[A Case of Synchronous Papillary Thyroid Cancer and Breast Ductal Cancer].

Occurrences of thyroid cancer and breast cancer metachronously or synchronously are common for women. Explanations for these associations include detection bias, shared hormonal risk factors, and genetic susceptibility, but the etiology behind specific associations is not elucidated well. The importance of the relationship between breast and thyroid cancer will continue to become evident and physicians should be aware of this association in caring for thyroid and breast cancer survivors. We report a case of synchronous papillary thyroid cancer and breast ductal cancer.

Diagnostic Strategies for Thyroid Nodules Based on Ultrasonographic Findings in Japan.

In recent years, the incidence of thyroid cancer has been increasing worldwide, which is believed to be mainly due to the widespread use of imaging examinations, such as ultrasonography. In this context, ultrasonography has become increasingly important because it can evaluate not only the presence or absence of nodules, but also the detailed characteristics of the nodule, making it possible to diagnose benign or malignant nodules before cytology is performed. In Japan, the third edition of the sonographic diagnostic criteria for thyroid nodules is currently widely used, and its content is similar to that of recent meta-analyses and guidelines from medical societies in other countries. In addition, since overdiagnosis of very-low-risk thyroid cancer has recently become an issue, criteria for the implementation of fine needle aspiration cytology (FNAC) have been published by various countries. The Japan Society of Breast and Thyroid Sonology provides guidelines for FNAC implementation for solid and cystic nodules. In the United States, the ATA, NCCA, and ACR have published guidelines, whereas in Europe, the ESMO and ETA have done the same. All of these guidelines used to classify risk are based on nodule size and sonographic findings. This article outlines the diagnostic criteria and management guidelines in Japan in comparison with those published in other countries. Case studies using actual images were also performed to examine the differences in the FNAC guidelines.

Reconfirmation of the accuracy of the taller-than-wide sign in multicenter collaborative research in Japan.

The taller-than-wide sign indicates that the anteroposterior dimension-to-transverse dimension ratio (AP/T ratio) is higher than 1. The aim of the present study was to reconfirm the accuracy of the taller-than-wide sign for diagnosing malignant thyroid nodules by ultrasonography in multicenter collaborative research, and investigate differences according to tumor sizes, histological types, and the influence of the tilt and orientation of the probe. At 6 registered institutes, 2,032 thyroid nodules were successively operated on and diagnosed pathologically. The accuracy of the taller-than-wide sign for diagnosing malignant tumors by ultrasonography was retrospectively analyzed across all nodules as well as in analyses separately stratified by tumor size and histology. The influence of the tilt and orientation of the probe was also assessed. The taller-than-wide sign showed high specificity for diagnosing malignancy in all nodules tested. It also showed high specificity regardless of the tumor size. When tumors were analyzed by histological types, the AP/T ratio of papillary carcinoma was significantly higher than that of benign nodules, whereas no significant difference was observed between follicular carcinoma and benign nodules. The specificity of longitudinal sections was significantly higher, while the AUC of longitudinal sections was significantly larger than those of transverse sections. The AP/T ratio obtained when the probe was tilted was not significantly different from that when it was straight. The present results support the usefulness of the taller-than-wide sign for diagnosing malignant tumors regardless of size, but not follicular carcinoma. The influence of the tilt and orientation of the probe was negligible.

Actual condition survey regarding mismatch of measurements between radioimmunoassay and enzyme-linked immunosorbent assay tests for anti-glutamic acid decarboxylase antibody in real-world clinical practice.

Anti-glutamic acid decarboxylase antibody (GADA) is an important islet cell-associated autoantibody for the diagnosis of autoimmune type 1 diabetes mellitus. In Japan, the GADA assay kit was recently changed from radioimmunoassay (RIA) to enzyme-linked immunosorbent assay (ELISA). Thereafter, a mismatched measurement between the two tests became apparent in clinical situations. The present study aimed to clarify the actual extent of mismatch between the two measurements on a larger-scale real-world clinical practice. In this cross-sectional non-local/non-hospital-based study, we collected anonymized data on GADA levels of 598 participants, who were simultaneously measured with GADA-RIA and GADA enzyme-linked immunosorbent assay tests. We found that 34% of the GADA-RIA-positive participants showed negative results in the GADA enzyme-linked immunosorbent assay test; the mismatch was predominantly observed in participants with relatively low GADA-RIA levels (<32 U/mL). This considerable mismatch might lead to physicians' confusion in diagnosing type 1 diabetes mellitus.

