AG

AA

bst

ract

s13C-SUC/GLU BT in which the second, serial 13C-GLU comparative substrate was super-dosed (5X) to negate any residual SUC effects. Delta enrichment measures attributed to theGLU were adjusted (X/5) before the sucrose CGO was calculated. The results between the2-day and 1-day test methods were compared and the best diagnostic time-point and cut-off were determined based on 99% confidence interval (C.I.). RESULTS: The CSID patientshad very low 2-day/2-stage 13C-sucrose CGO for both 60' & 75' time-points (0.25±0.19vs. 0.36±0.29, NSD) and CSID differed from BxC subjects (60':1.31±0.31; 75':1.31±0.27;p,0.01). 13C-SCGO enrichment values for BxC subjects did not differ from those obtainedfrom ASTC subjects at 60' (1.31±0.31 vs. 1.02±0.52, p=0.08), but improved at the 75' timepoint (1.27±0.27 vs. 0.95±0.36, p,0.01). Among the 19 ASTC subjects who also completedthe 1d-biphasic 13C-SUC/GLU BT, SCGO values for 60' were 1.13±0.63 vs. 0.99±0.26 (p=0.42); and for 75' were 0.99±0.43 vs. 0.99±0.13 (p=0.85). Using the 75' test outcomes, thelower limit sucrose CGO cut-off is ≤ 0.75 (99% C.I 1.00±0.24), the test sensitivity andspecificity to diagnose CSID was 100%. CONCLUSION: The 75' CGO cut-off was definedas ,0.75, the 1-day-biphasic SUC/GLU BT has excellent accuracy over the 2-day serial testand is convenient for non-invasive testing of mucosal sucrase activity.

Mo1396

Reduced Body Weight Recovery in Intestinal TIS7 Transgenic Mice Post-Intestinal Resection Is Mediated by Decreased Amino Acid Absorption andInhibition of Serum and Glucocorticoid-Induced Kinase 1 ExpressionJianyun Lu, Amy M. Garcia, Taylor Geisman, Derek Wakeman, Brad Warner, Marc S.Levin, Deborah C. Rubin

Expression of the immediate early gene Tis7 is markedly up-regulated in enterocytes as anadaptive response to small bowel resection in a mouse model of short bowel syndrome. Wehave previously shown that transgenic (TG) mice with intestinal overexpression of Tis7 haveincreased body fat but reduced skeletal muscle mass, accelerated triglyceride absorption,and a more rapid and proportionately greater weight gain on a high fat diet. Tis7 TG micehave an enhanced survival rate when fed a high fat diet post resection compared to wildtype (WT) mice, but do not show more rapid body weight recovery post resection. Tofurther explore this phenotype, we addressed the hypothesis that Tis7 may also regulateprotein and/or carbohydrate absorption. Methods: Glucose and proline uptakes were mea-sured in vitro in WT (n=6) and TG (n=5) intestines, using the everted sleeve technique.Total proline uptake rate in TG gut was significantly reduced compared to WT (77 vs. 165nmol/min/cm, p=0.0043). The active glucose uptake rate was unchanged in WT vs. TGproximal or distal small intestine. To begin to understand the mechanisms regulating reducedproline uptake, expression of a subset of candidate transporters and co-regulators wasmeasured by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Expres-sion of serum and glucocorticoid-induced kinase 1 (SGK1), a known activator of ion channelsand a subset of solute carriers, was significantly reduced in TG vs. WT intestine (p=0.0001).Expression of SLC6A20A, a proline-specific transporter, and the angiotensin-convertingenzyme 2 (ACE2) were unchanged. Unexpectedly expression of the neutral amino acidtransporter SLC6A19 was modestly increased (p=0.026) in jejunum only. Conclusions:Although intestinal Tis7 overexpression enhances survival in mice fed a high fat diet, bodyweight recovery is unchanged likely due to reduced protein absorption in TG vs. WTmice. Intestinal Tis7 overexpression reduces proline intake, at least partly due to decreasedexpression of SGK1, which may in turn attenuate the activity of a subset of amino acidtransporters. Glucose uptake is not compromised in TG mice. Ingestion of a high carbohy-drate, high fat diet may improve body weight recovery in these mice in our post-resectionshort bowel syndrome model.

