1014 plectin-1 as a biomarker in malignant pancreatic intraductal papillary mucinous neoplasms
TRANSCRIPT
rats, receiving an enteral infusion of either 5%glucose (glucose lymph) or long chain fattyacids in form of 2% olive oil (lipid lymph) before and after LPS (e-coli 5mg/kg i.p.) injection.Lymph was used for isolation of immune cells (analysed with FACS) and for measurementof TNFα. The immune cells (≈106) were stimulated invitro with LPS (10ng, 100ng, 1μg,10μg). TNFα was measured in all lymph samples and in the supernatant of the invitroexperiments. Results: Sepsis induced by LPS increased TNFα release into the mesentericlymph about 240 fold in glucose-treated rats, which was significantly reduced in lipid treatedrats (TNFα pg/ml, before vs. after LPS, glucose lymph: 44±12 vs. 10680±1400*; lipid lymph:33±15 vs. 2330±1297*; * p<0.005 glucose vs. lipid). Sepsis induced a significant 2 foldincrease in the release of CD11c/ED2 positive macrophages in both glucose and lipid treatedanimals; there was no difference between glucose or lipid treated rats. LPS induced asignificantly greater increase in release of TNFα in macrophages harvested from mesentericlymph during enteral glucose vs. lipid infusion (TNFα pg/ml, glucose vs. lipid, 100ng LPS:87±23 vs. 28±20*; 1μg LPS: 60±9 vs. 4±2*, p<0.01 vs. glucose). Conclusions: Duringsepsis, macrophages in the gut wall are activated releasing inflammatory mediators such asTNFα. However, an enteral immune modulating diet with long chain fatty acids in form ofolive oil was able to suppress TNFα release from macrophages in the gut. This is possiblymediated through the cholinergic anti-inflammatory pathway, thereby preventing the releaseof disease-inducing cytokines into the circulation. (Supported by the German Sepsis Founda-tion)
1014
Plectin-1 As a Biomarker in Malignant Pancreatic Intraductal PapillaryMucinous NeoplasmsDirk Bausch, Mari Mino-Kenudson, Carlos Fernandez del-Castillo, Andrew L. Warshaw,Kimberly Kelly, Sarah P. Thayer
Background: Intraductal papillary mucinous neoplasms (IPMN) are now being identifiedwith increasing frequency. IPMN of the main pancreatic duct (MD-IPMN) carries a significantrisk of malignancy and surgery is usually recommended. Side branch IPMN (BD-IPMN) hasa much lower risk of malignancy and can often be observed. However, BD-IPMN with thepresence of symptoms, mural nodules, positive cytology or a cyst size larger than 3 cm isconsidered to have a high risk of malignancy and surgery is usually recommended. Carcin-omas arising in IPMN are either the clinically more benign colloid carcinoma or the aggressiveductal adenocarcinoma. The diagnosis of carcinoma arising in IPMN using cytology or non-invasive imaging is challenging, often resulting in pre-emptive resection of benign lesions.Improved detection of malignancy using novel biomarkers may therefore improve diagnosticaccuracy. One such novel promising biomarker is Plectin-1 (Plec-1). Plec-1 was identifiedin a phage display screen looking for unique markers of PDAC. We validated its use byimmunohistochemistry (IHC) and In Vivo imaging and found that Plec-1 directed imagingmarkers identify PDAC and distinguish it from benign pancreatic changes. The aim of thisstudy was to determine whether Plec-1 can also be used to differentiate carcinoma arisingin IPMN from benign IPMN. Methods: To assess the utility of Plec-1 as a biomarker inhuman IPMN, we assayed Plec-1 expression in normal pancreas (n=4), PDAC (n=19), benign(n=15) IPMN as well as carcinoma arising in IPMN (n=11) using IHC. Nerves, which werepresent in all slides and strongly stain for Plec-1, were used as a reference and to comparestaining across slides. We evaluated benign IPMNs of all three epithelial phenotypes: gastrictype (n=9), intestinal type (n=4) and oncocytic type (n=2). 11 carcinomas arising in IPMNwere tested for Plec-1 expression: 6 colloid carcinomas and 5 ductal adenocarcinomas.Results: Plec-1 was not detected in normal pancreatic tissue (n=4) but was strongly expressedin all of the PDAC (n=19). Regardless of their epithelial type, none of the 15 benign IPMNsdid stain for Plec-1. However, 5 of 5 ductal adenocarcinomas arising in IMPN stained forPlec-1. Interestingly, only 1 of 6 colloid carcinomas expressed Plec-1. Conclusion: Thepresence of Plec-1 in IPMN accurately identifies carcinoma arising in IMPN and is a goodbiomarker for the more aggressive ductal adenocarcinoma. However, the absence of Plec-1can not be used to exclude cancer as colloid carcinomas rarely stain.
1015
Enhancing Detection of Free Peritoneal Cancer Cells in Gastric Cancer UsingNewcastle Disease VirusJoyce Wong, Allison Schulman, Kaitlyn Kelly, Dmitriy Zamarin, Peter Palese, Yuman Fong
Introduction:Cytological detection of free peritoneal cancer cells detected in gastric cancerpatients offers important prognostic information and may affect staging and treatment.However, conventional cytology by Papanicolaou staining clearly does not detect all casesof peritoneal disease. We evaluated a novel technique for detecting free peritoneal gastriccancer cells using Newcastle Disease Virus (NDV-GFP), a non-pathogenic virus containingthe enhanced green fluorescent protein (GFP) gene. Methods:NDV-GFP was tested uponMKN-1 human gastric adenocarcinoma cells plated against a background of normal rathepatocytes to determine tumor-specific viral infection and GFP expression. A clinical sampleof malignant ascites was then processed, incubated with increasing doses of virus, andevaluated with fluorescencemicroscopy for optimal NDV-GFP dose determination. Peritoneallavage samples from 22 patients with biopsy-proven gastric adenocarcinoma undergoingstaging laparoscopy were then evaluated with NDV-GFP. Green fluorescent cells were furthermolecularly characterized. Results: NDV-GFP at a dose of 5E6 PFU specifically infects MKN-1 gastric adenocarcinoma cells and can detect 1 cancer cell against 1 million benign rathepatocytes. GFP expression was seen at 6 hours from infection and was detectable for over24 hours. NDV-GFP at a dose of 5E4 plaque forming units (PFU) produced detectable GFPexpression in a clinical sample of malignant ascites, which was enhanced with higher viraldoses. For practicality, further samples were infected with 5E6 PFU. Non-cancerous cells,such as red blood cells, were found to be non-GFP expressing. GFP- expressing cellscounterstained positive for CEA expression, confirming their cancerous origin. GFP expres-sion was seen in lavage samples from all 22 patients, while cytology was positive in only 5of these patients. While 9/22 (40.9%) patients were stage IV with M1 disease, only 5/9(55.6%) were positive by cytology. In contrast, all 9 samples were positive by NDV-GFPdetection. Furthermore, when evaluating tumor size, GFP expression wasmarkedly enhancedin T3 disease, detecting 16 patients with T3 tumors versus 2 patients detected by cytology.
A-883 SSAT Abstracts
When considering nodal status, NDV-GFP detected 10 N1 patients compared to no N1patients detected by cytology. Conclusions: NDV-GFP specifically targets and infects gastriccancer cells. NDV-GFP enhances detection of free peritoneal cancer cells in gastric cancerpatients and offers a more rapid and sensitive diagnostic tool compared to conventionalcytology. This novel diagnostic modality may offer important prognostic information.
1016
Transoral Gastroplasty. A Novel Technique for Incisionless Weight LossSurgeryGregg K. Nishi, Simon K. Lo, Edward H. Phillips
We present a video of an incisionless weight loss procedure. A novel device is inserted perorum to create a stapled vertical gastroplasty. Following creation of the gastric pouch, asecond device is used to generate a restricted outlet. This results in a restrictive operationthat results in early satiety and weight loss. This procedure is currently being performedunder FDA protocol in a multicenter randomized and blinded trial.
1017
Single Incision Laparoscopic Surgery (SILS): CholecystectomyParag Butala, Brian Jacob, Neil Cambronero, George D. Xipoleas, Mark A. Reiner
Single incision laparoscopic surgery (SILS) is a novel approach to laparoscopic surgery usinga single small skin incision with either multiple low-profile trocars or a single access port.SILS is rapidly growing in popularity for use in a variety of elective general surgical applica-tions, and the introduction of safe and reproducible techniques is imperative. This videodemonstrates our method for a SILS cholecystectomy for symptomatic cholelithiasis. Thevideo stresses the initial technique for entry into the abdominal cavity and highlights theimportance of maintaining standard operative techniques intraabdominally. This video willdemonstrate the feasibility of SILS cholecystectomy.
1018
Natural Orifice Surgery for Early Stage Esophageal Malignancy: Proof ofConceptBart P. Witteman, Andres Gelrud, George M. Eid, Alejandro Nieponice, Stephen F.Badylak, Blair A. Jobe
Background Endoscopic therapies were introduced for treatment of superficial cancer withthe goal of esophageal preservation. These techniques have limitations based in samplingerrors and histologic accuracy. Objective To determine feasibility of transoral endoscopicresection of the esophageal mucosal-submucosal complex (MSC) in an animal model.Methods Using flexible endoscopic surgery, a sleeve of MSC is resected over the entireesophageal length. Conclusion This video demonstrates proof of concept for transoral endos-copic esophagectomy. When stricture formation is controlled with extra cellular matrixsubstitution, this technique may be an alternative to traditional esophagectomy.
1019
Optical Coherence Tomography of the Colon and Its Mesentery (IncludingVirtual Sentinel Node Biopsy) By Natural Orifice Transluminal EndoscopicSurgery (N.O.T.E.S.)Ronan A. Cahill, Mitsuhiro Asakuma, Joseph A. Trunzo, Steve J. Schomisch, Joel Leroy,Bernard Dallemagne, Jacques Marescaux, Jeffrey M. Marks
Natural Orifice Transluminal Endoscopic Surgery (NOTES) may supplement the oncologicalprovidence of intraluminal resectional techniques (eg Endoscopic Submucosal Dissection)for early stage colonic neoplasia by providing nodal staging information in a truly minimallyinvasive fashion. Catheter-based Optical Coherence Tomography deployed via NOTES per-itoneoscopy may advance this by providing high resolution (x400) optical analysis of boththe colon wall from outwith the intestine as well as mesenteric lymph node architecture.This facility to provide ‘virtual biopsy' of salient tissues (including sentinel nodes) by NOTESis demonstrated in this technical video utilizing a porcine model.
1020
Dissection Techniques for NOTES Cholecystectomy with the FlexibleEndoscopeKevin M. McGill, Nikalesh Ippagunta, Glenn Forrester, Julio Teixeira
Video: This video demonstrates a cholecystectomy performed using a two channel flexibleendoscope. Different techniques demonstrated are hydrodissection, dome-down technique,camera assisted dissection, coaxial dissection, and different retraction techniques. The differ-ent techniques demonstrated make NOTES cholecystectomy feasible and safe.
1021
Endoscopic Assisted Transgastric Removal of An Eroded Verticle Gastric BandSteven Hodgett, J Christopher Eagon
Our patient is a 54 year old female s/p vertical banded gastroplasty for morbid obesity,followed by revision for breakdown of her gastric staple line. She came to clinic with a onemonth history of abdominal pain, nausea, vomiting and hematemeis. EDG demonstratedan erosion of her gastric band into her stomach. Considering her previous gastric proceduresas well as a previous open incisional hernia repair we elected to remove her band by
SS
AT
Ab
stra
cts