의학석사학위논문 Long-term Outcomes of Symptomatic Gallbladder Sludge 유증상담낭담즙앙금의장기간 추적임상결과 2015 년 2 월 서울대학교대학원 임상의과학과 이윤석

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1 저작자표시 - 비영리 - 변경금지 2.0 대한민국 이용자는아래의조건을따르는경우에한하여자유롭게 이저작물을복제, 배포, 전송, 전시, 공연및방송할수있습니다. 다음과같은조건을따라야합니다 : 저작자표시. 귀하는원저작자를표시하여야합니다. 비영리. 귀하는이저작물을영리목적으로이용할수없습니다. 변경금지. 귀하는이저작물을개작, 변형또는가공할수없습니다. 귀하는, 이저작물의재이용이나배포의경우, 이저작물에적용된이용허락조건을명확하게나타내어야합니다. 저작권자로부터별도의허가를받으면이러한조건들은적용되지않습니다. 저작권법에따른이용자의권리는위의내용에의하여영향을받지않습니다. 이것은이용허락규약 (Legal Code) 을이해하기쉽게요약한것입니다. Disclaimer

2 의학석사학위논문 Long-term Outcomes of Symptomatic Gallbladder Sludge 유증상담낭담즙앙금의장기간 추적임상결과 2015 년 2 월 서울대학교대학원 임상의과학과 이윤석

3 A thesis of the Degree of Master of Science 유증상담낭담즙앙금의장기간 추적임상결과 Long-term Outcomes of Symptomatic Gallbladder Sludge February 2015 The Department of Clinical Medical Sciences, Seoul National University College of Medicine Yoon Suk Lee

4 Long-term Outcomes of Symptomatic Gallbladder Sludge 지도교수황진혁 이논문을의학석사학위논문으로제출함 2014 년 10 월 서울대학교대학원 임상의과학과임상의과학전공 이윤석 이윤석의의학석사학위논문을인준함 2014 년 12 월 위원장 ( 인 ) 부위원장 ( 인 ) 위 원 ( 인 )

5 Long-term Outcomes of Symptomatic Gallbladder Sludge by Yoon Suk Lee A thesis submitted to the Department of Clinical Medical Sciences in partial fulfillment of the requirements for the Degree of Master of Science in Clinical Medical Sciences at Seoul National University College of Medicine December 2014 Approved by Thesis Committee: Professor Professor Chairman Vice chairman Professor

6 학위논문원문제공서비스에대한동의서 본인의학위논문에대하여서울대학교가아래와같이학위논문 제공하는것에동의합니다. 1. 동의사항 1 본인의논문을보존이나인터넷등을통한온라인서비스목적으로복제할경우저작물의내용을변경하지않는범위내에서의복제를허용합니다. 2 본인의논문을디지털화하여인터넷등정보통신망을통한논문의일부또는전부의복제 배포및전송시무료로제공하는것에동의합니다. 2. 개인 ( 저작자 ) 의의무본논문의저작권을타인에게양도하거나또는출판을허락하는등동의내용을변경하고자할때는소속대학 ( 원 ) 에공개의유보또는해지를즉시통보하겠습니다. 3. 서울대학교의의무 1 서울대학교는본논문을외부에제공할경우저작권보호장치 (DRM) 를사용하여야합니다. 2 서울대학교는본논문에대한공개의유보나해지신청시즉시처리해야합니다. 논문제목 : Long-term Outcomes of Symptomatic Gallbladder Sludge 학위구분 : 석사 V 박사 학과 : 임상의과학과학번 : 연락처 : 저작자 : 이윤석 ( 인 ) 제출일 : 2014 년 12 월 30 일 서울대학교총장귀하

7 ABSTRACT Long-term Outcomes of Symptomatic Gallbladder Sludge Yoon Suk Lee Department of Clinical Medical Sciences The Graduate School Seoul National University Introduction: Long-term outcomes of symptomatic gallbladder (GB) sludge are not fully established. This study aimed to determine whether patients with symptomatic GB sludge could experience subsequent biliary events. Methods: This study investigated consecutive patients who presented with typical biliary pain and underwent abdominal ultrasonography from March 2003 to December A prospectively maintained database of these patients, excluding those with gallstones, was reviewed retrospectively. The development of biliary events such as acute cholecystitis, acute cholangitis, and acute pancreatitis was compared between both GB sludge and non-gb sludge cohorts. Results: In all, 58 and 70 patients were diagnosed with and without GB sludge, respectively. The 5-year cumulative biliary event rate was significantly higher in the GB sludge (33.9% vs. 15.8%, P = 0.021) and the HR of subsequent biliary events was (95% CI, ; P = 0.025) i

