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W1404 Accuracy of Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) for the Cytological Diagnosis of Solid Pancreatic Masses and Clinical Impact of On-Site Cytophatological Evaluation
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W1404
Differential Proteomic Analysis of Human Pancreatic Juice from Pancreatic Cancer, Chronic Pancreatitis and Choledocholithiasis Jun Gao, Feng Zhu, Zhaoshen Li, Shunli Lu
Accuracy of Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUSFNA) for the Cytological Diagnosis of Solid Pancreatic Masses and Clinical Impact of On-Site Cytophatological Evaluation Julio Iglesias-Garcia, Jose Larino-Noia, Elena Eugenyeva, Ihab Abdulkader, Antonio Lozano-Leon, Begoña Vieites, Jeronimo Forteza, Enrique Dominguez-Munoz
Background Early diagnosis and differential diagnosis of pancreatic cancer (pc) is always very difficult in clinical practices.It is a effective way to finding a diagnosis marker by researching differential proteins existing in pancreatic juice from patients with pc,cp and choledocholithiasis.OBJECTIVE To analyze the differential expression proteins among pancreatic juice from patients with pancreatic cancer (pc),chronic pancreatitis (cp) and choledocholithiasis by proteomics methods.METHODS pancreatic juice was collected by nasopancreatic drainage during endoscopic retrograde cholangiopancreatography.The total proteins of pooled pancreatic juice with equal amount from 5 pc patients, 6 cp patients and 3 choledocholithiasis patients were separated by immobilized pH gradient (IPG)-based twodimensional gel electrophoresis (2-DE) respectively.The differential expression proteins were analyzed using image analysis software,then identified using mass spectrometry and database searching.RESULTS Pancreatic juice was succeedly collected by naso-pancreatic drainage during endoscopic retrograde cholangiopancreatography with amount ranging from 35 to 200 ml and protein concentration ranging from 0.8-4.6µg/µl. Three gels of the same pancreatic juice had good reproducibility in protein location.Rates of matched proteins from pooled pancreatic juice with equal amount from 5 pc patients, 6 cp patients and 3 choledocholithiasis patients all exceeded 90% by self-contrast. Eight differential proteins obtained from image analysis software were analyzed by MALDI-TOF-MS and some were identified as differential expression proteins related to pancreatic cancer (Table 1).C0NCLUSIONS Protein spectra of pancreatic juice from pancreatic cancer patients, chronic pancreatitis patients and choledocholithiasis patients had certain difference and some differential proteins were characterized.These data will be helpful for screening the biomarker to further study on human pancreatic cancer. Table 1 Eight different proteins existing in the pancreatic juice from pancreatic cancer, chronic pancreatitis and choledocholithiasis
EUS-FNA has been shown to be an accurate technique for the cytological diagnosis of pancreatic cancer in selected series of patients. In this context, experts advocate on-site cytopathological assessment for sample adequacy, but there are few data to support this claim. AIM: To evaluate the diagnostic accuracy of EUS-FNA in an unselected consecutive series of patients with solid pancreatic masses, and to evaluate clinical impact of on-site cytopathology in this setting. METHODS: All patients who underwent EUS-FNA of solid pancreatic lesions between January 2005 and October 2007 were identified from a prospectively collected endoscopy database, and included in the study. EUS-FNA from previous years (n=73) were not included to avoid bias related to learning curve of endoscopists and pathologists. All EUS-FNA procedures were performed under conscious sedation by lineal scanning Pentax, and punctions were made by 22G needles. Results of EUS-FNA cytological findings were compared to the gold standard of surgical histopathology, or global clinical and radiological assessment and follow-up in non-operated cases. Before July 2006 no onsite pathologist was available, and samples were processed by an experienced endoscopist and sent to the Pathology Department for evaluation. From July 2006 one on-site pathologist was available for immediate processing and evaluation of the sample. The number of needle passes, complications and accuracy of EUS-FNA in the two periods of time were evaluated. RESULTS: A total of 182 patients underwent a EUS-FNA of solid pancreatic lesions in the study period, 87 cases (47.8%) without on-site pathologist and 95 (52.2%) with on-site pathologist. There was no difference between both groups in terms of age, sex, localization and size of the lesions. A significant higher number of passes were performed when no onsite pathologist was available (3,5±1.0 vs 2,0±0,7; p<0,0001), which was related to a higher number of complications (3.4% vs 0%). Presence of on-site pathologist was associated to a significantly lower number of inadequate samples (1,0% vs 12.6%, p<0.001) and thus a higher number of cases with a correct final cytological diagnosis (96.8% vs 86.2%, p<0.01). Diagnostic accuracy of EUS-FNA for detection of malignancy in both periods of time is shown in table.CONCLUSION: EUS-FNA is a highly accurate method for the cytological diagnosis of solid pancreatic masses. On-site cytopathological evaluation is essential to improve the diagnostic yield of EUS-guided FNA in this setting.
