Fine needle aspiration cytology of nodular fasciitis of the breast

We report a case of nodular fasciitis (NF) of the breast, which was cytologically diagnosed as a spindle cell proliferation with undetermined malignant potential. Owing to small size of the lesion (5.9 × 3.7 × 4.1 mm), only fine needle aspiration (FNA) cytology was performed under ultrasound guidance. The FNA smears were cellular, rich in single/clustered spindle cells but mammary ductal epithelial/myoepithelial cells were absent. These cytologic findings suggested spindle cell growth of mesenchymal origin. Pattern‐less arrangement of spindle cells, heterogeneous composition of the stromal matrix, lack of nuclear/cellular atypia, occasional mitosis but no aberrant mitotic figures, and lymphocyte infiltration indicated reactive rather than neoplastic nature of the lesion. Nonetheless, lumpectomy was conducted because the possibility of neoplasm was not completely ruled out. The histologic diagnosis of the resected nodule was NF. FNA specimens were reviewed thoroughly in an attempt to define the key cytomorphologic features of NF that are important for the correct diagnosis. Differential diagnoses from the lesions that show similar cytologic pictures are discussed in detail. Although NF arising from the breast is rare, cytopathologists should be aware of its clinical and cytopathologic characteristics. Knowledge of the possibility of NF in the breast and its cytologic findings may help cytopathologists to discern its reactive, not neoplastic, characteristics of the lesion. If the referring surgeon is alerted NF as a possibility along with other differential diagnoses, close observation would become a management option. In‐depth discussion of cytologic features and a review of the pertinent literature are also included. Diagn. Cytopathol. 2015;43:222–229. © 2014 Wiley Periodicals, Inc.     

Pulmonary metastasectomy for pulmonary metastasis of breast cancer has a limited prognostic impact: a multi-institutional retrospective analysis

BackgroundPulmonary metastasectomy (PM) for breast cancer-derived pulmonary metastasis is controversial. This study aimed to assess the prognostic factors and implication of PM for metastatic breast cancer using a multi-institutional database.MethodsClinical data of 253 females with pulmonary metastasis of breast cancer who underwent PM between 1982 and 2017 were analyzed retrospectively.ResultsThe median patient age was 56 years. The median follow-up period was 5.4 years, and the median disease-free interval (DFI) was 4.8 years. The 5- and 10-year survival rates after PM were 64.9% and 50.4%, respectively, and the median overall survival was 10.1 years. Univariate analysis revealed that the period of PM before 2000, a DFI <36 months, lobectomy/pneumonectomy, large tumor size, and lymph node metastasis were predictive of a worse overall survival. In the multivariate analysis, a DFI <36 months, large tumor size, and lymph node metastasis remained significantly related to overall survival. The 5- and 10-year cancer-specific survival rates after PM were 66.9% and 54.7%, respectively, and the median cancer-specific survival was 13.1 years. Univariate analyses revealed that the period of PM before 2000, DFI <36 months, lobectomy/pneumonectomy, large tumor size, lymph node metastasis, and incomplete resection were predictive of a worse cancer-specific survival. Multivariate analysis confirmed that a DFI <36 months, large tumor size and incomplete resection were significantly related to cancer-specific survival.ConclusionsAs PM has limited efficacy in breast cancer, it should be considered an optional treatment for pulmonary metastasis of breast cancer.     

Comparison of the in vitro Effects of One-day Exposure to Amodiaquine and Praziquantel on Schistosoma mansoni Adult Worm Pairs

