DM are therefore necessary.

BACKGROUND:We evaluated the therapeutic effects of the histone deacetylase inhibitor PXD101 alone and in combination with conventional chemotherapy in treating thyroid cancer. METHODOLOGY/PRINCIPAL FINDINGS:We studied eight cell lines from four types of thyroid cancer (papillary, follicular, anaplastic and medullary). The cytotoxicity of PXD101 alone and in combination with three conventional chemotherapeutic agents (doxorubicin, paclitaxel and docetaxel) was measured using LDH assay. Western blot assessed expression of acetylation of histone H3, histone H4 and tubulin, proteins associated with apoptosis, RAS/RAF/ERK and PI3K/AKT/mTOR signaling pathways, DNA damage and repair. Apoptosis and intracellular reactive oxygen species (ROS) were measured by flow cytometry. Mice bearing flank anaplastic thyroid cancers (ATC) were daily treated with intraperitoneal injection of PXD101 for 5 days per week. PXD101 effectively inhibited thyroid cancer cell proliferation in a dose-dependent manner. PXD101 induced ROS accumulation and inhibited RAS/RAF/ERK and PI3K/mTOR pathways in sensitive cells. Double-stranded DNA damage and apoptosis were induced by PXD101 in both sensitive and resistant cell lines. PXD101 retarded growth of 8505C ATC xenograft tumors with promising safety. Combination therapy of PXD101with doxorubicin and paclitaxel demonstrated synergistic effects against four ATC lines in vitro. CONCLUSIONS:PXD101 represses thyroid cancer proliferation and has synergistic effects in combination with doxorubicin and paclitaxel in treating ATC. These findings support clinical trials using PXD101 for patients with this dismal disease.

To investigate the correlation between gender and the clinical presentation of papillary thyroid cancer and the long-term followup results, 435 patients who underwent total or near-total thyroidectomy were enrolled in this study. Among these papillary thyroid cancer patients, 12.2% showed lymph node metastases and a higher incidence of male patients in the N1b group. There were 65 from 316 female (20.6%) and 49 from 120 male (40.8%) patients who had a postoperative disease progression. A total of 55 (12.6%) patients died of thyroid cancer. Male patients showed a higher thyroid cancer mortality than the females. Multiple regression analysis showed that male gender was an independent risk factor for cancer recurrence and mortality. Male patients with TNM stages II to IV of papillary thyroid cancer need to adopt aggressive surgical and postoperative 131I therapy.

BACKGROUND: We assessed the utility of the dual PI3K/mTOR inhibitor NVP-BEZ235 (BEZ235) as single agent therapy and in combination with conventional chemotherapy for thyroid cancer. METHODOLOGY/PRINCIPAL FINDINGS: Eight cell lines from four types of thyroid cancer (papillary, follicular, anaplastic, medullary) were studied. The cytotoxicity of BEZ235 and five conventional chemotherapeutic agents alone and in combination was measured using LDH assay. Quantitative western blot assessed expression of proteins associated with cell cycle, apoptosis and signaling pathways. Cell cycle distribution and apoptosis were measured by flow cytometry. Murine flank anaplastic thyroid cancers (ATC) were treated with oral BEZ235 daily. We found that BEZ235 effectively inhibited cell proliferation of all cancer lines, with ATC exhibiting the greatest sensitivity. BEZ235 consistently inactivated signaling downstream of mTORC1. BEZ235 generally induced cell cycle arrest at G0/G1 phase, and also caused apoptosis in the most sensitive cell lines. Baseline levels of p-S6 ribosomal protein (Ser235/236) and p27 correlated with BEZ235 sensitivity. Growth of 8505C ATC xenograft tumors was inhibited with BEZ235, without any observed toxicity. Combination therapy of BEZ235 and paclitaxel consistently demonstrated synergistic effects against ATC in vitro. CONCLUSIONS: BEZ235 as a single therapeutic agent inhibits thyroid cancer proliferation and has synergistic effects in combination with paclitaxel in treating ATC. These findings encourage future clinical trials using BEZ235 for patients with this fatal disease.

