PET-CT Versus EUS Lymph Node Detection in Esophageal Cancer Patients: Implications for Dilatation Requirement

Abstracts

retrospectively studied. All patients underwent conventional radial endosonography (frequency 5 MHz). Any suspicious appearing lymph nodes were sampled using a linear echoendoscope. Results: Twenty-two patients (Mean age 65 y; 82% Male) with HGD in flat Barrett’s mucosa had EUS examination prior to referral for therapy. 13 (59%) patients had long segment Barrett’s and 7 (32%) patients had multifocal HGD. In 2 patients the latter information was not available. EUS staging reported T0N0 in 20 patients. Two patients had detected lymphadenopathy, however FNA cytology in both patients was negative for malignancy. Of the 12 patients that underwent EMR, 8 had HGD on histological examination, 1 had low grade dysplasia and 2 had nondysplastic Barrett’s. An additional 3 patients underwent esophagectomy, and the surgical pathology revealed HGD with negative LNs. 5 patients underwent radiofrequency ablation without EMR, while 2 patients returned to their primary gastroenterologists for management. Conclusion: Patients with HGD in flat Barrett’s mucosa had no evidence of invasive disease or nodal involvement by conventional EUS  FNA. These findings correlated with pathologic staging in the 15 patients that had surgery or EMR. This study suggests that in patients with flat Barrett’s and HGD, EUS did not affect staging or management and may not be needed in the routine workup in this group of patients.

M1456 Comparison of Catheter-Based Ultrasound Probes Versus Radial Echoendoscopes for Evaluating Dysplastic Nodules in Barrett’s Esophagus Prior to Endoscopic Mucosal Resection Rabindra R. Watson, Kenneth F. Binmoeller, Tonya Kaltenbach, Roy M. Soetikno, Janak N. Shah Background: Endoscopic ultrasound (EUS) is often used to confirm potential resectability prior to endoscopic mucosal resection (EMR) of dysplastic nodules in Barrett’s esophagus (BE). Two main technologies for this application include catheter-based US miniprobes and dedicated echoendoscopes. There are few data comparing these EUS techniques. Aims: To compare catheter-based ultrasound probes to dedicated radial echoendoscopes in identifying focal dysplastic lesions within BE amenable to EMR. Methods: Our center routinely performs EUS prior to EMR to evaluate dysplastic nodules in BE. Use of miniprobe versus echoendoscope is at the discretion of the endoscopist and often based on immediate instrument availability at our high-volume center. We retrospectively identified all patients referred for EMR of dysplastic nodules over a 5-year period. The following data were collected: patient demographics, referral indication, EUS technique and findings, and pathology findings from EMR. Results: A total of 55 patients (mean age 68, male 86%) with BE were referred for potential EMR. Pathology specimens from prior forceps biopsies of the nodules revealed: high-grade dysplasia (75%), suspected carcinoma-in-situ (18%), and indeterminate (7%). EUS exams were performed with radial echoendoscopes (7.5MHz) in 38%, miniprobes (12MHz) in 49%, and both in 13%. EUS revealed invasion depth limited to the mucosal or submucosal layers in all patients. Indeterminate periesophageal lymph nodes (LN) were seen in 11%, all using radial echoendoscopes. Immediate EUS-FNA with onsite cytology revealed benign LN in all cases. All patients underwent EMR based on EUS findings. Final pathology from the miniprobe group included: high grade dysplasia (48%), carcinoma-in-situ (11%), and invasive carcinoma (19%). Pathology from the echoendoscope group included: high grade dysplasia (33%), carcinomain-situ (10%), and invasive carcinoma (14%). Of the 7 evaluated with both modalities, pathology revealed: high grade dysplasia (14%), carcinoma-in-situ (43%), and invasive carcinoma (29%). Three of ten patients with invasive carcinoma had positive submucosal resection margins (two evaluated with miniprobes, 1 with both), and were referred for esophagectomy. Two underwent esophagectomy, revealing adenocarcinoma limited to the submucosa without lymph node involvement. Conclusions: Miniprobes appears comparable to dedicated radial echoendoscopes in identifying dysplastic lesions amenable to EMR. Given start-up cost differences for these technologies, our findings have implications for endoscopic centers with limited resources interested in managing patients with dysplastic BE.

