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Krupa Ł, Staroń R, Dulko D, Łozińska N, Mackie AR, Rigby NM, Macierzanka A, Markiewicz A, Jungnickel C. Importance of Bile Composition for Diagnosis of Biliary Obstructions. Molecules 2021; 26:7279. [PMID: 34885858 PMCID: PMC8659177 DOI: 10.3390/molecules26237279] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 11/26/2021] [Accepted: 11/27/2021] [Indexed: 01/01/2023] Open
Abstract
Determination of the cause of a biliary obstruction is often inconclusive from serum analysis alone without further clinical tests. To this end, serum markers as well as the composition of bile of 74 patients with biliary obstructions were determined to improve the diagnoses. The samples were collected from the patients during an endoscopic retrograde cholangiopancreatography (ERCP). The concentration of eight bile salts, specifically sodium cholate, sodium glycocholate, sodium taurocholate, sodium glycodeoxycholate, sodium chenodeoxycholate, sodium glycochenodeoxycholate, sodium taurodeoxycholate, and sodium taurochenodeoxycholate as well as bile cholesterol were determined by HPLC-MS. Serum alanine aminotransferase (ALT), aspartate transaminase (AST), and bilirubin were measured before the ERCP. The aim was to determine a diagnostic factor and gain insights into the influence of serum bilirubin as well as bile salts on diseases. Ratios of conjugated/unconjugated, primary/secondary, and taurine/glycine conjugated bile salts were determined to facilitate the comparison to literature data. Receiver operating characteristic (ROC) curves were determined, and the cut-off values were calculated by determining the point closest to (0,1). It was found that serum bilirubin was a good indicator of the type of biliary obstruction; it was able to differentiate between benign obstructions such as choledocholithiasis (at the concentration of >11 µmol/L) and malignant changes such as pancreatic neoplasms or cholangiocarcinoma (at the concentration of >59 µmol/L). In addition, it was shown that conjugated/unconjugated bile salts confirm the presence of an obstruction. With lower levels of conjugated/unconjugated bile salts the possibility for inflammation and, thus, neoplasms increase.
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Affiliation(s)
- Łukasz Krupa
- Teaching Hospital No 1, Department of Gastroenterology and Hepatology with Internal Disease Unit, Chopina 2, 35-055 Rzeszów, Poland; (Ł.K.); (R.S.)
- Medical Department, University of Rzeszów, Kopisto 2a, 35-310 Rzeszów, Poland
| | - Robert Staroń
- Teaching Hospital No 1, Department of Gastroenterology and Hepatology with Internal Disease Unit, Chopina 2, 35-055 Rzeszów, Poland; (Ł.K.); (R.S.)
- Medical Department, University of Rzeszów, Kopisto 2a, 35-310 Rzeszów, Poland
| | - Dorota Dulko
- Department of Colloid and Lipid Science, Faculty of Chemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland; (D.D.); (N.Ł.); (A.M.)
| | - Natalia Łozińska
- Department of Colloid and Lipid Science, Faculty of Chemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland; (D.D.); (N.Ł.); (A.M.)
| | - Alan R. Mackie
- School of Food Science & Nutrition, University of Leeds, Leeds LS2 9JT, UK; (A.R.M.); (N.M.R.)
| | - Neil M. Rigby
- School of Food Science & Nutrition, University of Leeds, Leeds LS2 9JT, UK; (A.R.M.); (N.M.R.)
| | - Adam Macierzanka
- Department of Colloid and Lipid Science, Faculty of Chemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland; (D.D.); (N.Ł.); (A.M.)
| | - Aleksandra Markiewicz
- Laboratory of Translational Oncology Intercollegiate, Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, 80-211 Gdańsk, Poland;
| | - Christian Jungnickel
- Department of Colloid and Lipid Science, Faculty of Chemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland; (D.D.); (N.Ł.); (A.M.)
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Ishiwatari H, Satoh T, Sato J, Kaneko J, Matsubayashi H, Yabuuchi Y, Kishida Y, Yoshida M, Ito S, Kawata N, Imai K, Takizawa K, Hotta K, Ono H. Bile aspiration during EUS-guided hepaticogastrostomy is associated with lower risk of postprocedural adverse events: a retrospective single-center study. Surg Endosc 2021; 35:6836-6845. [PMID: 33398558 DOI: 10.1007/s00464-020-08189-w] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 11/17/2020] [Indexed: 12/07/2022]
Abstract
BACKGROUND In endoscopic retrograde cholangiopancreatography (ERCP), reduction of pressure inside of the bile duct by bile aspiration is a well-known method to lower the rate of adverse events (AEs) including cholangitis. Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) has been introduced as an alternative to ERCP. The use of self-expandable metallic stents is recommended in EUS-HGS to reduce bile leak; however, other methods to reduce the rate of AEs including bile leak, abdominal pain, fever, and sepsis, have not been elucidated yet. This study investigated whether bile aspiration during EUS-HGS decreased the rate of postprocedural AEs. METHODS Consecutive patients who underwent EUS-HGS between July 2016 and April 2020 were retrospectively evaluated in this study. EUS-HGS was performed at a tertiary cancer center. Patient characteristics, site of biliary obstruction, the quantity of bile aspirated during EUS-HGS, type of stent, whether or not antegrade stenting (AS) was performed, procedure time, and AEs were assessed based on a prospectively recorded institutional endoscopy database. Logistic regression analysis was performed to identify factors affecting postprocedural AEs. RESULTS Ninety-six patients were included in the study. EUS-guided HGS with and without AS was performed in 45 and 51 patients, respectively. Bile was aspirated in 71 patients (74%). The quantity of bile aspirated was 0-10 mL and > 10 mL in 40 and 56 patients, respectively. AEs including fever, abdominal pain, postprocedural cholangitis, sepsis, acute pancreatitis, and bleeding occurred in 45 patients (47%). The AE rates were 65% (26/40) and 34% (19/56), for 0-10 mL and > 10 mL bile, respectively (p = 0.004). Using multivariate analysis, the only independent factor affecting the occurrence of AEs was found to be an aspirated bile amount of 0-10 mL (odds ratio: 4.16; 95% CI 1.6-10.8). CONCLUSIONS Bile aspiration of more than 10 mL during EUS-HGS contributes to reducing the rate of postprocedural AEs.
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Affiliation(s)
- Hirotoshi Ishiwatari
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
| | - Tatsunori Satoh
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Junya Sato
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Junichi Kaneko
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Hiroyuki Matsubayashi
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
- Division of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yohei Yabuuchi
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Yoshihiro Kishida
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Masao Yoshida
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Sayo Ito
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Noboru Kawata
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Kenichiro Imai
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Kinichi Hotta
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
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Maeda T, Ebata T, Yokoyama Y, Igami T, Mizuno T, Yamaguchi J, Onoe S, Watanabe N, Nagino M. A case of small in situ perihilar cholangiocarcinoma incidentally accompanied by benign bile duct stricture after open cholecystectomy. Surg Case Rep 2019; 5:177. [PMID: 31707480 PMCID: PMC6842380 DOI: 10.1186/s40792-019-0745-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 10/31/2019] [Indexed: 11/19/2022] Open
Abstract
Background In situ cholangiocarcinoma is difficult to detect by imaging studies. Thus, cholangiocarcinoma is rarely resected with a preoperative definitive diagnosis, especially nonpapillary flat type in situ carcinoma, which is extremely rare. Case presentation A 70-year old man was diagnosed with gallbladder cancer and received open cholecystectomy with lymphadenectomy at a local hospital. Histologically, the tumor was localized in the mucosal layer, and no lymph node metastases were found. Three months later, hilar bile duct stricture due to delayed bile duct ischemia was found. Then, biliary drainage was performed with endoscopic biliary stenting. Three months later, the patient experienced cholangitis with septic shock, and percutaneous transhepatic biliary drainage (PTBD) into the left intrahepatic bile duct was performed. Unexpectedly, the aspiration bile cytology of the PTBD catheter showed malignant cells, and the patient was referred to our clinic for possible surgical treatment. According to additional studies, the hilar bile duct stricture was 3 cm in length. None of the imaging studies detected malignant cells in the bile duct around the hilar stricture. The left portal vein was obstructed due to inadvertent puncture of the PTBD. No findings indicated cholangiocarcinoma. We performed left hepatectomy with caudate lobectomy and extrahepatic bile duct resection. The postoperative course was uneventful. In the final pathology, flat type in situ carcinoma was found at the confluence of the right and left hepatic ducts, which was distant from the biliary stricture. Conclusions When a tumor is undetectable but cytology is positive, in situ cholangiocarcinoma may exist; thus, surgery should be carefully considered.