The purpose of this prospective study was to examine the effect of physical activity independent of obesity on metabolic risk factors. A total of 358 participants were recruited from the Department of Health Management of Chang Gung Medical Center. Physical activity was assessed using a 3-d activity record. Body-mass index (BMI) and metabolic risk factors were also assessed. Our findings demonstrate that an effect of obesity that was statistically independent of the levels of physical activity is associated with metabolic risk factors. Moreover, physical activity displayed inverse associations with triglycerides, and fasting plasma glucose and a positive association with HDL cholesterol. Those participants with time spent in moderate activity more than 0.5 h each day had significantly less risk of high fasting glucose. Significantly, these associations were independent of BMI. [ABSTRACT FROM AUTHOR]

Polo-like kinases (PLKs) are pivotal regulators of cell proliferation and cell survival; therefore, PLKs may be potential targets in the treatment of malignancy. The therapeutic effects of volasertib, a PLKs inhibitor for papillary and follicular thyroid cancer (known as well-differentiated thyroid cancer (WDTC)), were evaluated in this study. Volasertib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Volasertib treatment reduced cells in the S phase and increased cells in the G2/M phase. Volasertib activated caspase-3 activity and induced apoptosis. Drug combinations of volasertib and sorafenib showed mostly synergism in four welldifferentiated thyroid carcinoma cell lines in vitro. Volasertib treatment in vivo retarded the growth of a papillary thyroid tumor model. Furthermore, the combination of volasertib with sorafenib was more effective than a single treatment of either in a follicular thyroid cancer xenograft model. Promising safety profiles appeared in animals treated with either volasertib alone or volasertib and sorafenib combination therapy. These findings support volasertib as a potential drug for the treatment of patients with WDTC. [ABSTRACT FROM AUTHOR]

Aims. Hyperinsulinemia in overweight status, obesity, and type 2 diabetes mellitus (DM) is often accompanied by cancer. Gender is important in cancer epidemiology, clinical presentation, and response to therapy in different histological types of malignancy. Insufficient information is available concerning gender differences in DM with organ-specific and nonorgan-specific cancers. This study aimed to analyze gender differences in hospitalized cancer patients with or without type 2 DM. Methods. We retrospectively reviewed ten years of patients hospitalized in one institution, enrolling 36,457 female and 50,004 male cancer patients of which 5,992 females and 8,345 males were diagnosed as type 2 DM. Results. Statistically significant increases in incidence of type 2 DM were found in patients of both genders with pancreatic, liver, and urinary tract cancer. Increased incidence of type 2 DM was found in lung and hematologic malignancies in females and prostate cancer in males. Increases in mortality rates of females with type 2 DM (2.98%) were higher than those in males. DM increased mortality rates in gender-specific cancers from 1.91% (uterus, HR: 1.33) to 5.04% (ovary, HR: 1.49). Conclusion. Type 2 DM increased mortality of cancer patients of both genders, with higher increases in gender-specific than in nongender-specific cancers. [ABSTRACT FROM AUTHOR]

The prevalence of papillary thyroid microcarcinoma (PTMC) in thyroid cancer varies from 20.0% to 42.8% with a mean of 30.0%. Most of these patients have benign clinical courses and receive less aggressive therapeutic procedures in most medical centers. This study retrospectively reviewed 30 years data in one institute and compared it with recent publications to illustrate change in trends and influence of PTMC. Incidental PTMC is usually diagnosed as a postoperative microcarcinoma following thyroidectomy for presumably benign thyroid lesions. Subtotal thyroidectomy or lobectomy without radioactive iodide treatment is sufficient to treat incidental PTMC. In contrast, aggressive surgical treatment with 131I therapy is indicated for non-incidental PTMC. Those with PTMC in the absence of extra-thyroid invasion diagnosed by postoperative permanent section received follow-up if they had initially received subtotal thyroidectomy. In long-term follow-up studies, cancer-specific mortality for PTMC ranged from 0% to 4%. Most of the mortality cases had distant metastasis at the time of surgery. The clinical course and therapeutic strategies for the non-incidental PTMC patients depend on the TNM stage at the time of diagnosis. One-third of PTMC with clinically aggressive behavior cannot be treated as indolent disease. Invasive tumor markers or larger tumor size are useful to predict tumor recurrence or distant metastasis for PTMC. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the efficacy, safety, and tolerability of weekly alendronate administration on male osteoporosis in Taiwan. This 6-month, randomized, open-label controlled trial enrolled 46 men with osteoporosis who were randomized to either 70 mg alendronate once weekly (n = 23) or control (n = 23). Bone mineral density (BMD) of lumbar spine and hip and biochemical bone turnover markers were measured; adverse events and tolerability were assessed. Subjects treated with alendronate showed a significant increase in BMD of 5.5% (vs. 2% in control group) at the lumbar spine and 2.7% (vs. 0.7%) at the femoral neck (P < 0.05) at 6 months, respectively. There were also significant decreases in serum level of bone formation marker (bone-specific alkaline phosphatase) and urinary excretion of bone resorption marker (deoxypyridinoline) at 3 and 6 months. Thus, alendronate showed anti-osteoporotic effects by increasing BMD and decreasing the concentrations of bone markers. The adverse events were mild and showed no significant difference between the two groups on safety assessments. [ABSTRACT FROM AUTHOR]