Association between all-cause mortality and severity of depressive symptoms in patients with type 2 diabetes: Analysis from the Japan Diabetes Complications Study (JDCS).

OBJECTIVE: The aims of this study are to confirm whether the excess mortality caused by depressive symptoms is independent of severe hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and to evaluate the association between all-cause mortality and degrees of severity of depressive symptoms in Japanese patients with T2DM. METHODS: A total of 1160 Japanese patients with T2DM were eligible for this analysis. Participants were followed prospectively for 3years and their depressive states were evaluated at baseline by the Center for Epidemiologic Studies Depression Scale (CES-D). Cox proportional hazards model was used to evaluate the relative risk of all-cause mortality and was adjusted by possible confounding factors, including severe hypoglycemia, all of which are known as risk factors for both depression and mortality. RESULTS: After adjustment for severe hypoglycemia, each 5-point increase in the CES-D score was significantly associated with excess all-cause mortality (hazard ratio 1.69 [95% CI 1.26-2.17]). The spline curve of HRs for mortality according to total CES-D scores showed that mortality risk was slightly increased at lower scores but was sharply elevated at higher scores. CONCLUSION: A high score on the CES-D at baseline was significantly associated with all-cause mortality in patients with T2DM after adjusting for confounders including severe hypoglycemia. However, only a small effect on mortality risk was found at relatively lower levels of depressive symptoms in this population. Further research is needed to confirm this relationship between the severity of depressive symptoms and mortality in patients with T2DM.

Efficacy and safety of sitagliptin as compared with glimepiride in Japanese patients with type 2 diabetes mellitus aged ≥ 60 years (START-J trial).

The aim of this study was to evaluate the efficacy and safety of sitagliptin administered to elderly patients with type 2 diabetes mellitus (T2DM) for 1 year as compared with glimepiride. Patients aged ≥60 years with T2DM and inadequately controlled blood glucose were randomly assigned to sitagliptin 50 mg once daily or glimepiride 0.5 mg once daily for 52 weeks. The primary efficacy endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 52. Secondary efficacy endpoints included self-monitored blood glucose and weight. Safety endpoints were adverse events including hypoglycaemia. Administration of sitagliptin or glimepiride to elderly patients with T2DM resulted in a significant decrease in HbA1c change from baseline. At 52 weeks, the least squares mean difference between the treatments was 0.11% (95% confidence interval [CI] -0.02 to 0.24; P = .087) (1.2 mmol/mol [-0.2 to 2.6]). The upper limit of the CI was below the predefined non-inferiority margin (0.3% [3.3 mmol/mol]), demonstrating non-inferiority of sitagliptin to glimepiride for the primary endpoint. Sitagliptin resulted in a significantly lower incidence rate of non-serious hypoglycaemia than glimepiride during the 52 weeks (4.7% vs 16.1%; P = .002); thus, sitagliptin is a useful therapeutic option for elderly patients with T2DM.

Thyroid ultrasound findings in a follow-up survey of children from three Japanese prefectures: Aomori, Yamanashi, and Nagasaki.

We conducted ultrasound thyroid screening in cohort of 4,365 children aged between 3 to 18 years in three Japanese prefectures (Aomori, Yamanashi, and Nagasaki) using the same procedures as used in the Fukushima Health Survey. Forty-four children had nodules ≥ 5.1 mm in diameter or cysts ≥ 20.1 mm in diameter detected at the first screening, and 31 of these children underwent the second follow-up survey. We collected information from thyroid ultrasound examinations and final clinical diagnoses and re-categorized the thyroid findings after the second examination. Twenty children had nodules ≥ 5.1 mm in diameter or cysts ≥ 20.1 mm in diameter at the second examination; of these, one child was diagnosed with a thyroid papillary carcinoma and the remaining 19 children were diagnosed with possibly benign nodules such as adenomas, adenomatous nodules, and adenomatous goiters. A further 11 children were re-categorized as "no further examinations were required." Our results suggest that ultrasound thyroid findings in children may change with a relatively short-term passing period, and that thyroid cancer may exist at a very low but certain frequency in the general childhood population.

One-minute mental status examination for category fluency is more useful than mini-mental state examination to evaluate the reliability of insulin self-injection in elderly diabetic patients.

