Left atrial metastasis of renal cell carcinoma: a case report and review of the literature

Background: Cardiac metastasis of renal cell carcinoma is an exceptional event, particularly when there is lack of inferior vena cava involvement. Indeed, only a few cases have been reported worldwide thus far. Moreover, discussion of treatment and follow-up strategies for cardiac metastasis of renal cell carcinoma is important because of the high risk of sudden death. Case presentation. We report the case of a 75-year-old Japanese man with metastatic tumor in the left atrium from renal cell carcinoma. He had a history of right renal cell carcinoma, for which he had undergone hand-assisted laparoscopic nephrectomy. Lung and bone metastases were detected after nephrectomy, and treatment with interferon-alpha was initiated. After disease progression, he was treated concurrently with targeted molecular therapy and radiotherapy for bone metastasis. After these therapies, a 42 × 24 mm mass was found on transthoracic echocardiography in left atrium without involvement of the right atrium or inferior vena cava. The provisional diagnosis was metastatic mass or myxoma, and surgical resection was performed. Histopathological examination led to a final diagnosis of metastatic tumor from clear cell renal cell carcinoma. Conclusion: Cardiac metastasis, metastasis to the left atrium in particular, is rare in patients with renal cell carcinoma. In our study, surgery of the cardiac mass was effective to avoid sudden death and quality of life decline resulting from heart failure. We describe this case and review cardiac metastasis of renal cell carcinoma

Age, Symptomatic Metastatic Disease, and Malignant Pleural Effusion as Predictors of Poor Prognosis in Patients with Differentiated Thyroid Carcinoma Treated with Lenvatinib.

Background: Lenvatinib is one of the few therapeutic options available for radioiodine-refractory thyroid cancer. However, the factors that determine the therapeutic outcomes remain unknown.Methods: Patients with thyroid carcinoma treated with lenvatinib who had been dead or who had survived for longer than a halfyearwere retrospectively compared. We evaluated the clinical parameters when lenvatinib was started, and also studied the tumor volume reduction ratio, the duration until re-growth of the largest metastatic lesion, the thyroglobulin (Tg) reduction rate,and the duration until re-elevation of Tg after lenvatinib between survivors and dead patients.Results: We identified 16 patients, with an average age of 73.1±7.6 yrs and a male-to-female ratio of 5 to 11, who had advanced differentiated thyroid cancer that was treated with lenvatinib. Nine patients had died after 8.9±6.1 months, whereas 7 survived for 13.0±2.0 months after starting lenvatinib. The patients who died were older than the survivors (76.7±6.5 vs. 68.6±6.6 yrs, p=0.03).Malignant pleural effusion (p=0.017) and symptomatic metastatic disease (SMD) (p=0.039) were associated with death in a Kaplan-Meier survival analysis. Age (p=0.012, HR 1.150, CI 1.030-1.320) and SMD (p=0.014, HR 8.069, CI 1.503-61.34) wereassociated with poor outcome in a multivariate Cox proportional hazard model. The duration until the re-elevation of Tg waslonger in survivors than in patients who died (6.43±4.55 vs. 2.17±1.39 months, p=0.025).Conclusions: We identified multiple factors, including SMD, that were related to poor outcomes after lenvatinib treatment. This study suggests that lenvatinib might be started before patients develop SMD

Cyclooxygenase-2 is Involved in the Progression of Thyroid Cancer

Although the inducible form of cyclooxygenase (COX), COX-2, is highly expressed in various cancers and it is also involved in cancer progression, its role in thyroid cancer is not fully understood. We assessed in the situ cyclooxygenase expression in normal thyroids (n=6), Graves\u27 thyroids (n=6), thyroid adenomas (n=12), thyroid follicular (n=15) and papillary carcinomas (n=30). In comparison to the constitutive expression of COX-1, COX-2 was highly expressed in thyroid cancers (90.0% of thyroid papillary carcinomas and 73.3% of thyroid follicular carcinomas) and moderately in thyroid adenomas (25.5%), but barely expressed in normal and Graves\u27 thyroid tissues. This quantitative assessment employed immunohistochemical methods. Thereafter we compared the effect of COX-2 inhibition on a human follicular thyroid carcinoma cell line (WRO), and a human papillary carcinoma cell line (NPA), using selective COX-2 inhibitor(NS-398). The treatment with 50 μM NS-398 suppressed the growth of the COX-2 expressing cells, NPA cells (37.7%;p<0.01) and WRO cells (10.1%;p<0.05). Moreover, at concentrations ? 100 μM, NS-398 induced cell death a mitochondrial dysfunction. In addition, 50 μM of NS-398 inhibited the activation of extracellular signal-regulated kinase in NPA cells after the stimulation with fetal bovine serum. Our results indicate that COX-2 is involved in the progression of thyroid cancer

Clinical and genetic characteristics of autoimmune polyglandular syndrome type 3 variant in the Japanese population