Background: There is strong evidence for the beneficial effects of physical activity in diabetes. There has been little research demonstrating a dose-response relationship between physical activity and self-rated health in diabetics. The aim of this study was to explore the dose-response association between leisure time physical activity and self-rated health among diabetics in Taiwan.Methods: Data came from the 2001 Taiwan National Health Interview Survey (NHIS). Inclusion criteria were a physician confirmed diagnosis of diabetes mellitus and age 18 years and above (n = 797). Self-rated health was assessed by the question "In general, would you say that your health is excellent, very good, good, fair, or poor?" Individuals with a self perceived health status of good, very good, or excellent were considered to have positive health status.Results: In the full model, the odds ratio (OR) for positive health was 2.51(95% CI = 1.53-4.13), 1.62(95% CI = 0.93-2.84), and 1.35(95% CI = 0.77-2.37), for those with a total weekly energy expenditure of > or = 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. Those with duration over 10 years (OR = 0.53, 95%CI = 0.30-0.94), heart disease (OR = 0.50, 95%CI = 0.30-0.85), and dyslipidemia (OR = 0.65, 95% CI = 0.43-0.98) were less likely to have positive health than their counterparts. After stratified participants by duration, those with a duration of diabetes < 6 years, the adjusted OR for positive health was 1.95(95% CI = 1.02-3.72), 1.22(95% CI = 0.59-2.52), and 1.19(95% CI = 0.58-2.41) for those with a total weekly energy expenditure of > or = 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. In participants with a duration of diabetes > or = 6 years, total energy expenditure showed a gradient effect on self-perceived positive health. The adjusted OR for positive health was 3.45(95% CI = 1.53-7.79), 2.77(95% CI = 1.11-6.92), and 1.90(95% CI = 0.73-4.94) for those with a total weekly energy expenditure of > or = 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals.Conclusions: Our results highlight that regular leisure activity with an energy expenditure -- 500 kcal per week is associated with better self-rated health for those with longstanding diabetes. [ABSTRACT FROM AUTHOR]