M1457 DNA Mutational Analysis of Pancreatic Cyst Fluid Does Not Change Clinical Management and May Be Misleading Stacie A. Vela, Joseph Romagnuolo, Brenda Hoffman Pancreatic cyst lesions often pose a diagnostic and management dilemma to the gastroenterologist. Many cysts have (variable) malignant potential. Multiple laboratory and radiologic evaluation techniques have been proposed to predict this potential and, in turn, aid in management decisions. These include ultrasound characteristics and cyst fluid analysis such as carcinoembryonic antigen (CEA), cytology, and more recently, DNA mutational analysis (DNA-ma). While DNA-ma appears to be the most promising of those studied, it is expensive, and the added information has not yet proven to change management from that based on radiologic characteristics, cytology and CEA. Aim: To determine if DNA-ma of pancreatic cyst fluid changes clinical management of patients with pancreatic cysts.

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Methods: All patients that had endoscopic ultrasound evaluation and aspiration of a pancreatic cyst with fluid sent for DNA-ma (either at or referred to our institution) were included in the study. The reports from endoscopic ultrasound were reviewed and recommendations were recorded. DNA-ma reports were then evaluated and compared to EUS diagnosis. Management strategy changes, due to these results, were recorded. Results: 14 (50% male) eligible patients were identified. Average age was 67 yrs (50-81). 7% had their EUS done outside our institution. 50% of patients had high risk features on EUS: mural nodules, thick wall, large size (O3 cm), main duct involvement, and/or solid component. Mean CEA was 279.8 ng/dL(!0.51793.7 ng/dL). Diagnoses based on EUS and conventional fluid analysis were IPMN in 79% of the patients, inflammatory in 7% and indeterminate in 14%. All 14 (100%) DNA-ma results indicated benign lesions. This did not change clinical management or follow up interval in any of the patients, including the patients with high risk features. One indeterminate cyst with high risk features underwent surgical resection, despite low CEA and DNA-ma consistent with a serous cystadenoma; final pathology revealed a T2N0 solid pseudopapillary tumor with high grade pancreatic intraepithelial neoplasia. Conclusion: In our series, DNA-ma results did not change clinical management. In at least one case, DNA-ma suggested a benign condition, but surgical follow-up revealed malignancy. While DNA mutational analysis appears to a promising technology, further studies are needed to determine clinical utility beyond conventional tests.

M1458 How Good Is EUS to Detect Pancreatic Insulinomas? A MetaAnalysis and Systematic Review Srinivas R. Puli, Matthew L. Bechtold, Jyotsna Bk Reddy, Srinivas R. Bapoje, Mainor R. Antillon, William R. Brugge Background: The published data on accuracy of Endoscopic Ultrasound to detect pancreatic insulinomas (PI) has been varied. Detection of PI is critical from a therapeutic stand point. Aim: To evaluate the accuracy of EUS in detecting PI. Method: Study Selection Criteria: Only EUS studies confirmed by surgery or appropriate follow-up were selected. Only studies from which a 2 X 2 table could be constructed for true positive, false negative, false positive and true negative values were included. Data collection & extraction: Articles were searched in Medline, Pubmed, Ovid journals, Cumulative index for nursing & allied health literature, International pharmaceutical abstracts, old Medline, Medline nonindexed citations, and Cochrane Central Register of Controlled Trials & Database of Systematic Reviews. Two reviewers independently searched and extracted data. The differences were resolved by mutual agreement. 2 X 2 tables were constructed with the data extracted from each study. Statistical Method: Meta-analysis for the accuracy of EUS was analyzed by calculating pooled estimates of sensitivity, specificity, likelihood ratios, and diagnostic odds ratio. Pooling was conducted by both Mantel-Haenszel method (fixed effects model) and by the DerSimonian Laird method (random effects model). The heterogeneity among studies was tested using Cochran’s Q test based upon inverse variance weights. Results: Initial search identified 2610 reference articles, of these 130 relevant articles were selected and reviewed. Data was extracted from 9 studies (NZ 242) which met the inclusion criteria. Pooled sensitivity of EUS to detect PI was 87.5% (95% CI: 81.2 - 92.3). EUS had a pooled specificity of 97.4% (95% CI: 90.8 - 99.7). The positive likelihood ratio of EUS was 8.2 (95% CI: 3.7 - 18.3) and negative likelihood ratio was 0.17 (95% CI: 0.12 - 0.26). The diagnostic odds ratio, the odds of having anatomic PI in positive as compared to negative EUS studies was 67.6 (95% CI: 22.7 - 200.9). All the pooled estimates calculated by fixed and random effect models were similar. SROC curves showed an area under the curve of 0.94. Egger bias indicator for publication bias gave a value of -0.05 (95% CI Z -4.13 to 4.04, p Z 0.98), indicating no publication bias. The p for chi-squared heterogeneity for all the pooled accuracy estimates was O 0.10. Conclusions: EUS has excellent sensitivity and specificity to detect PI. EUS should be strongly considered for evaluation of PNT.

M1459 PET-CT Versus EUS Lymph Node Detection in Esophageal Cancer Patients: Implications for Dilatation Requirement Craig M. Womeldorph, Richard S. Kwon For the staging of esophageal cancer, endoscopic ultrasound (EUS) is the most sensitive modality to detect local and distant lymph nodes (LN). Dilatation of stenotic cancers to assess the celiac axis is often challenging and has a perforation risk up to 25%. Integrated positron emission tomography computed tomography (PET-CT) has reported incremental improvement for nodal staging over PET and CT alone. The aim of this study is to compare the detection of celiac LN by PET-CT and EUS. We specifically sought to determine whether a negative PET-CT could prevent the risks involved in dilatation at the time of EUS. Aim: To compare the detection of celiac lymph nodes by PET-CT and EUS. Methods: We retrospectively reviewed all staging EUS performed for esophageal carcinoma from January 2005 to December, 2008. Only patients treated with esophageal dilation with concomitant PET-CT reports were included in the analysis. Successful dilatations were defined by passage of the EUS scope into the stomach. Positive celiac LN detection by EUS was

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Abstracts

defined by the presence of any LN !2 cm away from the celiac axis with classic sonographic features of size O1.0 cm, round, and hypoechoic with distinct margins. Positive LN detection by PET-CT was defined by positive imaging by both modalities. Results: During the study period, 93 esophageal cancer patients underwent EUS; 34 also underwent dilation. 27 (79%) dilatations were successful. 10/27 patients were excluded (no PET-CT). Of the remaining 17 patients, 12 patients had both a negative EUS and PET-CT, 4 had a positive EUS and negative PET-CT, and 1 had a negative EUS and a positive PET-CT. In this cohort of patients with both EUS and PET-CT, and the negative predictive value for PET-CT was only 75%. Conclusion: PET-CT has a poor NPV and therefore a negative PET-CT does not eliminate the need for esophageal dilatation to assess celiac lymph nodes during EUS for esophageal cancer staging. Larger prospective studies comparing EUS and PET-CT are needed to determine the true accuracy of both staging modalities.

M1460 Endoscopic Ultrasound (EUS) Identifies Ampullary Masses Suitable for Endoscopic Ampullectomy (EA) Jason Conway, Sarba Kundu, John A. Evans, John Baillie, John H. Gilliam, Girish Mishra Background: EUS has become an important adjunct to ERCP for determining the most appropriate management of ampullary masses (endoscopic vs limited surgical resection vs Whipple procedure). Aim: To determine the accuracy of EUS in identifying ampullary lesions suitable for EA. Results: Majority of pts presented with jaundice (24%), abdominal pain (24%) or were asymptomatic (24%). Based on EUS staging, resection was endoscopic (nZ6), localized surgical resection (nZ8) or extensive resection (Whipple procedure) (nZ13). Histopathology showed 13 adenomas  high grade dysplasia(48%), 12 adenocarcinomas (adenoCA) (44%) and 2 inflammatory ampullary tissue (8%). All adenoCAs were found in pts having the Whipple procedure. EUS was highly sensitive for staging T1 ampullary masses but performed poorly distinguishing T2 from T3 lesions (Table 1). Conclusion: EUS is highly accurate for identifying pts with T1 ampullary adenomas, avoiding the need for aggressive surgery (Whipple procedure). Ampullary masses confined to the mucosa and submucosa are suitable for endoscopic and localized surgical ampullectomy. Invasive adenoCAs should be treated with Whipple procedure: all in this study were. Distinguishing T2 from T3 lesions was a challenge, however. EUS performance (Table 1) T Stage

