Review Article The Korean Journal of Pancreas and Biliary Tract 2017;22: pissn eissn 2288

Size: px

Start display at page:

Download "Review Article The Korean Journal of Pancreas and Biliary Tract 2017;22: pissn eissn 2288"

소리 오
5 years ago
Views:

1 Review Article The Korean Journal of Pancreas and Biliary Tract 2017;22: pissn eissn 증상없는아밀라아제, 리파아제증가에대한평가 서울대학교의과대학내과학교실및간연구소 이상협 Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea There are increasing number of cases of serum amylase and lipase levels being examined as part of health screening, but the clinical significance of these amylase and lipase levels is unclear. When the clinicians encounter patients with elevated pancreatic enzymes, the most common causes such as acute pancreatitis, hepatic or renal dysfunction should be ruled out first by thorough history taking, physical examination, and laboratory tests. Further tests including abdominal ultrasonography or computed tomography, lipid profile, tumor marker, isoenzyme, and calculation of amylase-tocreatinine clearance ratio or polyethylene glycol precipitation test should be performed to exclude other causes. If the pancreatic enzymes are continuously elevated through repeated tests without any apparent etiology, the diagnosis is made with chronic non-pathological pancreatic hyperenzymemia (CNPH). Magnetic resonance cholangiopancreatography is very useful and important modality for the patients with CNPH but the clinical significance of magnetic resonance cholangiopancreatography with secretin stimulation is still unclear. They can be evaluated through endoscopic ultrasonography with preference but it is less suitable for follow-up. Individualized approaches should be made after considering the need for active treatment or periodic follow-up for the benign pancreatic diseases associated with CNPH. It is difficult to conclude until more long-term data are reported because there are only limited number of researches and consensus on the range of tests to be performed for diagnosis, clinical significance of benign findings and end of follow-up in patients with CNPH. Keywords: Pancreas, Amylase, Lipase Received Jun. 22, 2017 Revised Jul. 11, 2017 Accepted Jul. 11, 2017 Corresponding author : Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel Fax ; gidoctor@snuh.org This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2017 by The Korean Journal of Pancreas and Biliary Tract Copyright 2017 by Korean Pancreatobiliary Association 103

2 서론 95% 5%.,,. 1.,.,. 본론아밀라아제및리파아제의생성과대사 -1,4-.,,,,,,,., (P-type) 40-45%, (S-type) 55-60% % 1%.,,,,,. 3,4 25%. (reticulo-endothelial system). 1, 5 50 ml/min,. 6 혈청아밀라아제와리파아제상승의가능한원인들 1. 일반적인접근.,...,,. 3, 85%, 91%, 7 98%. 8., 9. 10, phospholipase A2, elastase1, anionic trypsinogen. 11,,.,., 104

,,, (chronic non-pathological pancreatic hyperenzymemia, CNPH),, (computed tomography, CT) (magnetic resonance cholangiopancreatograpy, MRCP)., Fig. 1., macroamylasemia., /,. 1,. macroamylase,.

3 ,,, (chronic non-pathological pancreatic hyperenzymemia, CNPH),, (computed tomography, CT) (magnetic resonance cholangiopancreatograpy, MRCP)., Fig. 1., macroamylasemia., /,. 1,. macroamylase,. 12 macroamylas- Fig. 1. Possible diagnostic algorithm in patients with pancreatic hyperenzymemia. Based on detailed medical history, physical examination, basic blood test, abdominal ultrasound, and simple radiography, the possibility of acute pancreatitis, impaired excretion of pancreatic enezyme and adverse reaction of drug should be excluded. Subsequent exclusion of additional pancreatic or nonpancreatic causes via tumor markers, isoenzymes, ACCR/PEG precipitation test, and abdominal CT. If pancreatic enzyme elevation is confirmed during repeated tests and there is no specific abnormal finding for EUS or MRCP, CNPH may be diagnosed and should be followed-up appropriately. CBC, complete blood count; USG, ultrasonography; ACCR/PEG, amylase-to-cre atinine clearance ratio/polyethylene glycol; CT, computed tomography; MRCP, magnetic resonance cholangiopancreatography; EUS, endoscopic ultrasonography; CNPH, chronic non-pathological pancreatic hyperenzymemia. 105

