- Email: [email protected]
Fine needle aspiration of pancreatic masses: the clinical impact
AJG – Month, 2002
9.
10.
11. 12. 13. 14. 15.
16.
17. 18.
19.
quence of endoscopic sphincterotomy for bile duct stones. Gastrointest Endosc 1998;48:465–9. Periera-Lima JC, Jacobs R, Winter VH, et al. Long-term results (7 to 10 years) of endoscopic papillotomy for choledocholithiasis. Multivariate analysis of prognostic factors for recurrence of biliary symptoms. Gastrointest Endosc 1998;48: 457– 64. Gregg JA, DeGirolami P, Carr-Locke SL. Effects of sphincteroplasty and endoscopic sphincterotomy on the bacteriologic characteristics of the common bile duct. Am J Surg 1985;149: 668 –71. Nagase M, Hikasa Y, Soloway RD, et al. Gallstones in western Japan. Factors affecting the prevalence of intrahepatic gallstones. Gastroenterology 1980;78:684 –90. Cotton PB, Lehman S, Vennes J, et al. Endoscopic sphincterotomy complications and their management: An attempt at consensus. Gastrointest Endosc 1991;37:383–93. Hawes RH, Cotton PB, Vallon AG. Follow up 6 to 11 years after duodenoscopic sphincterotomy for stones in patients with prior cholecystectomy. Gastroenterology 1990;98:1008 –12. Bourke MJ, Elfant AB, Alhalel R, et al. Sphincterotomy associated biliary strictures: Features and endoscopic management. Gastroenterology 2000;52:494 –9. Bergman JJ, Van Berkel AM, Greon AK, et al. Biliary manometry bacterial characteristics, bile composition, and histologic changes fifteen to seventeen years after endoscopic sphincterotomy. Gastrointest Endosc 1997;45:400 –5. Kurumado K, Nagai T, Kondo Y, et al. Long-term observations on morphological changes of choledochal epithelium after choledochoenterostomy in rats. Dig Dis Sci 1994;39: 809 –20. Yasuda I, Tomita E, Enya M, et al. Can endoscopic papillary balloon dilation really preserve sphincter of Oddi function? Gut 2001;49:686 – 691. Yasuda I, Tomita E, Moriwaki H, et al. Endoscopic papillary balloon dilation for common bile duct stones: Efficacy of combination with extracorporeal shockwave lithotripsy for large stones. Eur J Gastroenterol Hepatol 1998;10:1045–50. Kwok-Hung L, Gin-Ho L, Chiun-ku L, et al. Do patients with recurrent choledocholithiasis after endoscopic sphincterotomy benefit from regular follow-up? Gastrointest Endosc 2002;55: 523– 6.
Reprint requests and correspondence: Sunil G. Sheth, M.D., Lahey Clinic, Division of Gastroenterology, 41 Mall Road, Burlington, MA 01805. Received Apr. 22, 2002; accepted June 12, 2002.
Fine Needle Aspiration of Pancreatic Masses: The Clinical Impact The ability to safely provide tissue sampling from a pancreatic mass using endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) represents one of the major advances in gastrointestinal endoscopy in the past decade (1). Linear endosonography coupled with Doppler imaging provides real-time ultrasound imaging during FNA (2). Cytologic material is aspirated using a small gauge needle directed through the gastrointestinal wall and into the pancreas (3). In this report by Fritscher-Ravens et al., the impact of EUS on the management of 200 patients with a
2701
pancreatic mass is described in detail. They found that the results of EUS-guided FNA changed the therapeutic approach to the pancreatic mass in 44% of patients. How should pancreatic FNA be used in clinical practice? There are several clinical scenarios where FNA of a pancreatic mass will have a significant impact on patient care. Previous investigators have documented the impact of EUS on patients with advanced pancreatic cancer (4). If there is evidence of advanced, unresectable pancreatic cancer, FNA of lymph nodes, liver metastases, or ascites can provide a tissue diagnosis and at the same time provide evidence of unresectability (5). EUS is very sensitive in the detection of these findings of metastatic disease. The use of EUS in this setting is a powerful tool and its cost-effectiveness has been demonstrated (6). In addition, there may be advantages over CT-guided biopsies (7). With a positive FNA combined with evidence of an advanced pancreatic malignancy, a costly surgical intervention can be avoided. The most common clinical scenario for the use of EUSguided FNA is in the setting of a focal pancreatic lesion as seen on a CT scan. The differential diagnosis of a focal pancreatic mass is very wide, ranging from an adenocarcinoma to a cystadenoma, islet cell tumor, or chronic pancreatitis. In this paper, the authors were confronted with a similar problem: of the 200 patients, 101 patients had benign