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Affiliation(s)
- Takashi Maeda
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Tsuyoshi Igami
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Takashi Mizuno
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Junpei Yamaguchi
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Shunsuke Onoe
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Nobuyuki Watanabe
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Masato Nagino
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
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Hayakawa C, Hoshikawa M, Imura J, Ueno T, Koike J. Bile cytology: A new scoring system for improving diagnostic accuracy. Diagn Cytopathol 2019; 47:641-647. [PMID: 30730608 DOI: 10.1002/dc.24076] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Revised: 07/16/2018] [Accepted: 08/20/2018] [Indexed: 11/11/2022]
Abstract
BACKGROUND Benign and malignant cells need to be distinguished in any cytological examination of bile. Here, we report an original scoring system to improve the diagnostic accuracy of bile cytology. METHODS The study used 158 bile aspiration samples obtained for cytological examination. Fourteen cytological findings were used to differentiate benign and malignant samples. Statistical significance tests and multivariate analysis were used to determine and quantify significant findings and develop a scoring system. RESULTS Four cytological findings were significant in discriminating between benign and malignant cells: abnormal chromatin, irregularly arranged nuclei, irregularly overlapped nuclei, and irregular cluster margins. Our newly developed scoring system based on these four cytological findings yielded excellent results with a sensitivity of 87%, specificity of 98%, and an odds ratio of 329. CONCLUSIONS The use of our new scoring system is expected to contribute to the diagnostic accuracy of cytological evaluations of bile samples.
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Affiliation(s)
- Chie Hayakawa
- Department of Diagnostic Pathology, Kawasaki Municipal Tama Hospital, Kawasaki, Japan
| | - Masahiro Hoshikawa
- Department of Pathology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Johji Imura
- Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
| | - Takahiko Ueno
- Unit of Medical Informatics, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Junki Koike
- Department of Diagnostic Pathology, Kawasaki Municipal Tama Hospital, Kawasaki, Japan.,Department of Pathology, St. Marianna University School of Medicine, Kawasaki, Japan
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Diagnostic Ability of Endoscopic Bile Cytology Using a Newly Designed Biliary Scraper for Biliary Strictures. Dig Dis Sci 2019; 64:241-248. [PMID: 30039240 DOI: 10.1007/s10620-018-5217-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Accepted: 07/18/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND A new device with metallic wires for scrape cytology was developed. AIMS To compare the diagnostic performance of scrape cytology and conventional cytology during endoscopic retrograde cholangiopancreatography for biliary strictures. METHODS A total of 420 cases with biliary stricture underwent transpapillary bile cytology. Among them, there are 79 cases with scrape cytology using the new device (scrape group) and 341 cases with conventional cytology (control group). Seventy-two and 174 cases underwent biliary biopsy at the same time as bile cytology in the scrape and control group, respectively. RESULTS The sensitivity for malignancy of bile cytology in the scrape and control group was 41.2% [pancreatic cancer (PC): 23.1%, biliary cancer (BC): 52.5%] and 27.1% (PC: 16.3%, BC: 38.0%), respectively (P = 0.023). When analyzed PC and BC, respectively, there was no significant difference between the two groups. In the both groups, the sensitivity was significantly higher for BC than PC. In the scrape group, there was no difference in the sensitivity between cytology and biopsy [39.7% (PC: 17.4%, BC: 55.3%)], but in the control group, a significantly lower sensitivity was observed with cytology than biopsy (36.4% (PC: 19.7%, BC: 50.0%)) (P = 0.046). When analyzed PC and BC, respectively, there was no significant difference between cytology and biopsy. The sensitivity of combined cytology and biopsy was 55.6% (PC: 30.4%, BC: 71.1%) in the scrape group and 47.0% (PC: 24.6%, BC: 64.3%) in the control group. CONCLUSION Scrape bile cytology for biliary strictures may be superior to conventional cytology.
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Cozzi G, Alasio L, Civelli E, Colnago MF, Salvetti M, Pilotti S, Rilke F, Severini A. Percutaneous Intraductal Sampling for Cyto-histologic Diagnosis of Biliary Duct Strictures. TUMORI JOURNAL 2018; 85:153-6. [PMID: 10426123 DOI: 10.1177/030089169908500301] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background Percutaneous transhepatic biliary drainage (PTBD) allows ductal material to be collected for cyto-histologic examination. We evaluated the data from a large series of patients with a PTBD in whom endobiliary cyto-histologic sampling techniques were employed in order to define a strategy for their use in the diagnostic work-up. Patients and Methods Ductal samples for cyto-histologic examination were obtained from 409 consecutive patients with a PTBD for stenosing lesions of the biliary tree. Bile aspirate cytology was performed for all patients and ductal biopsy specimens were obtained, generally after negative cytology, from 49 of them (11.9%), all candidates for a therapeutic procedure. The cyto-histologic results of intraductal sampling were compared with pathologic surgical data in 210 patients and with clinical-radiologic follow-up in 199. Results Overall, 22 out of the 409 patients had a final diagnosis of benign stenosis and 177 had samples positive for neoplastic disease. The sensitivity of bile cytology was 43.8% while ductal biopsies showed a sensitivity of 60.4%. The combination of the two sampling techniques achieved a sensitivity of 65.1%. For both sampling methods the specificity was 100%. Hilar metastases from neoplastic lesions of the GI tract and primary lesions of the biliary ducts showed the highest sensitivity. Conclusion Cyto-histologic assessment of stenosing lesions of the biliary ducts is mandatory when highly sophisticated interventions (e.g. wide hepatic resection or liver transplantation) or non-surgical treatments are envisaged. The collection of cyto-histologic samples from bile ducts, in patients with a percutaneous bile drainage, is an easy, safe and valuable method to obtain the diagnosis. In view of the absence of false positive results in our series and in others, intraductal biopsy serves no purpose when positive exfoliative cytology is positive for malignancy. In the presence of negative cytology it is felt that an intraductal biopsy should be mandatory when the choice of a therapeutic program depends on the result of the cyto-histologic diagnosis.
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Affiliation(s)
- G Cozzi
- Radiodiagnostics C Operative Unit, Istituto Nazionale Tumori, Milan, Italy
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Yamashita Y, Ueda K, Kawaji Y, Tamura T, Itonaga M, Yoshida T, Maeda H, Magari H, Maekita T, Iguchi M, Tamai H, Ichinose M, Kato J. The Wire-Grasping Method as a New Technique for Forceps Biopsy of Biliary Strictures: A Prospective Randomized Controlled Study of Effectiveness. Gut Liver 2017; 10:642-8. [PMID: 27021502 PMCID: PMC4933427 DOI: 10.5009/gnl15231] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Revised: 08/05/2015] [Accepted: 10/01/2015] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Transpapillary forceps biopsy is an effective diagnostic technique in patients with biliary stricture. This prospective study aimed to determine the usefulness of the wire-grasping method as a new technique for forceps biopsy. Methods Consecutive patients with biliary stricture or irregularities of the bile duct wall were randomly allocated to either the direct or wire-grasping method group. In the wire-grasping method, forceps in the duodenum grasps a guide-wire placed into the bile duct beforehand, and then, the forceps are pushed through the papilla without endoscopic sphincterotomy. In the direct method, forceps are directly pushed into the bile duct alongside a guide-wire. The primary endpoint was the success rate of obtaining specimens suitable for adequate pathological examination. Results In total, 32 patients were enrolled, and 28 (14 in each group) were eligible for analysis. The success rate was significantly higher using the wire-grasping method than the direct method (100% vs 50%, p=0.016). Sensitivity and accuracy for the diagnosis of cancer were comparable in patients with the successful procurement of biopsy specimens between the two methods (91% vs 83% and 93% vs 86%, respectively). Conclusions The wire-grasping method is useful for diagnosing patients with biliary stricture or irregularities of the bile duct wall.