4 emia (celiac disease), (human immunodeficiency virus),,,, (monoclonal gammopathy), 13,14 (gluten-free diet) macroamylasemia. macroamylasemia, (amylase-to-creatinine clearance ratio; [urine amylase/serum amylase] [serum creatinine/urine creatinine] 100, reference 1-4%) 고아밀라아제혈증과고리파아제혈증 Table 1.,,,,, CNPH,,, macroamylasemia,.,,,. 16 salivary hyperamylasemia,,,.,.,,, (Stype) C (hepatitis C virus)., 3. (endoscopic retrograde cholangiopancreatography, ERCP) (sarcoidosis) 3. 19,. Paracetamol, steroid, azathioprine, ephedrine, ritodrine, roxithromycin, cyclosporine, clozapine, pentamidine, didanosine. 만성비병인성혈중췌장효소증가증 (CNPH; Gullo s syndrome) 1. CNPH 의의미 1970 Warshaw Lee Gullo CNPH, benign pancreatic hyperenzymemia Gullo. Gullo (sporadical) (familial) 10, CFTR, SPINK1, PRSS1 gene mutation, Gullo

5 16, 17 Table 1. Possible causes of hyperamylasemia or hyperlipasemia Etiology of hyperamylasemia Hyperamylasemia associated with abdominal pain Pancreatic disorder Pancreatitis of any etiology: alcohol, biliary tract disease, trauma, hyperlipidemia Complications of acute pancreatitis: pancreatic abscess, pseudocyst, ascites, pleural effusion Pancreatic trauma (blunt trauma, abdominal/retroperitoneal surgery, endoscopic retrograde cholangiopancreatography) Pancreatic cancer Non-pancreatic gastrointestinal tract / vascular conditions Acute cholecystitis, choledocholithiasis Gastritis, duodenitis, gastroenteritis, peptic ulcer Inflammatory bowel disease Intestinal obstruction Peritonitis Dissecting/Ruptured abdominal aortic aneurysm Mesenteric infarction Abdominal trauma Non-pancreatic genitourinary conditions Urolithiasis Endometriosis, salpingitis Ectopic/ruptured tubal pregnancy Hyperamylasemia associated with salivary gland disorders Chronic alcoholism Anorexia nervosa/bulimia Duct obstruction/caliculi Sjögren s syndrome Mumps Trauma, surgery Injection of constrast medium into salivary ducts for sialography Miscellaneous causes Tumors: carcinoma of lung, ovary, breast, renal cell, colon, thymoma, multiple myeloma, hematologic malignancies, pheochromocytoma Renal failure Liver disease: hepatitis, liver cirrhosis, hepatocellular carcinoma Acute alcoholic abuse Diabetic ketoacidosis and non-ketotic acidosis Post-surgery: pancreatic, abdominal, hepatic, biliary, cardiovascular, post-ercp, liver transplantation Macroamylasemia Acute myocardiac infarction Acquired immune deficiency syndrome Acute porphyria Glycogen storage disease type 1 Drugs: anti-retroviral agents (atazanavir, cidofovir, enfuvirtide, foscarnet, indinavir, lamivudine, zidovudine), azathioprine, clozapine, cyclosporine, didanosine, sphedrine, oral contraceptives, paracetamol, pentamidine, propofol, ritodrine, roxithromycin, steroids, tamoxifen Table 1. Continued Etiology of hyperamylasemia Reduced clearance/physiological Renal impairment Macrolipase: presence of macrolipase may sometimes indicate an increased risk for associated disorders, such as autoimmune or lymphoproliferative disease Intra-abdominal pancreatic and non-pancreatic causes (other than pancreatitis) Inflammation: in adjacent organs/structures to pancreas such as biliary tranct and gastrointestinal tract Obstruction: biliary, pancreatic duct or bowel obstruction Alternative sources of lipase: stomach, small bowel, liver, gallbladder and other surrounding organs may potentially act as non-pancreatic sources of lipolytic enzymes Peritonitis Impaired hepatic function: chronic liver diseas, biliary atresia etc. Neoplasia: may be related to biliary or pancreatic ductal obstruction, macrolipase, or functional tumor mass Non-pathological pancreatic hyperenzymemia Critical illness Intensive care unit patients with critical illness or multi-organ failure Neurosurgical patients with severe head injuries Some alternative causes: diabetic ketoacidosis and type I diabetes mellitus Drugs: alcohol, morphine with prostigmine provocation, sorafenib (?), nilotinib (?), dipeptidyl-peptidase-4 inhibitors (?) ERCP, endoscopic retrograde cholangiopancreatography., Gullo.,. 2. CNPH 의평가 CNPH,,, (early chronic pancreatitis), delayed main pancreatic duct emptying, (pancreatic cytic lesions, PCLs),,, CNPH Table

