Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion

Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.     

Endogenous estrogen status, but not genistein supplementation, modulates 7,12-dimethylbenz[a]anthracene-induced mutation in the liver cII gene of transgenic big blue rats

A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats.     

Effect of toremifene on antipyrine elimination in the isolated perfused rat liver

Summary Toremifene is a triphenylethylene antioestrogen with significant antitumour activity. It is structurally very similar to tamoxifen. Both drugs undergo extensive hepatic metabolism and tamoxifen is known to inhibit hepatic mixed-function oxidases (MFO). Using the isolated perfused rat-liver model, we investigated the effect of toremifene on the elimination of antipyrine, a standard marker of MFO activity. Perfusate consisted of 20% red cells in a modified Krebs-Henseleit buffer, and 80 ml was recirculated at 14 ml/min for 3 h. High but clinically relevant steady-state toremifene levels of 3 and 10 g/ml were achieved using bolus plus constant infusion into the reservoir. Elimination of 2.5 mg antipyrine was not inhibited by steady-state toremifene, but methanol (maximal perfusate concentration, 1.29%), the vehicle used for toremifene administration, caused a statistically significant increase in the antipyrine elimination half-life (mean, 1.4±0.2 h for controls vs 2.2±0.3 h for methanol;P<0.05,n=4). Whereas the methanol had no apparent effect on liver viability as assessed by bile flow and perfusate back-pressure, toremifene at a steady-state concentration of 10 g/ml caused a statistically significant decrease in bile flow (value at 180 min, 0,22±0.05 ml/h as compared with 0.52±0.06 ml/h in the methanol control;P<0.05) and a statistically significant increase in perfusate back-pressure (value at 180 min, 17.5±1.8 cm vs 11.0±2.6 cm in the methanol control;P<0.05). Therefore, toremifene used at high doses can impair liver function in the isolated perfused rat liver, but it does not have any effect on antipyrine elimination.     

Health care executive education and training

This paper examines the new situation of unprecedented change in the health care field--in which yet greater demands are in place for executive performance--and studies the educational and learning resources available to health care executives. The virtual transformation of the field requires new skill sets, competencies, and knowledge for high performing executives. How well is the field as a whole doing in providing appropriate learning opportunities? How well are health care organizations doing in effectively utilizing these resources of the field? What are the most crucial and immediately pertinent competencies needed; what are the topics of prime interest? And, are the overall learning efforts cost-effective with efficacious means of evaluation? These are the questions addressed by this article ... with the answers drawn from health care executives themselves.     

Stages of change for increasing fruit and vegetable consumption among adults and young adults participating in the national 5-a-Day for Better Health community studies.

Higher fruit and vegetable consumption is associated with a reduced risk of certain cancers and chronic diseases. The 5-a-Day for Better Health community studies are evaluating population-based strategies to achieving dietary behavior change using the stages-of-change model and associated theories. The authors present baseline comparisons of stages of change for fruit and vegetable consumption among adults and young adults in eight study sites representing diverse regions of the United States and diverse populations and settings. Three dominant stages, precontemplation, preparation, and maintenance, were found across sites. Women and those with college degrees were more likely to be in action/maintenance. Fruit and vegetable consumption, self-efficacy, and knowledge of the 5-a-Day recommendation were positively associated with more advanced stages of change in all study sites. The authors discuss the findings in relation to possible limitations of this and other dietary stages-of-change measures and suggest directions for future research.     

A comparison of physiological responses to two types of particle barrier, vapor permeable clothing ensembles.

Chemical protective clothing (PC) use while working results in elevated rectal temperatures (Tre) that limit work time. Particle barrier, vapor permeable (PBVP) PCs allow workers to cool themselves by evaporating some sweat. The purpose of this study was to compare the effects on worker productivity of two types of PBVP suits, a Kleenguard (PPPC) (Kimberly Clark), and a Tyvek (PEPC) (DuPont) suit. Fifteen males in a repeated measures design performed four work tests consisting of a walk/arm curl combination at a time-weighted work rate of 1.0 L/min (300 kcal/hr), two in a wet bulb globe temperature (WBGT) of 26 degrees C and two in a WBGT of 18 degrees C, with subjects wearing each suit once in each environment. No significant difference (p > 0.05) was observed between the suits at 18 degrees C WBGT, but a significant difference was found (p < 0.05) between the suits, with the PPPC having a lower Tre in the WBGT = 26 degrees C at the 80th, 100th, and 120th min. A significant difference (p < .05) was also seen in the 26 degrees C WBGT with the PPPC resulting in a lower heart rate (HR) at the 40th, 60th, 80th, 100th, and 120th min and rate of perceived exertion (RPE) at the 75th, 90th, and 120th min. Additionally, a significant difference (p < .05) was seen between PEPC and PPPC for Tre, delta Tre, mean skin temp (mTsk), delta mTsk, and HR, each regressed against time in the 26 degrees C WBGT. Twelve of the 15 subjects also reported feeling cooler in the PPPC versus the PEPC in either WBGT environment.     

Vascular endothelial growth factor expression in human chronic renal allograft rejection

BACKGROUND: Chronic renal allograft rejection is characterized by interstitial fibrosis and vasculopathy. Vascular endothelial growth factor (VEGF) is an endothelial mitogen with increased expression in inflammation and vasculopathy. METHODS: Renal tissue from 17 patients with chronic rejection was examined for VEGF protein and the presence of CD 68-positive macrophages, and compared to biopsies from patients with temporary allograft dysfunction, acute rejection, and native kidneys with thin membrane disease. RESULTS: In the chronic rejection group, there was markedly increased expression of VEGF protein in the interstitium (P<0.0001). In serial sections, VEGF colocalized with the expression of CD 68-positive macrophages. Significantly more macrophages were in the tubulointerstitium in tissue with chronic rejection than in those with temporary allograft dysfunction (P<0.005). Additionally, VEGF protein expression in the glomeruli and the vascular compartment of patients with chronic rejection was increased. CONCLUSION: The up-regulation of VEGF in chronic renal allograft rejection may be important in inflammation and development of fibrosis.