Background:The occurrence of recurrent papillary and follicular thyroid carcinomas is not unusual. Numerous studies have reported the association between risk factors of initial surgery and recurrence of papillary and follicular thyroid carcinomas. However, we do not have sufficient data to analyze the time of postoperative recurrence associated with therapeutic results and cancer mortality. We hypothesized that an early recurrence of papillary and follicular thyroid cancers implies a rapid growth of cancer resulting in high mortality rate.Methods:We conducted a retrospective study in a medical center in northern Taiwan. The investigation included 2148 cases of papillary and follicular thyroid carcinoma, including 325 recurrent cases during the period between 1977 and 2006. The studied cases were categorized into early or late recurrence groups. Cases with an early recurrence were defined as those in which recurrence occurred in the first year following thyroid surgery.Results:Tumor size, radioactive iodide treatment, multifocality, and tumor-node metastasis stage were independent predictors of recurrence. After a mean follow-up of 8.7 ± 0.1 years, death due to thyroid cancer was observed to occur in 105 (32.3%) recurrent cases. Among the 325 recurrent cases, early recurrence was detected in 185 cases, and late recurrence was detected in 140 cases. Early recurrence was mostly observed in older male patients; a high mortality rate was associated with these cases. Distant metastases were observed in about 80% of the cases in the early recurrence group, whereas localized metastases in the neck region were observed in more than half the cases in the late recurrence group. The percentage of patients with a non–disease-free status and distant metastases in the early recurrence group was higher than that in the late recurrence group. The 10-year disease-specific survival rates were 52.5% and 85.1% for the early and late recurrence groups, respectively.Conclusions:Early recurrent papillary and follicular thyroid carcinomas are associated with high mortalities. Tumor size and multifocality deserve consideration as indicators of recurrence. Therefore, patients whose primary follicular or papillary thyroid carcinoma has features associated with early recurrence should probably receive more aggressive initial treatment. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to analyze the results of histopathological studies in neck masses observed in young patients. The neck masses were detected using ultrasonography and fine-needle aspiration cytology (FNAC).Methods: In this retrospective study, we analyzed 234 young patients who were surgically treated for neck masses at Chang Gung Medical Center in Linkou. The mean age of the 234 young patients was 16.3 +/- 4.0 years (range 1-20 years). Neck ultrasonography studies were conducted using a real-time ultrasonographic machine and a 10 MHz transducer. FNAC was performed for the suspected neck nodules.Results: Of the 234 cases, 187 (79.9%) were surgically confirmed to be benign lesions, including four cases that were diagnosed as atypical adenoma. Malignant thyroid masses were identified in 47 patients. Surgery confirmed 22 cases to be lesions that were non-thyroid in origin, including those developing from a cyst, soft tissue, and with a lymphatic origin. Diagnostic accuracies of the FNAC and frozen section examination were found to be 91.1 and 97.7%, respectively.Conclusions: In the study population, 20.1% of the neck masses were malignant. Except in cases of follicular thyroid neoplasm, neck ultrasonography with FNAC could effectively identify the thyroid or non-thyroid origin of these masses with high-diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background: To determine the incidence of cystic change of thyroid cancer detected by ultrasonography and to compare the diagnostic accuracy of fine-needle aspiration cytology (FNAC) postultrasonography in solid and cystic thyroid nodules. Methods: This retrospective study collected data for 6219 patients with thyroid nodules. Mean patient age was 49.7 ± 13.6 years. Of these 6219 patients, 1983 had cystic changes of thyroid nodules and 4236 had solid masses as detected by ultrasonography. Following FNAC, 506 of the patients with solid masses (11.9%) underwent surgical treatment, compared with 143 of those with cystic change of thyroid masses (7.2%). Results: Of the 649 nodules treated surgically in the solid and cystic change groups, 29.8% (151/506) and 9.1% (13/143) were malignant, respectively. Overall, after surgical treatment, 0.65% of cystic changes to thyroid lesions were diagnosed as thyroid cancer. Diagnostic accuracy of FNAC in cystic changes of the thyroid masses after ultrasonographic examination resembled that in solid thyroid nodules. Conclusions: Cystic changes of thyroid masses are common. Positive predictive value in diagnosing papillary carcinoma of thyroid masses with cystic changes is high. Notably, preoperative accurate diagnosis is difficult. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to determine whether conservative surgical therapy had been adequate for low-risk patients with papillary thyroid cancer. Study design and patients: 1,931 patients were categorized as either low risk or high risk, using tumor–node–metastasis (TNM) staging from the sixth edition of International Union Against Cancer (UICC); TNM stage I was designated low risk during this retrospective review. Main outcomes: After an average follow-up period of 8.7 years, 58 of 1,931 patients (3.0) died from thyroid cancer. Ten-year survival rates of papillary thyroid carcinoma from sixth edition TNM stages I to IV are 99.7, 95.6, 90.7, and 84.0, respectively. Age, tumor size, 131I therapeutic dose, and follow-up status were statistically significant when comparing high- and low-risk groups. Of the 1,432 patients in stage I, 338 underwent conservative surgical procedures. Among 338, 4 patients died of thyroid carcinomas (1.2) and 15 (4.4) had persistent or recurrent disease. In contrast, 2 of the 1,094 (0.2) patients who received near-total thyroidectomy or limited lymph node dissection died from thyroid cancer, and 32 (2.9) had persistent or recurrent disease. Conclusions: TNM stage I papillary thyroid carcinomas were with low cancer-specific mortality rate; otherwise, patients aged 45 years or younger should not be considered a homogeneous low-risk group. Initial extent of disease was an important predictor among these patients. In particular, local invasion with airway compression predicts outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To examine the associations between watching television and physical activity with the metabolic syndrome and its components. Study design: Cross-sectional study. Methods: This study was conducted among 358 subjects recruited from the Department of Health Management of Chang Gung Medical Centre in Linkou. After adjustment for gender, age and body mass index (BMI), the odds ratios (ORs) of the metabolic syndrome and its components were analysed for relative daily energy expenditure groups and time spent watching television categories. Results: After adjustment for gender, age and BMI, the OR of the metabolic syndrome in the most active subjects compared with the least active subjects was 0.27 [95% confidence interval (CI) = 0.08-0.88; P = 0.030]. There was inconclusive evidence of an association between watching television for more than 20 h/week and presence of the metabolic syndrome (OR = 2.99; 95% CI = 0.83-10.84; P = 0.095). Conclusions: Physical activity was a significant protective factor for presence of the metabolic syndrome and low levels of high-density-lipoprotein cholesterol. Watching television was positively associated with greater odds of high levels of triglycerides and fasting glucose. This study emphasized the importance of reducing the time spent watching television and increasing the level of physical activity for prevention of the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background and aims: This study retrospectively examined the characteristics of metabolic syndrome in an aged population and assessed the risk factors for these subjects. Methods: A total of 1332 aged subjects (≥65 years: mean age 71.0±5.0 years) were enrolled from 6903 subjects recruited from the Department of Health Management at Chang Gung Medical Center. Of these 6903 subjects, 1665 (814 females and 851 males) were diagnosed with metabolic syndrome. Whole body three-dimensional (3-D) laser scanning was employed for anthropometric measurements. Furthermore, health index (HI) was derived by the following equation: HI = (body weight x 2 x waist area)/[body height² x (breast area + hip area)]. Results: Among the 6903 subjects, no significant difference in gender was noted between groups with and without metabolic syndrome (p=0.142). For subjects >64 years, the incidence of metabolic syndrome in females is higher than in males. Subjects are categorized into four groups based on age and whether they had metabolic syndrome. Group A (4402 cases) consists of subjects <65 years old without metabolic syndrome. Group B (836 cases) comprises subjects >64 years old and without metabolic syndrome. Group C (1169 cases) contains subjects <65 years old with metabolic syndrome and group D (496 cases) is composed of subjects >64 years old with metabolic syndrome, Of the aged 1332 subjects, 595 were females (mean age, 70.6±4.6 years) and 737 were males (mean age, 71.3±5.3years). 37.2% (496/1332) had metabolic syndrome. 19.9% had DM and 21,8% had hypertension. These subjects had decreased BMI with age. Additionally, WHR peaked at an age range of 75-79 years. Of the aged subjects, also overweight, 42.8% and 33.6% were diagnosed with hypertension and DM, respectively: both ratios higher than those for non-overweight overweight subjects (25.3% and 26.2%, respectively). Of the four groups in this study, the ratios for DM, hypertension, and WHR, HI, and LDL levels progressively increased through groups A to D. WBC count differs statistically significantly between these groups. Statistical analysis of WBC count, RBC and hemoglobin (Hb) with different parameters demonstrates significant elevation of WBC counts with the components of metabolic syndrome in aged subjects. Conclusions: WBC count, RBC count and Fib are associated with metabolic syndrome components in younger and old adults of both genders. The incidence of metabolic syndrome marker increased after menopause onset in the female population in this study. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is an essential peptide in new vessel growth in physiology(endometrial growth, embryonic development); pathological conditions (diabetic retinopathy, rheumatoidarthritis); as well as in tumor cell growth, particularly distant metastases. This study focused on VEGFstructure, receptors, and angiogensis in tumors, especially their roles in thyroid cancer. The VEGF mRNAundergoes alternative splicing events that generate four homodimeric isoforms, including VEGF121,VEGF165, VEGF189, or VEGF206. Using VEGF purified from a culture medium conditioned by A-431human epidermoid carcinoma cells, VEGF-binding site complexes of 230, 170, and 125 kDa were detectedon human umbilical vein endothelial cells. The VEGF specifically induced the tyrosine phosphorylationof a 190-kDa polypeptide, which had similar mass to the largest binding site detected throughaffinity cross-linking. A transmembrane receptor belongs to the tyrosine kinase family, fms-like tyrosinekinase (FLT). These receptor tyrosine kinases encoded by the FLT gene family have distinct functions inregulating blood vessel growth and differentiation. Regulation of VEGF is a complex, multistep mechanismin various kinds of cells and tissues. Hypoxia-dependent and -independent mechanisms are illustratedin different cancer tissues. Hypoxic tumor cells may switch to a proangiogenic phenotype, whichincreases VEGF transcription. Clinical applications of VEGF in cancer have included diagnosis, predictionof prognosis, and treatment in different solid tumors, including thyroid tumors. Studies involving thyroidcancer cell lines, serum level determination, immunohistocytochemical staining, molecular biologicalstudies, and gene therapy to the in vivo clinical trials, have shown that antiangiogensis therapy canprovide another treatment modality for thyroid cancer. Future studies focused on recombinant humananti-VEGF research involving patients with advanced thyroid cancer, and investigation of the protectionof high-risk patients by using novel antiangiogenic vaccines, are warranted. [ABSTRACT FROM AUTHOR]

