Study on the composition, morphology and clinical features of common bile duct stones in elderly patients treated with endoscopic retrograde cholangiopancreatography

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

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  1. Journal of military pharmaco-medicine n o7-2017 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 CBD stones taken by surgeons but we are still lack of study about this issue in Bile duct disease, especially CBD stones elderly patients who were treated by are very common in gastroenterology, ERCP. Therefore, the objective of this study and often cause severe complications. is: To study the composition, morphology Studying the composition, morphology and clinical features of CBD stones in and clinical features of CBD stones in elderly patients treated with endoscopic elderly patients not only helps to define retrograde cholangiopancreatography. the pathogenesis of CBD stones but also helps to chose the methods of treatment SUBJECTS AND METHODS and prevent the recurrent of the diseases 1. Subjects. [1, 2, 6]. 198 patients treated from July, 2010 to In Vietnam, there are many studies April, 2014 in 103 Hospital, were divided about composition and morphology of the 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
  2. Journal of military pharmaco-medicine N o7-2017 - Group 1: elderly patients (equal or Fourier 8201 PC (Shimadzu, Japan) with more than 60 years old). 10 times of scan for each sample. The - Group 2: younger patients (less than gallstones were washed in saline solution, 60 years old). sliced in half, described, photographed, weighed, and sampled, assayed for All of the patients were diagnosed CBD stones by clinical and paraclinical bilirubin and cholesterol content. Insoluble data. residue was determined by decanting the supematant and weighing the dried 2. Methods. residue. Water content was determined A cross-sectional study. by heating pulverised stones to a constant * ERCP procedures: weight at 60°C. Gallstones were classified according to their visual appearance and - Two endoscopists. chemical composition. Visually, cholesterol - Sedation: because of the longer stones were lightly colored (brown, tan, duration and more potential discomfort fo yellow or beige) with a radial, crystalline the ERCP procedure, conscious sedation structure. Pigment stones were dark with intravenous propofol, which was shown brown, black, or eartby (like clay) and had to be safe when using in elderly patients, a dull, laminated, or haphazard structure. and requires hightly attention to dosing, Stones with intermediate features were with single dose of anti-spasmodic drug. classified according to their dominant - Canulation of the bile duct, components. cholangiography, verifying the presence - Chemically, cholesterol stones were of choledocholithiasis, then we did defined as containing more than 50 % sphinterotomy and stone extractions, cholesterol by weight, and pigment stones monitoring in hospital for 1 - 3 days. were defined as containing less than 50 % * Stone sample study: cholesterol by weight. Unclassified stones - The removal stones were sent to had small amounts of the either. Pigment Department of Pharmacy, University of stones were subdivided visually into earthy Hochiminh Medicine and Pharmacy, using stones and tarry stones. RESULTS AND DISCUSSION 1. Chemical composition of CBD stones. Table 1: Characteristics of the bile and CBD stones in two groups. Group I (n = 106) Group II (n = 92) Characteristics p n % n % Bile Yellow 54 50.9 33 35.9 0.033 Muddy 38 35.9 50 54.4 0.009 Pus 14 13.2 9 9.8 0.453 66
  3. Journal of military pharmaco-medicine n o7-2017 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 9.8 0.196 Mix stone 16 15.0 12 13.0 0.82 In group I, pyogenic bile (muddy and 15.0% vs. 13.0%); group I had more cases pus bile) was 52/106 patients (49.1%), with soft stone than group II (21.7% and lower than group II with 59/92 patients 10.9%; p = 0.041); otherwise group II had (64.2%) (p = 0.009); but there was no more cases of hard stone than group difference between the rate of pus bile (54.4% vs. 35.8%, p = 0.0001). Phan Thu (p = 0.453). Almost other authors agreed Phuong also had the same results in her that CBD stone had close relation to study [3]. The collection of gallstones at cholangitits [1, 7]. ERCP is difficult and unpredictable. Some About the characteristics of CBD stone, stones are fragile and may break when the rate of mud stone and mix stone were collecting in a dormia basket. Therefore, the same in two groups (11.3% vs. 11.9%; there is a risk that sampling may be biased. Table 2: Chemical composition of CBD stones. Group I (n = 30) Group II (n = 30) Composition p n % n % Bil-ca (*) 30 100.0 30 100.0 - Cholesterol 22 73.3 6 20.0 0.000 Protid 4 13.3 8 26.7 0.197 Calcite 0 0.0 1 3.33 - Bil-ca + chol 22 73.3 6 20.0 0.000 Bil-ca + protid 4 13.3 8 26.7 0.197 Bil-ca + calcite 0 0.0 1 3.33 - Bil-ca + protid + chol 1 3.3 0 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 2 components of stone (bil + chol) was 76.7%, and there was no cholesterol component [4]. 67