6 Table 2. Imaging findings in studies on asymptomatic subjects with chronic pancreatic hyperenzymemia Author (year) Modality N Normal Benign CP PCLs Ductal dilatation Pancreas divisum Delayed MPD emptying Mortelé et al MRCP (42.6) 9 (16.7) 7 (13) - 10 (18.5) - 5 (9.5) - (2004) 38 Gullo et al MRCP (90.5) - 2 (3.1) 1 (1.6) 2 (3.1) - 1 (1.6) - (2009) 51 Testoni et al MRCP (80) - 2 (8.0) 2 (8.0) 2 (8.0) (2009) 25 MRCP-S (48) - 2 (8.0) 13 (52) 2 (8.0) 3 (12) - - Pezzilli et al (2009) 30 MRCP, EUS Etc Malignancy (41.3) 20 (26.7) 8 (10.7) (17) 3 (4.0) Donati et al MRCP (50) 2 (2.5) 24 (30.0) - 12 (15.0) - 4 (5.1) - (2010) 26 MRCP-S (31.3) 14 (17.5) 22 (27.5) - 22 (27.5) - 4 (5.1) - Amodio et al MRCP (73.1) - 4 (2.5) 34 (21.3) (4.3) 1 (0.6) (2012) 27 MRCP-S (50) - 4 (2.5) MPD - 23 (14) 10 (6.1) 44 (26.3) BD 58 (36.2) Galassi et al MRCP (91.8) - 8 (4.4) - 6 (3.3) - 1 (0.5) - (2014) 28 EUS (39.7) 22 (32.4) 10 (14.7) - 11 (16.1) - 1 (1.5) - MRCP-S (48.5) 14 (20.6) 6 (8.9) - 12 (17.7) 4 (5.9) - Antonini et al MRCP, EUS (84.4) 1 (2.2) 1 (2.2) - 1 (2.2) - 1 (2.2) - (2017) 43 Values are presented as number (%). CP, chronic pancreatitis; PCLs, pancreatic cytic lesions; MPD, main pancreatic duct; MRCP, magnetic resonance cholangiopancreatography; MRCP-S, MRCP with secretin stimulation; EUS, endoscopic sonography.. CT,. ERCP, 3-7%. (endoscopic ultrasonography, EUS), MRCP, (MRCP with secretin stimulation, MRCP-S) MRCP-S. MRCP, MRCP-S (side branch pancreatic duct) delayed main pancreatic duct emptying EUS. 28,29 3. CNPH의일반적인접근 CNPH, CNPH (Table 2), %,. 2, 27,30 Pezzilli 30 4% (75 3 ),

