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The Role of Molecular Analysis in Pancreatic Cystic Neoplasms
Abstracts
M1425 Prospective Comparison of Colonoscopic High Frequency Mini Probe Ultrasound and Conventional Computed Tomography (CT) in the Local Staging of Colonic Cancers Amyn Haji, Suzanne Ryan, Ingvar T. Bjarnason, Savvas Papagrigoriadis Background: The introduction of the colorectal cancer screening programme may see an increase in mucosal lesions and early cancers amenable to advanced colonoscopic and laparoscopic techniques. In addition, locally advanced colonic cancers are being subject to neo-adjuvant chemotherapy. Therefore, accurate preoperative local staging of colonic cancers is becoming of paramount importance. Methods: Twenty five consecutive patients with colonic cancer were recruited after informed consent. Pre-operative investigations included colonoscopy and multislice CT with multiplanar reconstruction (read by an experienced colorectal radiologist pre-operatively). All patients underwent both 12.5 MHz and 20 MHz US (Olympus Keymed UM-3R, Japan) either during the primary colonoscopy or on table prior to colonic resection. The images were read by 2 authors who were blind to the results of the CT. The local staging by both modalities were compared to the histological stage of the resected specimen. Statistical differences were analysed using chi squared test and Fisher’s exact t test using Graphpad Prism 5 (Version 5.1, 2007). Results: The distribution of colonic cancers were: sigmoid (nZ8), caecum (nZ7), descending (nZ4), recto-sigmoid (nZ4), hepatic (nZ1) and splenic flexure (nZ1). Histological assessment of the resected specimens revealed 5 T1, 2 T2 and 18 T3 cancers. Conventional CT over staged all T1 tumours: 4 as T2 and 1 as T3. For T3 tumours, the sensitivity and specificity of CT was 72% and 71% respectively. This was significantly different to both 12 and 20 MHz US which accurately staged all T1 and T3 cancers offering 100% sensitivity and specificity (pZ!0.005). All imaging modalities correctly staged only 1 out of 2 T2 tumours, overstaging to T3. Overall, accuracy of T staging by CTwas 56% compared to 96% by both 12 and 20MHz US (pZ!0.005). Histologically 9/25 (36%) patients were positive for nodal disease. Both CT and 12 MHz were significantly better than 20 MHz US for detection of nodal disease (pZ!0.005), with no significant difference between CT and 12 MHz US (pZ0.30). The sensitivity and specificity for detection of nodal disease by conventional CT was 89% and 38% respectively. In comparison, staging by 12 MHz US had a sensitivity of 100% and a specificity of 75%, significantly better than that offered by 20 MHz US at 25% sensitivity and 86% specificity (pZ!0.005). Conclusion: Colonic ultrasound with miniprobes is significantly more accurate than CT staging of colorectal cancers. The technique has potential application as a routine procedure during colonoscopy.
M1426 The Value of Anorectal Ultrasound in Chronic Idiopathic Anal Pain Marc Beer-Gabel, Dany Carter, Yehudith Assulin, Benjamin Avidan, Simon Bar Meir Background: Anorectal pain has a prevalence of 6.6% in a sample of American householders. It is related to organic as well as functional conditions. The diagnosis is generally made by physical examination, sometimes under general anesthesia. Aim of the Study: This study was undertaken to evaluate the benefit of ultrasound in patients whose diagnosis was not made by clinical examination although the digital examination was painful. Methods: Consecutive patients who suffered from chronic idiopathic anal pain were studied from 2004 to 2006 . All had an anorectal ultrasound. The female patients had a perineal ultrasound as well. Results: Ninety seven patients were included in the study. Forty three were male. The average age was 52 years þ- 15 years. All patients suffered from anal pain for more than 6 months. In 40 cases the ultrasound were normal. A functional defecation disorder was diagnosed in 17 patients by perineal ultrasound only. Twenty four patients had an intersphincteric sepsis either a sinus or a small abscess without external drainage diagnosed by both methods. Associated findings such as rectocele in 17 patients, cystocele in 12 cases of female patients were diagnosed by perineal ultrasound. Anal tears in 6 patients, anal fissure in 2 patients, anal cysts in 2 patients and endometriosis in 1 patient were seen as well. Conclusion: Anal Ultrasound is a key examination since it can diagnose patients with intersphincteric sepsis missed by the clinical examination and change the management of these cases. The perineal approach allows avoiding an anal canulation. It is an adjunct to the diagnosis of functional defecation disorders.