8 in patients with GB sludge. The 5-year cumulative rate of each biliary event was higher in the GB sludge cohort (15.6% vs. 5.3 in acute cholecystitis, 15.5% vs. 5.3% in acute cholangitis, 18.4% vs. 11.1% in acute pancreatitis, respectively), although it was not statistically significant. Among the GB sludge cohort, subsequent biliary events were less frequent in patients who underwent cholecystectomy compared to those who did not (2/16, 12.5% vs. 17/42, 40.4%; P = 0.067). Conclusions: GB sludge accompanying typical biliary pain can cause subsequent biliary events and cholecystectomy may prevent subsequent biliary events. Therefore, GB sludge would be considered as a culprit of biliary events. *This work is published in Journal of Clinical Gastroenterology (reference format) Keywords: gallbladder sludge, gallstone, biliary event, cholecystectomy Student number: ii

9 CONTENTS Abstract... i Contents... iii List of tables and figures... iv Introduction... 1 Material and Methods... 2 Results... 5 Discussion References Abstract in Korean iii

10 LIST OF TABLES AND FIGURES Tables Table 1 Baseline characteristics of the patients between GB sludge and non-gb sludge cohort... 5 Table 2 Factors associated with biliary events... 8 Table 3 Biliary events in patients with GB sludge according to cholecystectomy for recurrent pain... 9 Figures Figure 1 Patient disposition and the overall outcomes in the two cohorts. CBD indicates common bile duct; EST, endoscopic sphincterotomy; GB, gallbladder Figure 2 (A) Cumulative rate of biliary events, (B) Cumulative rate of acute cholecystitis, (C) Cumulative rate of acute cholangitis, (D) Cumulative rate of acute pancreatitis between GB sludge and non-gb sludge cohort iv

11 INTRODUCTION Gallbladder (GB) sludge is defined as a suspension of cholesterol monohydrate crystals or calcium bilirubinate granules mixed with mucin and proteins. 1 GB sludge was first detected in the 1970s with the advent of ultrasonography (US). Thereafter, it has been more frequently identified as US resolution has improved, and routine check-ups that now regularly include abdominal US. GB sludge shares somewhat with gallstone in specific clinical situations, such as pregnancy, rapid weight loss, total parenteral nutrition, octreotide treatment, bone marrow transplantation, and ceftriaxone treatment. 2-7 However, the clinical significance of GB sludge has not been fully established, although a few reports suggest that it may be associated with acalculous cholecystitis, 8 acute cholangitis, 9 and biliary pancreatitis. 10,11 Furthermore, the clinical outcomes of GB sludge accompanying biliary pain remain elusive. Therefore, the aim of this study was to evaluate whether patients with symptomatic GB sludge could experience subsequent biliary events, such as acute cholecystitis, acute cholangitis, or acute pancreatitis. 1

12 MATERIALS AND METHODS 1. Patients Among the patients who visited the outpatient department of prof. Jin-Hyeok Hwang at Seoul National University Bundang Hospital from March 2003 to December 2012, those who presented with typical biliary pain and taken abdominal US were investigated retrospectively. According to the results of abdominal US, the patients were categorized into two separate cohorts (a GB sludge and a non-gb sludge cohort). The presumed diagnosis of those without GB sludge was functional gallbladder disorder based on the Rome III criteria. Exclusion criteria included: (1) GB stones or polyps; (2) common bile duct stones; (3) pregnancy; (4) malignancies; (5) patients with suspected causes of abdominal pain besides GB sludge; and (6) patients who had undergone a previous cholecystectomy or endoscopic sphincterotomy. If both sludge and stones were detected, the patient was excluded from the study (Fig.1). The medical records of eligible patients were then reviewed for development of any biliary events, such as acute cholecystitis, acute cholangitis, and acute pancreatitis. Subsequent biliary events after cholecystectomy were also evaluated in patients with GB sludge. Standardised telephone interviews were performed if the follow-up duration did not reach 12 months at the time of index study period. This study was approved by the human subjects committee of the Seoul National University Bundang Hospital, and it followed the ethical guidelines of the 1975 Declaration of Helsinki. 2

