Background: The question of how to manage patients with low-risk papillary thyroid microcarcinoma (PTMC; T1aN0M0) has recently become an important clinical issue. Two Japanese centers have conducted prospective clinical trials of active surveillance (AS) for low-risk PTMC since the 1990s, reporting favorable outcomes. This policy has thus seen gradual adoption worldwide to avoid overtreatment. Not all PTMCs are suitable for AS, however, and many physicians still hesitate to apply the management policy in daily clinical practice. A task force on management for PTMC created by the Japan Association of Endocrine Surgery collected and analyzed bibliographic evidence and has produced the present consensus statements regarding indications and concrete strategies for AS to facilitate the management of adult patients diagnosed with low-risk PTMC. Summary: These statements provide indications for AS in adult patients with T1aN0M0 low-risk PTMC. PTMCs with clinical lymph node metastasis, distant metastasis, recurrent laryngeal nerve (RLN) paralysis due to carcinoma invasion, or protrusion into the tracheal lumen warrant immediate surgery. Tumors suspected of aggressive subtypes on cytology are recommended for immediate surgery. Immediate surgery is also recommended for tumors adherent to the trachea or located along the course of the RLN. Practical strategies include diagnosis, decision-making, follow-up, and monitoring related to the implementation of AS. The rate of low-risk PTMC progression is lower in older patients. However, we recommend continuing AS as long as circumstances permit. Future tasks in optimizing management for low-risk PTMC are also described, including molecular markers and patient-reported outcomes. Conclusions: An appropriate multidisciplinary team is necessary to accurately evaluate primary tumors and lymph nodes at the beginning of and during AS, and to adequately reach a shared-decision with individual patients. If appropriately applied, AS of low-risk PTMC is a safe management strategy offering favorable outcomes and preserves quality of life at low cost.

awasaki disease (KD) is a systemic vasculitis that primarily affects small and medium-sized arteries. 1 Transient myocardial dysfunction in children with acute KD has been reported 2,3 and moreover, myocardial inflammation, including myocarditis and microvascular damage in the myocardium, has been shown to cause aberrations in cardiac function. 4 Several recent studies have discussed the usefulness of tissue Doppler imaging (TDI) to evaluate left ventricular (LV) function. [5][6][7][8][9][10][11][12][13][14] Tissue Doppler measurement of myocardial Doppler velocity can be used to measure long-axis functions, which seem to be both more sensitive to minor disturbances in LV function and relatively preload-independent. 11,[13][14] In the present study we used TDI to evaluate disturbance of myocardial function in acute KD patients. Circulation Journal Vol.71, March 2007The plasma brain natriuretic peptide (BNP) level is associated with cardiac function in adult patients with congestive heart failure. 15,16 Although elevation of BNP has been reported in acute KD patients,17 no relation between BNP and cardiac function has been found.Reports have suggested that increased systemic oxidative stress is associated with progression of cardiovascular disease, including ischemia -reperfusion injury, atherosclerosis, and heart failure. [18][19][20][21][22][23][24] The isoprostanes are a complex family of compounds produced from arachidonic acid via a free radical-catalyzed mechanism. 18,19 The level of 8-isoprostane is used as a pathophysiological marker of lipid peroxidation. We previously reported elevation of urinary 8-isoprostane levels in acute KD patients, 25 and although the exact pathological role of increased oxidative stress in acute KD is uncertain, we believe that it is associated with oxidative injury to systemic vessels. 25 We hypothesize that this combined with disturbance of myocardial microcirculation may contribute to myocardial dysfunction in acute KD. Therefore, the purpose of the present study was to investigate the relationship between abnormal myocardial performance and plasma BNP levels, and to investigate the association between abnormal myocardial performance and enhanced oxidative stress. Background The aims of this study were to evaluate myocardial mechanics using pulsed tissue Doppler imaging (TDI), and to determine the relationship between abnormal myocardial performance and plasma brain natriuretic peptide (BNP) levels and oxidative stress in acute Kawasaki disease (KD). Methods and ResultsConsecutive TDI parameters, including peak systolic velocity (Sw) and early (Ew) and late diastolic excursion of the mitral annuli were obtained in 42 patients with KD (mean age: 2.4±0.4 years) in weeks 1, 2, and 3, and during convalescence. Plasma BNP level and urinary 8-isoprostane were also examined during the acute phase. These data were then compared with TDI profiles from 62 healthy children, plasma BNP levels in 38 controls with other febrile illnesses, and urinary 8-isoprostane levels in 13 healthy chi...