M1427 Intra-Observer Agreement Among Endosonographers for EUS Features of Chronic Pancreatitis John G. Lieb, David T. Palma, Julia K. Leblanc, Joseph Romagnuolo, James J. Farrell, Thomas Savides, Mohamad A. Eloubeidi, Peter V. Draganov, Christopher E. Forsmark, Mihir S. Wagh Introduction: The inter-observer agreement of EUS in the diagnosis of chronic pancreatitis (CP) is relatively good among experienced endosonographers. Less is known about intra-observer agreement - what the same ultrasonographer thinks when shown the same images multiple times. Aim: To assess the intra-observer agreement and variability among endosonographers for EUS features of chronic pancreatitis. Methods: EUS images from patients with suspected or established chronic pancreatitis and normal patients were identified. Thirty still EUS images
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from 16 patients were shown to 5 experienced endosonographers at major tertiary care centers in the United States. Of these photos, 8 demonstrated obvious advanced CP, sixteen demonstrated minimal changes of CP, and 6 were normal. These experts were blinded to clinical information and to the nature of the study. The EUS experts assessed the following nine well accepted features of chronic pancreatitis: hyperechoic foci, hyperechoic strands, lobularity, cysts, stones, main pancreatic duct (PD) dilatation, pancreatic duct irregularity, hyperechoic duct margins, and visible side branches as ‘‘present’’, ‘‘not present’’ or ‘‘cannot assess.’’ Based on their overall assessment, they were also asked to report whether the images supported a final diagnosis of chronic pancreatitis. These same images were shuffled and once again shown in random order to these experts. Images were shown in 4 sets (15 images per set) over 6 weeks. Experts were unaware that the same images had been presented a second time. Kappa statistics were calculated for each endosonographer and for each criterion of CP. Results: Overall, endosonographers agreed with themselves in the interpretation of the EUS features of CP with a mean kappa of 0.75, range 0.65-0.88 (mean percent agreement 87%, range 84-95%). The mean kappa for each EUS characteristic of CP was 0.66 for foci, 0.66 for strands, 0.71 for lobularity, 0.88 for cysts, 0.88 for stones, 0.81 for pancreatic duct dilation, 0.79 for irregular pancreatic duct, 0.71 for hyperechoic pancreatic duct margins, 0.61 for visible side branches, and 0.73 for the overall diagnosis of CP. Conclusions: There was good intra-observer agreement in the interpretation of EUS features of CP among experienced endosonographers. These results appear better than the published inter-observer agreement for EUS features of CP and intraobserver agreement for ERCP images.
M1428 The Role of Molecular Analysis in Pancreatic Cystic Neoplasms Tamas A. Gonda, Peter S. Francisco, Shashin Shah, Vasudha Dhar, Charles J. Lightdale, Stavros N. Stavropoulos, Peter D. Stevens Introduction: Analysis of cyst fluid for DNA quantity, quality, Kras and loss of heterozygosity (LOH) mutations may contribute to the understanding of risk associated with pancreatic cystic neoplasms. Current guidelines identify lesions that are very low risk for neoplastic progression (serous cystadenomas, pseudocysts) and some that are very high risk (main duct IPMN or cystic lesions with associated mural nodule). However, less is known about suspected mucinous lesions that do not fall into either of these categories. Our goal was to examine the role of molecular markers in the diagnosis of these lesions. Methods: We retrospectively and prospectively collected data from patients who underwent EUS with FNA of pancreatic cysts. We excluded all patients with a recent history of pancreatitis, morphologic features of SCA, dilated MPD or mural nodule. Molecular analysis was performed by RedPath IP (Pittsburgh, PA) and lesions were categorized as serous or as one of three types of mucinous cysts (low, intermediate or high risk) based on DNA quantity, quality and Kras mutations and LOHs. Statistical analysis using chi square and Fisher’s exact test was performed. Results: 115 cystic lesions, with average size 20.6 þ/- 13 mm and CEA of 373 þ/- 1079 were identified. By molecular category the majority were low risk (72%), 21% were intermediate and 7% were high risk. Molecular categories showed a positive association with CEA level (p!0.0001) but not with size. Final pathology, when available, confirmed high grade histology in 4/5 lesions with high-risk features but low grade MCA or IPMN in all indolent and in 3/4 intermediate risk lesions. One intermediate risk lesion had IPMN with CIS. In addition, of the indolent and intermediate lesions follow-up of at least 12 months was available for 35% (nZ33) and only two lesions showed progression. Importantly, of the lesions with a CEAO800 or sizeO 3 cm and either indolent or intermediate molecular features none of the lesions that were operated had dysplasia. Conclusions. Our results show that there is a strong correlation between fluid molecular categories and CEA but not size. High risk molecular features are very suggestive of high grade dysplasia or carcinoma. On the contrary, indolent molecular features, even in a patient with elevated CEA, may identify a subset with more benign pathology. Therefore, these markers may be of added value in identifying the highest risk lesions and can also be used when an unexpectedly high CEA is found in a small otherwise morphologically low risk cystic lesion.
M1429 Early Needle Exchange in EUS-FNA Does Not Improve the Diagnostic Yield of Cytopathological Evaluation in Pancreatic Adenocarcinoma. Results from a Randomized Trial Alberto Herreros De Tejada, Jennifer S. Chennat, Tiffany Chang, Charles E. Dye, Isabel Millan, Barbara M. Cislo, Rachael Bartosch, Lynne Stearns, Irving Waxman Introduction: Fine Needle Aspiration (FNA) under EUS (Endoscopic ultrasonography) guidance is a useful tool in pancreatic adenocarcinoma (PA) diagnosis. On-site evaluation of FNA specimens by a cytopathologist increases the diagnostic yield of EUS-FNA. Factors such as excessive bending or channel occlusion in the needle can impair the quality of the sample obtained in FNA. The aim of this study was to evaluate if early needle exchange improves the diagnostic yield of EUS-FNA in PA. Methods: Prospective randomized study to compare two modalities of EUS-FNA in preliminary on-site diagnosis of PA. Standard Method (SM) using a single FNA needle was compared to the experimental method called Exchange Needle (EN), consisting on exchanging the FNA needle every two passes.
Volume 69, No. 5 : 2009 GASTROINTESTINAL ENDOSCOPY AB239
M1425 Prospective Comparison of Colonoscopic High Frequency Mini Probe Ultrasound and Conventional Computed Tomography (CT) in the Local Staging of Colonic Cancers Amyn Haji, Suzanne Ryan, Ingvar T. Bjarnason, Savvas Papagrigoriadis Background: The introduction of the colorectal cancer screening programme may see an increase in mucosal lesions and early cancers amenable to advanced colonoscopic and laparoscopic techniques. In addition, locally advanced colonic cancers are being subject to neo-adjuvant chemotherapy. Therefore, accurate preoperative local staging of colonic cancers is becoming of paramount importance. Methods: Twenty five consecutive patients with colonic cancer were recruited after informed consent. Pre-operative investigations included colonoscopy and multislice CT with multiplanar reconstruction (read by an experienced colorectal radiologist pre-operatively). All patients underwent both 12.5 MHz and 20 MHz US (Olympus Keymed UM-3R, Japan) either during the primary colonoscopy or on table prior to colonic resection. The images were read by 2 authors who were blind to the results of the CT. The local staging by both modalities were compared to the histological stage of the resected specimen. Statistical differences were analysed using chi squared test and Fisher’s exact t test using Graphpad Prism 5 (Version 5.1, 2007). Results: The distribution of colonic cancers were: sigmoid (nZ8), caecum (nZ7), descending (nZ4), recto-sigmoid (nZ4), hepatic (nZ1) and splenic flexure (nZ1). Histological assessment of the resected specimens revealed 5 T1, 2 T2 and 18 T3 cancers. Conventional CT over staged all T1 tumours: 4 as T2 and 1 as T3. For T3 tumours, the sensitivity and specificity of CT was 72% and 71% respectively. This was significantly different to both 12 and 20 MHz US which accurately staged all T1 and T3 cancers offering 100% sensitivity and specificity (pZ!0.005). All imaging modalities correctly staged only 1 out of 2 T2 tumours, overstaging to T3. Overall, accuracy of T staging by CTwas 56% compared to 96% by both 12 and 20MHz US (pZ!0.005). Histologically 9/25 (36%) patients were positive for nodal disease. Both CT and 12 MHz were significantly better than 20 MHz US for detection of nodal disease (pZ!0.005), with no significant difference between CT and 12 MHz US (pZ0.30). The sensitivity and specificity for detection of nodal disease by conventional CT was 89% and 38% respectively. In comparison, staging by 12 MHz US had a sensitivity of 100% and a specificity of 75%, significantly better than that offered by 20 MHz US at 25% sensitivity and 86% specificity (pZ!0.005). Conclusion: Colonic ultrasound with miniprobes is significantly more accurate than CT staging of colorectal cancers. The technique has potential application as a routine procedure during colonoscopy.