  4. Journal of military pharmaco-medicine N o7-2017 Table 3: Quantitative analysis of the composition of CBD stone. Group I (n = 30) Group II (n = 30) Rate (%) p 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 0 5 - 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 0 2 6.7 0.15 Mix stone 0 0 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
  5. Journal of military pharmaco-medicine n o7-2017 2. 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 After surgery After ERCP Surgery + ERCP Characteristics (n) (n = 58) (n = 31) (n = 9) (n = 8) n % n % n % n % Mud stone (12) 4 6.8 4 12.9 1 11.1 3 37.5 Soft stone (23) 13 22.4 6 19.4 2 22.2 2 25.0 Steady stone (38) 23 39.6 10 32.3 4 44.4 2 25.0 Hard stone (17) 9 15.5 6 19.4 1 11.1 0 0.0 Mix stone (16) 9 15.5 5 16.1 1 11.1 1 12.5 Total 58 100.0 31 100.0 9 100.0 8 100.0 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) Cholangitis Black/muddy Color of stones (18,3 ± 9,8) (n = 75) (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%) Mix (14) 23.2 ± 10.5 (10 - 45) 9 (12.0%) 7 (13.5%) p 0.059 d 0.815 c 0.778 c 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
  6. Journal of military pharmaco-medicine N o7-2017 CONCLUSION chính và m ột s ố y ếu t ố liên quan qua phân - Elderly patients had lower case with tích b ằng ph ươ ng pháp quang ph ổ h ồng ngo ại. Tạp chí Ngo ại khoa. 1998, s ố 1, tr.22-27. pyogenic bile than other patients (p = 0.009). 2. Nguy ễn Quang Quy ền, Lê V ăn C ường, - In elderly patients, they had soft Nguy ễn Quý Đạ o và CS. Nghiên c ứu thành stone with higher rate than group II, but ph ần hóa h ọc và các y ếu t ố có liên quan c ủa less case with hard stone (p = 0.041 and sỏi m ật, s ỏi ni ệu t ại Vi ệt Nam. Đề tài C ấp b ộ. 0.0001, respectively). Tr ường Đạ i h ọc Y D ược TP. Hồ Chí Minh. - Bil-ca component was in 100% of 1999. stone samples in both two groups; in 3. Phan Thu Ph ươ ng. Nghiên c ứu thành group I: 73.3% of stones have chol and ph ần c ấu t ạo s ỏi đường m ật có đố i chi ếu lâm bil-ca + chol, compared with 20% in group II sàng. Lu ận v ăn T ốt nghi ệp Bác s ỹ N ội trú. (p = 0.000). Tr ường Đạ i h ọc Y Hà Nội. 1998. 4. Nguy ễn Tr ọng Khìn, Nguy ễn Minh Kháng, - By quantitative analysis, there was no Đỗ Ng ọc Thanh. Xác định thành ph ần hóa difference between two groups about the học c ủa 60 m ẫu s ỏi m ật ng ười Vi ệt nam b ằng composition in CBD stones (p > 0.05). ph ươ ng pháp quang ph ổ h ồng ngo ại FT IR. - In group I: 100% were pigment Tạp chí Y h ọc Vi ệt Nam. 2006, 321, tr.35-40. stones, in group II: 93.3% were pigment 5. Lê V ăn C ường. Thành ph ần hóa h ọc stones and 6.7% was cholesterol stones, của 159 m ẫu s ỏi m ật ở ng ười Vi ệt nam b ằng there was no difference (p = 0.15). quang ph ổ h ồng ngo ại. T ạp chí Y h ọc TP. H ồ - Mud stone was more common in Chí Minh. 2004, t ập 8, tr.156-161. patients with history of surgery and ERCP 6. Bernhoft R.A et al. Composition and for stone extraction, this was recurrent morphologic and clinical features of CBD stones. Am J Surg. 1984, 148, pp.77-85. stone. Soft or steady stone were less common after ERCP or surgery. 7. Wu S.D, H Yu, J.M Sun. Bacteriological and electron microscopic examination of The yellow/tan stone (17.1 ± 8.9 primary intrahepatic stones. Hepatobiliary minutes) had the shortest procedure, the Pancreat Dis. 2006, 5, pp.228-231. longest was with mix stone (23.4 ± 9.8 8. Sanstad O et al. CBD stones are mainly minutes), p = 0.027. Cholangitis and brown and associated with duodenal black/muddy bile most frequently diverticula. Gut. 1994, 35, pp.1464-1467. happened in yellow/tan stone (47.8 and 9. Tazuma S. Epidemiology, pathogenesis 52.3%), and mix stone had the lowest rate and classification of biliary stones (CBD and of cholangitis and black/muddy bile intrahepatic). Best Practice and Research (14.1 and 10.8%). Clinical Gastroenterol. 2006. 20 (6), pp.1075-83. 10. Tsai W.L et al. Composition of CBD REFERENCES stones in Chinese patients during and after 1. Đỗ Kim S ơn, Đỗ Ng ọc Thanh, Tr ần Đình endoscopic sphincterotomy. World J Th ơ. Thành ph ần hóa h ọc c ủa s ỏi đường m ật Gastroenterol. 2005, 11 (27), pp.4246-4249. 70