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Affiliation(s)
- Yasunobu Yamashita
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Kazuki Ueda
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Yuki Kawaji
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Takashi Tamura
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Masahiro Itonaga
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Takeichi Yoshida
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Hiroki Maeda
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Hirohito Magari
- Department of Internal Medicine, Nokami Kosei General Hospital, Wakayama, Japan
| | - Takao Maekita
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Mikitaka Iguchi
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Hideyuki Tamai
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Masao Ichinose
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Jun Kato
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
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Yeo MK, Kim KH, Lee YM, Lee BS, Choi SY. The usefulness of adding p53 immunocytochemistry to bile drainage cytology for the diagnosis of malignant biliary strictures. Diagn Cytopathol 2017; 45:592-597. [DOI: 10.1002/dc.23729] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Revised: 03/23/2017] [Accepted: 03/30/2017] [Indexed: 11/06/2022]
Affiliation(s)
- Min-Kyung Yeo
- Department of Pathology; Chungnam National University School of Medicine; Daejeon Republic of Korea
| | - Kyung-Hee Kim
- Department of Pathology; Chungnam National University School of Medicine; Daejeon Republic of Korea
| | - Yong-Moon Lee
- Department of Pathology; Chungnam National University School of Medicine; Daejeon Republic of Korea
| | - Byung Seok Lee
- Department of Internal Medicine; Chungnam National University School of Medicine; Daejeon Republic of Korea
| | - Song-Yi Choi
- Department of Pathology; Chungnam National University School of Medicine; Daejeon Republic of Korea
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Abbasi MR, Ghazi Mirsaeed SM, Mohammad Alizadeh AH. Diagnosis of Malignant Biliary Strictures: Conventional or Negative Pressure Brush Cytology? Asian Pac J Cancer Prev 2016; 17:4563-4566. [PMID: 27892663 PMCID: PMC5454598 DOI: 10.22034/apjcp.2016.17.10.4563] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Background/Objective: The aim of this study was to perform a comparative evaluation of the yields of conventional brush cytology and brush cytology with negative pressure in the diagnosis of malignant biliary strictures. Methods: A total of 132 consecutive patients undergoing endoscopic were identified. Of these, 88.0 had brush cytology after ERCP and 44 were Brush cytology with negative pressure. Retrograde cholangiopancreatography (ERCP) including brush cytology and brush cytology with negative pressure in patients with biliary strictures between 2012-2015. Endoscopic retrograde cholangiography was performed with a standard videoduodenoscope Olympus TFJ 160-R (Olympus, Hamburg, Germany) and brush cytology with a Cook medical Double Lumen Biliary BrushTM (Cytology). Means and standard frequencies were used to calculate variables. Results: Positive results for malignancy were obtained in 22 of 88 patients (25%) by brush cytology and 31 of 44 patients (70.4 %) by brush cytology with negative pressure. Conclusions: Sensitivity of cytology sampling could be maximized by negative pressure during ERCP.
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Affiliation(s)
- Mohammad Reza Abbasi
- Shahid Behesti University of Medical Sciences, Taleghani Hospital, Parvaneh Ave, Tabnak Str, Evin ,Tehran, Iran.
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Affiliation(s)
- Paul Korc
- Indiana University Medical Center, University Hospital, Indianapolis, Indiana, USA; Hoag-USC Digestive Disease Center, Newport Beach, California, USA
| | - Stuart Sherman
- Indiana University Medical Center, University Hospital, Indianapolis, Indiana, USA
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Untereiner V, Sockalingum GD, Garnotel R, Gobinet C, Ramaholimihaso F, Ehrhard F, Diebold MD, Thiéfin G. Bile analysis using high-throughput FTIR spectroscopy for the diagnosis of malignant biliary strictures: a pilot study in 57 patients. JOURNAL OF BIOPHOTONICS 2014; 7:241-253. [PMID: 24677747 DOI: 10.1002/jbio.201300166] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Revised: 02/28/2014] [Accepted: 03/04/2014] [Indexed: 06/03/2023]
Abstract
This study aimed at determining whether FTIR spectroscopy is able to distinguish bile samples from patients with and without malignant biliary strictures. Bile samples were collected in 19 patients with malignant biliary strictures and 38 with benign biliary diseases during endoscopic procedures. FTIR spectra were acquired on dried drops of whole bile, aqueous and organic phases obtained after lipid extraction. Data were analyzed by principal component analysis and by the support vector machine classification using a leave-n-out cross validation procedure. This was applied to the whole set of spectra and the mean and median spectra of each patient. By leaving one patient out, the classifier allowed discriminating patients with and without malignant biliary strictures with a sensitivity between 82% and 95% and a specificity between 85% and 100%. Using a randomized leave-n -out cross-validation with n = 2, 5 and 10 patients, the sensitivity decreased slightly by about 5 to 10% while the specificity remained stable, suggesting the robustness of the classifier. FTIR spectroscopy combined with chemometrics therefore shows potential to differentiate bile from patients with and without malignant biliary strictures. Although promising, the results of this pilot study cannot be generalized and needs to be confirmed in a larger population.
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Affiliation(s)
- Valérie Untereiner
- Université de Reims Champagne-Ardenne, MéDIAN-Biophotonique et Technologies pour la Santé, UFR de Pharmacie, 51 rue Cognacq-Jay, 51096 REIMS cedex, France; CNRS UMR7369, Matrice Extracellulaire et Dynamique Cellulaire, MEDyC, Reims, France
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Nishikawa T, Tsuyuguchi T, Sakai Y, Sugiyama H, Tawada K, Mikata R, Tada M, Ishihara T, Miyazaki M, Yokosuka O. Factors affecting the accuracy of endoscopic transpapillary sampling methods for bile duct cancer. Dig Endosc 2014; 26:276-81. [PMID: 23826684 DOI: 10.1111/den.12140] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Accepted: 05/27/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Various methods for endoscopic transpapillary sampling have been developed. However, the factors affecting the accuracy of these methods for bile duct cancer are unknown. The aim of the present study was to determine the factors affecting the accuracy of endoscopic transpapillary sampling methods. METHODS We reviewed the results from 101 patients with bile duct cancer who underwent transpapillary sampling by aspiration bile cytology, brushing cytology, and fluoroscopic forceps biopsy. The final diagnosis of bile duct cancer was made on the basis of pathological evaluation of specimens obtained at surgery and the clinical course over at least 1 year in patients not operated on. We carried out subgroup analyses for the factors affecting the accuracy of each transpapillary sampling method. RESULTS Aspiration bile cytology was carried out 238 times in 77 patients, brushing cytology was carried out 67 times in 60patients, and fluoroscopic forceps biopsy was carried out 64 times in 53 patients. Accuracies of aspiration bile cytology were significantly higher for longer (≥15 mm) biliary cancerous lesions than for shorter (<15 mm) lesions (30% vs 18%, respectively, P = 0.049). Accuracies of brushing cytology and fluoroscopic forceps biopsy were significantly higher for non-flat than for flat-type biliary cancerous lesions (brushing: 58% vs 38%, respectively, P = 0.032; forceps biopsy: 60% vs 33%, respectively, P = 0.043). CONCLUSION Endoscopic transpapillary sampling methods are more accurate for longer or elevated (non-flat) biliary cancerous lesions than for shorter or flat lesions.
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Affiliation(s)
- Takao Nishikawa
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Kim JY, Choi JH, Kim JH, Kim CL, Bae SH, Choi YK, Ha Y, Song MJ, Choi JH, Hong SM, Kim MH. Clinical Usefulness of Bile Cytology Obtained from Biliary Drainage Tube for Diagnosing Cholangiocarcinoma. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2014; 63:107-13. [DOI: 10.4166/kjg.2014.63.2.107] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Jin Yong Kim
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Joon Hyuk Choi
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Hee Kim
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chang Lae Kim
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung Hyeon Bae
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Kwon Choi
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yeonjung Ha
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Min-Joo Song
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jun-Ho Choi
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Myung-Hwan Kim
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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14
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Tsuchiya T, Yokoyama Y, Ebata T, Igami T, Sugawara G, Kato K, Shimoyama Y, Nagino M. Randomized controlled trial on timing and number of sampling for bile aspiration cytology. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2013; 21:433-8. [PMID: 24353113 DOI: 10.1002/jhbp.61] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The issue on timing and number of bile sampling for exfoliative bile cytology is still unsettled. METHODS A total of 100 patients with cholangiocarcinoma undergoing resection after external biliary drainage were randomized into two groups: a 2-day group where bile was sampled five times per day for 2 days; and a 10-day group where bile was sampled once per day for 10 days (registered University Hospital Medical Information Network/ID 000005983). The outcome of 87 patients who underwent laparotomy was analyzed, 44 in the 2-day group and 43 in the 10-day group. RESULTS There were no significant differences in patient characteristics between the two groups. Positivity after one sampling session was significantly lower in the 2-day group than in the 10-day group (17.0 ± 3.7% vs. 20.7 ± 3.5%, P = 0.034). However, cumulative positivity curves were similar and overlapped each other between both groups. The final cumulative positivity by the 10th sampling session was 52.3% in the 2-day group and 51.2% in the 10-day group. We observed a small increase in cumulative positivity after the 5th or 6th session in both groups. CONCLUSIONS Bile cytology positivity is unlikely to be affected by sample time.
