Circadian disruption and biomarkers of tumor progression in breast cancer patients awaiting surgery.

Psychological distress, which can begin with cancer diagnosis and continue with treatment, is linked with circadian and endocrine disruption. In turn, circadian/endocrine factors are potent modulators of cancer progression. We hypothesized that circadian rest-activity rhythm disruption, distress, and diurnal cortisol rhythms would be associated with biomarkers of tumor progression in the peripheral blood of women awaiting breast cancer surgery. Breast cancer patients (n=43) provided actigraphic data on rest-activity rhythm, cancer-specific distress (IES, POMS), saliva samples for assessment of diurnal cortisol rhythm, cortisol awakening response (CAR), and diurnal mean. Ten potential markers of tumor progression were quantified in serum samples and grouped by exploratory factor analysis. Analyses yielded three factors, which appear to include biomarkers reflecting different aspects of tumor progression. Elevated factor scores indicate both high levels and strong clustering among serum signals. Factor 1 included VEGF, MMP-9, and TGF-ß; suggesting tumor invasion/immunosuppression. Factor 2 included IL-1ß, TNF-α, IL-6R, MCP-1; suggesting inflammation/chemotaxis. Factor 3 included IL-6, IL-12, IFN-γ; suggesting inflammation/TH1-type immunity. Hierarchical regressions adjusting age, stage and socioeconomic status examined associations of circadian, distress, and endocrine variables with these three factor scores. Patients with poor circadian coordination as measured by rest-activity rhythms had higher Factor 1 scores (R(2)=.160, p=.038). Patients with elevated CAR also had higher Factor 1 scores (R(2)=.293, p=.020). These relationships appeared to be driven largely by VEGF concentrations. Distress was not related to tumor-relevant biomarkers, and no other significant relationships emerged. Women with strong circadian activity rhythms showed less evidence of tumor promotion and/or progression as indicated by peripheral blood biomarkers. The study was not equipped to discern the cause of these associations. Circadian/endocrine aberrations may be a manifestation of systemic effects of aggressive tumors. Alternatively, these results raise the possibility that, among patients with active breast tumors, disruption of circadian activity rhythms and elevated CAR may facilitate tumor promotion and progression.

Development of an avian model for restenosis.

Recurrence of atherosclerotic plaque growth after interventional therapy, restenosis, is a significant clinical problem occurring in 20%-50% of cases. We have developed a new avian model for the investigation of restenosis after arterial injury in cholesterol fed White Leghorn roosters. Atherosclerotic plaque growth 1-30 weeks after angioplasty balloon mediated endothelial injury in the abdominal aorta was studied in 37 roosters. Roosters were maintained on either normal poultry diet or high cholesterol diet. Twelve cholesterol fed roosters were also fed a hormone supplemented diet in order to modify plaque morphology. The procedural success rate was high. Angiographic stenoses (mean 36% with maximum of 74%) were detectable in cholesterol fed roosters after balloon angioplasty with associated histological evidence of plaque growth (P < 0.017). Cholesterol feeding enhanced fatty plaque growth; hormone manipulation increased calcific and ulcerated plaque but with high associated morbidity. Three interventional devices were subsequently examined in 32 roosters (16 laser angioplasty, 7 atherectomy, and 9 stent implant). Plaque development was again assessed by contrast angiography and histological analysis. We conclude that balloon mediated arterial injury in cholesterol fed roosters produces early proliferative and late, complex atherosclerotic lesions providing an inexpensive model for plaque development after intimal injury.

Colobronchial fistula due to Crohn's disease.

Enteropulmonary fistulas may present as recurrent localized pneumonia. A case of one such fistula originating from the colon in a patient with Crohn's disease is discussed.

Lymphoma presenting as a Sister Mary Joseph's nodule.

Metastatic tumors to the umbilicus, often referred to as Sister Mary Joseph's nodules, are rare. In general, they have been described in association with intra-abdominal malignancy, especially adenocarcinomas, although there has been one case report of malignant myeloma spreading to the umbilicus. Lymphomas, however, historically seem to reject the umbilicus as a site of metastatic spread. The following case report is, to our knowledge, the first reported instance of lymphoma presenting as an umbilical nodule.

Vaginal metastasis of colon cancer.

True vaginal metastases from colonic cancer are exceedingly rare. This often signals an ominous prognosis. More frequently the vagina is synchronously involved by direct contiguous spread from the colonic lesion. We present a case of sigmoid carcinoma with true metastasis to the vagina that was discovered after an interval of 3 weeks when vaginal discharge became evident. To our knowledge, there are only two other papers in the English language previously documenting this phenomenon.

Laser-induced fluorescence: III. Quantitative analysis of atherosclerotic plaque content.

BACKGROUND AND OBJECTIVE: Laser-induced fluorescence (LF) spectroscopic analysis of the chemical composition of atherosclerotic plaque was examined. STUDY DESIGN/MATERIALS AND METHODS: The intima of 18 dog aortas was injected with chemical compounds found in atherosclerotic plaque. Spectra were recorded in air prior to and after injection of collagens I, III and IV, elastin, cholesterol, triglyceride, and beta-nicotinamide adenine dinucleotide (NADH). RESULTS: Significant changes in LF intensity were detected after injection of collagens I and III, cholesterol and elastin in thoracic aorta (P < 0.001), but not with triglyceride or NADH. Minor changes were detected in abdominal aorta. Multiple regression analysis of LF intensity ratios demonstrated a clear correlation with the quantity of injected collagens I (R2 = 0.90-0.99) and III (R2 = 0.84-1.0), cholesterol (R2 = 0.72-0.76), and triglyceride (R2 = 0.68-0.80) in both thoracic and abdominal aorta. The correlation between LF and atherosclerotic plaque composition was confirmed in a rooster model of atherosclerosis where multiple regression analysis predicted the measured aortic cholesterol (R2 = 0.78) and triglyceride content (R2 = 0.96). CONCLUSIONS: (1) Fluorescence spectra recorded from dog aorta were significantly altered by injection of collagens I and III, cholesterol, and elastin. (2) LF may allow quantitative assessment of plaque chemical content.