7 CNPH. 27,,. CNPH.?. MRCP, MRCP-S, EUS, MRCP 92%, 75%, 31,32 MRCP % MRCP-S MRCP-S, 35,36 MRCP MRCP-S. 25,27 MRCP-S, MRCP-S., EUS (intraductal papillary mucin-producing neoplasm, IPMN) MRCP-S EUS. 37 EUS, Rosemont criteria MRCP-S. 29, CNPH CT MRCP, MRCP-S,. MRCP EUS EUS. CNPH,. 4. CNPH에서발견된양성소견의관리 CNPH MRCP-S EUS 50% 60%, 25-27,30,37,38., IPMN PCLs,,. 39 CNPH. Mortele 38,, CNPH. Testoni 25 MRCP-S CNPH 52% 7.1%. Di Leo 37 EUS CNPH 39.7% 86.8%. CNPH. CNPH. MRCP-S, MRCP (63% vs. 5%). 40 MRCP EUS %, 25-27,37 EUS 26%. 30,37 1) 만성췌장염,, macroamylasemia

8 % Di Leo 37 (50.6 vs. 61.4, P = 0.007), Antonini ) IPMN과췌장낭성병변 CNPH 27.5% 1 cm, IPMN %. 28,30,43 IPMN 5%. 44 BD-IPMN 12-47%, 45. IPMN, invasive IPMN. 46 Pezzilli 47. IPMN,. 3) 분할췌와 delayed main pancreatic duct emptying %, CNPH %. 25,26,28,37,38,51, Delayed main pancreatic duct emptying, 1.5%. 53 delayed main pancreatic duct emptying.. Di Leo 37 (16.1%, 1.5%), Testoni 25 (8%, 3.6%). Delayed main pancreatic duct emptying Testoni 25 (12%, 10.7%). 4) 췌관확장,. 3 mm, 2 mm 5 mm. 29,54 51 (73%), (15%), (4%), IPMN (4%).,,. 55, 1, , ( 2.5 mm),

9 . 결론.,,,,,,, CNPH. CNPH CT, MRCP EUS. CNPH. 요약,.,,,,.,,, amylase-to-creatinine clearance ratio polyethylene glycol., (CNPH). CNPH,. (MRCP) CNPH, (MRCP-S).. CNPH,. CNPH. 국문색인 : 췌장, 아밀라아제, 리파아제 Conflicts of Interest The author has no conflicts to disclose. REFERENCES 1. Frulloni L, Patrizi F, Bernardoni L, Cavallini G. Pancreatic hyperenzymemia: clinical significance and diagnostic approach. JOP 2005;6: Matteucci E, Giampietro O. Diabetes and pancreas: why so difficult? Potential mechanisms of elevated serum pancreatic enzymes. Curr Med Chem 2016;23: Tietz NW, Shuey DF. Lipase in serum--the elusive enzyme: an overview. Clin Chem 1993;39: Terada T, Kida T, Nakanuma Y. Extrahepatic peribiliary glands express alpha-amylase isozymes, trypsin and pancreatic lipase: an immunohistochemical analysis. Hepatology 1993;18: Collen MJ, Ansher AF, Chapman AB, Mackow RC, Lewis JH. Serum amylase in patients with renal insufficiency and renal failure. Am J Gastroenterol 1990;85: Pezzilli R, Andreone P, Morselli-Labate AM, et al. Serum pancreatic enzyme concentrations in chronic viral liver diseases. Dig Dis Sci 1999;44: Kemppainen EA, Hedström JI, Puolakkainen PA, et al. Rapid measurement of urinary trypsinogen-2 as a screening test for acute pancreatitis. N Engl J Med 1997;336: Steinberg WM, Goldstein SS, Davis ND, Shamma'a J, Anderson K. Diagnostic assays in acute pancreatitis. A study of sensitivity and specificity. Ann Intern Med 1985;102: Lankisch PG, Burchard-Reckert S, Lehnick D. Underestimation of acute 111

