Journal List > Korean J Gastroenterol > v.63(2) > 1007193

Kim, Choi, Kim, Kim, Bae, Choi, Ha, Song, Choi, Hong, and Kim: Clinical Usefulness of Bile Cytology Obtained from Biliary Drainage Tube for Diagnosing Cholangiocarcinoma

Abstract

Background/Aims

Biliary drainage is performed in many patients with cholangiocarcinoma (CCA) to relieve obstructive jaundice. For those who have undergone biliary drainage, bile cytology can be easily performed since the access is already achieved. This study aims to determine the clinical usefulness of bile cytology for the diagnosis of CCA and to evaluate factors affecting its diagnostic yield.

Methods

A total of 766 consecutive patients with CCA underwent bile cytology via endoscopic nasobiliary drainage or percutaneous transhepatic biliary drainage from January 2000 to June 2012. Data were collected by retrospectively reviewing the medical records. We evaluated the diagnostic yield of bile cytology with/without other sampling methods including brush cytology and endobiliary forcep biopsy, and the optimal number of repeated bile sampling. Several factors affecting diagnostic yield were then analyzed.

Results

The sensitivity of bile cytology, endobiliary forceps biopsy, and a combination of both sampling methods were 24.7% (189/766), 74.4% (259/348), and 77.9% (271/348), respectively. The cumulative positive rate of bile sampling increased from 40.7% (77/189) at first sampling to 93.1% (176/189) at third sampling. On multivariate analysis, factors associated with positive bile cytology were perihilar tumor location, intraductal growing tumor type, tumor extent ≥20 mm, poorly differentiated grade tumor, and three or more samplings.

Conclusions

Although bile cytology itself has a low sensitivity in diagnosing CCA, it has an additive role when combined with endobiliary forceps biopsy. Due to the relative ease and low cost, bile cytology can be considered a reasonable complementary diagnostic tool for diagnosing CCA.