Hypothesis Total thyroidectomy followed by radioactive iodine I 131 treatment is effective in papillary thyroid microcarcinoma (PTM) with lymph node or extrathyroid invasion. Design Retrospective study. Setting Chang Gung Medical Center, Linkou, Taiwan. Patients A total of 227 patients with PTM, categorized into high-risk (n = 12) and low-risk (n = 215) groups according to age, metastases, extent, and size criteria. Interventions Diagnosis and treatment of PTM. Main Outcome Measures Time and method of diagnosis, operative method, metastases, and survival. Results In 51 patients, PTM was identified on preoperative fine-needle aspiration cytology; in 75 patients, diagnosed in frozen sections during operation; and in 101 patients, diagnosed incidentally in the final histopathological examination. Among these 3 groups, 18% (9/51), 17% (13/75), and 78% (79/101), respectively, underwent subtotal thyroidectomy or lobectomy for tumors. Four cases (1.8%) displayed distant metastases at diagnosis. Only 0.9% of patients with PTM (2 of 227) died of thyroid cancer. One hundred eighty-nine cases of PTM were confined to the thyroid, 22 had lymph node metastases, and 16 showed extrathyroid extension, including soft-tissue invasion and distant metastases. Sex, operative methods, follow-up status, and mortality showed differences in these groups. Five of 227 patients remained in non–disease-free status at follow-up. Conclusions Approximately 10% of PTMs exhibited progressive clinical courses, while less than 1% resulted in mortality. Age, sex, and postoperative thyroglobulin level were the main prognostic factors in the high-risk group of patients with PTM. Conservative treatment of the incidental finding of PTM after suitable postoperative assessment is justified. [ABSTRACT FROM AUTHOR]