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Breast cancer (BC) is the most common malignant tumor among women worldwide. Development of novel molecular targets is important to improve prognosis of BC patients. Derlin 3 (DERL3) gene is a member of derlin family, and its coding protein is critical to the endoplasmic reticulum-associated degradation mechanism. However, its oncological role in breast cancer remains unclear. This study evaluated DERL3 expression and function in BC. We analyzed DERL3 mRNA in 13 BC and two non-cancerous cell lines, and explored effects of DERL3 knockdown on BC proliferation, invasion and migration. We also evaluated correlation of DERL3 mRNA expression levels with clinicopathological factors and prognosis in 167 BC patients. DERL3 mRNA expression was detected in five (38%) BC cell lines. Inhibiting DERL3 expression significantly decreased proliferation and invasion in BC cells. Specimens from patients with lymph node metastasis had higher DERL3 mRNA expression than those without (P=0.030). Patients in the highest quartile for DERL3 mRNA expression (n=42) were more likely to experience shorter overall survival than other patients (P=0.032). These findings indicate that DERL3 promotes malignant phenotype in BC cells. DERL3 may serve as a potential prognostic marker and therapeutic target for BC.

xidative stress (OS) plays an important role in vascular diseases. Endothelial dysfunction activates the pathway that leads to elevated OS. 1 In particular, oxidative damage occurs when the delicate balance between pro-and antioxidant molecules, which act against free radical injury, is upset. This balance may be destroyed by certain risk factors; for example, atherosclerosis, hypertension, hyperlipidemia, diabetes and cigarette smoking. [2][3][4][5][6] The 8-isoprostaglandin F2α (8-iso-PG) is a nonenzymatic oxidation product of arachidonic acid and is widely recognized as a reliable marker of lipid peroxidation both in vitro and in vivo. 3,4,7 Enhanced endothelial dysfunction, as reflected by increased 8-iso-PG excretion, has been reported previously. [3][4][5] Kawasaki disease (KD) is a systemic vasculitis and an acute febrile illness (FI) in children. Recent studies have shown activation of the immune system is involved and multiple factors are likely to cause the pathologic changes seen in KD. [8][9][10][11] How OS contributes to the acute phase of KD is as yet unknown.In the present study, we investigated OS in the acute phase of KD by measuring urinary 8-iso-PG and evaluated its correlation to the efficacy of intravenous immunoglobulin (IVIG) treatment. Methods PatientsAll subjects of this study were typical KD patients admitted to Toho University Hospital between March 2002 and September 2004. They were given IVIG (1-2 g/kg) therapy in the acute phase: 62 patients (37 boys, 25 girls, median age: 4 years, range: 2 months to 11 years) were enrolled. None of the patients had other disorders, such as infection, collagen disease or congenital heart disease. We also studied 20 healthy children (HC, median age: 4 years, range: 1-11 years) and 20 patients with an acute FI such as viral pharyngitis and tonsillitis (median age: 5 years, range: 1-10 years). Informed consent was given by the parents of the patients participating in the study. Biochemical MeasurementsUrinary 8-iso-PG was measured by enzyme immunoassay and the concentration was corrected by urinary creatinine concentration. The samples were obtained before and after IVIG administration. In the HC and FI groups inflammatory markers such as C-reactive protein (CRP), white blood cell (WBC) count, neutrophil count, albumin level and erythrocyte sedimentation rate (ESR) were measured at the same time. Echocardiography was performed in the patients in the acute phase of KD. Statistical AnalysisDifferences between continuous variables were evaluated by t-test. The data for each group were analyzed using ANOVA. The relationship between 2 different parameters was obtained by simple regression analysis. A P-value <0.05 was considered statistically significant. (Received August 29, 2007; revised manuscript received February 2, 2009; accepted February 18, 2009; released online May 13, 2009) Pediatrics, Toho University Omori Medical Center, Tokyo, Japan Mailing address: Shinchi Takatsuki, MD, Pediatrics, Toho University Omori Medical Center, 6-11-1 Omorinishi, O...