M1426 The Value of Anorectal Ultrasound in Chronic Idiopathic Anal Pain Marc Beer-Gabel, Dany Carter, Yehudith Assulin, Benjamin Avidan, Simon Bar Meir Background: Anorectal pain has a prevalence of 6.6% in a sample of American householders. It is related to organic as well as functional conditions. The diagnosis is generally made by physical examination, sometimes under general anesthesia. Aim of the Study: This study was undertaken to evaluate the benefit of ultrasound in patients whose diagnosis was not made by clinical examination although the digital examination was painful. Methods: Consecutive patients who suffered from chronic idiopathic anal pain were studied from 2004 to 2006 . All had an anorectal ultrasound. The female patients had a perineal ultrasound as well. Results: Ninety seven patients were included in the study. Forty three were male. The average age was 52 years þ- 15 years. All patients suffered from anal pain for more than 6 months. In 40 cases the ultrasound were normal. A functional defecation disorder was diagnosed in 17 patients by perineal ultrasound only. Twenty four patients had an intersphincteric sepsis either a sinus or a small abscess without external drainage diagnosed by both methods. Associated findings such as rectocele in 17 patients, cystocele in 12 cases of female patients were diagnosed by perineal ultrasound. Anal tears in 6 patients, anal fissure in 2 patients, anal cysts in 2 patients and endometriosis in 1 patient were seen as well. Conclusion: Anal Ultrasound is a key examination since it can diagnose patients with intersphincteric sepsis missed by the clinical examination and change the management of these cases. The perineal approach allows avoiding an anal canulation. It is an adjunct to the diagnosis of functional defecation disorders.
M1427 Intra-Observer Agreement Among Endosonographers for EUS Features of Chronic Pancreatitis John G. Lieb, David T. Palma, Julia K. Leblanc, Joseph Romagnuolo, James J. Farrell, Thomas Savides, Mohamad A. Eloubeidi, Peter V. Draganov, Christopher E. Forsmark, Mihir S. Wagh Introduction: The inter-observer agreement of EUS in the diagnosis of chronic pancreatitis (CP) is relatively good among experienced endosonographers. Less is known about intra-observer agreement - what the same ultrasonographer thinks when shown the same images multiple times. Aim: To assess the intra-observer agreement and variability among endosonographers for EUS features of chronic pancreatitis. Methods: EUS images from patients with suspected or established chronic pancreatitis and normal patients were identified. Thirty still EUS images
www.giejournal.org
from 16 patients were shown to 5 experienced endosonographers at major tertiary care centers in the United States. Of these photos, 8 demonstrated obvious advanced CP, sixteen demonstrated minimal changes of CP, and 6 were normal. These experts were blinded to clinical information and to the nature of the study. The EUS experts assessed the following nine well accepted features of chronic pancreatitis: hyperechoic foci, hyperechoic strands, lobularity, cysts, stones, main pancreatic duct (PD) dilatation, pancreatic duct irregularity, hyperechoic duct margins, and visible side branches as ‘‘present’’, ‘‘not present’’ or ‘‘cannot assess.’’ Based on their overall assessment, they were also asked to report whether the images supported a final diagnosis of chronic pancreatitis. These same images were shuffled and once again shown in random order to these experts. Images were shown in 4 sets (15 images per set) over 6 weeks. Experts were unaware that the same images had been presented a second time. Kappa statistics were calculated for each endosonographer and for each criterion of CP. Results: Overall, endosonographers agreed with themselves in the interpretation of the EUS features of CP with a mean kappa of 0.75, range 0.65-0.88 (mean percent agreement 87%, range 84-95%). The mean kappa for each EUS characteristic of CP was 0.66 for foci, 0.66 for strands, 0.71 for lobularity, 0.88 for cysts, 0.88 for stones, 0.81 for pancreatic duct dilation, 0.79 for irregular pancreatic duct, 0.71 for hyperechoic pancreatic duct margins, 0.61 for visible side branches, and 0.73 for the overall diagnosis of CP. Conclusions: There was good intra-observer agreement in the interpretation of EUS features of CP among experienced endosonographers. These results appear better than the published inter-observer agreement for EUS features of CP and intraobserver agreement for ERCP images.