It has been demonstrated that continuous exposure to amodiaquine (AQ) alone elicits in vitro antischistosomal activities at concentrations of 1–10 μg/ml. However, orally administered drugs reach a peak blood concentration within one or two hours and then gradually decrease. The blood concentration does not remain at a constant level over several days as in vitro concentration of continuous drug exposure. In vitro activities by one day exposure to AQ better reflect the actual antischistosomal activities after oral administration than those elicited by continuous exposure.The objective of the present study is to compare the antischistosomal potential of one-day exposure to AQ with that to praziquantel (PZQ), a current antischistosomal drug. Schistosoma mansoni adult worm pairs were incubated with 0 (control), 1, 2, 5 and 10 μg/ml AQ as well as 0.01, 0.02, 0.05 and 0.1 μg/ml PZQ for the first day, and were subsequently incubated in drug-free media for a period of 14 days. The one-day exposure to AQ significantly reduced the daily egg output of the worm pairs at 1–10 μg/ml. The inhibitory effect on egg production continued at 5 and 10 μg/ml but proved temporary at 1 and 2 μg/ml. Furthermore, AQ-induced specific morphological alterations (severe swelling and/or localization of hemozoin) were observed in the worms at 5 and 10 μg/ml. The AQ-specific appearance of the male worms gradually faded during subsequent incubation in drug-free media, although the female worms showed elongation. Meanwhile, PZQ inhibited the egg output of adult worm pairs at concentrations of 0.01–0.1 μg/ml during exposure. The inhibitory effect on egg production continued at 0.05 and 0.1 μg/ml but proved temporary at 0.01 and 0.02 μg/ml. Furthermore, PZQ induced a visible contraction and shortening of the male and female worms at 0.05 and 0.1 μg/ml during exposure, but the PZQ-specific alterations quickly disappeared during subsequent incubation in drug-free media. To our knowledge, this is the first report showing that one-day exposure to AQ inhibits the egg production of adult worm pairs at 1–10 μg/ml and induces specific morphological alterations in the worms at 5 and 10 μg/ml. The present findings have important implications for the evaluation of the therapeutic effects of both AQ monotherapy and combination therapy with artesunate on schistosomiasis in clinical field trials.     

Prognostic significance of WNT signaling in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is associated with a variety of molecular abnormalities. Although WNT signaling through its canonical/non-canonical pathways is one of the major factors involved in oncogenesis or progression of PDA, the prognostic significance of WNT signaling still remains poorly investigated. In this study, the status of the WNT signaling pathways was immunohistochemically analyzed in 101 PDAs, and its potential association with patient postoperative survival was assessed. Nuclear expression of beta-catenin, a hallmark of the activated canonical pathway, was identified in 59 cases, and was associated with reduced survival compared to the patients lacking nuclear beta-catenin expression (P?=?0.002). In contrast, activation of the non-canonical pathway (25 cases), as indicated by co-expression of WNT2/5a and nuclear NFATc1, was not correlated with reduced survival (P?=?0.268). Co-activation of both pathways (16 cases) was associated with worse prognosis in comparison with cases with an activated non-canonical pathway (P?=?0.034). In addition, nuclear beta-catenin expression was an independent unfavorable prognostic factor (P?=?0.006). Our data indicate that activated WNT signaling through its canonical pathway has a significantly negative effect on the clinical course of PDA, and the canonical WNT pathway should be considered as a future therapeutic target for PDA.     

Relationship and factors responsible for regulating fasting and post‐challenge plasma glucose levels in the early stage development of type 2 diabetes mellitus

Aims/Introduction

Elevation of 2-h plasma glucose (2-h PG) levels keeps step with fasting plasma glucose (FPG) levels elevation, but some individuals show dominant elevation of 2-h PG and others FPG. We analyzed dependent and independent relationships between 2-h PG and FPG, and investigated the factors regulating 2-h PG and FPG.

Materials and Methods

In 1,657 Japanese participants who underwent a 75-g oral glucose tolerance test at the initial examination for a medical check-up, we carried out simple linear regression analysis between 2-h PG and FPG levels on the three patterns of independent variables. We divided the participants into two subgroups: the 2-h PG-side group and the FPG-side from the regression line, and examined the relationships between 2-h PG-FPG and factors responsible for elevation of plasma glucose levels.

Results

There was a significant positive correlation between 2-h PG and FPG levels. The regression line of both 2-h PG and FPG as independent variables was in accordance with the regression line of 2-h PG as an independent variable and FPG as a dependent variable. In 2-h PG-side group, age was the independent factor affecting 2-h PG in addition to insulinogenic index and insulin sensitivity index (ISI composite). In the FPG-side group, triglyceride was the independent factor affecting FPG in addition to insulinogenic index and ISI composite.

Conclusions

Two-hour PG was an independent predictor of FPG. In addition to the importance of decreased insulin secretion and insulin sensitivity, age was the strong factor to elevate 2-h PG levels in the 2-h PG-side group and triglyceride was the strong factor to elevate FPG levels in the FPG-side group in the early stage of development of type 2 diabetes.     