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Affiliation(s)
- Tomonori Tsuchiya
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
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15
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Kishimoto T, Eguchi H, Nagano H, Kobayashi S, Akita H, Hama N, Wada H, Kawamoto K, Tomokuni A, Tomimaru Y, Umeshita K, Doki Y, Mori M. Plasma miR-21 is a novel diagnostic biomarker for biliary tract cancer. Cancer Sci 2013; 104:1626-31. [PMID: 24118467 DOI: 10.1111/cas.12300] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Revised: 08/27/2013] [Accepted: 09/30/2013] [Indexed: 12/17/2022] Open
Abstract
Biliary tract cancer (BTC) has a generally poor prognosis. Furthermore, it is difficult to distinguish BTC from benign biliary disease (BBD) with commonly used modalities. Therefore, a novel biomarker to facilitate cancer detection is highly desirable. Recent studies have reported the use of circulating microRNAs (miRNAs) as biomarkers for cancers. The purpose of this study was to evaluate whether circulating miRNA-21 (miR-21) could be used as a biomarker for BTC. Plasma samples were obtained from 94 BTC patients, 50 healthy volunteers (HVs), and 23 BBD patients. miR-21 levels in the samples were measured by qRT-PCR. Plasma miR-21 levels in patients with BTC were significantly higher than in HVs or in patients with BBD (P < 0.0001 for both). Receiver-operator curve (ROC) curve analysis in differentiating BTC patients from HVs indicated that area under the curve (AUC), optimal sensitivity and specificity was 0.93, 85.1% and 100%, respectively, and those in differentiating BTC patients from BBD patients was 0.83, 72.3%, 91.3%, respectively. Validation of these results indicated that the negative predictive value, positive predictive value, sensitivity, specificity, and accuracy in differentiating BTC patients from HVs was 76.6%, 98.6%, 84.0%, 98.0%, and 88.9%, respectively, and those in differentiating BTC patients from BBD patients was 42.2%, 93.0%, 71.2%, 82.6%, and 72.6%, respectively. These sets of values were improved by combining miR-21 and CA19-9 measurements. Plasma miR-21 is a novel diagnostic biomarker for BTC, and may be useful in distinguishing between BTC and BBD patients.
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Affiliation(s)
- Tomoya Kishimoto
- Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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Gupta M, Pai RR, Dileep D, Gopal S, Shenoy S. Role of biliary tract cytology in the evaluation of extrahepatic cholestatic jaundice. J Cytol 2013; 30:162-8. [PMID: 24130407 PMCID: PMC3793352 DOI: 10.4103/0970-9371.117657] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background: Endoscopic evaluation is critical in assessing the cause of obstructive jaundice. Cytological techniques including bile aspiration and biliary brushings have become the initial diagnostic modality. Aim: The aim of this study is to evaluate the role of endoscopic biliary tract cytology as a diagnostic tool in the evaluation of extrahepatic cholestatic jaundice. Materials and Methods: A total of 56 biliary tract specimens including 34 bile aspirations and 22 biliary brushings from 41 consecutive patients who had presented with obstructive jaundice and underwent endoscopic retrograde cholangiopancreatography (ERCP) were assessed by cytological examination. The smears prepared were analyzed for standard cytological features. Results: Cytologic diagnosis was adenocarcinoma in 13 (31.7%) cases, atypical in 2 (4.9%), reactive in 3 (7.3%) and benign changes in 19 (46.3%) cases. 4 (9.8%) cases were non-diagnostic. Serum bilirubin was significantly elevated in the malignant group. Biliary stricture was the most common finding on ERCP (68.3%). On cytological examination, presence of solitary, intact atypical cells, enlarged nuclei, irregular nuclear membrane, coarse chromatin and nucleoli were important cytologic criteria for differentiating malignant from benign biliary specimens. Conclusions: Regular use of bile cytology and brushings during ERCP evaluation of extrahepatic cholestatic jaundice is invaluable in obtaining a morphologic diagnosis. A systematic approach, use of strict cytomorphologic criteria and inclusion of significant atypia as malignant diagnosis may improve the sensitivity.
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Affiliation(s)
- Mamta Gupta
- Department of Pathology, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
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17
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Noda Y, Fujita N, Kobayashi G, Ito K, Horaguchi J, Hashimoto S, Koshita S, Ishii S, Kanno Y, Ogawa T, Masu K, Tsuchiya T, Oikawa M, Honda H, Sawai T, Uzuki M, Fujishima F. Prospective randomized controlled study comparing cell block method and conventional smear method for bile cytology. Dig Endosc 2013; 25:444-52. [PMID: 23808950 DOI: 10.1111/j.1443-1661.2012.01404.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2012] [Accepted: 09/21/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM There is a paucity of data on the cell block (CB) method for bile cytology. We compared the diagnostic efficacy of the CB method with that of conventional smear cytology for bile obtained by endoscopic retrograde cholangiopancreatography (ERCP) in a randomized controlled trial manner. METHODS A total of 137 patients with biliary tract lesions suspicious of malignancy who had undergone bile collection under ERCP were recruited to this study. After sampling, the bile was randomized to the CB method (n = 69) or to smear cytology (n = 68). CB sections were prepared using the sodium alginate method and subjected to hematoxylin-eosin, Alcian blue-periodic acid-Schiff stain, and immunohistochemical stains. Both Papanicolaou and Giemsa stains were used for smear cytology. RESULTS The final diagnosis was malignancy in 94 patients: bile duct cancer, 42; pancreatic head cancer, 34; gallbladder cancer, 16; and ampullary cancer, two. The diagnostic accuracy of the CB method and that of smear cytology were 64% and 53%, respectively (P = 0.20). The sensitivity of the CB method (53%) was significantly better than that of smear cytology (28%; P = 0.014). Their respective sensitivities were 80% and 31% (P = 0.002) for bile duct cancer, 20% and 15% (P = 1.0) for pancreatic head cancer, and 30% and 67% (P = 0.30) for gallbladder cancer. CONCLUSION The CB method for bile cytology showed a higher diagnostic yield than smear cytology. Its diagnostic sensitivity was satisfactory in cases of bile duct cancer.
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Affiliation(s)
- Yutaka Noda
- Department of Gastroenterology, Sendai City Medical Center, Sendai, Japan.
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18
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Abdelghani YA, Arisaka Y, Masuda D, Takii M, Ashida R, Makhlouf MM, Fouad YM, Tsuji M, Kurisu Y, Higuchi K. Bile aspiration cytology in diagnosis of bile duct carcinoma: factors associated with positive yields. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2012; 19:370-378. [PMID: 21785970 DOI: 10.1007/s00534-011-0419-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND/PURPOSE In bile duct carcinoma (BDC) patients, bile aspiration cytology (BAC) is an established method for cytodiagnosis. However, almost all previous reports investigated the biliary strictures caused not only by BDC but also by gallbladder and pancreatic carcinomas. Therefore, BAC in BDC patients only has not yet been investigated sufficiently. The aim of this study was to evaluate the actual sensitivity of BAC and to evaluate the factors that affect positive yields of BAC in patients with defined BDC. METHODS Data on 47 consecutive patients with definite BDC, who underwent BAC via endoscopic nasobiliary drainage (ENBD) or percutaneous transhepatic cholangiodrainage (PTCD), were retrospectively collected. Fourteen factors were studied for association with positive BAC. RESULTS The number of cytological samplings ranged from 1 to 14 times. The cumulative diagnostic yield was 72.3% (34/47), and 32 positive results were obtained at a maximum of six samplings. Independent factors associated with positive BAC were perihilar location, stricture length ≥ 2 cm, and macroscopic papillary type. CONCLUSION In BDC patients with ENBD or PTCD, repeated BAC is useful, and six times was the optimum number of repeat samplings. Although the sensitivity of BAC is not sufficient for the preoperative diagnosis of malignant biliary stricture, the three independent factors noted above predict positive yields and indicate whether or not BAC should be repeated up to six times.
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Affiliation(s)
- Yasser A Abdelghani
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 568-8686, Japan
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19
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Dumonceau JM. Sampling at ERCP for cyto- and histopathologicical examination. Gastrointest Endosc Clin N Am 2012; 22:461-77. [PMID: 22748243 DOI: 10.1016/j.giec.2012.05.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Sampling at ERCP may be performed at the level of the papilla or of the biliopancreatic ducts. Samples collected at the level of the biliopancreatic ducts allow for diagnosing malignancy with a specificity close to 100% but present a moderate sensitivity in most studies. In this article, the different aspects of sampling at ERCP are discussed, and a special focus is placed on the means that are routinely available to the endoscopist for obtaining a high sensitivity for the diagnosis of malignancy.
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Affiliation(s)
- Jean-Marc Dumonceau
- Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva, Switzerland.
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20
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Yagioka H, Hirano K, Isayama H, Tsujino T, Sasahira N, Nagano R, Hamada T, Miyabayashi K, Ito Y, Mohri D, Kawakubo K, Kogure H, Sasaki T, Tada M, Koike K. Clinical significance of bile cytology via an endoscopic nasobiliary drainage tube for pathological diagnosis of malignant biliary strictures. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2011; 18:211-215. [PMID: 20931342 DOI: 10.1007/s00534-010-0333-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND/PURPOSE In patients in whom there is a suspicion of malignant biliary strictures, bile cytology via an endoscopic nasobiliary drainage tube (ENBD cytology) is often performed, in addition to aspirated bile cytology, brush cytology, and forceps biopsy, during the initial endoscopic retrograde cholangiopancreatography (ERCP). We aimed to reveal the significance of ENBD cytology for the pathological diagnosis of malignant biliary strictures. METHODS We studied 214 patients with malignant biliary strictures. We performed aspirated bile cytology, brush cytology, and forceps biopsy in 93, 130, and 114 patients, respectively. ENBD cytology was performed one or more times in 79 patients. We examined the sensitivity of each sampling method, and analyzed the utility of ENBD cytology. RESULTS The sensitivities of each sample acquisition method were as follows: 30% (28/93) for aspirated bile cytology, 48% (62/130) for brush cytology, 41% (47/114) for forceps biopsy, and 24% (19/79) for ENBD cytology. In 19 patients who showed positive ENBD cytology, other methods were performed in 11. Aspirated bile cytology, brush cytology, and forceps biopsy, were performed in 7, 5, and 6 patients, and the results were negative in 3 (43%), 2 (40%), and 1 (17%) patient, respectively. Three patients showed positive results only on ENBD cytology. CONCLUSIONS Although the sensitivity of ENBD cytology was inferior to that of the other methods used, ENBD cytology may contribute to the improvement of the total diagnostic sensitivity for malignancy.