Sensitivity

Specificity

Kappa

Accuracy

T1 T2 T3

100% 0% 25%

40% 91.3% 95.7%

0.46 -0.11 0.26

77.8% 77.8% 85.2%

M1461 Natural History of Intraductal Papillary Mucinous Neoplasms (IPMNs) Based On Followed Contast-Enhanced EUS (CE-EUS) Findings: Focusing On Malignant Alteration and Development of Ductal Cancer of the Pancreas Eizaburo Ohno, Yoshiki Hirooka, Akihiro Itoh, Hiroki Kawashima, Toshifumi Kasugai, Takuya Ishikawa, Hiroshi Matsubara, Ryoji Miyahara, Yoshiaki Katano, Naoki Ohmiya, Yasumasa Niwa, Hidemi Goto Background: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas vary from hyperplasia to invasive cancer pathologically, and the management of IPMN has been controversial. We reported the usefulness of EUS for diagnosis of mural nodules of IPMNs (‘‘Annals of Surgery’’ in-press). The purpose of this retrospective study is to verify our diagnostic strategy and to elucidate the natural course of long-term followed cases by evaluating serial changes of mural nodules in CE-EUS findings. Patients and Methods: Two hundred twenty-nine patients with IPMNs were examined by CE-EUS as the initial study since January, 2001. Our indications for resection were as follows: the case of main-duct type, existence of mural nodule with blood flow signal in CE-EUS (regardless of the nodule size) and coexistence of ductal cancer cases. As to the follow-up cases (patient refusal of operation, mural nodule lacking color signals and under our operative indications, and so on.), EUS and/or CT was performed every 6 months. We retrospectively reviewed 148 cases followed over 6 months. We assessed carcinogenic rate of IPMNs and investigated the relationship between the morphological changes of mural nodules by CE-EUS and the histological changes. We defined carcinogenic rate as the summation of development of ductal carcinoma cases and malignant alteration cases of IPMN. Results: Median follow-up term was 25.4months (6116months). Coexistence of ductal carcinoma developed in 2 of 143 (1.4%). Those two cases were inoperable. Three-year and 5-year carcinogenic rate was, respectively, 8.7% and 18.3%. As to thirty patients (21%) resected in the follow-up period, the sizes of mural nodule on CE-EUS findings (confirmed by pathological findings) in the cases of malignant IPMNs were significantly larger (4.51  0.69mm/

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yr vs 1.93  0.60mm/yr [pZ0.009]). Initial appearance of mural nodules were observed in 13cases. There were 10 with adenoma, 3 with carcinoma in situ and there was no invasive carcinoma derived from IPMN. Conclusion: As to our followup study, carcinogenic rate of IPMNs was not infrequent. Enlargement or occurrence of mural nodules may be a useful indicator to determine the timing of surgical treatment. Our diagnostic strategy was appropriate because there were no invasive cases pathologically in newly occurrence cases. In conclusion, CE-EUS is a very useful diagnostic method for follow-up.