Mo1397

PTEN Hamartoma Tumor Syndrome: Endoscopic Findings and GastrointestinalPathologyPeter P. Stanich, Jonathan Rock, Wendy L. Frankel, Robert Pilarski, Marty M. Meyer

Background: PTEN hamartoma tumor syndrome (PHTS) encompasses several rare disorders,including Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, arising from germ-line mutations in the PTEN gene and characterized by hamartomatous tumors. Gastrointesti-nal (GI) manifestations are now thought to be present in over 90% of patients, includingcolon polyps with an increased risk of colorectal cancer (standardized incidence ratio =10.3), gastric polyps, small bowel polyps and glycogenic acanthosis of the esophagus.Importantly, colorectal cancer surveillance starting at age 35 is now recommended. Limiteddata on clinical outcomes secondary to these findings have been reported. Aims: To describethe experience with PHTS and GI investigations at a tertiary-care medical center with aclinical genetics program. Methods: Retrospective review of patients with a diagnosis ofPHTS or a component syndrome with endoscopy and/or GI pathology interpretation at ourcenter. Results: Eight patients met inclusion criteria (6 Cowden syndrome, 2 Bannayan-Riley-Ruvalcaba syndrome) and all were female. Seven of 8 (87.5%) had identified PTENgene mutations. Five patients received 21 colonoscopies (mean 4.2, range 1 - 10), withmean age 45 years at first procedure (range 34 - 64). All patients had colon polyps,with pancolonic location in 3 and left-sided location in 2. Histology revealed tubular andtubulovillous adenomas in 2/4, ganglioneuromas in 1/4, juvenile\inflammatory in 1/4, andhyperplastic in 2/4 (one patient had no specimens removed). No malignant lesions wereidentified. Of note, no hamartomas were reported. Three patients had innumerable polypson initial exam. One underwent multiple procedures and polypectomies, one underwentcolectomy and one was lost to follow-up after recommendation to have repeat procedurewithout anticoagulation. Six patients received 9 upper endoscopies (mean 1.5, range 1 - 4).Glycogenic acanthosis was reported in 2/6, gastric polyps in 4/6 and duodenal polyps in 2/6. Biopsies of stomach polypswere performed in 2 patients and revealed chronic inflammatorychange. Biopsies of duodenal polyps were performed in both patients, with one findingtubular adenoma and the other normal tissue. No malignant lesions were identified. Conclu-sions: Our experience supports the high rate of endoscopic findings in PHTS patientsundergoing investigation. Hamartomatous polyps were not noted in our series, demonstratingthat this classic pathologic association cannot be counted on to suggest a diagnosis of PHTS.With recent recommendations to begin early colorectal cancer surveillance, patients should

S-656AGA Abstracts

be counseled regarding the possibility of multiple endoscopies for polyp removal or eventualcolectomy if polyps cannot be cleared.

Mo1398

Concomitant Gastrointestinal Graft Versus Host Disease and CytomegalovirusEnteritis in Hematopoietic Stem Cell Transplant PatientsAnne Liu, Laura Johnston, Everett Meyer, Lauren B. Gerson

Purpose: Gastrointestinal complaints are frequent after allogeneic hematopoietic stem celltransplantation (HSCT), with many patients inflicted by concomitant gastrointestinal acutegraft versus host disease (GI-GVHD) and cytomegalovirus (CMV) enteritis. However theprevalence is unknown given that symptomatology, endoscopic visualization, and evenhistopathological findings cannot distinguish GI-GVHD from concomitant GI-GVHD-CMV.Methods: We performed a retrospective study on HSCT patients who had undergone singleand/or bi-directional endoscopic procedures between 20 to 125 days post-HSCT betweenJanuary 2000 and September 2011. GI-GVHD status was determined by the Glucksbergclinical grading system. CMV enteritis cases were diagnosed by positive PCR of gut tissue,viral culture, shell vial, immunoperioxidase staining and/or visible cytopathic viral inclusion.Results: A total of 245 donor/recipient CMV seropositive HSCT patients underwent 302colonoscopies with diagnoses of 106 GI-GVHD (35%), 27 CMV enteritis (9%) and 27 GI-GVHD-CMV (9%). Mortality rates were 76 (56%) in the GI-GVHD specific group, 14 (52%)in the CMV enteritis specific group and 22 (81%) in the GI-GVHD-CMV group (p=0.05);Antiviral treatment did not have a significant impact on outcome. Endoscopic visualizationsof edema, erythema, and erosions occurred at similar rates among GI-GVHD, CMV and GI-GVHD-CMV. Ulcerations totaled 13 in GI-GVHD (12%), 1 in CMV enteritis (4%) and 6 inGI-GVHD-CMV (22%) groups (p=0.10), with more hemorrhagic ulcerations and friablemucosa in the last group. In the GI-GVHD cohort, positive histological grades for a bi-directional endoscopy had sensitivity 82% versus 48% for patients with an upper alone(p,0.0001) and 86% for lower alone (p=0.8). Sensitivity was highest at the terminal ileumbiopsy site (79%) and lowest at the esophagus (18%). In the CMV cohort, diarrhea waspresent in 70% of cases and 55% of controls (p-0.04). Diagnostic sensitivity was highest atthe cecum, ascending colon and descending colon. Conclusions: GI-GVHD-CMV presentsas a serious problem in HSCT patients with high mortality rates. Suspected GI-GVHDs and/or CMV enteritis cases are recommended to undergo full colonoscopic examinations includingbiopsies of the terminal ileum and clinical monitoring.