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Affiliation(s)
- Hiroshi Yagioka
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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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; 98:704-9. [PMID: 21290384 DOI: 10.1002/bjs.7412] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/26/2010] [Indexed: 12/19/2022]
Abstract
BACKGROUND The diagnostic value of biliary cytology for hilar bile duct stricture is uncertain. This study prospectively examined three methods for the evaluation of biliary cytology in a consecutive group of patients. METHODS Preoperative bile sampling by aspiration through a drainage catheter (aspiration samples), saline flush through a drainage catheter (saline samples) or direct sampling from a drainage bag (bag samples) was performed in consecutive patients with suspected perihilar cholangiocarcinoma who underwent resection after endoscopic nasobiliary drainage or percutaneous transhepatic biliary drainage. All bile sampling was performed three times on separate days. The accuracy of cytology in the diagnosis of carcinoma was determined. RESULTS Of 100 consecutive patients with hilar strictures, 97 had histologically proven cholangiocarcinoma. The proportion of these 97 patients who had a positive finding on cytology in at least one of three sampling sessions was 55 per cent for aspiration samples, 48 per cent for bag samples and 38 per cent for saline samples (P = 0·021, aspiration versus saline). Tumour length correlated significantly with overall positivity. For aspiration samples, sensitivity was 55 per cent, specificity was 100 per cent and accuracy 56·0 per cent. CONCLUSION For biliary cytology, sampling by catheter aspiration is more effective than catheter flushing or sampling from a drainage bag. Repeated sampling increases sensitivity. Biliary cytology has modest diagnostic yield, but is easy to perform, highly specific, and can provide a definitive diagnosis.
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Affiliation(s)
- M Hattori
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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22
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Wen H, Yoo SS, Kang J, Kim HG, Park JS, Jeong S, Lee JI, Kwon HN, Kang S, Lee DH, Park S. A new NMR-based metabolomics approach for the diagnosis of biliary tract cancer. J Hepatol 2010; 52:228-33. [PMID: 20036026 DOI: 10.1016/j.jhep.2009.11.002] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2009] [Revised: 08/27/2009] [Accepted: 09/01/2009] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS Biliary tract cancer is highly lethal at presentation, with increasing mortality worldwide. Current diagnostic measures employing multiple criteria such as imaging, cytology, and serum tumor markers are not satisfactory, and a new diagnostic tool is needed. Because bile is a cognate metabolite-rich bio-fluid in the biliary ductal system, we tested a new metabolomic approach to develop an effective diagnostic tool. METHODS Biles were collected prospectively from patients with cancer (n=17) or benign biliary tract diseases (n=21) with percutaneous or endoscopic methods. Nuclear magnetic resonance spectra (NMR) of these biles were analyzed using orthogonal partial least square discriminant analysis (OPLS-DA). RESULTS The metabolomic 2-D score plot showed good separation between cancer and benign groups. The contributing NMR signals were analyzed using a statistical TOCSY approach. The diagnostic performance assessed by leave-one-out analysis exhibited 88% sensitivity and 81% specificity, better than the conventional markers (CEA, CA19-9, and bile cytology). CONCLUSION The NMR-based metabolomics approach provides good performance in discriminating cancer and benign biliary duct diseases. The excellent predictability of the method suggests that it can, at least, augment the currently available diagnostic approaches.
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Affiliation(s)
- He Wen
- Department of Biochemistry, Inha University Hospital and Center for Advanced Medical Education by BK21 Project, College of Medicine, Inha University, Incheon, Republic of Korea
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HIROOKA Y, NAKAIZUMI A, OKA T, NAITO Y, ARISAKA Y, MINAMIGUCHI S, HABA R, TAKENAKA A, FURUHATA A, MASUDA D. Report of the clinical study for methods to improve the diagnostic accuracy of bile cytology (1)-Diagnostic bile cytology criteria-. ACTA ACUST UNITED AC 2010. [DOI: 10.5795/jjscc.49.7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Iqbal S, Stevens PD. Cholangiopancreatoscopy for targeted biopsies of the bile and pancreatic ducts. Gastrointest Endosc Clin N Am 2009; 19:567-77. [PMID: 19917462 DOI: 10.1016/j.giec.2009.06.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Establishing a tissue diagnosis in patients with suspected pancreaticobiliary malignancies remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP)-based sampling methods have been reviewed in a previous issue of this journal but, unfortunately, the diagnostic yield continues to be inadequate in a significant minority of patients. The availability and image quality of cholangioscopy and pancreatoscopy have advanced in the last few years and our ability to make a diagnosis on imaging alone is improving. However, a definitive diagnosis requires tissue; cholangiopancreatoscopy allows targeted biopsies of the epithelium of the biliary and pancreatic ducts. This article reviews the evidence that cholangioscopy- and pancreatoscopy-guided biopsies improves diagnostic yield over ERCP-based tissue sampling techniques.
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Affiliation(s)
- Shahzad Iqbal
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, P&S 10-508, 630 West 168th Street, NY 10032, USA
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25
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Uchida N, Kamada H, Ono M, Aritomo Y, Masaki T, Nakatsu T, Kuriyama S. How many cytological examinations should be performed for the diagnosis of malignant biliary stricture via an endoscopic nasobiliary drainage tube? J Gastroenterol Hepatol 2008; 23:1501-4. [PMID: 18028351 DOI: 10.1111/j.1440-1746.2007.05214.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM The sensitivity of bile cytology is recognized as being low. Repeating cytological sampling is likely to improve the sensitivity. The aim of this study is to determine the optimal number of repeated cytological sampling of bile obtained via an endoscopic nasobiliary drainage (ENBD) tube for the diagnosis of malignant biliary stricture. METHODS Ninety-eight patients with malignant biliary stricture who underwent ENBD were enrolled. Diagnoses included bile duct carcinoma (n = 53), pancreatic carcinoma (n = 28), carcinoma of the major papilla (n = 8), gallbladder carcinoma (n = 6), and hepatocellular carcinoma (n = 3). Bile was aspirated via an ENBD tube once a day and immediately evaluated cytologically. RESULTS The median number of cytological samplings via an ENBD tube was 2.8 times (range, 1-10). In 40 of 98 patients with malignant biliary stricture, cytology was positive at the first cytological sampling (sensitivity 40.8%). Cytology was cumulatively positive in 71 of 98 patients (sensitivity 72.4%) from which repeated samples were taken. In 71 patients with positive cytology, correlation of the positive rate and the number of cytological samplings performed was investigated. In 68 of 71 (95.8%) patients with positive cytology, positive results were obtained by or at the sixth examination. CONCLUSIONS Bile cytology via an ENBD tube is an easy method, and has been shown to have relatively high sensitivity. The optimal number of repeated cytological samplings using bile obtained via an ENBD tube for the diagnosis of malignant biliary stricture was concluded to be six.
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Affiliation(s)
- Naohito Uchida
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan.
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Cholangiocarcinoma: natural history, treatment, and strategies for surveillance in high-risk patients. J Clin Gastroenterol 2008; 42:178-90. [PMID: 18209589 DOI: 10.1097/mcg.0b013e31806daf89] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma is a primary malignancy of biliary epithelium. Risk factors for cholangiocarcinoma include primary sclerosing cholangitis and other conditions that produce chronic inflammation of the biliary tree. The diagnosis of cholangiocarcinoma can be elusive; it is often not made until advanced disease is present and at a stage when a curative surgical resection is not feasible. Currently used diagnostic modalities include serum and bile tumor markers, radiologic and endoscopic imaging, and pathologic analysis. Surveillance strategies to increase the chance of early diagnosis should be strongly considered in individuals at high risk for cholangiocarcinoma. Patients with long-standing primary sclerosing cholangitis would be the ideal candidates for a screening program.