Objective: Type 1 diabetes (T1D) iscommonlyassociated withautoimmunethyroid disease (AITD),and the occurrence of both T1D and AITD in a patient is defined as autoimmune polyglandular syndrome type 3 variant (APS3v). We aimed to clarify the differences in the clinical and genetic characteristics of APS3v patients and T1D patients without AITD [T1D/AITD(-)] in the Japanese population. Design/Patients: Our subjects were 54 APS3v patients and 143 T1D/AITD(-) patients who were consecutively diagnosed at Nagasaki University Hospital from 1983 to the present. Results: A remarkable female predominance, a slow and older age onset of T1D, and a higher prevalence of glutamic acid decarboxylase autoantibodies were observed in APS3v patients compared to T1D/AITD(-) patients. The older onset age of T1D in APS3v patients was associated with a higher proportion of slow-onset T1D. Among the two major susceptible human leukocyte antigen (HLA) class II haplotypes in Japanese T1D, DRB1*0405- DQB1*0401, but not DRB1*0901-DQB1*0303, was associated with APS3v patients. Furthermore, DRB1*0803-DQB1*0601 was not protective in patients with APS3v. The frequencies of the GG genotype in +49G>A and +6230G>A polymorphism in the CTLA4 gene were significantly higher in T1D/AITD(-) patients, but not in APS3v patients, compared to control subjects. Conclusions: In conclusion, we found notable differences in the clinical and genetic characteristics of APS3v patients and T1D/AITD(-) patients in the Japanese population, and the differences in the clinical characteristics between the two groups may reflect distinct genetic backgrounds including the HLA DRB1-DQB1 haplotypes and CTLA4 gene polymorphisms

A case of compressive optic neuropathy putatively caused by IgG4-related idiopathic orbital inflammation.

We report the case of a 58-year-old male presenting with an impairment of the left-sided visual acuity caused by compressiveoptic neuropathy, and marked bilateral proptosis. Blood test showed markedly elevated IgG4 (1830 mg/dl) and positiveTSH receptor-stimulating antibodies (200%), but the thyroid function test were normal. Orbital MRI revealed abnormal soft tissueproliferation around the optic nerve and fusiform enlargement of the extraocular muscles. Systemic CT analysis detectedmultiple lymph node swelling, pseudotumor in the lung, retroperitoneal fibrosis, and kidney lesions. We considered that the eyemanifestation was most likely caused by IgG4-related idiopathic orbital inflammation. Systemic administration of a moderatedose of prednisolone dramatically improved the compression of the optic nerve, as shown by the improvement of the visualacuity and the MRI findings. The clinical course made thyroid-associated ophthalmopathy unlikely. In conclusion, an overallconsideration of the clinical picture and extensive work-up of any possible differential diagnosis including measurement of theserum levels of IgG4 was highly useful in making the diagnosis of the patient

Graves\u27 disease complicated by ventricular fibrillation in three men who were smokers.

Thyrotoxicosis is known to be associated with sinus tachycardia and supraventricular tachyarrhythmias, but rarely with ventricular fibrillation (Vf), which has only occurred in some patients with hypokalemic periodic paralysis or ischemic heart disease. PATIENT FINDINGS: We present three men who were transferred to our hospital with Graves\u27 disease who developed idiopathic Vf. None of them had hypokalemic periodic paralysis or ischemic heart disease but all were smokers. None of other patients with thyrotoxicosis (587 females and 155 males) who were seen at our hospital, in the period during which the three men were seen, had idiopathic Vf. In our three men with thyrotoxicosis and idiopathic Vf, there was no identifiable underlying heart disease. One of the three patients died of hypoxic encephalopathy. The other two men did not have recurrent Vf after their thyroid function normalized

Risk for Progression to Overt Hypothyroidism in an Elderly Japanese Population with Subclinical Hypothyroidism

Background: Few population-based studies report the changes with time in thyroid function tests in patients with subclinical hypothyroidism. We compared the risk for developing overt hypothyroidism in patients with subclinical hypothyroidism and euthyroid controls from the same population of elderly Japanese. We also sought associations of selected parameters with the development of overt hypothyroidism in the subclinical hypothyroid and euthyroid groups. Methods: We measured thyrotropin (TSH) and free thyroxine (T4) levels at baseline examinations performed from 2000 to 2003 in the cohort of Japanese atomic-bomb survivors and identified 71 patients with spontaneous subclinical hypothyroidism (normal free T4 and TSH >4.5 mIU/L without a history of thyroid treatment, mean age 70 year) and 562 euthyroid controls. We re-examined TSH and free T4 levels an average of 4.2 years later (range, 1.9-6.9). Results: The risk for progression to overt hypothyroidism was significantly increased in subclinical hypothyroid patients (7.0%) compared with control subjects (1.6%) after adjusting for age and sex (odds ratio, 4.56; p=0.009). Higher baseline TSH levels were associated with progression from subclinical to overt hypothyroidism (p=0.02) in the multivariate analysis, including age, sex, antithyroid peroxidase antibody, and ultrasonography (US) findings. The analysis using binary TSH data suggested that a TSH level >8 mIU/L was a predictive value for development of overt hypothyroidism (p=0.005). On the other hand, serum TSH levels spontaneously normalized in 38 (53.5%) of the patients with subclinical hypothyroidism. In the multivariate analysis, normalization of TSH levels was associated with lower baseline TSH levels (p=0.004) and normal and homogenous thyroid US findings (p=0.04). Atomic-bomb radiation dose was not associated with subclinical hypothyroidism or its course. Conclusions: Subclinical hypothyroidism was four times more likely to be associated with development of overt hypothyroidism than euthyroid controls in the sample population of Japanese elderly. TSH levels in half of the patients normalized spontaneously when assessed after an average follow-up period of 4.2 years. Baseline TSH level and thyroid US findings are potential predictors of future thyroid function in subclinical hypothyroidism

Non-specific Activities against Ruthenium Crosslinker as a New Cause of Assay Interference in an Electrochemilluminescent Immunoassay

Clinical assays are very important for the diagnosis and management of clinical disorders. Each assay system consists of a specific method to detect and/or quantify a substance of interest in the clinical specimen. However, clinical assays can be unfavorably influenced by non-specific activities concomitantly present in the specimen, which may mislead clinical decisions. Thus, it is very important to know how each assay works, and how and when the assay is non-specifically influenced. Here, we report three cases shown clinical data of thyroid function influenced by new type of assay interference