disease, whereas 99 patients had a variety of pancreatic malignancies. How well did FNA document and exclude a malignancy? Overall, the results of FNA were excellent and comparable with those of previous reports (8). The sensitivity of FNA was 85% without any falsely positive biopsies. Nearly as important was the finding of a negative predictive value of 83%. These high rates of sensitivity and specificity are sufficiently high enough that they will have an impact on patient care. The patients with a positive FNA will be evaluated for a pancreatic resection or radiation/ chemotherapy. Those patients with a negative FNA will need additional evaluation, but many will not require surgical intervention for the purpose of obtaining diagnostic pancreatic tissue. One of the most difficult scenarios for an endosonographer is the evaluation of a focal pancreatic mass in the setting of chronic pancreatitis (9). There are two reasons why it is difficult to evaluate a patient with chronic pancreatitis. First, it is difficult to image the pancreas and be certain whether a malignant mass is present or not. Focal pancreatitis and adenocarcinoma may have a very similar appearance on endosonography. Secondly, cytologic evaluation of pancreatic tissue in the setting of chronic inflammation is very difficult because the inflammatory infiltrate may obscure or simulate a pancreatic malignancy. FritscherRavens et al. examined this problem by prospectively separating patients into two groups, those with ultrasound evidence of chronic pancreatitis and those with only a finding of a focal malignancy. Not surprisingly, they found that the performance of FNA was better in those patients without chronic pancreatitis. The
2702
Editorials
AJG – Vol. 97, No. 11, 2002
sensitivity for detecting malignancy was 89%, comparable with the results reported with CT-guided pancreatic biopsies. The use of FNA in patients with a focal respectable mass will impact patient management in two aspects. In this series, 27% of the pancreatic malignancies were not adenocarcinomas and in 25 of 32 patients the management was affected by the results of FNA. In another 34 patients who were scheduled for a surgical resection, the results of EUS (liver and lymph node metastases) deemed them unresectable and their surgery was cancelled. Overall, the results of EUS and FNA had an impact on the care of 44% of patients. The results of FNA in patients with chronic pancreatitis demonstrated a reduced sensitivity for detecting malignancy, only 54%. However, the specificity remained very high, 100%. In the clinical scenario of a patient with a pancreatic mass associated with chronic pancreatitis, we cannot rely on the results of FNA when the cytology is negative for malignancy. Instead, the clinical setting will have to dictate the clinical management. In addition to demonstrating a high sensitivity and specificity for EUS-guided FNA, this study has also shown the safety of the procedure. There were no complications of the procedure and there was no evidence of malignant seeding of the needle tract. In previous series, very few complications of FNA have been reported, and they consist of small amounts of bleeding and transient abdominal pain (10). In conclusion, EUS-guided FNA for pancreatic masses is a highly accurate test that will have a significant impact on patient management. The growing acceptance of the test will enable clinicians to diagnose pancreatic malignancies at an early stage. Hopefully, this type of testing will improve the dismal survival often associated with this dreaded malignancy. William R. Brugge, M.D. Massachusetts General Hospital Boston, Massachusetts
REFERENCES 1. Chang KJ, Katz KD, Durbin TE, et al. Endoscopic ultrasoundguided fine-needle aspiration. Gastrointest Endosc 1994;40: 694 –9. 2. Gress F, Savides T, Cummings O, et al. Radial scanning and linear array endosonography for staging pancreatic cancer: A prospective randomized comparison. Gastrointest Endosc 1997;45:138 – 42. 3. Brugge WR. EUS-guided pancreatic fine needle aspiration: Instrumentation, results, and complications. Tech Gastrointest Endosc 2000;2:149 –54. 4. Chang KJ, Nguyen P, Erickson RA, et al. The clinical utility of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of pancreatic carcinoma. Gastrointest Endosc 1997;45:387–93. 5. Erickson RA, Garza AA. Impact of endoscopic ultrasound on the management and outcome of pancreatic carcinoma. Am J Gastroenterol 2000;95:2248 –54. 6. Harewood GC, Wiersema MJ. A cost analysis of endoscopic
7. 8. 9.