AIMS/INTRODUCTION: We investigated the factors associated with the reliability of insulin self-injection in elderly diabetic patients receiving insulin therapy. MATERIALS AND METHODS: We enrolled diabetic patients aged ≥65 years and receiving insulin therapy, and assessed their cognitive function by the mini-mental state examination and 1-min mental status examination for category fluency. We also observed their technique of insulin self-injection, and evaluated whether or not patients were able to inject insulin by themselves according to nine defined details in terms of insulin self-injection. The predictive factors for the reliability of insulin self-injection were determined by univariate and multivariate logistic regression analysis. There were 278 participants (135 males, 143 females) enrolled in the present study. RESULTS: According to multivariate logistic regression analysis, only the 1-min mental status examination score was found to be a significant independent predictor of the reliability of insulin self-injection (odds ratio 0.75; 95% confidence interval 0.62-0.90; P = 0.002). CONCLUSIONS: The 1-min mental status examination for category fluency can be considered more useful than mini-mental state examination to evaluate the reliability of insulin self-injection in elderly diabetic patients receiving insulin therapy.

[Thyroid ultrasonography--considerations and progress in routine diagnostic examinations].

Thyroid ultrasonography is becoming increasingly important because it is easy to perform non-invasively and provides much more information than other imaging devices such as CT and MRI. It is possible to infer the causes of diffuse goiter and thyrotoxicosis by the internal echo level and blood flow analysis. The combination of B mode and color Doppler imaging is also useful for the diagnosis of thyroid nodules. Malignant B mode findings include an irregular shape, indistinct border, hypo and inhomogeneous internal echo, and fine calcification. New diagnostic criteria for thyroid nodules and a flow chart for the selection of indications of aspiration biopsy cytology have been developed by the Japan Association of Breast and Thyroid Sonology. Recent improvements in thyroid ultrasonography include 3D imaging, contrast agents and tissue elasticity imaging. 3D ultrasonography and contrast agents have made it possible to display vascular structures more accurately. Tissue elasticity imaging is expected to play an important role in the diagnosis of thyroid carcinomas since it evaluates tissue stiffness objectively. Tissue elastography may be useful for the differentiation of follicular adenomas from follicular carcinomas, which is still one of the most difficult clinical challenges for all endocrinologists. It also provides detailed information on the efficacy of thyroid interventions. New combinations with tissue elastography and other imaging devices are under development.

Thyroid ultrasound findings in children from three Japanese prefectures: Aomori, Yamanashi and Nagasaki.

Due to the likelihood of physical and mental health impacts following the unprecedented accident at the Fukushima Dai-ichi Nuclear Power Plant, the Fukushima prefectural government decided to conduct the Fukushima Health Management Survey to assist in the long-term health management of residents. This included thyroid ultrasound examination for all children in Fukushima. For appropriate evaluation of ultrasound screening of the thyroid, it is important to understand its reference data of thyroid findings in children in general. In order to analyze the frequencies of specific thyroid findings, we conducted ultrasound screening of the thyroid by the same procedures as used in Fukushima in 4,365 children, aged 3 to 18 years, from three Japanese prefectures. Overall, thyroid cysts were identified in 56.88% and thyroid nodules in 1.65% of the participants. Thyroid cysts and nodules with a maximum diameter of more than 5 mm were identified in 4.58% and 1.01%, respectively, and age-adjusted prevalences were 3.82% and 0.99%, respectively. Although the prevalence of cysts and nodules varied among the examination areas, no significant differences were observed among the three examination areas in the prevalence of cysts and nodules with a maximum diameter of more than 5 mm. Also, the prevalence of thyroid cysts and nodules, especially those with a maximum diameter of more than 5 mm, significantly increased with age, and showed a female predominance. We also identified ectopic thymus (1.95%), diffuse goiter (1.40%), ultimobranchial body (0.73%), lymph node swelling (0.21%) and thyroid agenesis (0.05%). This is the first ultrasound description of the age-adjusted prevalence of thyroid cysts and nodules, or of the prevalence of abnormalities other than cysts and nodules, such as ectopic thymus, in relation to age, in the general Japanese child population. We contend that this can provide relevant information for the Fukushima Health Management Survey and future population studies.

[A questionnaire survey on current status of anti-diabetic therapy for diabetic patients with dementia].