M1462 The Yield of Endoscopic Ultrasonography for Determining An Etiology in Patients with Idiopathic Acute Pancreatitis Brian R. Boulay, Stuart R. Gordon, Timothy B. Gardner Aims: Although Endoscopic Ultrasound (EUS) is often used as part of the evaluation of idiopathic acute pancreatitis, the success of the technique at identifying a disease etiology is unknown. We aimed to determine the rate at which EUS evaluation changed the diagnosis or management of patients with acute idiopathic pancreatitis. Methods: We retrospectively identified all patients sequentially referred to our medical center between March 1997 and July 2008 for EUS evaluation of acute or recurrent acute idiopathic pancreatitis. The etiology of acute pancreatitis was not known at the time of each EUS examination, despite an extensive outpatient work-up including cross-sectional imaging. All EUS exams were performed by expert endosonographers. Patient charts were abstracted by two reviewers for baseline patient characteristics, previous evaluation of pancreatitis, findings on EUS exam, and subsequent management. Results: Out of 3375 sequential EUS exams performed at our medical center, 110 patients underwent EUS specifically for evaluation of acute or recurrent acute idiopathic pancreatitis. The mean patient age was 51 years (range 10-88) and 63% were female. 71 (35%) patients had experienced multiple episodes of pancreatitis with a mean of four previous attacks. Nineteen patients (17%) had EUS findings which identified a disease etiology or changed patient management. Of these, 11 patients had findings of choledocholithiasis or microlithiasis, indicating a biliary source of pancreatitis. 3 patients (16%) had evidence of a dilated common bile duct without an intraluminal filling defect and underwent biliary sphincterotomy for presumed papillary stenosis. Additional findings included cystic neoplasms of the pancreas in two patients, islet cell tumor of the pancreas in one patient, inflammatory stricture of the pancreatic duct in one patient and one patient with pancreas divisum. 22 patients (20%) were diagnosed with chronic pancreatitis based on EUS criteria, although no etiology was determined in this group. None of these patients had been previously diagnosed with chronic pancreatitis. Conclusions: EUS examination determined an etiology of disease in 17% of patients undergoing evaluation for acute or recurrent acute idiopathic pancreatitis. Given the often significant challenges in identifying a cause of disease in this patient population, EUS does increase the diagnostic yield in some patients. All patients with recurrent pancreatitis should therefore undergo EUS evaluation before being labeled with idiopathic disease.

M1463 Risk of Malignancy in Patients with Isolated Dilation of Common Bile Duct and Without CBD Stones On Abdominal Imaging Amith V. Reddy, Naveen B. Krishna, Jeremy A. Hartman, Christopher D. Mehan, Banke Agarwal Background: Isolated dilation of common bile duct (with normal sized pancreatic duct) is frequently noted on abdominal US/CT/MRI. Further diagnostic evaluation of these patients is often determined by the presence of abnormal LFTs and obstructive jaundice. We investigated the prevalence of malignancy in these patients and made comparison based on abnormal LFTs and jaundice. Patients and Methods: From our prospectively maintained database, we identified 86 patients who underwent EUS for evaluation of dilated CBD (R7 mm) noted on US/CT/MRI scans. Patients with CBD stones or an identifiable mass lesion on imaging were not included. Obstructive jaundice was defined by presence of serum bilirubin O1.0 mg/ml that was predominantly conjugated. LFTs were considered abnormal if there were elevated alkaline phosphatase levels with or without increase in transaminases levels. The final diagnosis was based on surgical pathology or clinical follow up of R12 months. Results: The mean age of 86 study patients (57 female) was 62.6  13.9 years. 31 patients had jaundice (group A), 23 patients had abnormal LFTs (group B) and 32 patients had normal LFTs (group C). 54 patients had associated abdominal pain and 14 patients had weight lossO10 lbs. The mean size of CBD and final diagnosis are summarized in figure 1. There were 4 patients with false negative diagnosis: in 2 patients no focal mass lesion was noted by EUS and in other two patients a focal mass lesion was noted pressing on the common bile duct but the cytology failed to diagnose malignancy. EUS-FNA had 95.4% overall accuracy (87.1% in jaundice group), 63.6% sensitivity, 100% specificity, 100% PPV and 83.4% NPV for diagnosing malignancy in this group. Conclusions: Among the patients with isolated dilation of CBD and without identifiable stones on US/CT/MRI, the risk of malignancy is significant only in patients with associated obstructive jaundice and is quite low even in patients with abnormal LFTs but without jaundice. EUS-FNA can be helpful in further diagnostic work-up of these patients.

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