W1405 Heterogeneity in the Expression of Prognostic Markers in Liver Metastases of Pancreatic Endocrine Tumours Anne Couvelard, Lydia Deschamps, Philippe Ravaud, Gabriel Baron, Alain Sauvanet, Olivia Hentic, Jacques Belghiti, Pierre Bedossa, Philippe B. Ruszniewski
* indicate p<0.01 vs. cp or choledocholithiasis.
Liver biopsy of metastatic pancreatic endocrine tumors (PET) allows confirmation of the diagnosis and assessment of prognostic factors. However, sampling variability is a potential limitation. Our aim was to assess the heterogeneity of MIB-1 proliferation index, microvascular density (MVD) and somatostatin receptor type 2 (SST2) inside single, synchronous or metachronous liver metastases (LM) of PET. Methods: Tissue arrays were constructed, which included core biopsies taken from surgically resected LM in 29 patients. MIB-1, MVD and SST2 were evaluated after immunostaining. The heterogeneity was highlighted by the calculation of the reproducibility of the values of 2 cores randomly selected among all the cores studied in the 3 types of heterogeneity tested. For quantitative variables (MIB-1 and MVD), it was assessed by the intraclass correlation coefficient (ICC) and by a Bland-Altman approach to search for any systematic bias and reveal whether differences between scores depend on the level of scores. For qualitative variables (SST2), observed agreement and weighted kappa were given. Results: A total of 184 LM were analysed. Reproducibility for MIB-1 was substantial, as shown by ICCs of 0.63, 0.69 and 0.67 in single, synchronous or metachronous LM, respectively. Corresponding figures for MVD were 0.48, 0.60 and 0.00, respectively, indicating low reproducibility, especially for metachronous tumors. For SST2, the observed agreement was very good, i.e. 91% (kappa 0.81), 69% (kappa 0.49) and 79% (kappa 0.68) in single, synchronous or metachronous LM respectively. Conclusion: Heterogeneity of protein expression depends on the marker tested in liver metastases of
W1403 Pancreatic Lesions of Dysplasia (Panin) Are Observed in Hereditary Pancreatitis (HP): A Pathological Study Vinciane Rebours, Anne Couvelard, Jean-Yves Scoazec, Jean-François Fléjou, Marie Soubeyrand, Bruno Turlin, Pascal Hammel, Philippe B. Ruszniewski, Philippe Levy Hereditary pancreatitis is a well known risk factor of pancreatic adenocarcinoma. Patients with HP have 87 times relative risk of pancreatic adenocarcinoma (PA) compared to the general population (1). Aim to search for pancreatic lesions of dysplasia (PanIN) by pathological analyse of surgical specimens; to describe pathological lesions of HP and to compare these results with pathological data of alcoholic chronic pancreatitis (ACP). Methods This study was multicentric. Partial pancreatectomies were realized for HP complications. There was no resection for doubt of pancreatic adenocarcinoma. Pathological data included a gross and microscopic examination. Lesions as dysplasia were described thanks to the PanIN classification. A control group was composed by ACP. Results 6 surgical specimens of HP were studied: A Frey resection, a median pancreatectomy, 2 caudal pancreatectomies and 2 Whipple's interventions. Patients (3 males and 3 females) were 35 years old in median. We observed interlobular and intralobular fibrosis for all the patients with a Klöppel fibrosis
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AGA Abstracts
AGA Abstracts
score of 3 in median, duct dilatation (n=6) (main pancreatic duct n=5, brunch ducts n=5), maphilgien metaplasia (n = 2), periductal infiltration of lymphocytes (n=3), calcifications (n = 4) and epithelial granulocytar lesions (n = 4). Hyperplastic mucinous changes (PanIL) were observed in 4 cases; PanIN-1 lesions (low grade of dysplasia) in 4 cases and PanIN2 (moderate grade). The patient with PanIN-2 developed pancreatic adenocarcinoma 18 months after the partial surgical resection. A control group of 10 surgical specimens (Whipple's resections) for ACP was studied. It represented 7 males and 3 females, aged of 49 years in median. Histological examination revealed interlobular (perilobular) and intralobular cell-rich fibrosis 4/4 in median according to Klöppel fibrosis score, no epithelial lesion (n=0) and calcifications in 7 cases. PanIn lesions-1 were observed in 3 cases and hyperplastic mucinous changes in 2 cases of very inflammatory pancreatitis. Conclusion It is the first study which report the pathological features of chronic HP. The originality of this work was to describe very severe inflammatory duct lesions and PanIN lesions (type 1 and 2) in two third of the cases in patients aged of 35 years in median. These lesions existed in ACP but they were less frequent. These results, if they were confirmed, were a huge argument to propose a prophylactic pancreatectomy in HP patients. (1) Rebours V et al. Risk of Pancreatic Adenocarcinoma in Patients with Hereditary Pancreatitis: A National exhaustive series. Am J Gastroenterol 2007; in Press.
W1404
Differential Proteomic Analysis of Human Pancreatic Juice from Pancreatic Cancer, Chronic Pancreatitis and Choledocholithiasis Jun Gao, Feng Zhu, Zhaoshen Li, Shunli Lu
Accuracy of Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUSFNA) for the Cytological Diagnosis of Solid Pancreatic Masses and Clinical Impact of On-Site Cytophatological Evaluation Julio Iglesias-Garcia, Jose Larino-Noia, Elena Eugenyeva, Ihab Abdulkader, Antonio Lozano-Leon, Begoña Vieites, Jeronimo Forteza, Enrique Dominguez-Munoz
Background Early diagnosis and differential diagnosis of pancreatic cancer (pc) is always very difficult in clinical practices.It is a effective way to finding a diagnosis marker by researching differential proteins existing in pancreatic juice from patients with pc,cp and choledocholithiasis.OBJECTIVE To analyze the differential expression proteins among pancreatic juice from patients with pancreatic cancer (pc),chronic pancreatitis (cp) and choledocholithiasis by proteomics methods.METHODS pancreatic juice was collected by nasopancreatic drainage during endoscopic retrograde cholangiopancreatography.The total proteins of pooled pancreatic juice with equal amount from 5 pc patients, 6 cp patients and 3 choledocholithiasis patients were separated by immobilized pH gradient (IPG)-based twodimensional gel electrophoresis (2-DE) respectively.The differential expression proteins were analyzed using image analysis software,then identified using mass spectrometry and database searching.RESULTS Pancreatic juice was succeedly collected by naso-pancreatic drainage during endoscopic retrograde cholangiopancreatography with amount ranging from 35 to 200 ml and protein concentration ranging from 0.8-4.6µg/µl. Three gels of the same pancreatic juice had good reproducibility in protein location.Rates of matched proteins from pooled pancreatic juice with equal amount from 5 pc patients, 6 cp patients and 3 choledocholithiasis patients all exceeded 90% by self-contrast. Eight