Endoscopic Ultrasound (EUS) Detection of Pancreatic Neoplasms in Patients Without a Definitive Pancreatic Mass On Computed Tomography (CT) Scan

Abstracts

patients the lesion was located in the pancreatic head/uncinate, and in 12 (37.5%) in the neck/body/tail. Based on the location of the lesion, malignancy was diagnosed at the second EUS-FNA in 3 (15.78%) of the lesions in the head/uncinate process, and in 2 (25%) of the lesions in the neck, body and tail. The mean number of FNA passes on the repeat EUS examination was 4.14 (range 1-8). Overall repeat EUS-FNA established definitive tissue diagnosis of malignancy in 5/31 patients (16.2%). Conclusion: Repeat EUS-FNA has low yield in patients with suspected pancreatic cancer who had had prior negative EUS-FNA evaluation.

M1476 Causation of Pancreatic Pseudocyst Is the Key Influential Factors for the Success of EUS-Guided Treatment: The Therapeutic Strategy for Pancreatic Pseudocyst Based On Causative Factors Atsushi Irisawa, Takuto Hikichi, Goro Shibukawa, Tadayuki Takagi, Hidemichi Imamura, AI Sato, Masaki Sato, Tsunehiko Ikeda, Rei Suzuki, Katsutoshi Obara, Hiromasa Ohira Background: Pancreatic pseudocyst (PPc) can be divided into 3 types based on causative factors: type 1, acute post-necrotic pseudocyst; type 2, post-necrotic pseudocyst on chronic pancreatitis; and type 3, chronic pseudocyst (retention). Types 1 and 2 can be classified as post-necrotizing pseudocysts, and with the spread of inflammation outside pancreas, the omental sac that exists between pancreas and stomach itself forms a cystic cavity, resulting in pseudocyst. The gastric wall thus becomes a cystic wall, and EUS-guided pseudocyst drainage (EUS-CD) is safety indicated. Type 3 is basically an intrapancreatic cyst, and because the stomach is separate from cyst, EUS-CD may cause to leak the cyst contents into abdominal cavity. In recent years, a technique to debride/lavage of a cyst by inserting an endoscope via stomach has been reported, but whether it is required in all PPc is unclear. The aim of this study was to clarify the indications for EUS-CD based on causative factors. Methods: 31 patients with PPc O6 cm in diameter, including 7 with type-1, 20 with type 2, and 4 with type 3, were enrolled. As to therapy, the external drainage using a naso-biliary tube was performed to manage infections, the internal drainage using a stent between the cyst and stomach was employed if aspirated contents were serous. With external drainage, the tube was clamped 2 weeks after placement, and it was removed 3 days later if the cyst did not increase. Then, if the cyst increased, internal drainage was employed. (Results) Internal drainage was performed on 1 type-1 and 4 type-2 patients. External drainage was employed on 6 type-1, 16 type-2, and 4 type-3 patients. For these treatments, efficacy of EUS-CD for types 1, 2, and 3 was 57%, 90%, and 50%. In type-1, a small cyst remained in 3 patients who were treated using EUS-CD alone. In addition, in almost type-2, EUS-CD alone was sufficient to achieve favorable results. In 2 type-3, EUS-CD alone was not enough, and surgical treatment was required. Regarding complications, in 1 type-2 patient and 2 type-3 patient, cystic contents leaked into the abdominal cavity during the procedure. (Conclusions) In the treatment of type1, debridement / lavage of cyst via the stomach are appropriate. In type-2, management using a drainage tube is appropriate. Furthermore, in type-3, management using a drainage tube is pertinent if the cystic wall adheres to the gastrointestinal wall due to inflammation, but no therapy should be sufficient if no inflammation is present because of no adherence between cyst and stomach. The present study was retrospective, but demonstrates the importance of planning therapy based on pseudocyst type.