AIM: It is important to establish treatment goals and optimal anti-diabetic therapy for diabetic patients with dementia. However, there are currently no established treatment guidelines. Recently, the West Tokyo Diabetes Association has established the Diabetes and Dementia Study Group to investigate the status of anti-diabetic therapy for diabetic patients with dementia. Here, we assessed the current status of such patients by a questionnaire survey. METHODS: In November 2011, we conducted a mailed survey to the clinics and hospitals affiliated with Kita-Tama, Hachioji and Tachikawa Medical Associations in Tokyo, Japan. The survey evaluated the most suitable anti-diabetic therapy for elderly diabetic patients or diabetic patients with dementia, combined anti-diabetic therapy, insulin therapy for elderly diabetic patients and diabetic patients with dementia, combination therapy of insulin and oral anti-diabetic agents for diabetic patients with dementia, factors that make it difficult for diabetic patients with dementia to continue insulin therapy, and selection of treatment or care for diabetic patients with dementia. RESULTS: The responses indicated that the anti-diabetic agents appropriate for diabetic patients with dementia are dipeptidyl peptidase-4 inhibitors. Those inappropriate for the same patients are metformin and insulin. Family support was a major factor for insulin therapy continuation for diabetic patients with dementia. Moreover, anti-diabetic agents for these patients are selected according to their ease of use and compatibility with available familial and social resources. CONCLUSION: Our survey results can be utilized for the creation of new guidelines and educational resources for the anti-diabetic therapy of diabetic patients with dementia.

Ultrasonographic thyroid nodular findings in Japanese children.

PURPOSE: The Fukushima Health Management Survey conducted after the accident at the Fukushima Nuclear Power Plant included thyroid ultrasound examinations for children aged ≤18 years at the time of the accident. The purpose of this study was to investigate the frequency of thyroid nodular lesions detected using high-quality ultrasonography in a general population of Japanese children, in whom such data have not been previously characterized. METHODS: The current study investigated 4,365 free-living children aged between 3 and 18 years in three Japanese prefectures (Aomori, Yamanashi and Nagasaki). The same ultrasonography equipment as that used in the Fukushima Survey was employed to observe thyroid nodular lesions. The following categories of findings were used-'A', further examinations are not necessary; 'B', the presence of thyroid nodules with a diameter of ≥5.1 mm or thyroid cysts with a diameter of ≥20.1 mm; and 'C', immediate further examinations are required. As a sub-category of 'A', 'A1' was defined as the absence of nodules or cysts, and 'A2' was defined as the presence of thyroid nodules with a diameter of ≤5.0 mm or thyroid cysts with a diameter of ≤20.0 mm. RESULTS: Overall, 4,321 (99 %) of the total participants were classified with a status of 'A' and 44 (1 %) were classified with a status of 'B'. No participants were classified with a status of 'C'. A total of 56.5 % of the total participants was classified with a status of 'A2'. Thyroid nodules were identified in 1.6 % of the total participants and thyroid cysts were identified in 56.9 % of the participants. CONCLUSION: The current study provides data regarding the actual frequency of ultrasonographically detected thyroid nodular lesions among the Japanese children. These results would be useful for evaluating thyroid findings in Japanese children, although careful interpretation is required.

Randomized controlled trial of single-agent glimepiride and pioglitazone in Japanese patients with type 2 diabetes: A comparative study.

UNLABELLED: Aims/Introduction: To compare first-line, single-agent glimepiride and pioglitazone in Japanese patients with type 2 diabetes uncontrolled by diet and exercise with respect to glycemic control, safety and metabolic changes. MATERIALS AND METHODS: Patients with previously untreated type 2 diabetes were enrolled in a multicenter, randomized, non-blind, parallel-group trial of glimepiride (0.5-6 mg/day) or pioglitazone (15-45 mg/day) for 6 months. RESULTS: A total of 191 patients aged 30-75 years were randomized. Similar percentages of patients attained the primary end-point, with glycated hemoglobin < 6.9% at month 6 with glimepiride and pioglitazone, respectively (61.2 vs 56.8%, P = 0.64). At month 6, the following significant (P < 0.05) intragroup changes in mean plasma lipid concentrations were noted as compared with baseline: total cholesterol decreased from 203.5 to 195.5 mg/dL and low-density lipoprotein (LDL)-cholesterol decreased from 124.5 to 116.3 mg/dL in the glimepiride group, whereas high-density lipoprotein (HDL)-cholesterol increased from 51.6 to 56.0 mg/dL and triglycerides decreased from 167.6 to 143.6 mg/dL in the pioglitazone group. The only symptomatic adverse events were mild-to-moderate in four patients receiving pioglitazone, and constipation in one patient receiving glimepiride. Similar numbers of patients experienced asymptomatic hypoglycemia (<60 mg/dL) in the glimepiride and pioglitazone groups (n = 7 and 5, respectively). CONCLUSIONS: There was no statistically significant difference between glimepiride and pioglitazone with respect to glycemic control, and both agents were well tolerated. Glimepiride significantly lowered total cholesterol and LDL-cholesterol, whereas pioglitazone increased HDL-cholesterol. This trial was registered with University Hospital Medical Information Network (UMIN), Japan, UMIN000004582. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00115.x, 2011).