Mo1399

Plasma Markers for Anastomotic Leakage After Colorectal SurgeryKostan Reisinger, Joep Derikx, Karel Hulsewé, Annemarie A. van Bijnen, Maarten vonMeyenfeldt, Martijn Poeze

BackgroundAnastomotic leakage is a frequent complication after colorectal surgery (incidence8% in the Netherlands), associated with high short-term mortality rates of up to 40%.Moreover, anastomotic leakage negatively impacts cancer specific survival rates. Early re-intervention is critical to reduce mortality. As early clinical and radiological of anastomoticleakage are often non-specific, there is an urgent need for accurate biomarkers. Markers ofinflammation and gut damage may be suitable, as these are hallmarks of anastomotic leakage.Aim To find biomarkers that accurately detect anastomotic leakage at an early time-point.Methods In 50 patients (6 with anastomotic leakage (AL), confirmed by laparotomy orextraluminal contrast on CT) undergoing scheduled colorectal surgery with primary anasto-mosis, plasma samples were collected preoperatively, and daily after surgery until dischargefrom the hospital. The inflammatory markers C-reactive protein (CRP), calprotectin, andIL-6; and the markers of gut damage intestinal fatty acid binding protein (I-FABP), liverfatty acid binding protein (L-FABP), and ileal lipid binding protein (ILBP) were measuredby ELISA. Diagnostic accuracy of single markers or combinations of markers was analyzedby ROC curve analysis. Results CRP at postoperative day (POD) 3 predicted AL withsensitivity, 80%; specificity, 75%; positive likelihood ratio (LR+), 3.20 (95% confidenceinterval (CI), 1.10 - 9.35); negative likelihood ratio (LR-), 0.27 (95% CI, 0.04 - 1.61); p=0.03. IL-6 at POD 3 yielded comparable results, and calprotectin on POD 3 predicted ALwith sensitivity, 100%; specificity, 75%; LR+ 4.00 (95% CI, 1.35 - 8.59); LR-, 0.00 (95%CI, 0.01 - 1.67); p=0.02. I-FABP levels at POD 3 predicted AL with sensitivity, 83%;specificity, 81%; LR+, 4.37 (95% CI, 1.85 - 10); LR-, 0.21 (95% CI, 0.04 - 1.25); p=0.03.L-FABP and ILBP levels were not statistically different between groups. Combination ofcalprotectin and I-FABP levels on POD 3 yielded highest accuracy: sensitivity, 100%; specific-ity, 91%; LR+, 11 (95% CI, 1.61 - 34); LR-, 0.00 (95% CI, 0.01 - 1.37); p=0.002. ConclusionThe inflammatory markers CRP, IL-6 and calprotectin predict anastomotic leakage withreasonable accuracy on day 3 following colorectal surgery. When combining with I-FABP,a marker of intestinal epithelial damage, accuracy increases drastically. This pleads forimplementation of these markers in daily practice.

Mo1400

Loss of Bone Morphogenetic Protein Receptor IA Predicts Poor Survival inPatients With Pancreatic Cancer and Is Responsible for Invasiveness andProliferation of Cancer CellsPhilip Voorneveld, Rutger J. Jacobs, Suzanne Lam, Noel De Miranda, Hans Morreau,Liudmila L. Kodach, James C. Hardwick

Introduction: The expression of SMAD4, the central component of Transforming GrowthFactor beta (TGF-β) and Bone Morphogenic Protein (BMP) signalling pathways, is lost in50% of the pancreatic cancers and is associated with a poor survival. Although the TGF- βpathway has been extensively studied and characterized in pancreatic cancer, very limiteddata are available about BMP signaling, a well-known tumour suppressor pathway. BMPsignalling can be lost not only at the level of SMAD4 but also at the level of BMPReceptors(BMPR) as has been described in colorectal cancer. We therefore set out to investigate the roleof BMP signalling in pancreatic cancer by performing analysis of BMP signalling components