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Objectives: To study the composition, morphology and clinical features of common bile duct (CBD) stones in elderly patients by endocopic retrograde cholangiopancreatography (ERCP). Subjects and methods: A cross-sectional study was conducted on 198 patients (106 patients over 60 years old) with CBD stones.
Journal of military pharmaco-medicine no7-2017 STUDY ON THE COMPOSITION, MORPHOLOGY AND CLINICAL FEATURES OF COMMON BILE DUCT STONES IN ELDERLY PATIENTS TREATED WITH ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY Duong Xuan Nhuong*; Dao Truong Giang* Nguyen Quang Duat*; Dang Viet Dung*; Mai Hong Bang** SUMMARY Objectives: To study the composition, morphology and clinical features of common bile duct (CBD) stones in elderly patients by endocopic retrograde cholangiopancreatography (ERCP) Subjects and methods: A cross-sectional study was conducted on 198 patients (106 patients over 60 years old) with CBD stones Results and conclusion: Patients over 60 years old had the lower rate of cholangitis than patients under 60 years old We assessed the chemical composition and morphologic characteristics of CBD stones in 60 patients: bilirubinate calcium in 100% of stones The chemical composition in CBD stones was the same between two groups (p > 0.05); pigment stones in 100% of elderly patients, 93.3% of patients under 60 years old There was no difference between two groups (p > 0.05) There were relationships between morphologic characteristics and recurrent rate of CBD stones, between pigment stones with time of ERCP and cholangitis * Keywords: Common bile duct stone; Endoscopic retrograde cholangiopancreatography; Elderly patients INTRODUCTION Bile duct disease, especially CBD stones are very common in gastroenterology, and often cause severe complications Studying the composition, morphology and clinical features of CBD stones in elderly patients not only helps to define the pathogenesis of CBD stones but also helps to chose the methods of treatment and prevent the recurrent of the diseases [1, 2, 6] In Vietnam, there are many studies about composition and morphology of the CBD stones taken by surgeons but we are still lack of study about this issue in elderly patients who were treated by ERCP Therefore, the objective of this study is: To study the composition, morphology and clinical features of CBD stones in elderly patients treated with endoscopic retrograde cholangiopancreatography SUBJECTS AND METHODS Subjects 198 patients treated from July, 2010 to April, 2014 in 103 Hospital, were divided into two groups: * 103 Military Hospital ** 108 Central Military Hospital Corresponding author: Dao Truong Giang (giangle@gmail.com) Date received: 25/07/2017 Date accepted: 30/08/2017 65 Journal of military pharmaco-medicine No7-2017 Fourier 8201 PC (Shimadzu, Japan) with 10 times of scan for each sample The gallstones were washed in saline solution, sliced in half, described, photographed, weighed, and sampled, assayed for bilirubin and cholesterol content Insoluble residue was determined by decanting the supematant and weighing the dried residue Water content was determined by heating pulverised stones to a constant weight at 60°C Gallstones were classified according to their visual appearance and chemical composition Visually, cholesterol stones were lightly colored (brown, tan, yellow or beige) with a radial, crystalline structure Pigment stones were dark brown, black, or eartby (like clay) and had a dull, laminated, or haphazard structure Stones with intermediate features were classified according to their dominant components - Group 1: elderly patients (equal or more than 60 years old) - Group 2: younger patients (less than 60 years old) All of the patients were diagnosed CBD stones by clinical and paraclinical data Methods A cross-sectional study * ERCP procedures: - Two endoscopists - Sedation: because of the longer duration and more potential discomfort fo the ERCP procedure, conscious sedation with intravenous propofol, which was shown to be safe when using in elderly patients, and requires hightly attention to dosing, with single dose of anti-spasmodic drug - Canulation of the bile duct, cholangiography, verifying the presence of choledocholithiasis, then we did sphinterotomy and stone extractions, monitoring in hospital for - days - Chemically, cholesterol stones were defined as containing more than 50% cholesterol by weight, and pigment stones were defined as containing less than 50% cholesterol by weight Unclassified stones had small amounts of the either Pigment stones were subdivided visually into earthy stones and tarry stones * Stone sample study: - The removal stones were sent to Department of Pharmacy, University of Hochiminh Medicine and Pharmacy, using RESULTS AND DISCUSSION Chemical composition of CBD stones Table 1: Characteristics of the bile and CBD stones in two groups Characteristics Group I (n = 106) n % Group II (n = 92) n % p Bile Yellow 54 50.9 33 35.9 0.033 Muddy 38 35.9 50 54.4 0.009 Pus 14 13.2 9.8 0.453 66 Journal of military pharmaco-medicine no7-2017 CBD stones Mud stone 12 11.3 11 11.9 0.949 Soft stone 23 21.7 10 10.9 0.041 Steady stone 38 35.8 50 54.4 0.0001 Hard stone 17 16.0 9.8 0.196 Mix stone 16 15.0 12 13.0 0.82 In group I, pyogenic bile (muddy and pus bile) was 52/106 patients (49.1%), lower than group II with 59/92 patients (64.2%) (p = 0.009); but there was no difference between the rate of pus bile (p = 0.453) Almost other authors agreed that CBD stone had close relation to cholangitits [1, 7] About the characteristics of CBD stone, the rate of mud stone and mix stone were the same in two groups (11.3% vs 11.9%; 15.0% vs 13.0%); group I had more cases with soft stone than group II (21.7% and 10.9%; p = 0.041); otherwise group II had more cases of hard stone than group (54.4% vs 35.8%, p = 0.0001) Phan Thu Phuong also had the same results in her study [3] The collection of gallstones at ERCP is difficult and unpredictable Some stones are fragile and may break when collecting in a dormia basket Therefore, there is a risk that sampling may be biased Table 2: Chemical composition of CBD stones Composition Group I (n = 30) Group II (n = 30) p n % n % Bil-ca 30 100.0 30 100.0 - Cholesterol 22 73.3 20.0 0.000 Protid 13.3 26.7 0.197 Calcite 0.0 3.33 - Bil-ca + chol 22 73.3 20.0 0.000 Bil-ca + protid 13.3 26.7 0.197 Bil-ca + calcite 0.0 3.33 - Bil-ca + protid + chol 3.3 0 - (*) ((*) Bil-ca: bilirubinate calcium, chol: cholesterol) Almost of stones had bil-ca component in two groups (100%); in group I: 73.3% of stones had chol and bil-ca + chol, compared with 20% in group II (p = 0.000) The other components (1 - 5%) were protid and calcite These findings were also the same with Do Kim Son et al, within 38 of 40 samples had bil-ca [1] Nguyen Trong Khin et al found that components of stone (bil + chol) was 76.7%, and there was no cholesterol component [4] 67 Journal of military pharmaco-medicine No7-2017 Table 3: Quantitative analysis of the composition of CBD stone Group I (n = 30) Group II (n = 30) X ± SD X ± SD Bilirubinat calcium 93 ± 2.5 87.8 ± 22.6 0.558 Cholesterol 5.6 ± 3.0 32.2 ± 44.9 0.977 Protid 2.6 ± 1.3 3.1 ± 0.9 0.424 Calcite - Rate (%) p With quantitative analysis of the composition of stone, we saw that bilirubinate calcium accounted for 93 ± 2.5% in group I and 87.8 ± 22.6% in group II; cholesterol accounted for 32.2 ± 44.9% in group II, compared with 5.6 ± 3.0% in group I, and there was no significant difference between two groups (p = 0.558 and p = 0.424, respectively) Pham Duy Hien also saw in his study that bilirubinat accounted for 54.7 ± 3.9%, but cholesterol accounted for only 18.8 ± 1.7% In the study by Sandstad O, cholesterol accounted for 29%, bilirubinate 56% [7] Table 4: Classifying CBD stone based on quantitative analysis of composition Group I (n = 30) Group II (n = 30) Classify p n % n % Pigment stone 30 100 28 93.3 0.15 Cholesterol stone 0 6.7 0.15 Mix stone 0 0 - When classifying stone, all stones in group I were pigment stones (100%), in group II, 93.3% was pigment stones and 6.7% was cholesterol stones (p = 0.15) Most of the studies in Asia countries found that the majority of stones were pigment stones [4, 5, 9] In visual inspection, pigment stone was black, dark brown or earthy with higher rate of bilirubinate calcium; cholesterol stones were lightly colored (brown, tan, yellow, or beige) with a radial, crystalline structure [2] Do Kim Son in his study also said that there was no difference between dark brown and black stone about the chemical composition Tsai W.L et al also had the same results [1, 10] So that, the rate of cholesterol stone in Vietnamese patients was so low 68 Journal of military pharmaco-medicine no7-2017 The relationships between CBD stones and clinical appearances in elderly patients Table 5: The relation between characteristics of CBD stone with the nature of relapse First time Characteristics (n) After surgery (n = 31) (n = 58) After ERCP Surgery + ERCP (n = 9) (n = 8) n % n % n % n % Mud stone (12) 6.8 12.9 11.1 37.5 Soft stone (23) 13 22.4 19.4 22.2 25.0 Steady stone (38) 23 39.6 10 32.3 44.4 25.0 Hard stone (17) 15.5 19.4 11.1 0.0 Mix stone (16) 15.5 16.1 11.1 12.5 Total 58 100.0 31 100.0 100.0 100.0 Mud stone was more common in patients with history of surgery and ERCP for stone extraction, this was recurrent stone Soft or steady stones were less common after ERCP or surgery But hard stone and mix stone often happen in patients in the first time or recurrence after surgery for CBD stone or gallbladder stone We care much on density of stone because it can bother to the success of ERCP In case of hard stone, we prefer lithotripsy or stenting if its size is over 1.5 cm, but with soft or steady stone, we can easily extract by ERCP although it can be in a big size Table 6: The relation between the duration of procedure, cholangitis complication and quality of bile with the color of stones Duration of procedure (minute) (18,3 ± 9,8) Cholangitis (n = 75) Black/muddy (n = 52) Earthy/tarry (34) 18.7 ± 8.9 (10 - 40) 25 (33.3%) 15 (28.9%) Yellow/tan (58) 16.9 ± 9.8 (5 - 60) 41 (54.7%) 30 (57.7%) 23.2 ± 10.5 (10 - 45) (12.0%) (13.5%) Color of stones Mix (14) p d 0.059 c 0.815 0.778c About duration of procedure, the shortest time belongs to the yellow/tan stone (17.1 ± 8.9 minutes), the longest is with mix stone (23.4 ± 9.8 minutes) (p = 0.027) Cholangitis and black/muddy bile most frequently happen in yellow/tan stone (47.8 and 52.3%), and mix stone has the lowest rate of cholangitis and black/muddy bile (14.1 and 10.8%) Le Van Cuong [5] saw that 91.6% of CBD stone had cholangitis Bernhoft R.A et al [3] found that pigment stone caused jaundice, cholangitis and pancreatitis more than that of cholesterol stone (83 (60%); 39 (10%); 17 (0%), respectively) 69 Journal of military pharmaco-medicine No7-2017 CONCLUSION - Elderly patients had lower case with pyogenic bile than other patients (p = 0.009) - In elderly patients, they had soft stone with higher rate than group II, but less case with hard stone (p = 0.041 and 0.0001, respectively) - Bil-ca component was in 100% of stone samples in both two groups; in group I: 73.3% of stones have chol and bil-ca + chol, compared with 20% in group II (p = 0.000) - By quantitative analysis, there was no difference between two groups about the composition in CBD stones (p > 0.05) - In group I: 100% were pigment stones, in group II: 93.3% were pigment stones and 6.7% was cholesterol stones, there was no difference (p = 0.15) - Mud stone was more common in patients with history of surgery and ERCP for stone extraction, this was recurrent stone Soft or steady stone were less common after ERCP or surgery The yellow/tan stone (17.1 ± 8.9 minutes) had the shortest procedure, the longest was with mix stone (23.4 ± 9.8 minutes), p = 0.027 Cholangitis and black/muddy bile most frequently happened in yellow/tan stone (47.8 and 52.3%), and mix stone had the lowest rate of cholangitis and black/muddy bile (14.1 and 10.8%) REFERENCES Đỗ Kim Sơn, Đỗ Ngọc Thanh, Trần Đình Thơ Thành phần hóa học sỏi đường mật 70 số yếu tố liên quan qua phân tích phương pháp quang phổ hồng ngoại Tạp chí Ngoại khoa 1998, số 1, tr.22-27 Nguyễn Quang Quyền, Lê Văn Cường, Nguyễn Quý Đạo CS Nghiên cứu thành phần hóa học yếu tố có liên quan sỏi mật, sỏi niệu Việt Nam Đề tài Cấp Trường Đại học Y Dược TP Hồ Chí Minh 1999 Phan Thu Phương Nghiên cứu thành phần cấu tạo sỏi đường mật có đối chiếu lâm sàng Luận văn Tốt nghiệp Bác sỹ Nội trú Trường Đại học Y Hà Nội 1998 Nguyễn Trọng Khìn, Nguyễn Minh Kháng, Đỗ Ngọc Thanh Xác định thành phần hóa học 60 mẫu sỏi mật người Việt nam phương pháp quang phổ hồng ngoại FT IR Tạp chí Y học Việt Nam 2006, 321, tr.35-40 Lê Văn Cường Thành phần hóa học 159 mẫu sỏi mật người Việt nam quang phổ hồng ngoại Tạp chí Y học TP Hồ Chí Minh 2004, tập 8, tr.156-161 Bernhoft R.A et al Composition and morphologic and clinical features of CBD stones Am J Surg 1984, 148, pp.77-85 Wu S.D, H Yu, J.M Sun Bacteriological and electron microscopic examination of primary intrahepatic stones Hepatobiliary Pancreat Dis 2006, 5, pp.228-231 Sanstad O et al CBD stones are mainly brown and associated with duodenal diverticula Gut 1994, 35, pp.1464-1467 Tazuma S Epidemiology, pathogenesis and classification of biliary stones (CBD and intrahepatic) Best Practice and Research Clinical Gastroenterol 2006 20 (6), pp.1075-83 10 Tsai W.L et al Composition of CBD stones in Chinese patients during and after endoscopic sphincterotomy World J Gastroenterol 2005, 11 (27), pp.4246-4249 ... of the either Pigment stones were subdivided visually into earthy stones and tarry stones * Stone sample study: - The removal stones were sent to Department of Pharmacy, University of Hochiminh... pharmaco-medicine no7-2017 The relationships between CBD stones and clinical appearances in elderly patients Table 5: The relation between characteristics of CBD stone with the nature of relapse... stone was more common in patients with history of surgery and ERCP for stone extraction, this was recurrent stone Soft or steady stones were less common after ERCP or surgery But hard stone and