M1428 The Role of Molecular Analysis in Pancreatic Cystic Neoplasms Tamas A. Gonda, Peter S. Francisco, Shashin Shah, Vasudha Dhar, Charles J. Lightdale, Stavros N. Stavropoulos, Peter D. Stevens Introduction: Analysis of cyst fluid for DNA quantity, quality, Kras and loss of heterozygosity (LOH) mutations may contribute to the understanding of risk associated with pancreatic cystic neoplasms. Current guidelines identify lesions that are very low risk for neoplastic progression (serous cystadenomas, pseudocysts) and some that are very high risk (main duct IPMN or cystic lesions with associated mural nodule). However, less is known about suspected mucinous lesions that do not fall into either of these categories. Our goal was to examine the role of molecular markers in the diagnosis of these lesions. Methods: We retrospectively and prospectively collected data from patients who underwent EUS with FNA of pancreatic cysts. We excluded all patients with a recent history of pancreatitis, morphologic features of SCA, dilated MPD or mural nodule. Molecular analysis was performed by RedPath IP (Pittsburgh, PA) and lesions were categorized as serous or as one of three types of mucinous cysts (low, intermediate or high risk) based on DNA quantity, quality and Kras mutations and LOHs. Statistical analysis using chi square and Fisher’s exact test was performed. Results: 115 cystic lesions, with average size 20.6 þ/- 13 mm and CEA of 373 þ/- 1079 were identified. By molecular category the majority were low risk (72%), 21% were intermediate and 7% were high risk. Molecular categories showed a positive association with CEA level (p!0.0001) but not with size. Final pathology, when available, confirmed high grade histology in 4/5 lesions with high-risk features but low grade MCA or IPMN in all indolent and in 3/4 intermediate risk lesions. One intermediate risk lesion had IPMN with CIS. In addition, of the indolent and intermediate lesions follow-up of at least 12 months was available for 35% (nZ33) and only two lesions showed progression. Importantly, of the lesions with a CEAO800 or sizeO 3 cm and either indolent or intermediate molecular features none of the lesions that were operated had dysplasia. Conclusions. Our results show that there is a strong correlation between fluid molecular categories and CEA but not size. High risk molecular features are very suggestive of high grade dysplasia or carcinoma. On the contrary, indolent molecular features, even in a patient with elevated CEA, may identify a subset with more benign pathology. Therefore, these markers may be of added value in identifying the highest risk lesions and can also be used when an unexpectedly high CEA is found in a small otherwise morphologically low risk cystic lesion.
M1429 Early Needle Exchange in EUS-FNA Does Not Improve the Diagnostic Yield of Cytopathological Evaluation in Pancreatic Adenocarcinoma. Results from a Randomized Trial Alberto Herreros De Tejada, Jennifer S. Chennat, Tiffany Chang, Charles E. Dye, Isabel Millan, Barbara M. Cislo, Rachael Bartosch, Lynne Stearns, Irving Waxman Introduction: Fine Needle Aspiration (FNA) under EUS (Endoscopic ultrasonography) guidance is a useful tool in pancreatic adenocarcinoma (PA) diagnosis. On-site evaluation of FNA specimens by a cytopathologist increases the diagnostic yield of EUS-FNA. Factors such as excessive bending or channel occlusion in the needle can impair the quality of the sample obtained in FNA. The aim of this study was to evaluate if early needle exchange improves the diagnostic yield of EUS-FNA in PA. Methods: Prospective randomized study to compare two modalities of EUS-FNA in preliminary on-site diagnosis of PA. Standard Method (SM) using a single FNA needle was compared to the experimental method called Exchange Needle (EN), consisting on exchanging the FNA needle every two passes.
Volume 69, No. 5 : 2009 GASTROINTESTINAL ENDOSCOPY AB239