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Sa1581 Natural History of Pancreatic Cysts <6 CM With Benign EUS Appearance Without Surgical Resection
Abstracts
Sa1580 Mutational Profiling of the Cytocentrifugation Supernatant Fluid and Microdissected Stained Cytology Can Significantly Improve Detection of Cancer in Pancreatic Solid Mass FNA and Pancreatic/Bile Duct Brushing Nadim Haddad*1, Harjiwander P. Sidhu1, Nidhi Malhotra1, Michael M. Bechara1, Eric Ellsworth2, Sydney D. Finkelstein2 1 Gastroenterology, Georgetown Univeristy Hospital, Washington, DC; 2 Redpath Integrated Pathology, Pittsburgh, PA Introduction: Cytology diagnosis of pancreatic solid mass fine needle aspiration (FNA) and pancreatic/biliary brushing is limited by sampling variation and low cellularity which together reduce sensitivity for detection of cancer. Two new molecular approaches were used to improve cancer detection sensitivity: 1) extraction of DNA from the cytocentrifugation supernatant fluid which contains free DNA from the extracellular space in the region around the site of sampling and 2) microdissection of stained cytology cells which may lack sufficient microscopic features of cancer. We report our experience with 13 pts negative by first line cytology evaluation but suspected to have aggressive disease.Design: Residual cytology materials (cytocentrifugation supernatant fluid and/or stained cytology slides) were collected from 13 pts (8 pancreatic solid mass, 5 duct brushing) suspected to have pancreaticobiliary cancer but with indeterminate diagnosis or suspected false negative cytology diagnosis (8-insufficient cellularity, 5-benign morphology). DNA was extracted (qiagen) from 1-2 mls of cytocentrifugation supernatant fluid and/or from a single stained cytology slide. DNA mutational analysis used a broad panel of markers (KRAS point mutation by sequencing, loss of heterogeneity at 1p, 3p, 5q, 9p, 10q, 17p, 17q, 21q, 22q). Detectable mutational change was the criteria for molecular detection of cancer. Surgical pathology outcome was available in 5 pts. Results: Mutational change was found in 8/13 pts (KRAS point mutation detected in 4/8 pts, LOH present in 6/8 pts). Surgical pathology was available in 5 pts and confirmed cancer. The finding of KRAS point mutation was highly specific for pancreatic ductal origin cancer. Effective mutational analysis was accomplished in all cytocentrifugation supernatant fluid samples (10/10) notwithstanding low cellularity of cytology. Mutational analysis of microdissected stained cytology could be performed in 4/6 pts despite low cellularity. Conclusions: Second line mutation detection testing can significantly improve the detection of cancer when first line cytology examination is assessed as inadequate or potentially false negative. Cancer was detected in 8/13 (62%) pts using materials remaining after cytology evaluation. In particular, molecular analysis of the cytocentrifugation supernatant fluid, otherwise discarded, could serve as an adjunct method to reduce sampling variability through its capacity to make available representative DNA from a neoplastic process at a distance from the precise site of needle aspiration or duct brushing.