References

1. Khan SA, Davidson BR, Goldin RD, et al. British Society of Gastroenterology. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut. 2012; 61:1657–1669.
crossref
2. Coelho-Prabhu N, Baron TH. Endoscopic retrograde cholangiopancreatography in the diagnosis and management of cholangiocarcinoma. Clin Liver Dis. 2010; 14:333–348.
crossref
3. Glasbrenner B, Ardan M, Boeck W, Preclik G, Möller P, Adler G. Prospective evaluation of brush cytology of biliary strictures during endoscopic retrograde cholangiopancreatography. Endoscopy. 1999; 31:712–717.
crossref
4. Ponchon T, Gagnon P, Berger F, et al. Value of endobiliary brush cytology and biopsies for the diagnosis of malignant bile duct stenosis: results of a prospective study. Gastrointest Endosc. 1995; 42:565–572.
crossref
5. Pugliese V, Conio M, Nicolò G, Saccomanno S, Gatteschi B. Endoscopic retrograde forceps biopsy and brush cytology of biliary strictures: a prospective study. Gastrointest Endosc. 1995; 42:520–526.
crossref
6. Ohshima Y, Yasuda I, Kawakami H, et al. EUS-FNA for suspected malignant biliary strictures after negative endoscopic transpapillary brush cytology and forceps biopsy. J Gastroenterol. 2011; 46:921–928.
crossref
7. Tummala P, Munigala S, Eloubeidi MA, Agarwal B. Patients with obstructive jaundice and biliary stricture ± mass lesion on imaging: prevalence of malignancy and potential role of EUS-FNA. J Clin Gastroenterol. 2013; 47:532–537.
8. Barr Fritcher EG, Kipp BR, Slezak JM, et al. Correlating routine cytology, quantitative nuclear morphometry by digital image analysis, and genetic alterations by fluorescence in situ hybridization to assess the sensitivity of cytology for detecting pan-creatobiliary tract malignancy. Am J Clin Pathol. 2007; 128:272–279.
crossref
9. Harewood GC, Baron TH, Stadheim LM, Kipp BR, Sebo TJ, Salomao DR. Prospective, blinded assessment of factors influencing the accuracy of biliary cytology interpretation. Am J Gastroenterol. 2004; 99:1464–1469.
crossref
10. Razumilava N, Gores GJ. Classification, diagnosis, and management of cholangiocarcinoma. Clin Gastroenterol Hepatol. 2013; 11:13–21.e1.
crossref
11. Liver Cancer Study Group of Japan. The general rules for the clinical and pathological study of primary liver cancer. Jpn J Surg. 1989; 19:98–129.
12. Lim JH. Cholangiocarcinoma: morphologic classification according to growth pattern and imaging findings. AJR Am J Roentgenol. 2003; 181:819–827.
crossref
13. Sasaki A, Aramaki M, Kawano K, et al. Intrahepatic peripheral cholangiocarcinoma: mode of spread and choice of surgical treatment. Br J Surg. 1998; 85:1206–1209.
crossref
14. Mansfield JC, Griffin SM, Wadehra V, Matthewson K. A prospective evaluation of cytology from biliary strictures. Gut. 1997; 40:671–677.
crossref
15. Foutch PG, Kerr DM, Harlan JR, Kummet TD. A prospective, controlled analysis of endoscopic cytotechniques for diagnosis of malignant biliary strictures. Am J Gastroenterol. 1991; 86:577–580.
16. Davidson B, Varsamidakis N, Dooley J, et al. Value of exfoliative cytology for investigating bile duct strictures. Gut. 1992; 33:1408–1411.
crossref
17. Sugiyama M, Atomi Y, Wada N, Kuroda A, Muto T. Endoscopic transpapillary bile duct biopsy without sphincterotomy for diagnosing biliary strictures: a prospective comparative study with bile and brush cytology. Am J Gastroenterol. 1996; 91:465–467.
18. Mohandas KM, Swaroop VS, Gullar SU, Dave UR, Jagannath P, DeSouza LJ. Diagnosis of malignant obstructive jaundice by bile cytology: results improved by dilating the bile duct strictures. Gastrointest Endosc. 1994; 40:150–154.
crossref
19. Kurzawinski TR, Deery A, Dooley JS, Dick R, Hobbs KE, Davidson BR. A prospective study of biliary cytology in 100 patients with bile duct strictures. Hepatology. 1993; 18:1399–1403.
crossref
20. Abdelghani YA, Arisaka Y, Masuda D, et al. Bile aspiration cytology in diagnosis of bile duct carcinoma: factors associated with positive yields. J Hepatobiliary Pancreat Sci. 2012; 19:370–378.
crossref
21. Yagioka H, Hirano K, Isayama H, et al. Clinical significance of bile cytology via an endoscopic nasobiliary drainage tube for pathological diagnosis of malignant biliary strictures. J Hepatobiliary Pancreat Sci. 2011; 18:211–215.
crossref
22. Hattori M, Nagino M, Ebata T, Kato K, Okada K, Shimoyama Y. Prospective study of biliary cytology in suspected perihilar cholangiocarcinoma. Br J Surg. 2011; 98:704–709.
crossref
23. Uchida N, Kamada H, Ono M, et al. How many cytological exami-nations should be performed for the diagnosis of malignant biliary stricture via an endoscopic nasobiliary drainage tube? J Gastroenterol Hepatol. 2008; 23:1501–1504.
crossref
24. Igami T, Nagino M, Oda K, et al. Clinicopathologic study of cholangiocarcinoma with superficial spread. Ann Surg. 2009; 249:296–302.
crossref
25. Weinbren K, Mutum SS. Pathological aspects of cholangiocarcinoma. J Pathol. 1983; 139:217–238.
crossref
26. Polkowski M, Larghi A, Weynand B, et al. European Society of Gastrointestinal Endoscopy (ESGE). Learning, techniques, and complications of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Guideline. Endoscopy. 2012; 44:190–206.
crossref
27. Athanassiadou P, Grapsa D. Value of endoscopic retrograde cholangiopancreatography-guided brushings in preoperative assessment of pancreaticobiliary strictures: what's new? Acta Cytol. 2008; 52:24–34.
28. Yamaguchi K, Nakano K, Nagai E, et al. Ki-ras mutations in codon 12 and p53 mutations (biomarkers) and cytology in bile in patients with hepatobiliary-pancreatic carcinoma. Hepatogastroenterology. 2005; 52:713–718.