10.
ultrasound in the evaluation of pancreatic head adenocarcinoma. Am J Gastroenterol 2001;96:2651– 6. Mallery JS, Chang Y, Hahn P, et al. Pancreatic tissue sampling guided by EUS, CT/US and surgery: A comparison of sensitivity and specificity. Gastrointest Endosc 2002;56:218 –24. Gress F, Gottlieb K, Sherman S, et al. Endoscopic ultrasonography-guided fine-needle aspiration biopsy of suspected pancreatic cancer. Ann Intern Med 2001;134:459 – 64. Becker D, Strobel D, Bernatik T, Hahn EG. Echo-enhanced color- and power-Doppler EUS for the discrimination between focal chronic pancreatitis and pancreatic carcinoma. Gastrointest Endosc 2001;53:784 –9. Voss M, Hammel P, Molas G, et al. Value of endoscopic ultrasound guided fine needle aspiration biopsy in the diagnosis of solid pancreatic masses. Gut 2000;46:244 –9.
Reprint requests and correspondence: William R. Brugge, M.D., Massachusetts General Hospital, 55 Fruit Street - Blake 452C, Boston, MA 02114.
Anti–Tissue Transglutaminase Antibody as the First Line Screening for Celiac Disease: Good-Bye Antigliadin Tests? Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. The ingestion of prolamins (alcohol soluble fractions of wheat, barley, and rye) leads to an immunologically mediated, selfperpetuating small intestinal mucosal damage, and the elimination of these substances results in full mucosal recovery. The disease is strongly associated with certain human leukocyte antigen alleles, particularly DQA1*0501/DQB1*0201 (1). CD has been found in approximately 0.4–1.1% of the general population worldwide (2–5). The prevalence is much higher in certain groups at risk, ranging from 3% in children with symptoms or conditions associated with CD but without a positive family history (6), to 5.5% in asymptomatic individuals who have a first degree relative with biopsy-proven CD (7). The clinical manifestations of CD are extremely protean in nature and vary markedly with the age of the patient, the duration of exposure to gluten, the extent of small intestinal mucosal damage, and the presence of extraintestinal pathology. In addition to the classical GI form, a variety of other clinical manifestations have been described, including extraintestinal (so-called “atypical”) and asymptomatic forms (8). Reports from Germany and the United States demonstrate a mean duration of 11 yr between the onset of symptoms and diagnosis of celiac disease in some adults (9, 10). During this interval, patients had numerous visits to their doctors and underwent many diagnostic investigations (11), no doubt at considerable cost to the health care system. Apart from the obvious benefits to symptomatic individuals, early diagnosis and treatment of CD has additional benefits of equal or greater significance. Studies suggest that delayed diagnosis is associated with increased prevalence of other autoimmune conditions (12), mor-
9.
10.
11. 12. 13. 14. 15.
16.
17. 18.
19.
quence of endoscopic sphincterotomy for bile duct stones. Gastrointest Endosc 1998;48:465–9. Periera-Lima JC, Jacobs R, Winter VH, et al. Long-term results (7 to 10 years) of endoscopic papillotomy for choledocholithiasis. Multivariate analysis of prognostic factors for recurrence of biliary symptoms. Gastrointest Endosc 1998;48: 457– 64. Gregg JA, DeGirolami P, Carr-Locke SL. Effects of sphincteroplasty and endoscopic sphincterotomy on the bacteriologic characteristics of the common bile duct. Am J Surg 1985;149: 668 –71. Nagase M, Hikasa Y, Soloway RD, et al. Gallstones in western Japan. Factors affecting the prevalence of intrahepatic gallstones. Gastroenterology 1980;78:684 –90. Cotton PB, Lehman S, Vennes J, et al. Endoscopic sphincterotomy complications and their management: An attempt at consensus. Gastrointest Endosc 1991;37:383–93. Hawes RH, Cotton PB, Vallon AG. Follow up 6 to 11 years after duodenoscopic sphincterotomy for stones in patients with prior cholecystectomy. Gastroenterology 1990;98:1008 –12. Bourke MJ, Elfant AB, Alhalel R, et al. Sphincterotomy associated biliary strictures: Features and endoscopic management. Gastroenterology 2000;52:494 –9. Bergman JJ, Van Berkel AM, Greon AK, et al. Biliary manometry bacterial characteristics, bile composition, and histologic changes fifteen to seventeen years after endoscopic sphincterotomy. Gastrointest Endosc 1997;45:400 –5. Kurumado K, Nagai T, Kondo Y, et al. Long-term observations on morphological changes of choledochal epithelium after choledochoenterostomy in rats. Dig Dis Sci 1994;39: 809 –20. Yasuda I, Tomita E, Enya M, et al. Can endoscopic papillary balloon dilation really preserve sphincter of Oddi function? Gut 2001;49:686 – 691. Yasuda I, Tomita E, Moriwaki H, et al. Endoscopic papillary balloon dilation for common bile duct stones: Efficacy of combination with extracorporeal shockwave lithotripsy for large stones. Eur J Gastroenterol Hepatol 1998;10:1045–50. Kwok-Hung L, Gin-Ho L, Chiun-ku L, et al. Do patients with recurrent choledocholithiasis after endoscopic sphincterotomy benefit from regular follow-up? Gastrointest Endosc 2002;55: 523– 6.