differential proteins obtained from image analysis software were analyzed by MALDI-TOF-MS and some were identified as differential expression proteins related to pancreatic cancer (Table 1).C0NCLUSIONS Protein spectra of pancreatic juice from pancreatic cancer patients, chronic pancreatitis patients and choledocholithiasis patients had certain difference and some differential proteins were characterized.These data will be helpful for screening the biomarker to further study on human pancreatic cancer. Table 1 Eight different proteins existing in the pancreatic juice from pancreatic cancer, chronic pancreatitis and choledocholithiasis
EUS-FNA has been shown to be an accurate technique for the cytological diagnosis of pancreatic cancer in selected series of patients. In this context, experts advocate on-site cytopathological assessment for sample adequacy, but there are few data to support this claim. AIM: To evaluate the diagnostic accuracy of EUS-FNA in an unselected consecutive series of patients with solid pancreatic masses, and to evaluate clinical impact of on-site cytopathology in this setting. METHODS: All patients who underwent EUS-FNA of solid pancreatic lesions between January 2005 and October 2007 were identified from a prospectively collected endoscopy database, and included in the study. EUS-FNA from previous years (n=73) were not included to avoid bias related to learning curve of endoscopists and pathologists. All EUS-FNA procedures were performed under conscious sedation by lineal scanning Pentax, and punctions were made by 22G needles. Results of EUS-FNA cytological findings were compared to the gold standard of surgical histopathology, or global clinical and radiological assessment and follow-up in non-operated cases. Before July 2006 no onsite pathologist was available, and samples were processed by an experienced endoscopist and sent to the Pathology Department for evaluation. From July 2006 one on-site pathologist was available for immediate processing and evaluation of the sample. The number of needle passes, complications and accuracy of EUS-FNA in the two periods of time were evaluated. RESULTS: A total of 182 patients underwent a EUS-FNA of solid pancreatic lesions in the study period, 87 cases (47.8%) without on-site pathologist and 95 (52.2%) with on-site pathologist. There was no difference between both groups in terms of age, sex, localization and size of the lesions. A significant higher number of passes were performed when no onsite pathologist was available (3,5±1.0 vs 2,0±0,7; p<0,0001), which was related to a higher number of complications (3.4% vs 0%). Presence of on-site pathologist was associated to a significantly lower number of inadequate samples (1,0% vs 12.6%, p<0.001) and thus a higher number of cases with a correct final cytological diagnosis (96.8% vs 86.2%, p<0.01). Diagnostic accuracy of EUS-FNA for detection of malignancy in both periods of time is shown in table.CONCLUSION: EUS-FNA is a highly accurate method for the cytological diagnosis of solid pancreatic masses. On-site cytopathological evaluation is essential to improve the diagnostic yield of EUS-guided FNA in this setting.
W1405 Heterogeneity in the Expression of Prognostic Markers in Liver Metastases of Pancreatic Endocrine Tumours Anne Couvelard, Lydia Deschamps, Philippe Ravaud, Gabriel Baron, Alain Sauvanet, Olivia Hentic, Jacques Belghiti, Pierre Bedossa, Philippe B. Ruszniewski
* indicate p<0.01 vs. cp or choledocholithiasis.