Survival Curve Based on Cyst Size
Sa1582 Cost Effectiveness of EUS Before ERCP in the Management of Suspected Choledocholithiasis Shubham Garg*1, Pradeep K. Vaitla1, Jayaprakash Sreenarasimhaiah2, Deepak Agrawal2 1 Internal Medicine, Texas Tech University Health Sciences Centre, Midland, TX; 2Gastroenterology, University of Texas Southwestern, Dallas, TX
Sa1581 Natural History of Pancreatic Cysts <6 CM With Benign EUS Appearance Without Surgical Resection Ingrid Gonzalez*, Raymond S. Tang, Craig A. Munroe, Syed M Abbas Fehmi, Mary L. Krinsky, Rosanna Overholser, Thomas J. Savides Gastroenterology, University of California, San Diego (UCSD), San Diego, CA Background: With the increasing prevalence of incidentally found pancreatic cysts, the need for surgical resection of all cysts is now questioned. The purpose of this study is to evaluate the risk of development of pancreatic cancer and the 5-year survival of patients referred for EUS of pancreatic cysts ⬍6 cm who do not undergo surgery. Methods: Retrospective review of pancreatic cysts referred for EUS between 12/2000-12/2006. Overall survival was based on national death registry. Patient follow-up to determine pancreatic cancer incidence required patient contact in clinic or by phone. A total of 248 patients were found in the database. Patient were excluded if EUS findings of solid mass, mural nodule, main PDⱖ6 mm, cyst diameter ⱖ60 mm, calcifications, no cyst on EUS, or clinical suspicion for recent acute pancreatitis (⬍3 months) with pseudocyst. After exclusions 145 patients were evaluated for overall survival, and 80 patients for development of pancreatic cancer. Results: Demographics revealed mean age 68 years, 69% female, 55% asymptomatic. Mean cyst lesion long axis diameter 22 mm. Main cyst located in pancreatic head in 48% and body/tail in 52%. Mean PD size in body 2 mm. EUS revealed single cyst 59%, multiple separate cysts 14%, multiple abutting cysts 27%. EUS morphology: septae 15%, honeycombing 10%, internal debris 9%. 31% underwent EUS FNA. Median follow-up 72 months. 13% patients underwent surgery with pathology revealing 4 benign simple cysts, 3 mucinous cystadenoma, 2 branch-IPMN, 1 adenocarcinoma. Pancreatic cancer was diagnosed in a total of 4/80 (5%) patients during follow-up. One patient with a negative EUS FNA of a pancreatic head cyst developed pancreatic tail cancer 1 year later. The 5-year rate of no diagnosis of cancer was 0.94 (95% CI 0.89,1.0).The 5-year survival of all patients in the study was 0.87 (95% CI 0.82,0.93). No statistical difference in risk of developing cancer or overall survival for cysts ⬍3 cm (mean 1.7 cm) compared to cysts 3-6 cm (mean 3.7 cm). EUS FNA performance resulted in no difference in either pancreatic cancer diagnosis
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or survival. Conclusions: Patients with benign appearing ⬍6 cm pancreatic cysts based on EUS findings who do not undergo surgical resection have a 5% risk of developing pancreatic cancer during 5 year follow-up, and overall have an 86% 5-year survival which is similar to age-matched population. Patients with benign appearing cysts 3-6 cm in size do not have an increased rate of pancreatic cancer or decreased survival compared to cysts ⬍3 cm. 25% of the pancreatic cancers developed at a site unrelated to the pancreatic cyst. These findings suggest most patients with benign appearing pancreatic cysts ⬍6 cm can be observed rather than undergo surgical resection.
Background: Controlled trials suggest that Endoscopic Ultrasound (EUS) is very sensitive for detecting common bile duct (CBD) stones and should be considered before Endoscopic Retrograde Cholangiopancretography (ERCP) in patients with intermediate probability of bile duct stones. ERCP should be performed only if stone(s) or sludge is seen in the bile duct. This will decrease the need for diagnostic ERCPs and associated complications. However, little information is available about the cost-effectiveness of EUS before ERCP in this patient group.AIM: To evaluate the cost effectiveness of performing EUS to detect stones in the bile duct, prior to ERCP, in patients with intermediate probability of stones Methods: A deterministic Monte Carlo decision model was constructed to simulate the progression of a hypothetical cohort of patients with dilated CBD and intermediate probability of stones as determined by Barkun Model. (Pretest probability based on Age, Bilirubin Level and CBD dilatation on Ultrasound) The strategies evaluated were 1) EUS first, followed by ERCP only if stones or sludge seen in the bile duct 2) ERCP for all patients. Health care costs for each intervention and their complication were obtained from the Healthcare Costs and Utilization Project and Medicare payment information for each procedure. The rates of completion of diagnostic testing and therapeutic