Fig. 1.
The cumulative positive rates of bile cytology examination. In 189 patients with positive cytology results, the cumulative positive rate rose to 93.1% (176/189) at third examination.
kjg-63-107f1.tif
Table 1.
Patients Characteristics
Characteristic Value
Age (yr) 66 (59–73)
Sex  
 Male 521 (68.0)
 Female 245 (32.0)
Drainage method  
 ENBD 657 (85.8)
 PTBD 109 (14.2)
Tumor location  
 Perihilar 151 (19.7)
 Distal 615 (80.3)
Macroscopic type  
 Mass forming 152 (19.8)
 Periductal infiltrating 472 (61.6)
 Intraductal growing 142 (18.5)
Tumor multiplicity  
 Solitary 729 (95.2)
 Multiple 37 (4.8)
Tumor extent (mm) 20 (16–26)
CA 19-9 (U/mL) 51.2 (21.8-174.5)
Total bilirubin (mg/dL) 5.9 (1.9-12.3)
Histological finding  
 Adenocarcinoma, well differentiated 131 (17.1)
 Adenocarcinoma, unclassified differentiation 352 (46.0)
 Adenocarcinoma, poorly differentiated 93 (12.1)
 Adenocarcinoma, unclassified differentiation grade 64 (8.4)
 None 126 (16.4)

Values are presented as median (interquartile range) or n (%).

ENBD, endoscopic nasobiliary drainage; PTBD, percutaneous transhepatic biliary drainage.

Table 2.
Sensitivities of Each Diagnostic Methods and Combined Approaches
Method Bile cytology of entire group Positive ratio 24.7 (189/766) p-value
Drainage method   0.47
 Bile cytology through ENBD 24.2 (159/657)  
 Bile cytology through PTBD 27.5 (30/109)  
Bile cytology after bile duct manipulation   0.22
 Bile cytology alone 26.7 (78/292)  
 After brush cytology/endobiliary forceps biopsy 22.2 (81/365)  
Combined with brush cytology   0.50
 Brush cytology alone 34.5 (19/55)  
 Bile cytology+brush cytology 38.2 (21/55)  
Combined with endobiliary forcep biopsy   <0.001
 Endobiliary forceps biopsy alone 74.4 (259/348)  
 Bile cytology+endobiliary forceps biopsy 77.9 (271/348)  

Values are presented as percentage (n/total n).

ENBD, endoscopic nasobiliary drainage; PTBD, percutaneous transhepatic biliary drainage.

Table 3.
All Variables Studied for Positive Bile Cytology
Variable Negative Positive p-value
Tumor location     <0.001
 Perihilar 89 (58.9) 62 (41.1)  
 Distal 488 (79.3) 127 (20.7)  
Macroscopic tumor typ pe   <0.001
 Mass forming 112 (73.7) 40 (26.3)  
 Periductal infiltratin g 381 (80.7) 91 (19.3)  
 Intraductal growing 84 (59.2) 58 (40.8)  
Tumor extent (mm)     <0.001
 <20 283 (85.2) 49 (14.8)  
 ≥20 294 (67.7) 140 (32.3)  
Tumor multiplicity     0.025
 Solitary 555 (76.1) 174 (23.9)  
 Multiple 22 (59.5) 15 (40.5)  
Differentiation grade     0.021
 Well 107 (81.7) 24 (18.3)  
 Moderate 264 (75.0) 88 (25.0)  
 Poor 60 (64.5) 33 (35.5)  
Total bilirubin 5.2 (1.7-10.7) 8.7 (2.7-15.6) <0.001
CA 19-9 47.1 (20.4-150) 72.2 (27.5-335) 0.562
Number of samplings     <0.001
 1 or 2 373 (80.7) 89 (19.3)  
 ≥3 204 (67.1) 100 (32.9)  
Drainage method     0.457
 ENBD 498 (75.8) 159 (24.2)  
 PTBD 79 (72.5) 30 (27.5)  

Values are presented as n (%) or median (interquartile range).

ENBD, endoscopic nasobiliary drainage; PTBD, percutaneous transhepatic biliary drainage.

Table 4.
Multivariate Analysis on Factors Affecting Diagnostic Yield of Bile Cytology
Variable OR (95% CI) p-value
Tumor location   <0.001
 Perihilar 1  
 Distal 0.4 (0.3-0.6)  
Macroscopic tumor type   <0.001
 Mass forming 1  
 Periductal infiltrating 0.9 (0.6-1.5)  
 Intraductal growing 2.5 (1.5-4.3)  
Tumor extent (mm)   0.001
 <20 1  
 ≥20 2.0 (1.3-3.0)  
Differentiation grade   0.009
 Well 1  
 Moderate 2.0 (1.1-3.4)  
 Poor 2.5 (1.3-4.8)  
Number of samplings   <0.001
 1 or 2 1  
 ≥3 2.0 (1.4-2.9)  
TOOLS
Similar articles