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Although there are many biomarkers for heart failure, limited data are available regarding their prognostic value in adult congenital heart disease (ACHD). We investigated the potential of various biomarkers to predict ACHD mortality in a single-center, retrospective cohort study. Blood levels of neurohormones [angiotensin II, endothelin-1 (ET-1), norepinephrine (NE), aldosterone, and plasma renin activity]; inflammatory biomarkers [high-sensitivity C-reactive protein (hs-CRP), high-sensitivity tumor necrosis factor, soluble TNF receptor type I and II (sTNF-RI and sTNF-RII), and interleukin-6 (IL-6)]; and brain natriuretic peptide (BNP) were measured in 103 ACHD patients (median age 28 years). Subjects were divided into patients with single-ventricle physiology (SV group, n = 61) and those with two-ventricle physiology (TV group, n = 42); and into patients with a systemic right ventricle (SRV group, n = 25) and those with a systemic left ventricle (SLV group, n = 78). During a median follow-up period of 6.5 years, 12 patients (11 %) died of acute decompensated heart failure (ADHF). Predictive biomarkers, which are related to the New York Heart Association class and cardiothoracic ratio, were as follows: elevated levels of BNP, ET-1, sTNF-RI, NE, and IL-6 in the overall patient group; IL-6, NE, hs-CRP, BNP, and ET-1 in the TV group; BNP and ET-1 in the SV group; BNP, NE, hs-CRP, sTNF-RI, IL-6, and ET-1 in the SLV group. Elevated levels of ET-1 in SRV groups were slightly although not significantly associated with these. Various clinical biomarkers are associated with ADHF mortality in ACHD patients. The most prominent mortality predictors in biomarker profiles may vary according to differences in ventricular physiology and systemic ventricle morphology.

Breast cancer (BC) is the most common malignant tumor in females. Development of novel biomarkers or therapeutic targets may contribute toward the improvement of a patient's prognosis. Marginal zone B and B1 cell-specific protein (MZB1) is an unfolded protein response-related chaperone and mainly exists in the endoplasmic reticulum of B lymphocytes, although little is known regarding its role in BC cells. The present study aimed to investigate the significance of MZB1 expression in BC. To begin with, MZB1 mRNA expression levels in 13 BC cell lines and two non-cancerous mammary cell lines were evaluated. Next, mRNA and protein expression of MZB1 in BC patient tumor specimens was evaluated to assess the association between expression and clinicopathological factors or prognosis. MZB1 mRNA expression levels were detectable in four estrogen receptor (ER)-positive BC cell lines. When ratios of MZB1 mRNA expression levels between BC and non-cancerous specimens were evaluated, patients with stage III disease exhibited a higher ratio than patients with stage 0/I/II disease (P=0.009). Using immunohistochemistry, patients with ER-positive BC more frequently expressed MZB1, compared with patients with ER-negative BC (P=0.003). In patients with ER-positive BC, patients with MZB1-positive BC experienced shorter disease-free survival (DFS) times than patients with negative BC (P=0.026). Multivariate analysis of DFS demonstrated that MZB1 positivity was an independent prognostic factor (P=0.022). The results of the present study suggested that MZB1 expression may be associated with a more advanced stage of BC. Furthermore, in patients with ER-positive BC, MZB1 may be a potential prognostic marker.