The immunobiology of colitis and cholangitis in interleukin-23p19 and interleukin-17a deleted dominant negative form of transforming growth factor beta receptor type ii mice

Dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII) mice, expressing a dominant negative form of TGFβ receptor II under control of the CD4 promoter, develop autoimmune colitis and cholangitis. Deficiency in interleukin (IL)-12p40 lead to a marked diminution of inflammation in both the colon and the liver. To distinguish whether IL-12p40 mediates protection by the IL-12 or IL-23 pathways, we generated an IL-23p19(-/-) dnTGFβRII strain deficient in IL-23, but not in IL-12; mice were longitudinally followed for changes in the natural history of disease and immune responses. Interestingly, IL-23p19(-/-) mice demonstrate dramatic improvement in their colitis, but no changes in biliary pathology; mice also manifest reduced T-helper (Th)17 cell populations and unchanged IFN-γ levels. We submit that the IL-12/Th1 pathway is essential for biliary disease pathogenesis, whereas the IL-23/Th17 pathway mediates colitis. To further assess the mechanism of the IL-23-mediated protection from colitis, we generated an IL-17A(-/-) dnTGFβRII strain deficient in IL-17, a major effector cytokine produced by IL-23-dependent Th17 cells. Deletion of the IL-17A gene did not affect the severity of either cholangitis or colitis, suggesting that the IL-23/Th17 pathway contributes to colon disease in an IL-17-independent manner. These results affirm that the IL-12/Th1 pathway is critical to biliary pathology in dnTGFβRII mice, whereas colitis is caused by a direct effect of IL-23. (HEPATOLOGY 2012).     

Reversal of slow growth and heartbeat through the restoration of mitochondrial function in clk-1-deficient mouse embryos by exogenous administration of coenzyme Q10

The longevity gene clk-1/coq7 encodes an enzyme that is essential for the biosynthesis of coenzyme Q (CoQ) in mitochondria and regulates the lifespan and behavioral timing in Caenorhabditis elegans and the chronological lifespan in fission yeast. However, whether the mammalian clk-1/coq7 ortholog (clk-1) regulates these phenotypes in mammals remains to be fully evaluated due to the embryonic lethality of clk-1-deficient (clk-1(-/-)) mice. To investigate whether clk-1 regulates biological functions, such as growth and heartbeat, through CoQ in mouse embryos, we cultivated the cells and hearts of clk-1(-/-) mouse embryos at embryonic day 10.5 (E10.5) for at least 10 days in the presence of fetal bovine serum. In embryonic cells, cardiomyocytes, and hearts, the growth and heart rates were significantly slowed in clk-1(-/-) compared with wild-type or heterozygous mouse tissues. Moreover, frequent apoptosis and a significant reduction in mitochondrial functions, including membrane potential and ATP production, were observed in the clk-1(-/-) cells and hearts. The slowed growth and heart rates and the reduced mitochondrial function of clk-1(-/-) embryonic cells and hearts in culture were almost completely rescued by the administration of exogenous CoQ(10). The results indicate that clk-1 regulates growth and heart rates through CoQ-mediated mitochondrial functions in mouse embryos.     

Effects of Atrial Natriuretic Peptide After Prolonged Hypothermic Storage of the Isolated Rat Heart

Primary graft failure (PGF) caused by ischemia‐reperfusion injury (IRI) is the strongest determinant of perioperative mortality after heart transplantation. Atrial natriuretic peptide (ANP) has been found to reduce the IRI of cardiomyocytes and may be beneficial in alleviating PGF after heart transplantation, although there is a lack of evidence to support this issue. The purpose of this study was to investigate the cardioprotective effects of ANP after prolonged hypothermic storage. For this purpose, an isolated working‐heart rat model was used. After the preparation, the hearts were arrested with and stored in an extracellular‐based cardioplegic solution at 3–4°C for 6 h and followed by 25 min of reperfusion. The hearts were divided into four groups (n = 7 in each group) according to the timing of ANP administration: Group 1 (in perfusate before storage), Group 2 (in cardioplegia), Group 3 (in reperfusate), and control (no administration of ANP). Left ventricular functional recovery and the incidence of ventricular fibrillation (VF) were compared. ANP administration at the time of reperfusion improved the percent recovery of left ventricular developed pressure (control, 45.5 ± 10.2; Group 1, 47.4 ± 8.8; Group 2, 45.3 ± 12 vs. Group 3, 76.3 ± 7; P < 0.05) and maximum first derivative of the left ventricular pressure (control, 47.9 ± 8.7; Group 1, 46.7 ± 8.8; Group 2, 49.6 ± 10.8 vs. Group 3, 76.6 ± 7.5; P < 0.05). The incidence of VF after reperfusion did not differ significantly among these four groups (71.4, 85.7, 57.1, and 85.7% in Groups 1, 2, 3, and control, respectively). This result suggests that the administration of ANP at the time of reperfusion may have the potential to decrease the incidence of PGF after heart transplantation.