13 Figure 1. Patient disposition and the overall outcomes in the two cohorts CBD indicates common bile duct; EST, endoscopic sphincterotomy; GB, gallbladder. 2. Definition of gallbladder sludge and biliary events GB sludge was defined on US as the presence of low-level echoes that shift with position changes and had no post-acoustic shadowing. 12 Patients with hyperechoic foci without associated acoustic shadowing were also defined as having GB sludge for the purposes of this study. All the abdominal US were performed by radiologists who specialize in performing gallbladder US with a standard imaging protocol, using a 3.5- to 7.0-MHz rotatory sector scanning transducer. Typical biliary pain was defined when all the following were noted: (i) severe, 3

14 steady pain located in the epigastrium or the right upper quadrant; (ii) episodes lasting 30; and (iii) symptoms occurring on one or more occasions in the previous 12 months. 13,14 A biliary event was defined as the occurrence of one of the following: acute cholecystitis, acute cholangitis, or acute pancreatitis. Acute cholecystitis and acute cholangitis was diagnosed according to the revised Tokyo guidelines. 15,16 Acute pancreatitis was diagnosed according to the revised Atlanta classification Statistical analyses The baseline characteristics were compared by using an independent t-test or Mann-Whitney U test for the continuous variables, and Chi-square test or Fisher s exact test was used for the categorical variables. After that, the cumulative rate from each type of biliary events was calculated during followup by using Kaplan-Meier analysis, and the rates were compared by using a log-rank test. All potential prognostic factors with a probability value <0.05 on univariate analyses were entered into the multivariable Cox regression models, by which the hazard ratio (HR) and 95% confidence interval (CI) were calculated. A two-sided P-value < 0.05 was considered statistically significant in all of the analyses. All the statistical analyses were performed with SPSS software (version 20.0 for Windows). 4

15 RESULTS 1. Baseline clinical characteristics The characteristics of the patients in the GB sludge and non-gb sludge cohorts are summarized in Table 1. The following characteristics were observed for GB sludge vs. non-gb sludge cohorts: age (54.6 vs. 44.9, P < 0.001); male sex (44.8% vs. 24.3%, P = 0.014); body mass index (BMI) (23.6 vs. 22.9, P = 0.374); prevalence of diabetes (15.5% vs. 5.7%, P = 0.068); prevalence of hypertension (31.0% vs. 11.6%, P = 0.007); current smoking status (8.6% vs. 11.6%, P = 0.582); and alcohol use (20.7% vs. 15.9%, P = 0.489). Characteristics GB sludge (n = 58) non-gb sludge (n = 70) p Value Age, yr mean (SD) 54.6 (14.4) 44.9 (14.1) Sex, male - no. (%) 26 (44.8) 17 (24.3) BMI, kg/m 2 - mean (SD) 23.6 (3.0) 22.9 (2.7) Diabetes mellitus no. (%) 9 (15.5) 4 (5.7) Hypertension no. (%) 18 (31.0) 8 (11.6) Current smoker no. (%) 5 (8.6) 8 (11.6) Alcohol user no. (%) 12 (20.7) 11 (15.9) SD, standard deviation; BMI, body mass index. Obesity was defined as BMI >25 5

16 Table 1 Baseline characteristics of the patients between GB sludge and non-gb sludge cohort 2. Cumulative biliary event rates between GB sludge and non-gb sludge cohort. The 58 patients with GB sludge were followed up for a mean of 35.4 months and 70 patients with no GB sludge for a mean of 31.5 months. During the follow-up, biliary events occurred in 19 patients (32.7%) in the GB sludge cohort and 8 patients (11.4%) in the non-gb sludge cohort. The 2-year and 5- year cumulative rates of biliary events were 30.7% and 33.9% in the GB sludge cohort and 12.9% and 15.8% in the non-gb sludge cohort, respectively (P = 0.021) (Fig. 2A). Acute cholecystitis, acute cholangitis, and acute pancreatitis occurred in 6 (10.3%), 6 (10.3%), and 10 (17.2%) patients in the GB sludge cohort and 2 (2.8%), 2 (2.8%), and 6 (8.5%) patients in the non- GB sludge cohort, respectively, during the follow-up. The 2- and 5-year cumulative rates of acute cholecystitis, acute cholangitis, and acute pancreatitis were 10.7% and 15.6%, 11.5% and 15.5%, and 18.4% and 18.4%, respectively in the GB sludge cohort and 2.0% and 5.3%, 2.0% and 5.3%, and 11.1% and 11.1%, respectively in the non-gb sludge cohort (Fig. 2C, B, D). 6