Papillary or follicular microcarcinoma of the thyroid comprises 10–20% of all thyroid malignancies. Most of these diseases exhibit slow progression and have a favorable prognosis. Distant metastasis caused by thyroid microcarcinoma is uncommon, and is usually found in the lung or bone. Thyroid microcarcinoma with metastasis to the kidney has not previously been reported. Clinically detectable well-differentiated metastatic thyroid carcinoma to the kidney is rare, and only 16 cases have been reported. Herein we describe a case of metastatic papillary thyroid microcarcinoma to the kidney in a patient with a pelvic fracture and pulmonary metastasis. The patient underwent a total thyroidectomy, radiotherapy, ablation treatment with 131 I and thyroxine suppressive therapy. In conclusion, microcarcinoma cannot be ignored. Although uncommon, metastases may arise. [ABSTRACT FROM AUTHOR]

Video-assisted thyroidectomy, although an increasingly used method to treat benign thyroid nodules, is rarely used to treat thyroid cancer. We performed gasless video-assisted total thyroidectomy for the treatment of papillary carcinoma of the thyroid. The patients were two men and five women with ages ranging from 29 to 52 years (median 35 years). Tumor size ranged from 0.7 to 3.8 cm (median 1.8 cm). The remnants of functional thyroid tissues were ablated with 1110 MBq of131I following total thyroidectomy. One year after radioiodine ablation uptake of 74 MBq131I shown by scintigraphy ranged from 0.29% to 0.70% (median 0.57%), and the serum thyroglobulin level was less than 1 µg/L. No perioperative complications occurred. The follow-up period ranged from 1 year 5 months to 3 years 7 months (median 2 years 10 months). In conclusion, gasless video-assisted total thyroidectomy is a feasible means for treating relatively small, noninvasive, clinically solitary, differentiated thyroid carcinomas. [ABSTRACT FROM AUTHOR]