intervention, test characteristics (sensitivity and specificity), morbidity, and mortality for all procedures were calculated from controlled prospective trials. The utility values (Quality adjusted life years) of short-term states of varying severity, were estimated by subtracting the number of days of hospitalization from the total estimate of life expectancy of a 50 year old standard patient. Treeage Software was used to conduct the Cost Effectiveness and Sensitivity Analysis over the range of probabilities. Results: Our analysis of the decision tree revealed that at 60 percent pretest probability of biliary stones, EUS strategy clearly dominated the ERCP strategy. The cost associated with EUS strategy ($ 1662) was lower than ERCP ($ 1752). On sensitivity analysis, the strategies had similar costs at 68% pretest probability of stones. [Picture 1] The results
Volume 75, No. 4S : 2012
GASTROINTESTINAL ENDOSCOPY
AB209
Sa1580 Mutational Profiling of the Cytocentrifugation Supernatant Fluid and Microdissected Stained Cytology Can Significantly Improve Detection of Cancer in Pancreatic Solid Mass FNA and Pancreatic/Bile Duct Brushing Nadim Haddad*1, Harjiwander P. Sidhu1, Nidhi Malhotra1, Michael M. Bechara1, Eric Ellsworth2, Sydney D. Finkelstein2 1 Gastroenterology, Georgetown Univeristy Hospital, Washington, DC; 2 Redpath Integrated Pathology, Pittsburgh, PA Introduction: Cytology diagnosis of pancreatic solid mass fine needle aspiration (FNA) and pancreatic/biliary brushing is limited by sampling variation and low cellularity which together reduce sensitivity for detection of cancer. Two new molecular approaches were used to improve cancer detection sensitivity: 1) extraction of DNA from the cytocentrifugation supernatant fluid which contains free DNA from the extracellular space in the region around the site of sampling and 2) microdissection of stained cytology cells which may lack sufficient microscopic features of cancer. We report our experience with 13 pts negative by first line cytology evaluation but suspected to have aggressive disease.Design: Residual cytology materials (cytocentrifugation supernatant fluid and/or stained cytology slides) were collected from 13 pts (8 pancreatic solid mass, 5 duct brushing) suspected to have pancreaticobiliary cancer but with indeterminate diagnosis or suspected false negative cytology diagnosis (8-insufficient cellularity, 5-benign morphology). DNA was extracted (qiagen) from 1-2 mls of cytocentrifugation supernatant fluid and/or from a single stained cytology slide. DNA mutational analysis used a broad panel of markers (KRAS point mutation by sequencing, loss of heterogeneity at 1p, 3p, 5q, 9p, 10q, 17p, 17q, 21q, 22q). Detectable mutational change was the criteria for molecular detection of cancer. Surgical pathology outcome was available in 5 pts. Results: Mutational change was found in 8/13 pts (KRAS point mutation detected in 4/8 pts, LOH present in 6/8 pts). Surgical pathology was available in 5 pts and confirmed cancer. The finding of KRAS point mutation was highly specific for pancreatic ductal origin cancer. Effective mutational analysis was accomplished in all cytocentrifugation supernatant fluid samples (10/10) notwithstanding low cellularity of cytology. Mutational analysis of microdissected stained cytology could be performed in 4/6 pts despite low cellularity. Conclusions: Second line mutation detection testing can significantly improve the detection of cancer when first line cytology examination is assessed as inadequate or potentially false negative. Cancer was detected in 8/13 (62%) pts using materials remaining after cytology evaluation. In particular, molecular analysis of the cytocentrifugation supernatant fluid, otherwise discarded, could serve as an adjunct method to reduce sampling variability through its capacity to make available representative DNA from a neoplastic process at a distance from the precise site of needle aspiration or duct brushing.
Survival Curve Based on Cyst Size
Sa1582 Cost Effectiveness of EUS Before ERCP in the Management of Suspected Choledocholithiasis Shubham Garg*1, Pradeep K. Vaitla1, Jayaprakash Sreenarasimhaiah2, Deepak Agrawal2 1 Internal Medicine, Texas Tech University Health Sciences Centre, Midland, TX; 2Gastroenterology, University of Texas Southwestern, Dallas, TX