17 Figure 2. (A) Cumulative rate of biliary events, (B) Cumulative rate of acute cholecystitis, (C) Cumulative rate of acute cholangitis, (D) Cumulative rate of acute pancreatitis between GB sludge and non-gb sludge cohort. 3. Cox regression analysis for biliary events The Cox model showed that the hazard ratio (HR) for subsequent biliary events was (95% CI, ; P = 0.022) in patients >60 years old; (95% CI, ; P = 0.021) in female patients; (95% CI, ; P = 0.018) in current smokers; (95% CI, ; P = 7

18 0.003) in alcohol users; and (95% CI, ; P = 0.027) in patients with GB sludge. Adjusted for age, sex, current smoker status, and alcohol use, GB sludge and alcohol use were statistically significant factors with HR (95% CI, ; P = 0.035) and HR (95% CI, ; P = 0.003), respectively (Table 2). Crude Hazard Ratio *Adjusted Hazard Ratio Variable on Univariate p Value on Multivariate Analysis p Value Analysis (95% CI) (95% CI) Age(>60yr) 2.415( ) ( ) Female 2.441( ) ( ) BMI 1.073( ) DM 1.732( ) HTN 1.713( ) Smoker 3.007( ) ( ) Alcohol user 3.190( ) ( ) GB sludge 2.546( ) ( ) *Adjusted for age, sex, current smoker, alcohol user, and GB sludge BMI indicates body mass index; CI, confidence interval; DM, diabetes mellitus; GB, gallbladder; HTN, hypertension. Table 2 Factors associated with biliary events 4. Biliary events in patients with GB sludge after cholecystectomy The patients in the GB sludge cohort were further evaluated for biliary events after cholecystectomy. Patients who underwent cholecystectomy experienced less biliary events than those who retained their gallbladders (2/16, 12.5% vs. 8

19 17/42, 40.4%, respectively), although it did not reach statistical significance (P = 0.067) (Table 3). Serial abdominal US examinations were performed in 13 of the 58 patients with GB sludge and 14 of the 70 patients without GB sludge. Among the patients with GB sludge, the sludge disappeared in 3 patients (23.1%) and persisted in 5 (38.5%) and gallstones developed in 5 patients (38.5%). Gallstones developed in 4 patients (28.5%) in the cohort without GB sludge. with without Factor cholecystectomy cholecystectomy p Value (n=16) (n=42) Biliary events 2 17* acute cholecystitis. 6 acute pancreatitis 2 8 acute cholangitis 0 6 *Three patients with acute cholangitis were accompanied with two of acute cholecystitis & one of biliary pancreatitis. Table 3 Biliary events in patients with GB sludge according to cholecystectomy for recurrent pain 9

20 DISCUSSION The natural course of GB sludge is diverse and remains unclear. Sometimes, GB sludge disappears spontaneously on removing the predisposing factors. Otherwise, gallstones develop in some patients during follow-up. 8,10 However, the clinical outcome of GB sludge accompanying typical biliary pain has never been reported. This study showed that biliary events occurred more frequently in symptomatic patients with GB sludge, compared to patients without GB sludge and cholecystectomy in symptomatic GB sludge patients reduced subsequent biliary events. Therefore, it is suggested that GB sludge is an independent risk factor for subsequent biliary events in patients with typical biliary pain. To the best of my knowledge, this is the first study to demonstrate that GB sludge is an important risk factor for subsequent biliary events in patients with typical biliary pain. The 6% annual rate of biliary events in the GB sludge cohort might seem a little higher than expected. This may be explained by the fact that almost half of biliary events were acute pancreatitis, which is usually caused by small stones or sludge migrating to the distal common bile duct. 11,18,19 Moreover, considering gallstones were observed in about 38% in GB sludge cohort using serial US examination, GB sludge may physiologically function as small gallstones, which can cause acute pancreatitis. In patients without GB sludge, the 5-year cumulative rate of biliary events was 15.8% in our study. Patients with microlithiasis may have been included in the study because abdominal US has a low sensitivity for microlithiasis or 10

