Effects of age and cholecystectomy on common bile duct diameter as measured by endoscopic ultrasonography

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1 Surg Endosc (2013) 27: DOI /s and Other Interventional Techniques Effects of age and cholecystectomy on common bile duct diameter as measured by endoscopic ultrasonography Fabiana Benjaminov George Leichtman Timna Naftali Elizabeth E. Half Fred M. Konikoff Received: 28 January 2012 / Accepted: 7 June 2012 / Published online: 18 August 2012 Ó Springer Science+Business Media, LLC 2012 Abstract Background and aim Increased common bile duct (CBD) diameter has been attributed to aging and previous cholecystectomy. These relationships are, however, controversial and based mainly on old studies and methodologies. Our objective is to evaluate the relationship between age, cholecystectomy, and other clinical factors and CBD diameter, as measured by endoscopic ultrasound (EUS). Methods We carried out a retrospective cohort study including patients who underwent EUS in our institution. Patients with an obstructing lesion of the bile ducts, previous sphincter manipulation, or insufficient data were excluded. CBD diameter was measured as a routine part of the examination, in the most distal extrapancreatic portion, between its two exterior margins. The patients were divided into five age groups. The mean CBD diameter in each group was calculated and compared with the other groups. Effects of cholecystectomy, gender, time from operation, and elevated liver enzymes were also evaluated. Results Six hundred forty-seven patients were included in the study (66 % women). Twenty-three percent were postcholecystectomy. There was no difference between the first three groups regarding CBD diameter, but it was significantly wider in groups 4 and 5 (p \ 0.001). In all age groups, the postcholecystectomy patients had significantly F. Benjaminov (&) G. Leichtman T. Naftali E. E. Half F. M. Konikoff Department of Gastroenterology and Hepatology, Meir Medical Center, Kfar-Saba and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel wider CBD than those with an intact gallbladder (in all groups, p \ 0.01). Conclusions This EUS study confirms that the CBD dilates significantly after the age of 70 years, but even in the most elderly patients, with an intact gallbladder, the normal CBD does not exceed 7.6 mm, thus a wider CBD warrants further investigation. The single additional factor contributing to dilatation of the CBD was cholecystectomy. A linear regression equation is proposed for the prediction of CBD diameter. Keywords Common bile duct (CBD) Diameter Endoscopic ultrasound (EUS) Cholecystectomy Age The diameter of the common bile duct (CBD) is subject to change due to a variety of factors. Obstructing lesions, such as tumors of the bile ducts or pancreas, choledocholithiasis, previous surgery, or periampullary diverticulum may all increase the CBD diameter [1 3]. Age and gallbladder resection have also been suggested to cause dilatation of the CBD. More than 30 years ago, Wu et al. [4] reported that the CBD diameter increases by 1 mm every decade. Later, other studies supported this observation [5, 6]. However, more recently, controversial results were reported [7, 8]. Controversies exist especially regarding CBD diameter postcholecystectomy [9 13]. All the above studies were performed by transabdominal ultrasonography, computed tomography, or based on observational data from animal surgery and post mortem autopsies. In the last few years, endoscopic ultrasound (EUS) has established itself as a most sensitive and accurate tool for assessing the common bile duct [14, 15]. The aim of our study is to determine the effects of age, cholecystectomy, and other clinical factors on CBD diameter measured by EUS.