Reprint requests and correspondence: Sunil G. Sheth, M.D., Lahey Clinic, Division of Gastroenterology, 41 Mall Road, Burlington, MA 01805. Received Apr. 22, 2002; accepted June 12, 2002.
Fine Needle Aspiration of Pancreatic Masses: The Clinical Impact The ability to safely provide tissue sampling from a pancreatic mass using endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) represents one of the major advances in gastrointestinal endoscopy in the past decade (1). Linear endosonography coupled with Doppler imaging provides real-time ultrasound imaging during FNA (2). Cytologic material is aspirated using a small gauge needle directed through the gastrointestinal wall and into the pancreas (3). In this report by Fritscher-Ravens et al., the impact of EUS on the management of 200 patients with a
2701
pancreatic mass is described in detail. They found that the results of EUS-guided FNA changed the therapeutic approach to the pancreatic mass in 44% of patients. How should pancreatic FNA be used in clinical practice? There are several clinical scenarios where FNA of a pancreatic mass will have a significant impact on patient care. Previous investigators have documented the impact of EUS on patients with advanced pancreatic cancer (4). If there is evidence of advanced, unresectable pancreatic cancer, FNA of lymph nodes, liver metastases, or ascites can provide a tissue diagnosis and at the same time provide evidence of unresectability (5). EUS is very sensitive in the detection of these findings of metastatic disease. The use of EUS in this setting is a powerful tool and its cost-effectiveness has been demonstrated (6). In addition, there may be advantages over CT-guided biopsies (7). With a positive FNA combined with evidence of an advanced pancreatic malignancy, a costly surgical intervention can be avoided. The most common clinical scenario for the use of EUSguided FNA is in the setting of a focal pancreatic lesion as seen on a CT scan. The differential diagnosis of a focal pancreatic mass is very wide, ranging from an adenocarcinoma to a cystadenoma, islet cell tumor, or chronic pancreatitis. In this paper, the authors were confronted with a similar problem: of the 200 patients, 101 patients had benign disease, whereas 99 patients had a variety of pancreatic malignancies. How well did FNA document and exclude a malignancy? Overall, the results of FNA were excellent and comparable with those of previous reports (8). The sensitivity of FNA was 85% without any falsely positive biopsies. Nearly as important was the finding of a negative predictive value of 83%. These high rates of sensitivity and specificity are sufficiently high enough that they will have an impact on patient care. The patients with a positive FNA will be evaluated for a pancreatic resection or radiation/ chemotherapy. Those patients with a negative FNA will need additional evaluation, but many will not require surgical intervention for the purpose of obtaining diagnostic pancreatic tissue. One of the most difficult scenarios for an endosonographer is the evaluation of a focal pancreatic mass in the setting of chronic pancreatitis (9). There are two reasons why it is difficult to evaluate a patient with chronic pancreatitis. First, it is difficult to image the pancreas and be certain whether a malignant mass is present or not. Focal pancreatitis and adenocarcinoma may have a very similar appearance on endosonography. Secondly, cytologic evaluation of pancreatic tissue in the setting of chronic inflammation is very difficult because the inflammatory infiltrate may obscure or simulate a pancreatic malignancy. FritscherRavens et al. examined this problem by prospectively separating patients into two groups, those with ultrasound evidence of chronic pancreatitis and those with only a finding of a focal malignancy. Not surprisingly, they found that the performance of FNA was better in those patients without chronic pancreatitis. The
2702
Editorials
AJG – Vol. 97, No. 11, 2002
sensitivity for detecting malignancy was 89%, comparable with the results reported with CT-guided pancreatic biopsies. The use of FNA in patients with a focal respectable mass will impact patient management in two aspects. In this series, 27% of the pancreatic malignancies were not adenocarcinomas and in 25 of 32 patients the management was affected by the results of FNA. In another 34 patients who were scheduled for a surgical resection, the results of EUS (liver and lymph node metastases) deemed them unresectable and their surgery was cancelled. Overall, the results of EUS and FNA had an impact on the care of 44% of patients. The results of FNA in patients with chronic pancreatitis demonstrated a reduced sensitivity for detecting malignancy, only 54%. However, the specificity remained very high, 100%. In the clinical scenario