21 sludge, especially stones of < 3 mm diameter or stones located in the GB infundibulum. 11,20,21 Furthermore, even in cases of normal abdominal US finding, GB sludge can be detected through microscopic examination of the duodenal bile. 21 Therefore, in this study, both undetected microlithiasis and sludge might have considerable effect on the development of biliary events. Abdominal US is the gold standard for the diagnosis of cholecystolithiasis with sensitivity ranging between 92% and 96%. 22 However, it is unlikely to detect biliary events when stones are located in the infundibulum or if stones <3-mm diameter or GB sludge are present. 23 Besides, there are some obstacles to getting clear US images, such as obesity or intestinal loops and gas interposition. Recent studies have shown that the sensitivity of endoscopic US for GB sludge is up to 96%. 21 Therefore, if classical biliary pain without abnormal gallbladder is found on abdominal US, further investigations such as endoscopic US should be considered to identify the culprit because even in patients without GB sludge, subsequent biliary events were as high as 15.8% and 28.5% of the patients eventually developed gallstones on serial abdominal US. Although cholecystectomy is the treatment of choice in patients with symptomatic gallstones, the role of cholecystectomy for GB sludge has not been well evaluated. Lee et al. emphasized that GB sludge should be treated as gallstones when it is accompanied by biliary pain or recurrent attacks of acute pancreatitis. 11,24 However, there are few reports supporting cholecystectomy having a prophylactic role for subsequent biliary events in symptomatic GB sludge. Cholecystectomy in symptomatic GB sludge patients 11

22 reduced subsequent biliary events in our data. Moreover, gallstones were observed in one third of patients with symptomatic GB sludge during the follow-up. Therefore, it is suggested that cholecystectomy is a definite treatment in symptomatic GB sludge patients and early cholecystectomy within 2 years after detection of GB sludge is preferable because fewer biliary events developed later than the first 2 years. This data had certain limitations. First, this was a retrospective study, whereas the data was collected prospectively. Second, the diagnosis of GB sludge was made exclusively on abdominal US, which has a low sensitivity for detecting GB sludge and microlithiasis, so false negatives may have occurred in the non-gb sludge cohort. Finally, functional gallbladder and sphincter of Oddi disorders were not evaluated, which may be accompanied by features of biliary complications. 25 Since the prevalence of functional gallbladder disorder among patients with biliary type pain and a normal abdominal US occurs up to 8% in men and 21% in women, 26,27 it might be a confounder. In spite of the limitations, this study provides evidence that GB sludge with typical biliary pain can cause subsequent biliary events frequently, and cholecystectomy may prevent subsequent biliary events. 12

23 REFERENCES 1. Jungst C, Kullak-Ublick GA, Jungst D. Gallstone disease: Micro lithiasis and sludge. Best Pract Res Clin Gastroenterol. 2006;20: Maringhini A, Ciambra M, Baccelliere P, et al. Biliary sludge a nd gallstones in pregnancy: incidence, risk factors, and natural h istory. Ann Intern Med. 1993;119: Messing B, Bories C, Kunstlinger F, et al. Does total parenteral nutrition induce gallbladder sludge formation and lithiasis? Gast roenterology. 1983;84: Shiffman ML, Sugerman HJ, Kellum JM, et al. Gallstone format ion after rapid weight loss: a prospective study in patients under going gastric bypass surgery for treatment of morbid obesity. A m J Gastroenterol. 1991;86: Park HZ, Lee SP, Schy AL. Ceftriaxone-associated gallbladder sl udge. Identification of calcium-ceftriaxone salt as a major compo nent of gallbladder precipitate. Gastroenterology. 1991;100: Bolondi L, Gaiani S, Testa S, et al. Gall bladder sludge formati on during prolonged fasting after gastrointestinal tract surgery. G ut. 1985;26: Pazzi P, Gamberini S, Buldrini P, et al. Biliary sludge: the slug gish gallbladder. Digestive and Liver Disease. 2003;35:

24 8. Janowitz P, Kratzer W, Zemmler T, et al. Gallbladder sludge: sp ontaneous course and incidence of complications in patients with out stones. Hepatology. 1994;20: Grier JF, Cohen SW, Grafton WD, et al. Acute suppurative chol angitis associated with choledochal sludge. Am J Gastroenterol. 1994;89: Lee SP, Maher K, Nicholls JF. Origin and fate of biliary sludge. Gastroenterology. 1988;94: Lee SP, Nicholls JF, Park HZ. Biliary sludge as a cause of acut e pancreatitis. N Engl J Med. 1992;326: Ko CW, Beresford SA, Schulte SJ, et al. Incidence, natural hist ory, and risk factors for biliary sludge and stones during pregna ncy. Hepatology. 2005;41: Shaffer E. Acalculous biliary pain: new concepts for an old enti ty. Dig Liver Dis. 2003;35 Suppl 3:S Tomida S, Abei M, Yamaguchi T, et al. Long-term ursodeoxych olic acid therapy is associated with reduced risk of biliary pain and acute cholecystitis in patients with gallbladder stones: a coh ort analysis. Hepatology. 1999;30: Kiriyama S, Takada T, Strasberg SM, et al. New diagnostic crite ria and severity assessment of acute cholangitis in revised Tokyo Guidelines. J Hepatobiliary Pancreat Sci. 2012;19: Yokoe M, Takada T, Strasberg SM, et al. New diagnostic criteri a and severity assessment of acute cholecystitis in revised Tokyo 14