M1477 Isolated Thickening of the Common Bile Duct At EUS: Is It Clinically Relevant? Pietro Fusaroli, Simona Guglielmo, Antonino Grillo, Giancarlo G. Caletti Background: A thickened wall of the common bile duct (CBD) is a relatively common finding in several pancreaticobiliary EUS; however, little is known about its clinical significance. In patients with major findings such as biliary stones, pancreatic cancer, and CBD stenting the thickening of the CBD wall is considered of secondary importance and ruled out. On the other hand, it may happen that it were the only atypical finding in the absence of clear causative lesions and in an otherwise normal EUS. Our aim was to determine the clinical significance of EUS detection of an isolated CBD wall thickening. Patients and Methods: We reviewed retrospectively our database in the period 2004-2007 searching for ‘‘thickened CBD wall’’ in the report of patients referred for pancreaticobiliary EUS with one of these indications: recent jaundice, biliary colic and/or acute pancreatitis. All relevant cases were contacted by telephone and pertinent medical reports were analyzed to follow up their clinical conditions up after EUS. Results: Overall, 101 patients had CBD thickening at EUS. Of these, 57 were excluded because other relevant pathological conditions were identified (CBD stones, pancreatic cancer, CBD stent, chronic pancreatitis). Also patients with previous endoscopic sphincterotomy were excluded. Other 22 patients were excluded due to the finding of stones in the gallbladder. Thus, 22 cases were left with the isolated finding of a thickened CBD wall constituting our study group (19 with previous cholecystectomy, 5 with acalcolous gallbladder in situ) (14F,8M; age 45-88, median 67). All these patients were symptomatic at the time of EUS (4/22 acute pancreatitis, 15/22 biliary colic

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with elevations of liver enzymes, 3/22 transient jaundice). After EUS, 19/22 patients remained symptom-free for a follow-up of 12-48 months (median 31). Only three/22 patients (14%) underwent ERCP with sphincterotomy for recurrent biliary pain with elevation of liver enzymes (nZ2) or jaundice (nZ1). Conclusions: The finding of a thickened CBD at pancreaticobiliary EUS is relatively common in a variety of clinical settings and can be exclusively appreciated by EUS in contrast to other imaging techniques. The isolated thickening of the CBD does not appear to prelude either to worsening of the presenting clinical conditions or to their recurrence. Due to the low number of patients who had recurrent symptoms, a clinical follow up is warranted in all the cases without the need for an immediate endoscopic sphincterotomy.

M1478 Prevention and/or Early Detection of Pancreatic Cancer: From Forming a Registry Through Risk Factor Intervention and EUS Screening Tests: From Concept to Cure Jesse Lachter The aims of the present study include identifying and assessing the risk factors for pancreatic cancer (PCA) among first-degree relatives (FDRs) of PCA patients, and assessment of EUS to screen for early pancreatic cancer. A regional registry of PCA patients and their FDRs was compiled. 110 consenting PCA patients and 420 of their FDRs were enrolled. Consenting FDRs attended informative lectures, and completed forms assessing risk factors. Data was collated on ethnic origin, presence of any previous or current diseases, BMI, tobacco use, alcohol consumption, dietary habits, and presence of any symptoms typical for PCA. Endoscopic ultrasound (EUS) examination was offered, without cost, for PCA screening. More than one case of PCA was found in 4.5% of the 110 families. 52% of the FDRs were Ashkenazi Jews. Diabetes was found to be higher in kindreds than the average local agecorrected prevalence (p!0.01); no chronic pancreatitis was reported. 8.8% of the kindred suffer from symptoms or diseases that may mimic some pancreatic cancer symptoms. Excessive BMI was found in 76.5% of FDRs. Tobacco use was reported by 15.5%. The reported level of drinking alcohol was minimal and probably irrelevant. The average diet of the FDRs included 13 portions of fruits a week. EUS for screening was performed in 15 asymptomatic FDRs. One 54yo male was thus found to have carcinoma of the ampulla of vater which was curatively removed surgically, the other 14 had normal exams. Conclusions: Acceptable and effective PCA screening and risk reduction interventions are needed, particularly for FDRs. No screening test to detect early curable PCA has as yet been proven acceptable effective and accurate, but EUS appears promising for this purpose. Extended registries of FDRs for long-term follow-up including of various screening interventions appears justified, thus the author is seeking collaborators for this project. This work was supported by the Israel Cancer Association