Liver biopsy of metastatic pancreatic endocrine tumors (PET) allows confirmation of the diagnosis and assessment of prognostic factors. However, sampling variability is a potential limitation. Our aim was to assess the heterogeneity of MIB-1 proliferation index, microvascular density (MVD) and somatostatin receptor type 2 (SST2) inside single, synchronous or metachronous liver metastases (LM) of PET. Methods: Tissue arrays were constructed, which included core biopsies taken from surgically resected LM in 29 patients. MIB-1, MVD and SST2 were evaluated after immunostaining. The heterogeneity was highlighted by the calculation of the reproducibility of the values of 2 cores randomly selected among all the cores studied in the 3 types of heterogeneity tested. For quantitative variables (MIB-1 and MVD), it was assessed by the intraclass correlation coefficient (ICC) and by a Bland-Altman approach to search for any systematic bias and reveal whether differences between scores depend on the level of scores. For qualitative variables (SST2), observed agreement and weighted kappa were given. Results: A total of 184 LM were analysed. Reproducibility for MIB-1 was substantial, as shown by ICCs of 0.63, 0.69 and 0.67 in single, synchronous or metachronous LM, respectively. Corresponding figures for MVD were 0.48, 0.60 and 0.00, respectively, indicating low reproducibility, especially for metachronous tumors. For SST2, the observed agreement was very good, i.e. 91% (kappa 0.81), 69% (kappa 0.49) and 79% (kappa 0.68) in single, synchronous or metachronous LM respectively. Conclusion: Heterogeneity of protein expression depends on the marker tested in liver metastases of
W1403 Pancreatic Lesions of Dysplasia (Panin) Are Observed in Hereditary Pancreatitis (HP): A Pathological Study Vinciane Rebours, Anne Couvelard, Jean-Yves Scoazec, Jean-François Fléjou, Marie Soubeyrand, Bruno Turlin, Pascal Hammel, Philippe B. Ruszniewski, Philippe Levy Hereditary pancreatitis is a well known risk factor of pancreatic adenocarcinoma. Patients with HP have 87 times relative risk of pancreatic adenocarcinoma (PA) compared to the general population (1). Aim to search for pancreatic lesions of dysplasia (PanIN) by pathological analyse of surgical specimens; to describe pathological lesions of HP and to compare these results with pathological data of alcoholic chronic pancreatitis (ACP). Methods This study was multicentric. Partial pancreatectomies were realized for HP complications. There was no resection for doubt of pancreatic adenocarcinoma. Pathological data included a gross and microscopic examination. Lesions as dysplasia were described thanks to the PanIN classification. A control group was composed by ACP. Results 6 surgical specimens of HP were studied: A Frey resection, a median pancreatectomy, 2 caudal pancreatectomies and 2 Whipple's interventions. Patients (3 males and 3 females) were 35 years old in median. We observed interlobular and intralobular fibrosis for all the patients with a Klöppel fibrosis
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AGA Abstracts
AGA Abstracts
score of 3 in median, duct dilatation (n=6) (main pancreatic duct n=5, brunch ducts n=5), maphilgien metaplasia (n = 2), periductal infiltration of lymphocytes (n=3), calcifications (n = 4) and epithelial granulocytar lesions (n = 4). Hyperplastic mucinous changes (PanIL) were observed in 4 cases; PanIN-1 lesions (low grade of dysplasia) in 4 cases and PanIN2 (moderate grade). The patient with PanIN-2 developed pancreatic adenocarcinoma 18 months after the partial surgical resection. A control group of 10 surgical specimens (Whipple's resections) for ACP was studied. It represented 7 males and 3 females, aged of 49 years in median. Histological examination revealed interlobular (perilobular) and intralobular cell-rich fibrosis 4/4 in median according to Klöppel fibrosis score, no epithelial lesion (n=0) and calcifications in 7 cases. PanIn lesions-1 were observed in 3 cases and hyperplastic mucinous changes in 2 cases of very inflammatory pancreatitis. Conclusion It is the first study which report the pathological features of chronic HP. The originality of this work was to describe very severe inflammatory duct lesions and PanIN lesions (type 1 and 2) in two third of the cases in patients aged of 35 years in median. These lesions existed in ACP but they were less frequent. These results, if they were confirmed, were a huge argument to propose a prophylactic pancreatectomy in HP patients. (1) Rebours V et al. Risk of Pancreatic Adenocarcinoma in Patients with Hereditary Pancreatitis: A National exhaustive series. Am J Gastroenterol 2007; in Press.