25 guidelines. J Hepatobiliary Pancreat Sci. 2012;19: Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis 2012: revision of the Atlanta classification and def initions by international consensus. Gut. 2013;62: Venneman NG, Renooij W, Rehfeld JF, et al. Small gallstones, p reserved gallbladder motility, and fast crystallization are associate d with pancreatitis. Hepatology. 2005;41: Venneman NG, Buskens E, Besselink MG, et al. Small gallstone s are associated with increased risk of acute pancreatitis: potenti al benefits of prophylactic cholecystectomy? Am J Gastroenterol. 2005;100: Kurol M, Forsberg L. Ultrasonography in the diagnosis of acute cholecystitis. Acta Radiol Diagn (Stockh). 1984;25: Dahan P, Andant C, Levy P, et al. Prospective evaluation of en doscopic ultrasonography and microscopic examination of duoden al bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography. Gut. 1996;38: Lee CL, Wu CH, Chen TK, et al. Prospective study of abdomin al ultrasonography before laparoscopic cholecystectomy. J Clin G astroenterol. 1993;16: Thorboll J, Vilmann P, Jacobsen B, et al. Endoscopic ultrasonog raphy in detection of cholelithiasis in patients with biliary pain and negative transabdominal ultrasonography. Scand J Gastroente rol. 2004;39:

26 24. Ko CW, Sekijima JH, Lee SP. Biliary sludge. Ann Intern Med. 1999;130: Behar J, Corazziari E, Guelrud M, et al. Functional gallbladder and sphincter of oddi disorders. Gastroenterology. 2006;130: Barbara L, Sama C, Morselli Labate AM, et al. A population st udy on the prevalence of gallstone disease: the Sirmione Study. Hepatology. 1987;7: The epidemiology of gallstone disease in Rome, Italy. Part I. Pr evalence data in men. The Rome Group for Epidemiology and Prevention of Cholelithiasis (GREPCO). Hepatology. 1988;8:

27 국문초록 서론 : 담성통증 (biliary pain) 을동반한담낭담즙앙급 (gallbladder sludge) 에대해서장기간관찰한임상연구는거의없는실정이다. 본연구는 유증상담낭담즙앙금이담도질환을야기하는지알아보고자하였다. 방법 : 이연구는 2003 년 3 월부터 2012 년 12 월까지담성통증을주소로내원하여복부초음파검사를시행한일련의환자를대상으로하였다. 담석이발견된경우는제외하였고, 전향적으로수집되는자료를연구시점에서후향적으로분석하였다. 담도질환은급성담낭염, 급성담관염그리고급성췌장염으로정의하였고, 이러한담도질환의발생률을 담낭담즙앙금 (GB sludge) 군 과 비담낭담즙앙금 (non-gb sludge) 군 으로나누어서비교하였다. 결과 : 담낭담즙앙금군 에 58 명, 비담낭담즙앙금군 에 70 명이확인되었다. 5 년누적담도질환발생률은 담낭담즙앙금군 에서유의하게높았고 (33.9% vs. 15.8%, P = 0.021), 담도질환발생에대한 HR 는 (95% CI, ; P = 0.025) 로확인되었다. 담도질환을 3 개의세부질환으로나누어서비교를하였을때도 담낭담즙앙금군 에서 5 년누적발생률이더높은경향성이확인되었다 ( 급성담낭염, 15.6% vs. 5.3; 급성담관염, 15.5% vs. 5.3%; 급성 17

28 췌장염, 8.4% vs. 11.1%). 비록통계적으로유의하지는않았지만, 담낭담즙앙금군 에서담낭절제술을시행하였을때담도질환의발생이적게발생하는경향이확인되었다 (2/16, 12.5% vs. 17/42, 40.4%; P = 0.067). 결론 : 담성통증이동반된담낭담즙앙금은추후담도질환의발생을야기할수있으며, 그것의예방을위해서담낭절제술이도움이될수있을것으로생각된다. 따라서, 담낭담즙앙금이담도질환의유발인자임을고려해야하겠다 주요어 : 담낭담즙앙금, 담석, 담도질환, 담낭절제술학번 :

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