Changes in interventional treatment--from the viewpoint of percutaneous ethanol injection therapy.

The environment surrounding secondary hyperparathyroidism treatment has changed and the transition of the guidelines on selective percutaneous ethanol injection therapy (PEIT) for secondary hyperparathyroidism from 2000 to 2006 has been made. The new guidelines emphasize the point that PEIT is best indicated for patients with one enlarged gland. Among treatments, including local vitamin D injection, selective PEIT and parathyroidectomy, cinacalcet is a potent medical treatment and will be a very effective new post-treatment intervention. However, it is expected that some patients will require active intervention based on morphological examination even if biochemical control is possible with cinacalcet administration.

Percutaneous ethanol injection therapy for advanced renal hyperparathyroidism in Japan: 2004 survey by the Japanese Society for Parathyroid Intervention.

Background. Marked hyperplasia of the parathyroid gland (PTG) is a characteristic feature of severe hyperparathyroidism in patients under chronic haemodialysis treatment. Percutaneous ethanol injection therapy (PEIT) is now becoming popular in Japan as a treatment option for secondary hyperparathyroidism (SHPT) and its cost is covered by the National Health Insurance (NHI) System. The Japanese Society for Parathyroid Intervention surveyed its membership in 2004 to revise the guidelines for the use of PEIT. Methods. The project was approved by the Executive Committee of the Society, and the primary questionnaire was addressed to 3268 centres (departments) affiliated with the Japanese Society for Dialysis Therapy. A follow-up questionnaire was sent to all the centres that responded. Results. Although the number of centres to which the questionnaire was sent in 2004 was 3268, compared with 2653 in 1998, the number of responses decreased from 1425 (53.7%) in 1998 to 962 (29.4%) in 2004. To the question of whether the centre performed PEIT, 114 (11.9%) answered 'Yes' and 848 (88.1%) answered 'No' in 2004. It was an increase from 1998 when only 83 (5.8%) of 1425 centres answered 'Yes'. In the 1998 survey, 612 patients underwent PEIT at 74 centres, and in 2004, 2098 patients underwent PEIT at 111 centres. Conclusions. PEIT may become the frequently performed treatment for SHPT patients who become resistant to medical therapy. However, the same problems as in 1998 remain unsolved; that is, recurrent nerve paralysis, difficulty of post-PEIT PTx and lack of evidence showing the long-term effectiveness of PEIT.

New clinical guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients.

In 2000, the Japanese Society for Parathyroid Intervention issued the 'Guidelines for percutaneous ethanol injection therapy of the parathyroid glands in chronic dialysis patients'. Since then, the concept of 'selective PEIT' has been well accepted and the number of patients treated by this method in Japan has increased. Recently, it has been reported that the effect of PEIT differs depending on the degree of nodular hyperplasia. Several new drugs have become available since 2000, and active vitamin D and its analogue have also been used for direct injection into the parathyroids. We present the new 'Guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients', a revised version of the 2000 Guidelines. We believe that these new guidelines are useful for selecting direct injection therapy in patients with advanced secondary hyperparathyroidism.

[Fine-needle aspiration biopsy of the thyroid nodule: uses and limitations].

Thyroid nodules are a common occurrence in the general population, but only a small number of them are eventually diagnosed as cancers. Fine-needle aspiration biopsy (FNAB) is currently safe, the most accurate, and cost-effective method for the presurgical management of thyroid nodules, but there is a difficulty of the differential diagnosis between thyroid follicular adenomas and follicular carcinomas. The use of cellular markers may be useful in distinguishing follicular carcinoma from follicular adenomas. Several markers such as galectin 3 and HBME-1 initially appeared promising, but some discrepant results have been reported for these cellular markers. At the present time, assessing the likelihood of malignancy by examining various clinical parameters is an useful approach for follicular neoplasm.