Surgical management of primary colonic lymphoma: Big data for a rare problem

Background and ObjectivesPrimary colonic lymphoma (PCL) is rare, heterogeneous, and presents a therapeutic challenge for surgeons. Optimal treatment strategies are difficult to standardize, leading to variation in therapy. Our objective was to describe the patient characteristics, short‐term outcomes, and five‐year survival of patients undergoing nonpalliative surgery for PCL.MethodsWe performed a retrospective cohort analysis in the National Cancer Database. Included patients underwent surgery for PCL between 2004 to 2014. Patients with metastases and palliative operations were excluded. Univariate predictors of overall survival were analyzed using multivariable Cox proportional hazard analysis.ResultsWe identified 2153 patients. Median patient age was 68. Diffuse large B‐cell lymphoma accounted for 57% of tumors. 30‐ and 90‐Day mortality were high (5.6% and 11.1%, respectively). Thirty‐nine percent of patients received adjuvant chemotherapy. For patients surviving 90 days, 5‐year survival was 71.8%. Chemotherapy improved survival (surgery+chemo, 75.4% vs surgery, 68.6%; P = .01). Adjuvant chemotherapy was associated with overall survival after controlling for age, comorbidity, and lymphoma subtype (HR 1.27; 95% CI, 1.07‐1.51; P = .01).ConclusionsPatients undergoing surgery for PCL have high rates of margin positivity and high short‐term mortality. Chemotherapy improves survival, but <50% receive it. These data suggest the opportunity for improvement of care in patients with PCL.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150597/1/jso25582_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150597/2/jso25582.pd

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

IHC staining for HD5 agrees with final diagnostic outcome in a sample of IC patients even when there was no agreement with the attending physician.

<p>IHC staining for HD5 agrees with final diagnostic outcome in a sample of IC patients even when there was no agreement with the attending physician.</p

Double stain of PCs, lyzosomes and HD5.

<p>Double staining analyses from <i>de novo</i> Crohn’s (<b>Fig. 5A</b> and <b>D</b>), and normal ileum/control (<b>Fig. 5G</b>) are presented. Image deconvolutions are displayed vertically to evaluate lysozyme-specific permanent red (<b>Fig. 5B, E</b> and <b>H</b>) and HD5α-specific DAB (<b>Fig. 5C, F</b> and <b>I</b>). The normal colon image (<b>Fig. 5J</b>), which lacks PCs, was not further processed.</p

Assessment of HD5 and Paneth cells in inflamed and normal, adjacent tissue.

<p>HD5 staining of CC inflamed and normal, adjacent tissue shows expression of HD5 in all patient samples examined (<b>Fig. 6A</b>), compared to inflamed and adjacent, normal tissue of UC patients (<b>Fig. 6B</b>). H&E stains for Paneth Cells (<b>Fig. 6C and D</b>), were negative for PCs in all tissues.</p