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27
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Kitajima Y, Ohara H, Nakazawa T, Ando T, Hayashi K, Takada H, Tanaka H, Ogawa K, Sano H, Togawa S, Naito I, Hirai M, Ueno K, Ban T, Miyabe K, Yamashita H, Yoshimura N, Akita S, Gotoh K, Joh T. Usefulness of transpapillary bile duct brushing cytology and forceps biopsy for improved diagnosis in patients with biliary strictures. J Gastroenterol Hepatol 2007; 22:1615-20. [PMID: 17573833 DOI: 10.1111/j.1440-1746.2007.05037.x] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM Transpapillary bile duct brushing cytology and/or forceps biopsy was performed in the presence of an indwelling guidewire in patients with biliary stricture, and the treatment time, overall diagnosis rate, diagnosis rate of each disease, complications, and influences on subsequent biliary drainage were investigated. METHODS After endoscopic retrograde cholangiography, brushing cytology was performed, followed by forceps biopsy. In patients with obstructive jaundice, endoscopic biliary drainage (EBD) was subsequently performed. To investigate the influences of bile duct brushing cytology and forceps biopsy on EBD, patients who underwent subsequent EBD by plastic stent were compared with patients who underwent EBD alone. RESULTS The samples for cytology were collected successfully in all cases, and the sensitivity for malignancy/benignity, specificity, and accuracy were 71.6%, 100%, and 75.0%, respectively. The biopsy sampling was successful in 51 patients, and samples applicable to the evaluation were collected in all 51 patients. The sensitivity for malignancy/benignity, specificity, and accuracy were 65.2%, 100%, and 68.6%, respectively. Combination of the two procedures increased the sensitivity and accuracy to 73.5% and 76.6%, respectively. The time required for cytology and biopsy was 11.7 min, which is relatively short. Cytology and biopsy did not affect drainage. Regarding accidents, bile duct perforation occurred during biopsy in one patient (1.9%), but was rapidly improved by endoscopic biliary drainage. CONCLUSIONS Transpapillary brushing cytology and forceps biopsy could be performed in a short time. The diagnosis rate was high, and the incidence of complication was low, having no influence on subsequent biliary drainage.
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Affiliation(s)
- Yasuhiro Kitajima
- Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
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Kipp BR, Stadheim LM, Halling SA, Pochron NL, Harmsen S, Nagorney DM, Sebo TJ, Therneau TM, Gores GJ, de Groen PC, Baron TH, Levy MJ, Halling KC, Roberts LR. A comparison of routine cytology and fluorescence in situ hybridization for the detection of malignant bile duct strictures. Am J Gastroenterol 2004; 99:1675-81. [PMID: 15330900 DOI: 10.1111/j.1572-0241.2004.30281.x] [Citation(s) in RCA: 252] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM The aim of this study was to assess the relative sensitivities and specificities of fluorescence in situ hybridization (FISH) and routine cytology for the detection of malignancy in biliary tract strictures. METHODS Bile duct brushing and aspirate specimens were collected from 131 patients being evaluated for possible malignant bile duct strictures. Both specimen types were assessed by FISH but only brushing specimens were assessed by cytology. The FISH assay used a mixture of fluorescently-labeled probes to the centromeres of chromosomes 3, 7, and 17 and chromosomal band 9p21 (Vysis UroVysion) to identify cells having chromosomal abnormalities. A case was considered positive for malignancy if five or more cells exhibited polysomy. RESULTS Sixty-six of the 131 patients had surgical pathologic and/or clinical evidence of malignancy. Thirty-nine patients had cholangiocarcinoma, 19 had pancreatic carcinoma, and 8 had other types of malignancy. The sensitivity of cytology and FISH for the detection of malignancy in bile duct brushing specimens in these patients was 15% and 34% (p < 0.01), respectively. The sensitivity of FISH for the bile aspirate specimens was 23%, and the combined sensitivity of FISH for aspirate and brushing specimens was 35%. The specificity of FISH and cytology brushings were 91% and 98% (p= 0.06), respectively. CONCLUSIONS FISH is significantly more sensitive than and nearly as specific as conventional cytology for the detection of malignant biliary strictures in biliary brushing specimens. FISH may improve the clinical management of patients who are being evaluated for malignancy in bile duct strictures.
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Affiliation(s)
- Benjamin R Kipp
- Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
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Qin XL, Wang ZR, Shi JS, Lu M, Wang L, He QR. Utility of serum CA19-9 in diagnosis of cholangiocarcinoma: In comparison with CEA. World J Gastroenterol 2004; 10:427-32. [PMID: 14760772 PMCID: PMC4724921 DOI: 10.3748/wjg.v10.i3.427] [Citation(s) in RCA: 124] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: The diagnosis of cholangiocarcinoma is often difficult, making management approaches problematic. A reliable serum marker for cholangiocarcinoma would be a useful diagnostic test. The aims of our study were to evaluate the usefulness of a serum CA19-9 determination in the diagnosis of cholangiocarcinoma.
METHODS: We prospectively measured serum CA19-9 and CEA concentrations in patients with cholangiocarcinoma (n = 35), benign biliary diseases (n = 92), and healthy individuals (n = 15). Serum CA19-9 and CEA concentrations were measured by an immunoradiometric assay without knowledge of the clinical diagnosis.
RESULTS: The sensitivity of a CA19-9 value > 37 KU·L-1 and a CEA value > 22 μg·L-1 in diagnosing cholangiocarcinoma were 77.14% and 68.57%, respectively. When compared with the benign biliary diseases group, the true negative rates of serum CA19-9 and CEA were 84.78% and 81.52%, respectively. The false positive rates of serum CA19-9 and CEA were 15.22% and 18.48%, whereas the accuracy of serum CA19-9 and CEA were 82.68% and 77.95%, respectively. Serum CA19-9 and CEA concentrations were significantly elevated (P < 0.001 and P < 0.05) in patients with cholangiocarcinoma (290.31 ± 5.34 KU·L-1 and 36.46 ± 18.03 μg·L-1) compared with patients with benign biliary diseases (13.38 ± 2.59 KU·L-1 and 13.84 ± 3.85 μg·L-1) and healthy individuals (12.78 ± 3.69 KU·L-1 and 11.48 ± 3.37 μg·L-1). In 15 patients undergoing curative resection of cholangiocarcinoma, the mean serum CA19-9 concentration was decreased from a preoperative level of 286.41 ± 4.36 KU·L-1 to a postoperative level of 62.01 ± 17.43 KU·L-1 (P < 0.001), and the mean serum CEA concentration from 39.41 ± 24.35 μg·L-1 to 28.69 ± 11.03 μg·L-1(P < 0.05). In patients with cholangiocarcinoma, however, no correlation was found between serum CEA and CA19-9 concentrations (r = 0.036).
CONCLUSION: These data suggest that the serum CA19-9 determination is a useful addition to the available tests for the differential diagnosis of cholangiocarcinoma. Serum CA19-9 is an effective tumor marker in diagnosing cholangiocarcinoma, deciding whether the tumor has been radically resected and monitoring effect of treatment.
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Affiliation(s)
- Xing-Lei Qin
- Department of Hepatobiliary Surgery, First Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
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30
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Kim HJ, Lee KT, Kim SH, Lee JK, Lim JH, Paik SW, Rhee JC. Differential diagnosis of intrahepatic bile duct dilatation without demonstrable mass on ultrasonography or CT: benign versus malignancy. J Gastroenterol Hepatol 2003; 18:1287-1292. [PMID: 14535986 DOI: 10.1046/j.1440-1746.2003.03169.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The purpose of the present study was to define the differential diagnostic markers of benign and malignant bile duct strictures without demonstrable mass on ultrasonography (US) or computed tomography (CT) using aspects of clinical, laboratory and imaging findings. METHODS Between February 1995 and February 2001, 24 patients who underwent surgical resection for dilations of the bile duct (peripheral and hilar) without visible mass lesion on US or CT were included in our study. Hospital records, laboratory results, findings of imaging studies and pathological findings were reviewed retrospectively. RESULTS For laboratory results, levels of alkaline phosphatase (benign 163.9 +/- 145.1 vs malignant 407.25 +/- 481.7; p < 0.05) and CA 19-9 (benign 25.0 +/- 41.1 vs malignant 614.6 +/- 818.5; p < 0.05) levels were significantly elevated in the malignant group compared with that of the benign group. Findings such as thickening of the bile duct wall >/= 5 mm (P < 0.05) on radiological examination, significant regional lymph node enlargement (> 1 cm, p = 0.01) on CT scan and abrupt cut-off (P < 0.01), and separation of bile ducts (P < 0.05) on cholangiogram were differential diagnostic markers between the two groups. CONCLUSIONS Preoperative laboratory data such as alkaline phosphatase and CA 19-9, and imaging findings such as significant wall thickening and regional lymph node enlargement on CT, abrupt cut-off and separation of bile duct on cholangiogram are useful differential diagnostic markers for benign and malignant bile duct strictures without demonstrable mass on US or CT.
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Affiliation(s)
- Hong Joo Kim
- Division of Gastroenterology and Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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de Bellis M, Fogel EL, Sherman S, Watkins JL, Chappo J, Younger C, Cramer H, Lehman GA. Influence of stricture dilation and repeat brushing on the cancer detection rate of brush cytology in the evaluation of malignant biliary obstruction. Gastrointest Endosc 2003; 58:176-82. [PMID: 12872082 DOI: 10.1067/mge.2003.345] [Citation(s) in RCA: 128] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The sensitivity for cancer detection of brush cytology at ERCP is relatively low. Manipulation of the stricture and repeated tissue sampling may increase the yield. This study compared the cancer detection rate of brush cytology before and after biliary stricture dilation. METHODS In patients with a biliary stricture at ERCP of suspected malignant origin, the stricture was sampled with a cytology brush and then dilated with either a graduated dilating catheter or a dilating balloon (4-8 mm). Brushing was then repeated in all patients. Specimens were interpreted as normal, atypical (benign), highly atypical (suspicious for cancer), and malignant. Final diagnoses were based on cytology plus surgery, EUS, percutaneous biopsy, autopsy, or clinical follow-up. RESULTS A total of 139 patients with suspected malignant obstructive jaundice underwent 143 ERCPs (116 ultimately found to have malignant obstruction, and 27 benign disease). Dilation was performed with a catheter in 68 cases, balloon in 73, and both in 2. Brush cytology had a sensitivity of 34.5% (40/116) before dilation and 31% (36/116) after dilation (p = NS). However, sensitivity with predilation and postdilation brushing specimens combined was 44% (51/116), which was higher than that for either the predilation or postdilation brush cytology (p = 0.001). Cancer detection rates were 34.7% (17/49) after dilation with the catheter and 27.7% (18/65) after balloon dilation (p = NS). CONCLUSIONS Stricture dilation does not improve the sensitivity of brush cytology for the detection of cancer, which remains relatively low. However, repeat brushing increases the diagnostic yield and should be performed when sampling biliary strictures with a cytology brush at ERCP.
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Affiliation(s)
- Mario de Bellis
- Division of Gastroenterology/Hepatology, Department of Pathology and Laboratory Medicine, Indiana University Medical Center, Indianapolis, Indiana, USA
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32
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De Bellis M, Sherman S, Fogel EL, Cramer H, Chappo J, McHenry L, Watkins JL, Lehman GA. Tissue sampling at ERCP in suspected malignant biliary strictures (Part 1). Gastrointest Endosc 2002. [PMID: 12297773 DOI: 10.1016/s0016-5107(02)70442-2] [Citation(s) in RCA: 113] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Mario De Bellis
- Division of Gastroenterology/Hepatology, Department of Pathology and Laboratory Medicine, Indiana University Medical Center, Indianapolis, Indiana 46202, USA
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Binkley CE, Eckhauser FE, Colletti LM. Unusual causes of benign biliary strictures with cholangiographic features of cholangiocarcinoma. J Gastrointest Surg 2002; 6:676-81. [PMID: 12399056 DOI: 10.1016/s1091-255x(01)00062-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Focal strictures occurring at the hepatic duct confluence, or within the common hepatic duct or common bile duct in patients without a history of prior surgery in that region or stone disease, are usually thought to represent cholangiocarcinoma until proved otherwise. However, not uncommonly, patients undergo surgical exploration for a preoperative diagnosis of cholangiocarcinoma, based on the cholangiographic appearance of the lesion, only to find histologically that the stricture was benign in nature. Despite sophisticated radiographic, endoscopic, and histologic studies, it is often impossible before laparotomy to distinguish malignant from benign strictures when they have the characteristic radiographic appearance of cholangiocarcinoma. Even at the risk of overtreating some benign cases, most agree that aggressive surgical resection is the treatment of choice, given the serious consequences resulting from a failure to diagnose and adequately treat cholangiocarcinoma. Four patients who presented to our institution between February 1991 and June 2000 underwent laparotomy for a preoperative diagnosis of biliary tract malignancy based on clinical presentation and cholangiographic findings. The final pathology report in all patients showed marked fibrosis and inflammation of the biliary duct without evidence of malignancy. A review of the patient data and the relevant literature identified benign causes of focal extrahepatic biliary strictures associated with concomitant disease processes in two of the four patients. We present these cases and discuss the benign etiologies with emphasis on the role of surgery in both diagnosis and treatment.
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Affiliation(s)
- Charles E Binkley
- Division of Gastrointestinal Surgery, Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan 48109-0331, USA
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Krishnamurthy S, Katz RL, Shumate A, Strohlein K, Khanna A, Tucker SL, Raijman I, Lahoti S. DNA image analysis combined with routine cytology improves diagnostic sensitivity of common bile duct brushing. Cancer 2001; 93:229-35. [PMID: 11391612 DOI: 10.1002/cncr.9034] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Cytologic evaluation of common bile duct brushings has a low sensitivity for diagnosing malignancy because of scant cellularity, poor cellular preservation, or sampling errors occur. The aim of this study was to evaluate whether cytology combined with image analysis improves the diagnostic accuracy of bile duct brushing in comparison with cytology alone. METHODS Forty-nine specimens of bile duct brushings obtained from 45 patients during endoscopic retrograde cholangiopancreatography were evaluated using cytology and image analysis. Specimens were classified as negative, atypical, suspicious, or malignant by using cytologic evaluation. DNA histograms were classified as diploid (D), broad diploid (BD), aneuploid (A), or tetraploid (T). Degree of hyperploidy (DH), representing cells with a DNA content > 5C was evaluated using a cutoff value of > or = 1%. Final diagnosis of cancer was based on tissue specimens that were obtained by fine-needle aspiration or surgical biopsy and clinical fol- low-up. RESULTS Thirty-four patients ultimately proved to have a malignancy. Cytology revealed 19 negative cases, 15 atypical cases, 9 suspicious cases, and 6 malignant cases. Together, suspicious and malignant cytology cases yielded a sensitivity of 44% and a specificity of 100% for a cytologic diagnosis of cancer. The DNA histogram pattern was D in 24 cases, BD in 9 cases, and A in 16 cases. BD and A patterns were significantly associated with malignancy (P < 0.001). A DH > or = 1% was noted in 22 cases. DH alone had a sensitivity of 62% and a specificity of 91% and was significantly associated with malignancy (P < 0.004). Atypical cytology alone had a false-negative rate of 29%, but in combination with a DH > or = 1%, the false-negative rate decreased to 7%. Additionally, when the authors combined atypical, suspicious, and malignant cytology with a DH > or = 1%, the diagnostic sensitivity increased to 88%, but the specificity decreased to 73%. CONCLUSIONS Combined cytology and image analysis of bile duct brushing increased diagnostic sensitivity compared with cytology alone. The findings suggest that image analysis may help select patients having atypical cytology who should undergo a more rigorous evaluation for malignancy. A larger prospective study of the usefulness of combined cytology and image analysis of bile duct brushing is warranted.
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Affiliation(s)
- S Krishnamurthy
- Department of Cytopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
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Jailwala J, Fogel EL, Sherman S, Gottlieb K, Flueckiger J, Bucksot LG, Lehman GA. Triple-tissue sampling at ERCP in malignant biliary obstruction. Gastrointest Endosc 2000; 51:383-90. [PMID: 10744806 DOI: 10.1016/s0016-5107(00)70435-4] [Citation(s) in RCA: 230] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Procurement of cytologic samples by brushing is common practice at endoscopic retrograde cholangiopancreatography (ERCP) but has low sensitivity for cancer detection. Limited data are available on other techniques, including endoluminal fine-needle aspiration and forceps biopsy. This series reviews the yield of these three stricture sampling methods. METHODS In this prospective study, patients with biliary obstruction with a clinical suspicion of malignancy underwent triple-tissue sampling at one ERCP session. Final cancer diagnosis was based on all sampling methods plus surgery, autopsy, and clinical follow-up. Tissue specimens were reported as normal, atypia, or malignant. RESULTS A total of 133 patients were evaluated: 104 had cancer and 29 had benign strictures. Tissue sampling sensitivity varied according to the type of cancer; the highest yield was seen in ampullary cancers (62% to 85%). The cumulative sensitivity of triple-tissue sampling in the cancer patients was as follows: sensitivity was 52% if atypia was considered benign and 77% if it was considered malignant. The addition of a second or third technique increased sensitivity rates in most instances. No serious complications occurred from the tissue sampling methods. CONCLUSIONS Tissue sampling sensitivity varied according to the type of cancer. Combining a second or third method increased sensitivity; general use of at least two sampling methods is therefore recommended.