2 304 Surg Endosc (2013) 27: Table 1 Distribution and characteristics of the five age groups Group Age (years) Number (total 647) Men/women (%) Postcholecystectomy / (17.8 %) 33.3/ / (18.4 %) 21.4/ / (22.4 %) 29.4/ /66 46 (30.3 %) 17.4/ \ / (11.2 %) 17.6/82.4 Postcholecystectomy, men/women (%) Patients and methods All patients who underwent EUS in our institution between January 2001 and December 2009 were included. The EUS examinations were performed by two dedicated endoscopists using a Pentax linear echoendoscope (FG 36-UX or EG-3830UT). Exclusion criteria were findings known to cause bile duct obstruction, such as hepatopancreatic tumor, pancreatic cyst (including pseudocyst), choledocholithiasis, periampullary diverticulum, and history of CBD exploration (by surgery or endoscopy). Patients with insufficient data on their EUS report were also excluded from the study. The diameter of the CBD was measured as a routine part of the examination, at the most distal extrapancreatic portion of the duct. The diameter was measured between the two exterior margins of the CBD. The patients were divided into five age groups (group 1: \49 years; group 2: years; group 3: years; group 4: years; group 5: [80 years). Sex, indication for the study, gallbladder status, presence of elevated liver enzymes, and the result of the study were documented. The mean CBD diameter of each group was calculated and compared with the other groups. The influences of cholecystectomy, gender, and liver function tests (LFTs) on CBD diameter were also assessed. Statistical analysis Nominal data were described as frequencies and percentage. Continuous parameters were described as mean ± standard deviation. Differences between two groups were analyzed by Chi-square or t test, each as appropriate to the type of data. Differences among age groups were analyzed by one-way analysis of variance (ANOVA) and Bonferroni post hoc comparisons. Multivariant linear regression analysis was done to predict CBD dilatation. A p value of less than 0.05 was considered significant. Statistical analysis was carried out using SPSS-19 software. Results Six hundred forty-seven patients were included in the study, 427 (66 %) women and 220 (34 %) men. Mean age was 60.8 ± 17.2 years (range years). In total, 152 (23.6 %) were postcholecystectomy. Table 1 describes the number of patients, age, gender, and gallbladder status in each age group. The indication for the EUS examination was abdominal pain in 218 patients (33.9 %), s/p pancreatitis in 118 (18.3 %), elevated liver function tests in 108 (16.8 %), and abnormal findings on other diagnostic imaging in 88 patients (13.7 %). Other indications were s/p cholecystitis (10.6 %), s/p cholangitis (2.2 %), weight loss (1.1 %), elevated CA19-9 (0.6 %), and jaundice (2.8 %). Three hundred eleven patients (48.1 %) had a normal study, 309 (47.8 %) had cholelithiasis, and 25 (3.9 %) had a dilated CBD with no obstructive findings. Mean CBD diameter in groups 1 5 in patients with an intact gallbladder was 4.4 ± 1.2, 4.9 ± 1.4, 5.4 ± 1.6, 5.7 ± 1.7, and 6 ± 1.6 mm, respectively. There was no difference in CBD diameter between the first three groups, but it was significantly wider in groups 4 and 5 (p \ 0.001). In all age groups the postcholecystectomy patients had a significantly wider CBD than those with an intact gallbladder (group 1: 5.1 vs. 4.4 mm; group 2: 5.8 vs. 4.9 mm; group 3: 6.6 vs. 5.4 mm; group 4: 6.6 vs. 5.7 mm; group 5: 9.6 vs. 6 mm; p = 0.006, 0.008, 0.001, 0.006, \0.001, respectively) (Table 2). Although the CBD diameter increased linearly with time from cholecystectomy, it only reached a significant statistical difference between the group that was recently resected (up to 1 year) and the group in which the gallbladder was resected in the distant past (more than 15 years ago), being 6.2 ± 2.3 and 7.5 ± 2.3 mm, respectively (p \ 0.05). No significant age difference was noted Table 2 Mean CBD in the five age groups depending on gallbladder (GB) status Group Mean ± SD CBD diameter, intact GB (mm) 1 (18 49 years) 4.4 ± 1.2* 5.1 ± 1.8 # 2 (50 59 years) 4.9 ± 1.6* 5.8 ± 1.5 # 3 (60 69 years) 5.4 ± 1.6* 6.6 ± 2 # 4 (70 79 years) 5.7 ± 1.7* 6.6 ± 1.7 # 5([80 years) 6 ± 1.6* 9.6 ± 0.7 # * p \ between groups 1, 2, 3 and 4, 5 Mean ± SD CBD diameter, postcholecystectomy (mm) # p \ 0.05 between the same age group with/without GB