of a patient with a pancreatic mass associated with chronic pancreatitis, we cannot rely on the results of FNA when the cytology is negative for malignancy. Instead, the clinical setting will have to dictate the clinical management. In addition to demonstrating a high sensitivity and specificity for EUS-guided FNA, this study has also shown the safety of the procedure. There were no complications of the procedure and there was no evidence of malignant seeding of the needle tract. In previous series, very few complications of FNA have been reported, and they consist of small amounts of bleeding and transient abdominal pain (10). In conclusion, EUS-guided FNA for pancreatic masses is a highly accurate test that will have a significant impact on patient management. The growing acceptance of the test will enable clinicians to diagnose pancreatic malignancies at an early stage. Hopefully, this type of testing will improve the dismal survival often associated with this dreaded malignancy. William R. Brugge, M.D. Massachusetts General Hospital Boston, Massachusetts
REFERENCES 1. Chang KJ, Katz KD, Durbin TE, et al. Endoscopic ultrasoundguided fine-needle aspiration. Gastrointest Endosc 1994;40: 694 –9. 2. Gress F, Savides T, Cummings O, et al. Radial scanning and linear array endosonography for staging pancreatic cancer: A prospective randomized comparison. Gastrointest Endosc 1997;45:138 – 42. 3. Brugge WR. EUS-guided pancreatic fine needle aspiration: Instrumentation, results, and complications. Tech Gastrointest Endosc 2000;2:149 –54. 4. Chang KJ, Nguyen P, Erickson RA, et al. The clinical utility of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of pancreatic carcinoma. Gastrointest Endosc 1997;45:387–93. 5. Erickson RA, Garza AA. Impact of endoscopic ultrasound on the management and outcome of pancreatic carcinoma. Am J Gastroenterol 2000;95:2248 –54. 6. Harewood GC, Wiersema MJ. A cost analysis of endoscopic
7. 8. 9.
10.
ultrasound in the evaluation of pancreatic head adenocarcinoma. Am J Gastroenterol 2001;96:2651– 6. Mallery JS, Chang Y, Hahn P, et al. Pancreatic tissue sampling guided by EUS, CT/US and surgery: A comparison of sensitivity and specificity. Gastrointest Endosc 2002;56:218 –24. Gress F, Gottlieb K, Sherman S, et al. Endoscopic ultrasonography-guided fine-needle aspiration biopsy of suspected pancreatic cancer. Ann Intern Med 2001;134:459 – 64. Becker D, Strobel D, Bernatik T, Hahn EG. Echo-enhanced color- and power-Doppler EUS for the discrimination between focal chronic pancreatitis and pancreatic carcinoma. Gastrointest Endosc 2001;53:784 –9. Voss M, Hammel P, Molas G, et al. Value of endoscopic ultrasound guided fine needle aspiration biopsy in the diagnosis of solid pancreatic masses. Gut 2000;46:244 –9.
Reprint requests and correspondence: William R. Brugge, M.D., Massachusetts General Hospital, 55 Fruit Street - Blake 452C, Boston, MA 02114.
Anti–Tissue Transglutaminase Antibody as the First Line Screening for Celiac Disease: Good-Bye Antigliadin Tests? Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. The ingestion of prolamins (alcohol soluble fractions of wheat, barley, and rye) leads to an immunologically mediated, selfperpetuating small intestinal mucosal damage, and the elimination of these substances results in full mucosal recovery. The disease is strongly associated with certain human leukocyte antigen alleles, particularly DQA1*0501/DQB1*0201 (1). CD has been found in approximately 0.4–1.1% of the general population worldwide (2–5). The prevalence is much higher in certain groups at risk, ranging from 3% in children with symptoms or conditions associated with CD but without a positive family history (6), to 5.5% in asymptomatic individuals who have a first degree relative with biopsy-proven CD (7). The clinical manifestations of CD are extremely protean in nature and vary markedly with the age of the patient, the duration of exposure to gluten, the extent of small intestinal mucosal damage, and the presence of extraintestinal pathology. In addition to the classical GI form, a variety of other clinical manifestations have been described, including extraintestinal (so-called “atypical”) and asymptomatic forms (8). Reports from Germany and the United States demonstrate a mean duration of 11 yr between the onset of symptoms and diagnosis of celiac disease in some adults (9, 10). During this interval, patients had numerous visits to their doctors and underwent many diagnostic investigations (11), no doubt at considerable cost to the health care system. Apart from the obvious benefits to symptomatic individuals, early diagnosis and treatment of CD has additional benefits of equal or greater significance. Studies suggest that delayed diagnosis is associated with increased prevalence of other autoimmune conditions (12), mor-