Hypothyroidism is commonly thought to cause decreased gastric emptying but is mostly associated with autoimmune disease. In the present study the gastric emptying function of thyroid cancer patients with severe hypothyroidism of short duration was evaluated with a radionuclide solid meal gastric emptying study. Hypothyroidism status was confirmed by the marked change of the serum thyroxine and thy- roid-stimulating hormone 4 weeks and 6 weeks after withdrawal of the thyroxine replacement (P < 0.001). The gastric half-emptying time and emptying rate changed significantly after short-term severe thyroid hormone deficiency (P < 0.005). However, the length of the lag phase did not have a sta- tistically significant change at 4 weeks or 6 weeks after withdrawal of the thyroxin replacement (P = 0.219 and 0.142). Hypothyroidism following the withdrawal of the thyroxine replacement in thyroid cancer patients preparing for 131 I cancer work-up can significantly prolong gastric half-emptying time and emptying rate. © 2004 Blackwell Publishing Asia Pty Ltd [ABSTRACT FROM AUTHOR]

Data on four male and four female patients with insular carcinoma of the thyroid were reviewed to elucidate the clinical characteristics of this malignancy. The median age of the patients was 62.5 years (range 29­78 years). The size of the tumors ranged from 3.0 to 10.0 cm (median 4.7 cm). One patient with extensive neck disease and distant metastases underwent palliative debulking of the tumor mass and died of respiratory failure 10 days after surgery. Seven patients underwent total thyroidectomy. In addition to being given thyroxine supplement, three patients were treated with postoperative iodine-131 (131I) therapy, two with external radiation after 131I treatment, and two with external radiation. Local invasion of the malignancy into strap muscles was observed in two patients, into the trachea in two patients, into the recurrent laryngeal nerve in one patient, and into the internal jugular vein in one patient. The median follow-up was 26 months (range 3­80 months). Lung metastases occurred in four patients and metastases at the neck lymph nodes in four patients; recurrence at the thyroid bed was observed in one patient. Four patients died of distant metastases and progressive recurrent disease. Of the three surviving patients, two remained disease-free, and one remained alive with lung metastases. In conclusion, insular carcinomas behave aggressively, so we believe they should be treated by total thyroidectomy plus neck dissection when nodal metastases are present. [ABSTRACT FROM AUTHOR]

Presents a response to a letter to the editor about insular carcinoma.

Context • Other than weight reduction by dieting or physical activity, there are no well-documented medical treatments for fatty liver disease. Objective • To evaluate the efficacy of the add-on Gynostemma pentaphyllum (GP) in research subjects with nonalcoholic fatty liver disease. Design . A randomized, single-blind, controlled clinical trial. Setting. Hospital-based clinic. Patients . Fifty-six research subjects who were diagnosed with nonalcoholic fatty liver by abdominal ultrasound scanning. Interventions • The treatment group and the control group followed a controlled diet for 2 months. After 2 months, the treatment group continued to diet and received 80 mL GP extraction for 4 months; the control group continued to diet and received a placebo capsule for 4 months. Main Outcome Measures• Body mass index (BMI), biochemistry data, and fatty liver score were measured at baseline, at 2 months, and at 6 months. Results • After 2 months of dieting, BMI and most biochemistry data decreased in both study groups. There were no significant differences in BMI or biochemistry data at month 2 between the 2 study groups. At month 6, BMI, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, insulin (ALP), insulin resistance index (HOMA-TR), and fatty liver score were reduced in both groups. The treatment group saw significant reductions in BMI, AST, ALP, insulin, and HOMA-IR, however. Changes in uric acid levels in the 2 groups from month 2 to month 6 were statistically significant (P = .028) Conclusion • GP is an effective adjunct treatment to diet therapy for patients with nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]