3 Surg Endosc (2013) 27: Table 3 CBD diameter depending on time from cholecystectomy Group Number Mean ± SD age (years) between these two groups (59.9 ± 16.5 vs ± 9.6 years, p [ 0.05) (Table 3). There was no difference in the CBD diameter between men and women with an intact gallbladder, but after cholecystectomy, women had a wider CBD than men (p \ 0.02) (Table 4). Fifty-eight percent of patients with elevated LFTs with an intact gallbladder had cholelithiasis, in comparison with only 30 % of patients with normal LFTs (p \ 0.001). Linear regression analysis demonstrated that age older than 70 years and cholecystectomy predicted CBD dilatation. Gender and the time past from cholecystectomy were found to be significant on univariant analysis, but not on multivariant analysis. Subanalysis of our cohort in respect to the relationship between LFTs and CBD diameter demonstrated that the group with normal LFTs (249 patients) had a wider CBD than patients with elevated LFTs. Parameters were entered into a linear regression equation for predicting the CBD diameter (Fig. 1). Discussion Mean ± SD CBD diameter (mm) Up to 1 year ± 16.5 # 6.2 ± 2.3* Up to 5 years ± ± 2.2 Up to 10 years ± ± 2.2 Up to 15 years ± 4.8 # 6.9 ± 2.1 More than 15 years ± ± 2.3* * p \ 0.05 between groups 1 and 5 # p \ 0.05 between groups 1 and 4 Table 4 Effect of gender on CBD diameter with/without gallbladder (GB) N Female, CBD diameter (mm ± SD) The upper limit of normal for CBD diameter is, traditionally, considered to be 6 mm [16, 17]. This conclusion was adapted from three studies conducted in the late 1970s [18 20]. A later study, by Niedrau et al. [21], confirmed this observation. As mentioned before, many factors can influence the diameter of the CBD. N Male, CBD diameter (mm ± SD) GB? ± ± 1.6 GB ± 2.3* ± 1.9* * p \ 0.02 CBD (mm) = (1.08*age)-1.08*gallbladder- 0.85*LFT's+0.24*gender. Age<70y=0, age>70y=1 Post cholecystectomy=0, gallbladder in situ=1, LFT's normal=0, LFT's elevated=1 Female=0, male=1. Fig. 1 Linear regression equation for predicting CBD diameter. In the present study we have demonstrated that the CBD dilates significantly after the age of 70 years. However, even in the most elderly patients, with a gallbladder in situ, the normal CBD diameter does not exceed 7.6 mm. Cholecystectomy is also associated with CBD dilatation. In 1984, Wu et al. [4] and Kaude et al. [22] found an increase in CBD diameter with age. The patient cohort in these studies consisted of a large number of patients in the pediatric age group and only a small number of patients over age 70 years. As is well known, the CBD diameter is narrower in children than in adults [23], demanding cautious interpretation of their results. More recently, studies including a sufficient number of elderly patients showed conflicting data. While Horrow et al. [7] did not find a significant dilatation of the CBD with age, other studies [6, 8, 24] did (although not exceeding 8.5 mm). Chawala et al. [13] further demonstrated that the dilatation of the CBD begins after the age of 65 years. These studies support our own findings that CBD dilatation is influenced by age, begins at an older age (more than 70 years) and is limited (in our own study to 7.6 mm). The widening of the CBD with age may be explained by loss of elastic fibers or from proximal compensatory dilatation due to sclerosis in the distal CBD [25, 26]. In addition, drugs such as calcium channel blockers and nitroglycerin, often taken by elderly patients, may contribute to the loss of contractility and tonus of the ductal wall. Unfortunately, this information was not available in our study. Conflicting data have been reported, also, on the effect of cholecystectomy on CBD diameter. Old data [9, 10] from observational studies on animals and post mortem autopsies showed postcholecystectomy dilatation. Newer data [11, 27] do not support this observation. Feng et al. [27] studied a large cohort (234 patients) of postcholecystectomy patients and found no dilatation of the CBD up to mean follow-up of 360 days postsurgery (range 7 2, 160 days). Recently, several studies [12, 13], using diverse methodology, found increase in postcholecystectomy CBD diameter, but differed regarding the influence of age. The present study demonstrates a significant increase in CBD diameter in postcholecystectomy