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Affiliation(s)
- J Jailwala
- Indiana University Medical Center, Indianapolis, Indiana 46202, USA
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Patel AH, Harnois DM, Klee GG, LaRusso NF, Gores GJ. The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis. Am J Gastroenterol 2000; 95:204-7. [PMID: 10638584 DOI: 10.1111/j.1572-0241.2000.01685.x] [Citation(s) in RCA: 284] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The diagnosis of cholangiocarcinoma is often difficult, making management approaches problematic. A reliable serum tumor marker for cholangiocarcinoma would be a useful additional diagnostic test. Previous studies have demonstrated that elevated serum concentrations of CA 19-9, a tumor-associated antigen, have good sensitivity and specificity for cholangiocarcinoma in patients with primary sclerosing cholangitis. However, the value of this tumor marker for cholangiocarcinoma unassociated with primary sclerosing cholangitis is unclear. Thus, the aims of this study were to determine the usefulness of a serum CA 19-9 determination in the diagnosis of de novo cholangiocarcinoma. METHODS We prospectively measured serum CA 19-9 concentrations in patients with cholangiocarcinoma (n = 36), nonmalignant liver disease (n = 41), and benign bile duct strictures (n = 26). Serum CA 19-9 concentrations were measured by an immunoradiometric assay (CIS Bio International) without knowledge of the clinical diagnosis. RESULTS The sensitivity of a CA 19-9 value >100 U/ml in diagnosing cholangiocarcinoma was 53%. When compared with the nonmalignant liver disease and the benign bile duct stricture groups, the true negative rates were 76% and 92%, respectively. Patients with unresectable cholangiocarcinoma had significantly greater mean CA 19-9 concentrations compared to patients with resectable cholangiocarcinoma. CONCLUSIONS These data suggest that the serum CA 19-9 determination is a useful addition to the available tests for the differential diagnosis of cholangiocarcinoma.
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Affiliation(s)
- A H Patel
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA
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Carrasco L, Sanchez-Bueno F, Sola J, Robles R, Rodriguez JM, Ramirez P, Lujan JA, Acosta F, Parrilla P. Use of bile cytology for early diagnosis of complications in orthotopic liver transplantation. Cytopathology 1998; 9:406-414. [PMID: 9861533 DOI: 10.1046/j.1365-2303.1998.00100.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
We conducted a daily analysis of bile cellularity in 25 patients undergoing 29 orthotopic liver transplants (OLT) and correlated the cytological parameters with the clinical outcome of each patient. The 16 patients without complications only showed slides with cells during the first 4-5 postoperative days. The four patients with primary non-function (PNF) of the graft had a high cell density up to the time of the retransplant, with a preponderance of polymorphonuclear (PMN) leucocytes (59.2%) and epithelial cells (29.2%). During the episodes of sepsis (n = 3) and rejection (n = 7) we noted the sudden appearance of high cellularity, almost exclusively PMN leucocytes (96.5%), and a preponderance of PMN leucocytes (84.2%) with appreciable percentages of mononuclear cells and macrophages as well as the early appearance of lymphoblasts in the rejection episodes. Our results show that bile cytology can be a useful method for diagnosing graft complications in liver transplantation.
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Affiliation(s)
- L Carrasco
- Department of Surgery, University Hospital Virgen de la Arrixaca, Murcia, Spain
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Savader SJ, Lynch FC, Radvany MG, Kudryk BT, Andrews RT, Geschwind JF, Singh H, Hamet MR. Single-specimen bile cytology: a prospective study of 80 patients with obstructive jaundice. J Vasc Interv Radiol 1998; 9:817-21. [PMID: 9756072 DOI: 10.1016/s1051-0443(98)70397-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
PURPOSE To determine the sensitivity, specificity, and charges associated with single-specimen bile cytologic study in patients with obstructive jaundice. MATERIALS AND METHODS Eighty consecutive patients with presumed malignant biliary strictures underwent percutaneous biliary drainage (PBD). Cytologic evaluation was performed on a single bile specimen from each patient collected at the time of the PBD. Final diagnoses were obtained from either percutaneous (n = 14) or surgical (n = 66) histologic specimens (gold standard). Both data sets were then compared to determine the sensitivity and specificity of bile cytology. The charges associated with bile cytodiagnosis were compared to those for other biopsy procedures utilized in the same setting. RESULTS Eighty bile specimens were obtained with a mean of 14 mL (range, 3-65 mL) per patient with 79 (99%) specimens adequate for cytologic processing. Eleven (13%) specimens were acellular. The overall sensitivity was 15% and specificity was 100%; these values were not dependent on the volume of the bile specimen (P > .10) or type of malignancy (P = .10). For bile cytodiagnosis, the mean charge was $160 and the successful biopsy rate (true-positive plus true-negative results/total number procedures) was 27%. CONCLUSION Single-specimen bile cytology has a low sensitivity; however, because of its convenience, simplicity, atraumatic nature, and low relative charge versus comparable procedures, it may be useful as an adjunct to PBD in patients with suspected malignant biliary disease.
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Affiliation(s)
- S J Savader
- Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
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Tamada K, Ueno N, Tomiyama T, Oohashi A, Wada S, Nishizono T, Tano S, Aizawa T, Ido K, Kimura K. Characterization of biliary strictures using intraductal ultrasonography: comparison with percutaneous cholangioscopic biopsy. Gastrointest Endosc 1998; 47:341-9. [PMID: 9609424 DOI: 10.1016/s0016-5107(98)70216-0] [Citation(s) in RCA: 133] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND We determined the accuracy of intraductal ultrasonography (IDUS) in distinguishing between bile duct cancer and benign bile duct disease. METHODS Patients (n=42) who required bile duct biopsy using percutaneous transhepatic cholangioscopy (PTCS) to evaluate bile duct strictures or filling defects were studied. A thin-caliber ultrasonic probe (2.0 mm diameter and 20 MHz frequency) was inserted into the bile duct, and its images were prospectively reviewed before PTCS. RESULTS Disruption of the bile duct wall structure, seen on IDUS, was associated with malignancy in 25 of 26 patients. When IDUS demonstrated a lesion with normal bile duct structure, six of nine patients were found to have no malignancy. IDUS demonstrated no intraductal lesion in seven patients, and bile duct biopsy also did not indicate cancer in any of these patients. The accuracy, sensitivity, and specificity of IDUS for diagnosing bile duct cancer were 76%, 89%, and 50%, respectively. When used in tandem with IDUS, the sensitivity of bile cytology (64%) and PTCS (93%) improved to 96% and 100%, respectively. CONCLUSIONS The accuracy of IDUS for diagnosing bile duct cancer was less than that of PTCS (95%). However, the sensitivity for bile cytology, or bile duct biopsy improved when performed in combination with IDUS.
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Affiliation(s)
- K Tamada
- Department of Gastroenterology, Jichi Medical School, Tochigi, Japan
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Abstract
Benign biliary strictures can now be effectively treated with endoscopic therapy in a variety of clinical situations. Despite recent developments in imaging techniques (endoscopic ultrasound and magnetic resonance imaging), it is often difficult to differentiate benign from malignant biliary strictures. The sensitivity of tissue diagnosis (cytology and needle biopsy) at endoscopic retrograde cholangiopancreatography (ERCP) remains poor (40-50%), and further diagnostic methods are required. Endoscopic therapy offers a definitive treatment in 70-90% of patients following post-operative biliary stricture, including anastomotic strictures following liver transplant. Endoscopic therapy successfully achieves symptomatic, biochemical, and cholangiographic response, and may improve survival in patients with primary sclerosing cholangitis. Strictures secondary to chronic pancreatitis are resistant to standard endoscopic therapy and metallic endoprotheses have been trialed with varying success. Endoscopic therapy is technically difficult and should be performed in specialized centres using a multidisciplinary approach.
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Affiliation(s)
- J C Gibbons
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, NSW, Australia
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Abstract
BACKGROUND Bile duct strictures may be benign or malignant. A definite diagnosis is desirable to advise patients of their prognosis and to identify any amenable to curative surgery. AIMS To compare different methods of cytology sampling from biliary strictures and evaluate the use of cytology in this context. PATIENTS AND METHODS In a prospective study 54 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) had cytology samples obtained as follows: (1) biliary stricture brushings, (2) from the screw thread of a "Soehendra stent retriever" inserted through the stricture, (3) from the proximal end of a blocked biliary stent, and (4) cellular material spun down from a 20 ml specimen of bile. Examination of slides and rinsings was performed by an expert cytologist who graded them for the adequacy of the sample and for evidence of malignancy. RESULTS Prolonged follow up disclosed malignancy in 52 of the 54 cases, the other two being chronic pancreatitis. Bile samples provided adequate cytology samples in 44%, the Soehendra stent retriever in 70%, retrieved stents in 84%, and cytology brush sampling in 96%. Overall, 28 malignancies were detected by cytology, including 14 of 28 pancreatic carcinomas and 12 of 16 cholangiocarcinomas. Twenty two of the malignancies were detected by brush sampling and the other methods added a total of another six cases. CONCLUSIONS Cytology sampling is best done by brushing the biliary stricture. Cytology sampling can confirm the diagnosis in 75% of cholangiocarcinomas and 50% of pancreatic carcinomas. The techniques involved are simple to perform and should be routine clinical practice whenever potentially malignant biliary strictures are encountered at ERCP.
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Affiliation(s)
- J C Mansfield
- Gastroenterology Unit, Royal Victoria Infirmary, Newcastle upon Tyne
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de Peralta-Venturina MN, Wong DK, Purslow MJ, Kini SR. