1034 Spectral Biomarkers of Pancreatic Cancer

1034 Spectral Biomarkers of Pancreatic Cancer

Abstracts the CBD. After duodenal guidewire access, the gastroscope was exchanged OTW for a duodenoscope, through which antegrade transpapillary ball...

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Abstracts

the CBD. After duodenal guidewire access, the gastroscope was exchanged OTW for a duodenoscope, through which antegrade transpapillary balloon dilation and placement of a second fully covered SEMS were carried out. The duodenoscope was exchanged again for the transnasal gastroscope, and antegrade cholangioscopy performed as described earlier. The scope was passed into the duodenum through both SEMS, retroflexed, and sphincterotomy performed over the transpapillary SEMS. Total procedure time was 105 minutes. No complications ensued and the patient remained asymptomatic for 8 months. At follow-up endoscopy, both SEMS were retrieved via repeat cholangioscopy using a tripod forceps. To ensure durable papillary stricture remodeling, a double 10F-15cm pig-tail stent was placed throughand-through across the EUS-hepaticojejunostomy and the papilla. Comments: Antegrade cholangioscopy and sphincterotomy were successfully performed in a single-session through EUS-guided hepatico-jejunostomy with a covered SEMS in a patient with strictured surgical sphincteroplasty and Roux-en-Y total gastrectomy. Temporary EUS-guided anastomoses with covered SEMS offer novel minimally approaches to patients with anatomically and clinically complex biliary disease.

patients. Initial screening test included EUS (nZ8) and MRI/MRCP (nZ15). Abnormal findings were noted on initial examinations in 11/23 patients; 47% and 50% of MRI and EUS exams, respectively. Cysts were identified in 4 initial MRI exams, but no initial EUS examinations (Table 2). Subjects underwent an average of 3 screening exams (range 1-9) with average follow up of 30.3 months (range 0-327). Six patients developed incident abnormalities on subsequent screening examinations, including new cysts (nZ4), progressive chronic pancreatitis changes (nZ2), and a solid mass (nZ1). Two individuals ultimately underwent surgery. The mass (2 cm pancreatic adenocarcinoma in the head of pancreas) was diagnosed in a CDKN2A mutation carrier 14 months after a previous MRI which had noted only a tail cyst. Another patient had a strong family history of PC and underwent a Whipple resection of a focally dilated pancreatic duct (final pathology showed benign fibrotic tissue). Conclusions: Less than one-third of patients meeting consensus criteria undergo screening for PC. Nearly half of HRIs screened had abnormalities noted on initial examinations, with cysts and chronic pancreatitis changes being the most common. Overall, 17/23 (74%) HRIs had at least one abnormal screening test. Emergence of PC within one year of a screening MRI highlights the need for studies to identify the most sensitive and specific screening modality.

1007 Novel Endoscopic Approach for a Large Intraluminal Duodenal (“Windsock”) Diverticulum Vivek Kumbhari*, Alan H. Tieu, Alba Azola, Saowanee Ngamruengphong, Mohamad H. El Zein, Mouen Khashab Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, MD Background: A 59 yr-old female presents for evaluation of recurrent acute pancreatitis. She has had three documented episodes over 8 yrs and is status post cholecystectomy. She has a longstanding history of foregut symptoms. She had undergone multiple EGDs and no abnormality was identified. Investigations demonstrated a dilated CBD with no mass lesion. We arranged an EUS and if no abnormality was seen, an ERCP with biliary sphincterotomy would be performed for papillary stenosis. At attempted ERCP, a structure was identified that was in the correct location for the major papilla but was odd in appearance. This was subsequently found to be a large intraluminal duodenal diverticulum, otherwise known as a “windsock” diverticulum. This is a congenital abnormality characterized by a septum across the duodenal lumen and can be missed at endoscopy. This has been known to cause pancreatitis. In this patient, the apex of the duodenum had an opening and this is not uncommon in those with a longstanding diverticulum. Management approaches include a surgical or endoscopic strategy. With regards to an endoscopic approach, multiple modalities are available with no consensus as to which accessory is best. The objectives of this video are to demonstrate a novel endoscopic technique to obliterate a symptomatic intraluminal duodenal septum. Endoscopic Methods: A cap fitted endoscope was used to perform the endoscopic diverticulotomy. A through the scope 18 x 80mm fully covered self-expandable metallic stent was inserted into the diverticulum such that the distal end exited into the true lumen of the second part of the duodenum. The stent was secured with a single endoscopic clip. Epinephrine was injected along the long axis of the septum as a measure to prevent bleeding. The septum was cut using a thick blade needle knife with care being taken to cut towards and onto the stent. At completion of the procedure only one lumen exists. Care was taken to avoid the major papilla. Clinical Implications: We herein demonstrate a novel technique of managing an intraduodenal diverticulum. This technique using a TTS stent facilitated both an efficient and safe procedure. Additionally, the use of a pre-injection of epinephrine along the line of the incision appeared to help prevent intraprocedural bleeding allowing for optimal endoscopic views which results in an efficient and safe procedure.

1033 Prevalent and Incident Lesions Identified With Pancreatic Cancer Screening in High Risk Individuals Sean T. Mccarthy*, Amy E. Hosmer, James Scheiman, Victoria M. Raymond, Richard S. Kwon, Elena M. Stoffel University of Michigan, Ann Arbor, MI Background: Expert opinion advocates screening for pancreatic cancer (PC) in individuals with inherited predisposition, in hopes that early detection will reduce mortality; however outcome data are lacking. Our aim was to describe our center’s experience screening a cohort of high-risk individuals (HRIs) for pancreatic cancer. Methods: Subjects with a history suggestive of genetic risk for PC were identified through queries of the Cancer Genetics Registry at the University of Michigan. HRIs met R1 of the following criteria: 1) familial pancreatic cancer (defined as 3 or more relatives, or 2 first degree relatives (FDRs), with PC), 2) germline CDKN2A mutation associated with familial atypical multiple mole melanoma syndrome (FAMMM), 3) germline STK11mutation associated with Peutz-Jeghers syndrome, 4) germline mutation of PRSS1 or SPINK associated with hereditary pancreatitis, 5) germline BRCA1 or BRCA2 mutation with PC in a FDR, 6) DNA mismatch repair (MMR) mutation with Lynch syndrome with PC in a FDR. Chart reviews were performed to collect demographics, findings of screening tests and clinical outcomes. Results: A total of 93 HRIs were identified, with the largest proportion fulfilling criteria for familial pancreatic cancer (nZ34, 37%). Of the 93 individuals, 43 (46%) were counseled to undergo screening and 28 (30%) underwent at least one screening examination (Table 1). Results of screening tests were available in 23

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1034 Spectral Biomarkers of Pancreatic Cancer Bohus Bunganic*1, Michal Tatarkovic2, Martin Laclav1, Stepan Suchanek1, Lucie Stovickova2, Lucie Kocourkova2, Vladimir Setnicka2, Miroslav Zavoral1 1 Department of Medicine, 1 Faculty of Medicine, Military University Hospital, Charles University, Prague, Czech Republic; 2Department of Analytical Chemistry, Institute of Chemical Technology, Prague, Czech Republic The search and definition of biomarkers of pancreatic cancer (PC) remains a subject of great interest. The specificity and sensitivity of the current tested biomarkers are below the required values. In order to make a diagnosis of early pancreatic cancer, establishing a new biomarker is essential. During cancer diseases, many changes may occur within the 3D structure of proteins, peptides and other biomolecules. Therefore, we tested a new approach in PC diagnosis based on a specific molecular signature of blood plasma components using chiroptical and vibrational spectroscopy. Chiroptical methods such as electronic circular dichroism (ECD) and Raman optical activity (ROA) are inherently sensitive to these 3D structures and were supplemented by conventional infrared (IR) absorption and Raman spectroscopies. We collected blood plasma samples from 23 healthy control persons and 34 pancreatic cancer patients (PCs). The ECD spectra of the PCs showed generally not only a lower intensity profile in the UV spectral region than the healthy controls, but also the spectral patterns were slightly changed. There were as well distinct differences between the Raman and ROA spectra of PCs and controls. The Raman and

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Abstracts

ROA spectra of controls showed several bands in the amide I and extended amide III regions. Their positions and spectral band-shapes are characteristic of a mainly alpha-helical peptide/protein conformation with a low content of beta-sheet structures. The more intense negative band in the amide I region of the ROA spectra of PCs cohered with changes in intensities of bands belonging to unordered and betasheet structures. Other observed changes corresponded to aliphatic and saccharide/ glycoprotein moieties. The spectra obtained from all four spectral methods were consequently processed by linear discriminant analysis (LDA) showing clear separation of controls and PCs (Figure 1). The quality of the established statistical model was confirmed by leave-one-out cross-validation (Table 1), where sensitivity and specificity reached 91% and 87%, respectively. The results obtained in this pilot study show a high potential of the combination of chiroptical and vibrational spectroscopy as a promising tool in the identification of new spectral biomarkers for PC diagnosis.

The LDA confusion matrix for the cross-validation results from / to Cancer Control Total

Cancer

Control

Total

% correct

31 3 34

3 20 23

34 23 57

91.2% 87.0% 89.5%

2-!3 cm). Results: Of the 287 patients with suspected IPMN 39% were males; their mean age was 65.9 +/- 12.6 years at baseline and size distribution was as follows: 121 had cyst !1cm, 133 had cyst 1 to !2 cm and 33 had cyst 2 to 3 cm in size. They had a median follow up of 4.8 (1 to 14.2) years. Probability of developing worrisome or high-risk features (Fukuoka positive), pancreatic surgery for PCL or PC were 8.2%, 1.4% and 1.4% for cysts !1cm; 2.9%, 0% and 0% for cysts 1-!2 cm; 42.9%, 4.8% and 0% for cysts 2-!3 cm at 5 years. Conclusions: On conservative follow up PCLs without high risk or worrisome features (Fukuoka negative) suspected to be IPMN have a extremely low risk of developing pancreatic cancer or undergoing cyst related surgery.

Cyst characteristics of included cases !1 cm (n[121)

1-!2 cm (n[133)

2-!3 cm (n[33)

Total (n[287)

78 (64.5%)

80 (60.2%)

17 (51.5%)

63.6 +/12.1

67.2 +/13.1

68.7 +/11.4

175 (61.0%) 65.9 +/-12.6

101 (83.5%) 20 (16.5%)

116 (87.2%) 17 (12.8%)

31 (93.9%)

89 (73.6%)

88 (66.2%)

25 (75.8%)

2 3 4 5+ Location of Cyst Head

18 (14.9%) 6 (5.0%) 0 8 (6.6%)

17 2 1 25

(12.8%) (1.5%) (0.8%) (18.8%)

1 (3.0%) 1 (3.0%) 0 6 (18.2%)

44 (36.4%)

49 (36.8%)

14 (42.4%)

Neck Body Tail Presence of septations Pancreas atrophy Parenchymal calcifications Lymphadenopathy Uncinate duct dilation Bile duct dilation Other cysts (Renal, Hepatic, Splenic) Family history of pancreatic cancer Follow up (years)*

7 (5.8%) 40 (33.1%) 30 (24.8%) 0 2 (1.7%) 1 (0.8%) 0 0 0 58 (47.9%)

17 39 28 5 4 7

(12.8%) (29.3%) (21.1%) (3.8%) (3.0%) (5.3%) 0 1 (0.8%) 0 79 (59.4%)

3 (9.1%) 9 (27.3%) 7 (21.2%) 2 (6.1%) 5 (15.2%) 1 (3.0%) 0 1 (3.0%) 1 (3.0%) 17 (51.5%)

10 (8.3%)

12 (9.0%)

0

107 (37.3%) 27 (9.4%) 88 (30.7%) 65 (22.6%) 7 (2.4%) 11 (3.8%) 9 (3.1%) 0 2 (0.7%) 1 (0.3%) 154 (53.7%) 22 (7.7%)

5.0 (3.3, 6.8)

4.7 (2.8, 6.9)

4.4 (3.0, 6.7)

4.8 (3.0, 6.8)

Female Age (years)^ Type of imaging CT MRI/MRCP Number of cysts 1

Figure 1. Graphical results of LDA of blood plasma samples analyzed by a combination of ECD, Raman, ROA and IR absorption spectroscopy: control persons (blue) and pancreatic cancer patients (red)

2 (6.1%)

248 (86.4%) 39 (13.6%) 202 (70.4%) 36 (12.5%) 9 (3.1%) 1 (0.3%) 39 (13.6%)

^Mean +/- Standard deviation *Median (Interquartile range)

1035 Risk for Developing Adverse Outcomes in Suspected Intraductal Papillary Mucinous Neoplasms Without High Risk or Worrisome Features Saurabh S. Mukewar*1, Anupama Aryal-Khanal1, Naoki Takahashi2, Santhi Swaroop Vege1, Mark Topazian1, Michael J. Levy1, Suresh T. Chari1 1 Gastroenterology, Mayo Clinic, Rochester, MN; 2Radiology, Mayo Clinic, Rochester, MN Background: International Consensus Guidelines for intraductal papillary mucinous neoplasm (IPMN) at Fukuoka provide indications for surgical resection in pancreatic cystic lesions (PCL) suspected to be IPMN. However, data concerning the outcome of conservative follow-up of PCLs without high-risk or worrisome features (Fukuoka negative) are limited. In such lesions we estimated the 3 and 5-year risk of adverse cyst outcomes defined by new development of high risk or worrisome features, pancreatic surgery and/or pancreatic cancer (PC). Methods: From Mayo Clinic Rochester’s electronic databases we identified 766 randomly selected patients who had PCLs diagnosed on CT or MRI. We excluded patients with i) inflammatory PCL (nZ 104) ii) definite or suspected non-IPMN PCL (nZ29), iii) Fukuoka positive (with high risk or worrisome features) PCLs (nZ106), main duct IPMN (nZ4) and mixed IPMN (nZ14) on initial imaging, iv) !1 year follow up, and v) pancreatic surgery or pancreas cancer !1 year from cyst diagnosis (nZ153). We re-reviewed all cross-sectional imaging and abstracted clinical and follow-up data on Fukuoka negative PCLs suspected to be branched duct IPMN (nZ287). We estimated adverse cyst outcomes in this cohort and in subgroups categorized by maximum diameter of cyst size (!1cm, 1-!2 cm,

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1036 Follow up IPMN for Early Detection of Pancreatic Cancer Reiko Ashida*1, Tatsuya Ioka1, Ryoji Takada2, Nobuyasu Fukutake2, Hiroyuki Uehara2, Kazuyoshi Ohkawa2, Kazuhiro Katayama1 1 Departments of Cancer Survey and Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; 2 Department of Hepato-Biliary and Pancreato Oncology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan Background and Aims: The updated 2012 international consensus guidelines for the management of intraductal papillary mucinous neoplasms (IPMN) recommend surveillance with non-invasive imaging such as CT/MRI for small size of presumed branch duct IPMN (BD-IPMN). However, there is little data regarding the optimal frequency,

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