4 306 Surg Endosc (2013) 27: Table 5 CBD diameter of patients with elevated/normal LFTs depending on their GB status in all age groups combined LFTs GB status N CBD diameter (mm ± SD) Elevated Intact ± 1.3* Normal Intact ± 2* Elevated Postcholecystectomy ± 2* Normal Postcholecystectomy ± 2.3* * p \ 0.01 retrospective nature, which prevented us from doing multiple measurements at several points along the CBD. Acknowledgments This study was presented in part as a distinguished poster during the Digestive Disease Week in Chicago May 10th, 2011 (Gastroenterology 2011; 140 (5): s-749). Disclosures Drs. Fabiana Benjaminov, George Leichtman, Timna Naftali, Elizabeth E. Half, and Fred M Konikoff have no conflicts of interest or financial ties to disclose. patients. The significant change was noted between patients with and without a gallbladder in the same age group, and also an increase in CBD diameter with age. In contrast to previous studies where the mean age of patients was low and/or mean follow-up was short (5 years), in our study the mean age was 60.8 ± 17.2 years (range years), with follow-up of more than 15 years after surgery [12, 13, 27]. This observation cannot be explained by an age difference, but may be attributed to the different method of cholecystectomy. Laparoscopic cholecystectomy was introduced, in our country, in the mid-1990s, so part of the group with distant cholecystectomy had the operation done openly. Our study included patients with normal and elevated LFTs. Patients with normal LFTs had a wider CBD than patients with elevated LFTs, regardless of their gallbladder status. We believe that the subgroup of patients with normal LFTs represents the patients with true/completely normal EUS and thus the true CBD diameter. Table 5 presents the CBD diameter in relation to the LFTs. We have no clear explanation for the larger CBD diameter in patients with normal LFTs; however, in both groups the CBD diameter was wider postcholecystectomy, substantiating this relationship. All previous studies were done with transabdominal ultrasound (TAUS) or computed tomography (CT). Many ultrasonographic studies were done 30 years ago when the quality of ultrasound images was significantly inferior to present standards [24]. Both CT and TAUS still remain inferior to EUS [14, 15]. Our study is the first one, to our knowledge, conducted with endoscopic ultrasonography, including a large number of patients with long follow-up. Our cohort included 647 patients aged between 18 and 98 years, with 169 being between ages 71 and 79 years and 83 patients C80 years old. Our study was able to show that there is an age-related dilatation of the CBD. However, even in elderly patients (over 80 years) with an intact gallbladder, CBD diameter more than 8 mm is probably pathological and warrants further investigation. Cholecystectomy is also associated with CBD dilatation. The main drawback of our study is its References 1. Reinus WR, Shady K, Lind M et al (1992) Ultrasound evaluation of the common bile duct in symptomatic and asymptomatic patients. Am J Gastroenterol 87: Campbell WL, foster RG, Miller WJ et al (1992) Changes in extrahepatic bile duct caliber in liver transplant recipients without evidence of biliary obstruction. AJR 158: Rajnakova A, goh PM, Ngoi SS, Lim SG (2003) ERCP in patients with periampullary diverticulum. Hepatogastroenterology 50: Wu CC, Ho YH, Chen CY (1984) Effect of aging on CBD diameter: a real-time ultrasonographic study. J Clin Ultrasound 12: Kaim A, Steinke K, Frank M et al (1998) Diameter of the common bile duct in elderly patients: measurements by ultrasound. 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5 Surg Endosc (2013) 27: Sample WF, Sarti DA, Goldstein LI et al (1978) Gray-scale ultrasonography of the jaundiced patient. Radiology 128: Cooperberg PL (1978) High-resolution real-time ultrasound in the evaluation of the normal and obstructed biliary tract. Radiology 128: Parulekar SG (1979) Ultrasound evaluation of the common bile duct size. Radiology 133: Niedrau C, Muller J, Sonnenberg A et al (1983) Extrahepatic bile ducts in healthy subjects, in patients with cholelithiasis, and in postcholecystectomy patients: a prospective ultrasonic study. J Clin Ultrasound 11: Kaude JV (1983) The width of the common bile duct in relation to age and stone disease: an ultrasonographic study. Eur J Radiol 3: Hernandez-Schulamn M, Ambrosino MM, Freeman PC, Quinn CB (1995) Common bile duct in children: sonographic dimensions. Radiology 195: Senturk S, Miroglu TC, Bilici A, et al. Diameters of the common bile duct in adults and postcholecystectomy patients: a study with 64-slice CT. Eur J Radiol. In press (accepted Nov 2010) 25. Takahashi Y, Takahashi T, Takahashi W et al (1985) Morphometric evaluation of the extra hepatic bile ducts in reference to their structural changes with aging. Tohoko J Exp Med 147: Nahada A (1981) Changes in morphology of the distal CBD associated with aging. Gastroenterology Jpn 16(1): Feng B, Song Q (1995) Does the common bile duct dilate after cholecystectomy? Sonographic evaluation in 234 patients. AJR 165:

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