10 pancreatitis: patients with only a small increase in amylase/lipase levels can also have or develop severe acute pancreatitis. Gut 1999;44: Shah AM, Eddi R, Kothari ST, Maksoud C, DiGiacomo WS, Baddoura W. Acute pancreatitis with normal serum lipase: a case series. JOP 2010;11: Yadav D, Agarwal N, Pitchumoni CS. A critical evaluation of laboratory tests in acute pancreatitis. Am J Gastroenterol 2002;97: Sachdeva CK, Bank S, Greenberg R, Blumstein M, Weissman S. Fluctuations in serum amylase in patients with macroamylasemia. Am J Gastroenterol 1995;90: Eleccion CB, Hathaway AA. Macroamylasemia in HIV infection. Tex Med 1998;94: Rabsztyn A, Green PH, Berti I, Fasano A, Perman JA, Horvath K. Macroamylasemia in patients with celiac disease. Am J Gastroenterol 2001;96: Van Gossum A, Cremer M. Macroamylasemia disappearance after gluten withdrawal. Dig Dis Sci 1989;34: Borovickova I, Bhatt NR, Boran GP, Ridgway PF. Persistent chronic hyperamylasemia: clinical interpretation and diagnostic approach. JOP 2016;17: Hameed AM, Lam VW, Pleass HC. Significant elevations of serum lipase not caused by pancreatitis: a systematic review. HPB (Oxford) 2015;17: Malloy J, Gurney K, Shan K, Yan P, Chen S. Increased variability and abnormalities in pancreatic enzyme concentrations in otherwise asymptomatic subjects with type 2 diabetes. Diabetes Metab Syndr Obes 2012;5: Duerksen DR, Tsang M, Parry DM. Chronic hyperlipasemia caused by sarcoidosis. Dig Dis Sci 2000;45: Warshaw AL, Lee KH. Macroamylasemia and other chronic nonspecific hyperamylasemias: chemical oddities or clinical entities? Am J Surg 1978;135: Gullo L. Benign pancreatic hyperenzymemia. Dig Liver Dis 2007;39: Gullo L. Day-to-day variations of serum pancreatic enzymes in benign pancreatic hyperenzymemia. Clin Gastroenterol Hepatol 2007;5: Gullo L. Familial pancreatic hyperenzymemia. Pancreas 2000;20: Gullo L. Chronic nonpathological hyperamylasemia of pancreatic origin. Gastroenterology 1996;110: Testoni PA, Mariani A, Curioni S, Giussani A, Masci E. Pancreatic ductal abnormalities documented by secretin-enhanced MRCP in asymptomatic subjects with chronic pancreatic hyperenzymemia. Am J Gastroenterol 2009;104: Donati F, Boraschi P, Gigoni R, et al. Secretin-stimulated MR cholangiopancreatography in the evaluation of asymptomatic patients with nonspecific pancreatic hyperenzymemia. Eur J Radiol 2010;75:e Amodio A, Manfredi R, Katsotourchi AM, et al. Prospective evaluation of subjects with chronic asymptomatic pancreatic hyperenzymemia. Am J Gastroenterol 2012;107: Galassi E, Birtolo C, Migliori M, et al. A 5-year experience of benign pancreatic hyperenzymemia. Pancreas 2014;43: Anaizi A, Hart PA, Conwell DL. Diagnosing Chronic Pancreatitis. Dig Dis Sci 2017;62: Pezzilli R, Morselli-Labate AM, Casadei R, et al. Chronic asymptomatic pancreatic hyperenzymemia is a benign condition in only half of the cases: a prospective study. Scand J Gastroenterol 2009;44: Zhang XM, Shi H, Parker L, Dohke M, Holland GA, Mitchell DG. Suspected early or mild chronic pancreatitis: enhancement patterns on gadolinium chelate dynamic MRI. Magnetic resonance imaging. J Magn Reson Imaging 2003;17: Zhang XM, Mitchell DG, Dohke M, Holland GA, Parker L. Pancreatic cysts: depiction on single-shot fast spin-echo MR images. Radiology 2002;223: de Jong K, Nio CY, Hermans JJ, et al. High prevalence of pancreatic cysts detected by screening magnetic resonance imaging examinations. Clin Gastroenterol Hepatol 2010;8: Kimura W, Nagai H, Kuroda A, Muto T, Esaki Y. Analysis of small cystic lesions of the pancreas. Int J Pancreatol 1995;18: Pascual I, Soler J, Peña A, et al. Morphological and functional evaluation of the pancreatic duct with secretin-stimulated magnetic resonance cholangiopancreatography in alcoholic pancreatitis patients. Dig Dis Sci 2008;53: Czakó L. Diagnosis of early-stage chronic pancreatitis by secretin-enhanced magnetic resonance cholangiopancreatography. J Gastroenterol 2007;42 Suppl 17: Di Leo M, Petrone MC, Zuppardo RA, et al. Pancreatic morphofunctional imaging as a diagnostic approach for chronic asymptomatic pancreatic hyperenzymemia. Dig Liver Dis 2016;48: Mortelé KJ, Wiesner W, Zou KH, Ros PR, Silverman SG. Asymptomatic nonspecific serum hyperamylasemia and hyperlipasemia: spectrum of MRCP findings and clinical implications. Abdom Imaging 2004;29: Frulloni L, Amodio A. Endoscopic ultrasonography in chronic asymptomatic pancreatic hyperenzymemia: the more we see, the less we know. Dig Liver Dis 2017;49: Cappeliez O, Delhaye M, Devière J, et al. Chronic pancreatitis: evaluation of pancreatic exocrine function with MR pancreatography after secretin stimulation. Radiology 2000;215: Gubergrits N, Golubova O, Lukashevich G, Fomenko P. Elevated serum amylase in patients with chronic pancreatitis: acute attack or macroamylasemia? Pancreatology 2014;14: van Geenen EJ, Smits MM, Schreuder TC, van der Peet DL, Bloemena E, Mulder CJ. Smoking is related to pancreatic fibrosis in humans. Am J Gastroenterol 2011;106: ; quiz Antonini F, Belfiori V, Pagano N, et al. Endoscopic ultrasonography may select subjects having asymptomatic chronic pancreatic hyperenzyme

11 mia who require a more strict follow-up. Pancreas 2017;46: Pezzilli R, Calculli L. Branch-type intraductal papillary mucinous neoplasm of the pancreas: clinically and patient-reported outcomes. Pancreas 2015;44: Stark A, Donahue TR, Reber HA, Hines OJ. Pancreatic cyst disease: a review. JAMA 2016;315: Roch AM, Parikh JA, Al-Haddad MA, et al. Abnormal serum pancreatic enzymes, but not pancreatitis, are associated with an increased risk of malignancy in patients with intraductal papillary mucinous neoplasms. Surgery 2014;156: Pezzilli R, Melzi d'eril G, Barassi A. Can serum pancreatic amylase and lipase levels be used as diagnostic markers to distinguish between patients with mucinous cystic lesions of the pancreas, chronic pancreatitis, and pancreatic ductal adenocarcinoma? Pancreas 2016;45: Liao Z, Gao R, Wang W, et al. A systematic review on endoscopic detection rate, endotherapy, and surgery for pancreas divisum. Endoscopy 2009;41: Kim HJ, Kim MH, Lee SK, et al. Normal structure, variations, and anomalies of the pancreaticobiliary ducts of Koreans: a nationwide cooperative prospective study. Gastrointest Endosc 2002;55: Kin T, Shapiro AM, Lakey JR. Pancreas divisum: a study of the cadaveric donor pancreas for islet isolation. Pancreas 2005;30: Gullo L, Lucrezio L, Calculli L, et al. Magnetic resonance cholangiopancreatography in asymptomatic pancreatic hyperenzymemia. Pancreas 2009;38: Levy MJ, Geenen JE. Idiopathic acute recurrent pancreatitis. Am J Gastroenterol 2001;96: Small AJ, Kozarek RA. Sphincter of oddi dysfunction. Gastrointest Endosc Clin N Am 2015;25: Glaser J, Stienecker K. Pancreas and aging: a study using ultrasonography. Gerontology 2000;46: Edge MD, Hoteit M, Patel AP, Wang X, Baumgarten DA, Cai Q. Clinical significance of main pancreatic duct dilation on computed tomography: single and double duct dilation. World J Gastroenterol 2007;13: Tanaka S, Nakao M, Ioka T, et al. Slight dilatation of the main pancreatic duct and presence of pancreatic cysts as predictive signs of pancreatic cancer: a prospective study. Radiology 2010;254:

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract