Detecting temporal and spatial effects of epithelial cancers with Raman spectroscopy.

PublishedJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Hindawi Publishing Corporation via the DOI in this record.Epithelial cancers, including those of the skin and cervix, are the most common type of cancers in humans. Many recent studies have attempted to use Raman spectroscopy to diagnose these cancers. In this paper, Raman spectral markers related to the temporal and spatial effects of cervical and skin cancers are examined through four separate but related studies. Results from a clinical cervix study show that previous disease has a significant effect on the Raman signatures of the cervix, which allow for near 100% classification for discriminating previous disease versus a true normal. A Raman microspectroscopy study showed that Raman can detect changes due to adjacent regions of dysplasia or HPV that cannot be detected histologically, while a clinical skin study showed that Raman spectra may be detecting malignancy associated changes in tissues surrounding nonmelanoma skin cancers. Finally, results of an organotypic raft culture study provided support for both the skin and the in vitro cervix results. These studies add to the growing body of evidence that optical spectroscopy, in this case Raman spectral markers, can be used to detect subtle temporal and spatial effects in tissue near cancerous sites that go otherwise undetected by conventional histology.The authors acknowledge the financial support of the NCI/NIH (R01-CA95405 and R21-CA95995), as well as the Howard Hughes Medical Institute (pre-doctoral fellowship for MK). We would also like to thank the doctors and staff at Vanderbilt University Medical Center and Tri-state Women’s Health for all their assistance

Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

<p>Abstract</p> <p>Background</p> <p>Familial adenomatous polyposis (FAP) is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the <it>APC </it>gene mutation, possible genotype-phenotype correlations largely remain to be defined for the extracolonic manifestations.</p> <p>Methods</p> <p>Full genomic sequencing combined with multiplex ligation-dependent probe amplification was used to identify <it>APC </it>gene mutations, which were correlated to the clinical presentations.</p> <p>Results</p> <p>10 novel <it>APC </it>gene mutations were identified in 11 families. A broad spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC) both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'<it>APC </it>mutation (c.5030_5031insAA) developed colon cancer at age 72 as the first manifestation of attenuated FAP.</p> <p>Conclusion</p> <p>With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel <it>APC </it>mutations and present two FAP cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer.</p

Mortality in very long-stay pediatric intensive care unit patients and incidence of withdrawal of treatment

Background: The mortality for children with prolonged stay in pediatric intensive care units (PICU) is much higher than overall mortality. The incidence of withdrawal or limitation of therapy in this group is unknown. Purpose: To assess mortality and characteristics of children admitted for ≥28 days to our ICU, and to describe the extent to which limitations of care were involved in the terminal phase preceding death. Methods: For the period 2003 to 2005 clinical data were collected retrospectively for children with prolonged stay (defined as ≥28 days) in a medical/surgical PICU of a university children's hospital. Results: In the PICU, 4.4% of the children (116/2,607, equal gender, mean age 29 days) had a prolonged stay. Median (range) stay was 56 (28-546) days. These children accounted for 3% of total admissions and occupied 63% of total admission days. Mortality during admission for this group was fiv

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Effect of Normal Variations on Classification of Raman Spectra of Cervical Tissue

In this paper, we examine how variations in normal tissue can influence disease classification of Raman spectra. Raman spectra from normal areas may be affected by previous disease or proximity to areas of dysplasia. Spectra were acquired in vivo from 172 patients and classified into five tissue categories: true normal (no history of disease), previous disease normal (history of disease, current normal diagnosis), adjacent normal (disease on cervix, spectra acquired from visually normal area), low grade, and high grade. Taking into account the various normal states of the tissue before statistical analysis led to a disease classification accuracy of 97%. These results indicate that abnormal changes significantly affect Raman spectra, even when areas are histopathologically normal. The sensitivity of Raman spectroscopy to subtle biochemical differences must be considered in order to successfully implement it in a clinical setting for diagnosing cervical dysplasia and cancer

Application of Raman spectroscopy for Cervical Dysplasia Diagnosis

Cervical cancer is the second most common malignancy among women worldwide, with over 490 000 cases diagnosed and 274 000 deaths each year. Although current screening methods have dramatically reduced cervical cancer incidence and mortality in developed countries, a See and Treat method would be preferred, especially in developing countries. Results from our previous work have suggested that Raman spectroscopy can be used to detect cervical precancers; however, with a classification accuracy of 88%, it was not clinically applicable. In this paper, we describe how incorporating a woman\u27s hormonal status, particularly the point in menstrual cycle and menopausal state, into our previously developed classification algorithm improves the accuracy of our method to 94%. The results of this paper bring Raman spectroscopy one step closer to being utilized in a clinical setting to diagnose cervical dysplasi