Sa1581 Natural History of Pancreatic Cysts <6 CM With Benign EUS Appearance Without Surgical Resection Ingrid Gonzalez*, Raymond S. Tang, Craig A. Munroe, Syed M Abbas Fehmi, Mary L. Krinsky, Rosanna Overholser, Thomas J. Savides Gastroenterology, University of California, San Diego (UCSD), San Diego, CA Background: With the increasing prevalence of incidentally found pancreatic cysts, the need for surgical resection of all cysts is now questioned. The purpose of this study is to evaluate the risk of development of pancreatic cancer and the 5-year survival of patients referred for EUS of pancreatic cysts ⬍6 cm who do not undergo surgery. Methods: Retrospective review of pancreatic cysts referred for EUS between 12/2000-12/2006. Overall survival was based on national death registry. Patient follow-up to determine pancreatic cancer incidence required patient contact in clinic or by phone. A total of 248 patients were found in the database. Patient were excluded if EUS findings of solid mass, mural nodule, main PDⱖ6 mm, cyst diameter ⱖ60 mm, calcifications, no cyst on EUS, or clinical suspicion for recent acute pancreatitis (⬍3 months) with pseudocyst. After exclusions 145 patients were evaluated for overall survival, and 80 patients for development of pancreatic cancer. Results: Demographics revealed mean age 68 years, 69% female, 55% asymptomatic. Mean cyst lesion long axis diameter 22 mm. Main cyst located in pancreatic head in 48% and body/tail in 52%. Mean PD size in body 2 mm. EUS revealed single cyst 59%, multiple separate cysts 14%, multiple abutting cysts 27%. EUS morphology: septae 15%, honeycombing 10%, internal debris 9%. 31% underwent EUS FNA. Median follow-up 72 months. 13% patients underwent surgery with pathology revealing 4 benign simple cysts, 3 mucinous cystadenoma, 2 branch-IPMN, 1 adenocarcinoma. Pancreatic cancer was diagnosed in a total of 4/80 (5%) patients during follow-up. One patient with a negative EUS FNA of a pancreatic head cyst developed pancreatic tail cancer 1 year later. The 5-year rate of no diagnosis of cancer was 0.94 (95% CI 0.89,1.0).The 5-year survival of all patients in the study was 0.87 (95% CI 0.82,0.93). No statistical difference in risk of developing cancer or overall survival for cysts ⬍3 cm (mean 1.7 cm) compared to cysts 3-6 cm (mean 3.7 cm). EUS FNA performance resulted in no difference in either pancreatic cancer diagnosis
www.giejournal.org
or survival. Conclusions: Patients with benign appearing ⬍6 cm pancreatic cysts based on EUS findings who do not undergo surgical resection have a 5% risk of developing pancreatic cancer during 5 year follow-up, and overall have an 86% 5-year survival which is similar to age-matched population. Patients with benign appearing cysts 3-6 cm in size do not have an increased rate of pancreatic cancer or decreased survival compared to cysts ⬍3 cm. 25% of the pancreatic cancers developed at a site unrelated to the pancreatic cyst. These findings suggest most patients with benign appearing pancreatic cysts ⬍6 cm can be observed rather than undergo surgical resection.
Background: Controlled trials suggest that Endoscopic Ultrasound (EUS) is very sensitive for detecting common bile duct (CBD) stones and should be considered before Endoscopic Retrograde Cholangiopancretography (ERCP) in patients with intermediate probability of bile duct stones. ERCP should be performed only if stone(s) or sludge is seen in the bile duct. This will decrease the need for diagnostic ERCPs and associated complications. However, little information is available about the cost-effectiveness of EUS before ERCP in this patient group.AIM: To evaluate the cost effectiveness of performing EUS to detect stones in the bile duct, prior to ERCP, in patients with intermediate probability of stones Methods: A deterministic Monte Carlo decision model was constructed to simulate the progression of a hypothetical cohort of patients with dilated CBD and intermediate probability of stones as determined by Barkun Model. (Pretest probability based on Age, Bilirubin Level and CBD dilatation on Ultrasound) The strategies evaluated were 1) EUS first, followed by ERCP only if stones or sludge seen in the bile duct 2) ERCP for all patients. Health care costs for each intervention and their complication were obtained from the Healthcare Costs and Utilization Project and Medicare payment information for each procedure. The rates of completion of diagnostic testing and therapeutic intervention, test characteristics (sensitivity and specificity), morbidity, and mortality for all procedures were calculated from controlled prospective trials. The utility values (Quality adjusted life years) of short-term states of varying severity, were estimated by subtracting the number of days of hospitalization from the total estimate of life expectancy of a 50 year old standard patient. Treeage Software was used to conduct the Cost Effectiveness and Sensitivity Analysis over the range of probabilities. Results: Our analysis of the decision tree revealed that at 60 percent pretest probability of biliary stones, EUS strategy clearly dominated the ERCP strategy. The cost associated with EUS strategy ($ 1662) was lower than ERCP ($ 1752). On sensitivity analysis, the strategies had similar costs at 68% pretest probability of stones. [Picture 1] The results
Volume 75, No. 4S : 2012
GASTROINTESTINAL ENDOSCOPY
AB209