M1479 Endoscopic Ultrasound (EUS) Detection of Pancreatic Neoplasms in Patients Without a Definitive Pancreatic Mass On Computed Tomography (CT) Scan Alexander Shpaner, William A. Ross, Gauri R. Varadhachary, Milind Javle, Douglas B. Evans, Jason B. Fleming, Eric Tamm, Jeffrey H. Lee Objective: To determine the ability of EUS with fine needle aspiration (FNA) to diagnose pancreatic neoplasms in patients with inconclusive findings (without a visible mass) on multi-detector CT scan optimized for pancreas imaging. Methods: Retrospective chart review of patients who underwent EUS of the pancreas from January 2002 to April 2008. Results: A total of 1061 pancreatic EUS were performed in 983 patients. Among those, 93 patients (58 M, 35 F, mean age 64.2 þ/- 11.6 y) with 112 EUSFNA performed met the inclusion criteria. The most common indications for CT were jaundice (43), abdominal pain (28), nausea and vomiting (15), weight loss (12), and/or diarrhea (12) with 33 patients (35%) having two or more symptoms. The CT findings were dilated ducts (42), abnormal pancreas texture (47), abnormal pancreas size (16), ductal prominence (11). In 12 patients, CT showed no obvious pancreatic abnormality. EUSFNA established diagnoses of pancreatic adenocarcinoma (49), islet cell tumors (8), cholangiocarcinoma (5), intrapapillary mucinous neoplasm (3), ampullary adenocarcinoma (2), and metastatic disease from renal cell carcinoma (1), bladder cancer (1) and large B cell lymphoma (1). In 23 patients, EUSFNA diagnosed non-, or pre-malignant conditions, chronic pancreatitis (7), autoimmune pancreatitis (4), mucinous cystadenoma (1), biliary adenomyoma (1), and atypical cells (1). Nine had normal pancreas on cytology (FNA for questionable findings on EUS). These 23 were followed for a mean of 18.3 months (0-91m). Two patients died, one from an unknown cause, and the other from complications of HIV. During the follow-up period, 3 had laparotomy, 3 Whipple surgery, and 1 CT-guided FNA. The final diagnoses were unchanged from EUSFNA findings. There were 55 with no pancreatic mass on CT but with a discrete mass on EUS; the mean size of a pancreatic mass detected by EUS was 2.5 þ/- 0.93 cm. Among the 112 EUSFNA performed, the sensitivity, specificity, positive predictive value, and negative predictive value of diagnosing a pancreatic neoplasm were 87.8%, 97.4%, 98.5%, and 80.4%, respectively. Thirteen patients had more than one EUSFNA. Among

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Abstracts

those, one patient was diagnosed with metastatic lymphoma by the third EUSFNA, and one with pancreatic cancer by a second EUSFNA. No complications were seen in 112 EUSFNA. Conclusions: Even when high quality CT is inconclusive for presence of a pancreatic neoplasm in patients with suspicious symptoms, the prevalence of malignancy is high. EUS is more sensitive than CT for detecting a mass smaller than 2.5 cm. EUSFNA is sensitive and specific in providing a tissue diagnosis with minimal complication rates.

M1480 Predictors of Diagnostic Accuracy of EUS-FNA for Pancreatic Malignancy Kayode Olowe, Brian Story, Andrew S. Ross, Drew Schembre Background: Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is an established useful modality for the diagnosis of malignant lesions of the pancreas. However, EUS-FNA may be inconclusive for malignancy in a subset of cases. Objective: To evaluate the sensitivity, specificity, predictive value, and determinants of accuracy of EUS-FNA of the pancreas for malignancy in a series of patients evaluated at a large tertiary referral hospital for pancreatic disease. Methods: Retrospective case series of all EUS-FNAs of mass lesions of the pancreas performed specifically to evaluate for malignancy at a tertiary referral center for pancreatic disorders from January 2005 through June 2008. Multivariate analysis of a variety of factors was performed by logistic regression. These included: indication for EUS, presence of a biliary or pancreatic stent, location of the mass, number of FNA passes, and utilization of ‘‘in-room’’ quick read preliminary cytology by a cytopathologist or trained technologist. For inclusion, a final diagnosis must have been confirmed by histological analysis of a surgical specimen and/or clinical follow up. Results: Of 344 cases reviewed, 284 met the inclusion criteria. The most common indications for the procedure were a mass lesion seen on prior imaging (82.4%), biliary obstruction without evidence of a mass (14.1%), and chronic pancreatitis (2.8%). Among patients with a mass on EUS, the location was in the head in 53.5%, body in 25.4%, neck in 9.2%, tail in 6.3%, and uncinate process in 5.6%. A biliary or pancreatic stent was present in 28.5% of cases. On average, 4.42.5 FNA passes were made into the pancreas for each case. Quick read preliminary cytology was utilized in 145 cases (51.1%). Malignancy was ultimately diagnosed in 239 (84.2%). These malignancies included adenocarcinoma (90%), neuroendocrine tumor (7.9%), lymphoma (1.3%), and metastatic renal cell carcinoma (0.8%). Pancreatitis was the final diagnosis is 27 (9.5%). EUS-FNA of the pancreas had a sensitivity of 83.7%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 53.6% for malignancy. Overall accuracy for malignancy was 86.2%. On multivariate analysis, only utilization of quick read preliminary cytology had a statistically significant affect on diagnostic accuracy for malignancy (pZ0.002). Conclusions: EUS-FNA has good sensitivity and excellent specificity for the diagnosis of pancreatic malignancy. Quick read preliminary cytology should be obtained in order to maximize the accuracy of EUS-FNA for malignant lesions of the pancreas.

M1481 Do Cyst Fluid CEA and Amylase Levels Help Differentiate Between Mucinous Pancreatic Cysts? Abdullah Rashdan, Mohammad A. Al-Haddad, Julia K. Leblanc, Lee McHenry, Stuart Sherman, John M. DeWitt Background: EUS-FNA cytology and fluid analysis are frequently utilized to evaluate pancreatic cysts. Elevated cyst fluid CEA is usually indicative of a mucinous pancreatic cyst but whether CEA or amylase values can subclassify various mucinous cysts is unknown. Aim: To determine whether cyst fluid CEA and amylase obtained by EUS-FNA can differentiate between mucinous cystadenomas (MCAs) and intraductal papillary mucinous neoplasms (IPMNs). Methods: Using our prospective hospital EUS and surgical databases, we identified all patients from January 2000 to December 2006 who underwent EUS of a pancreatic cyst prior to surgical resection. Cysts were pathologically subclassified as MCAs or IPMNs; all other cysts were considered non-mucinous. IPMNs were further classified as branched cysts only (IPMN-Br) or involving the main pancreatic duct with or without sidebranched cysts (IPMN-M). Malignant mucinous cysts demonstrated were defined as the presence of invasive carcinoma; all other neoplasms (including high grade dysplasia [HGD]) were considered benign. Values of cyst fluid CEA and amylase were correlated to corresponding surgical histopathology and compared using the Mann-Whitney Test. Results: 134 patients underwent surgery for pancreatic cysts including 72 (54%) that also had preoperative EUS. EUS-FNA was performed in 61/72 (85%) and cyst fluid analysis in 35/61 (57%) including CEA and amylase in 35 and 33 patients, respectively. Histopathology in these 35 cysts demonstrated nonmucinous cysts in 10 and mucinous cysts in 25 including: MCAs (nZ9, no HGD or cancer), IPMN-Br (nZ11, including one cancer and 5 HGD), and IPMN-M (nZ5, including one cancer). Comparison between cyst fluid CEA and amylase for all 25 mucinous cysts are shown in the Table. For IPMN-Br and MCAs alone, cyst fluid CEA (pZ0.34) and amylase (pZ0.92) were also similar. Conclusion: In this single center study, pancreatic cyst fluid amylase and CEA do not aid in distinguishing MCAs from IPMNs.

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Histopathology Cyst fluid result

MCA (nZ9)

IPMN (nZ16)

p-value

Mean CEA (SD) Median CEA (range) Mean amylase (SD) Median amylase (range)

21119 (60045) 813 (0.8 - 181196) 45567 (56237) 31437 (28 - 162400)

466.3 (1190) 144.5 (0.8 - 4878) 42280 (38790) 32154 (223 - 122532)

0.19 0.64

M1482 Survival in Patients with Pancreatic Cancer Following the Diagnosis of Malignant Ascites or Liver Metastases By EUS-FNA John M. DeWitt, Mohammad A. Al-Haddad, Stuart Sherman, Lee McHenry, Julia K. Leblanc, Thomas F. Imperiale Background: The diagnosis of malignant ascites or liver metastases during EUS staging of pancreatic cancer signifies inoperable malignancy and implies a poor prognosis. However, there are limited data on expected survival following EUS in these patients. The purpose of this study is to report survival for a large cohort of patients with pancreatic cancer following the diagnosis of malignant ascites or liver metastases by EUS-FNA. Methods: A prospectively updated EUS database was searched from June 1998 and March 2008 for all patients in whom EUS-FNA of the liver or ascitic fluid was performed. Those with cytology-confirmed hepatic metastases or malignant ascites from pancreatic cancer were identified and comprise the study population. The diagnosis of pancreatic cancer was confirmed in the study population by: 1) presence of a pancreatic mass and; 2) positive EUSFNA cytology from the liver or ascites with or without biopsy of the pancreatic mass. EUS was performed by one of seven endosonographers with on-site cytology support. Survival was determined by use of the Social Security Death Index (SSDI). Results: During the study period, EUS-FNA of a liver mass and ascites were performed in a total of 176 and 103 patients, respectively and 126/176 (72%) and 26/103 (25%) of these biopsies demonstrated malignancy. Of those with malignant biopsies, liver metastases and malignant ascites from primary pancreatic cancer were diagnosed in 75/126 (60%) and 13/26 (50%), respectively. Tumors in these 88 patients (49 male, median age: 66 years, range: 42-90) were located in the pancreatic head in 38 (43%), neck in 4 (4.5%), body in 34 (39%), tail in 8 (9%) but were unknown in 4 (4.5%). Median tumor size was 36 mm (range: 9-80). Follow-up was available in all patients and all 88 died during that time. Overall 1-year and median survival was 4.5% (95% CI, 1.4-11.5%) and 82 days (range: 2-754), respectively. The 1-year survival rates for those with liver metastases and malignant ascites and were 4.8% (CI, 1.5-12.1%) and 0% (CI, 0-26.6%), respectively. Median survival for patients with liver metastases was 83 days (range: 2-754) and median survival for those malignant ascites was 64 days (range: 2-153), respectively. Conclusion: In patients with pancreatic cancer, identification of malignant ascites or liver metastases by EUS-FNA is associated with a very poor prognosis. Therefore, we advocate sampling of any visible ascites or suspicious liver lesions during EUS staging of these patients. These survival data may aid clinicians treating these patients.

M1483 Endoscopic Transplantation of Human Oral Mucosal Epithelial Cell Sheets-World’s First Case of Regenerative Medicine Applied to Endoscopic Treatment Takeshi Ohki, Masayuki Yamato, Masaho Ota, Daisuke Murakami, Ryo Takagi, Makoto Kondo, Tsutomu Nakamura, Teruo Okano, Masakazu Yamamoto Background: Recently, esophageal EMR/ESD have been performed even on a huge early esophageal carcinoma in Japan. Ulcerative esophageal stricture and its treatment by painful frequent balloon dilation of the stenosis severely decrease the quality of life of patients. Previously, we reported that a novel treatment using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets successfully prevented such complications in a canine model (Gut, 55, 1704-1710, 2006). Since then, we endeavored to start the clinical research adhering to rigorous medical and ethical guidelines by Japanese FDA. After much hard work, the clinical research started in January 2008. We will present the early outcomes of the consecutive two patients. Methods: Primary epithelial cells isolated from patient’s own oral mucosa were seeded on temperature responsive culture inserts without 3T3 feeder layers, and cultured with autologous serum for 2 weeks at 37 C. Oral mucosal epithelial cell sheets (23 mm in diameter) were harvested by reducing the culture temperature to 20 C. Autologous cell sheets were transplanted with endoscopic forceps onto the esophageal ulceration after EMR/ESD. Following the treatment, we observed the various stages of ulceration at intervals of one week. Results: (Case 1) A 52-year old man with a type 0-IIc esophageal carcinoma underwent esophageal EMR. A cultured autologous oral mucosal epithelial cell sheet was transplanted to the half circumferential ulceration. Three weeks after EMR, the wound healed completely. The EMR area did not contract significantly and retained its original shape and size. (Case 2) A 70-year old man with a a type

Volume 69, No. 5 : 2009 GASTROINTESTINAL ENDOSCOPY AB253