Biomedical Paper Surface Registration for Use in Interactive, Image- Guided Liver Surgery

ABSTRACT Objective: Liver surgery is difficult because of limited external landmarks, significant vascularity, and inexact definition of intra-hepatic anatomy. Intra-operative ultrasound (IOUS) has been widely used in an attempt to overcome these difficulties, but is limited by its two-dimensional nature, inter-user variability, and image obliteration with ablative or resectional techniques. Because the anatomy of the liver and intra-operative removal of hepatic ligaments make intrinsic or extrinsic point-based registration impractical, we have implemented a surface registration technique to map physical space into CT image space, and have tested the accuracy of this method on an anatomical liver phantom with embedded tumor targets. Materials and Methods: Liver phantoms were created from anatomically correct molds with “tumors ” embedded within the substance of the liver. Helical CT scans were performed with 3-mm slices. Using an optically active position sensor, the surface of the liver was digitized according to anatomical segments. A surface registration was performed and RMS errors of the locations of internal tumors are presented as verification. An initial point-based marker registration was performed and considered the “gold standard ” for error measurement. Results: Errors for surface registration were 2.9 mm for the entire surface and 2.8 mm for embedded targets. Conclusion: This is an initial study considering the use of surface registration for the purpose of physical-to-image registration in the area of liver surgery. Comp Aid Surg 5:11–17 (2000). ©2000 Wiley-Liss, Inc. Key words: image-guided surgery, liver surgery, registratio

Abstract LB-450: Gene expression of colonic submucosa differs between the inflammatory colitides. A possible reason for differences in IBD-associated CRC incidences

Abstract Purpose: Differentiating ulcerative colitis (UC) and Crohn's colitis (CC) may be inaccurate in up to 30% of inflammatory bowel disease (IBD) cases due to overlapping features of these colitides. IBD-associated colorectal cancer (CRC) is frequently diagnosed in an advanced stage. Mass-spectrometric (MS) proteomic patterns found in colonic submucosa have been shown to discriminate UC and CC. To verify this, we aimed to conduct pilot gene expression analyses via microarray assessment of colonic submucosa. The significances of these genes to CRC initiation is as yet not been elucidated. Methods: Laser capture microdissection of colonic submucosa from UC (n=8), CC (n=8), and normal (NL, n=8) samples was performed. The submucosal mRNA was extracted using the PicoPure(TM) RNA Isolation Kit. Comprehensive gene expression analysis of the pooled mRNA from each group was then performed using the Affymetrix GeneChip® Gene 1.0 ST Array System. To detect changes for UC, we compared UC to CC and UC to NL; and for CC, we compared CC to UC and CC to NL. Results: 28,869 genes were represented on the array by 26 probes spread across the full length of each gene. When comparing UC to CC, 138 genes showed at least a 5-fold significant overexpression (p<0.01) with 5 of these genes showing a greater than 30-fold overexpression (Table, all p<0.0001). When comparing CC to UC, 5 different genes were overexpressed at greater than 30-fold change (Table, all p<0.0001). The results of the comparisons of these highly overexpressed genes in UC and CC vs. NL is noted in Table. Conclusions: Microarray assessments show significantly different gene overexpression in UC and CC colonic submucosa, with a few select genes showing dramatic overexpression. Preliminary results indicate that we have the tools in hand to successfully validate the results from the microarray analysis using TR-qPCR and immunohistochemistry (IHC). These genes may assist in delineation of the previously identified differentiating MS submucosal proteomic peaks, potentially facilitating protein biomarker identification to discriminate the inflammatory colitides. These genes may relate to CRC initiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-450. doi:10.1158/1538-7445.AM2011-LB-45

Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease

<div><p>Inability to distinguish Crohn's colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn's colitis, <b><i>p< 0</i>.<i>0001</i></b>. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable differentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn's colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn's colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to <i>de novo</i> Crohn's disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn's colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn's colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn's colitis.</p></div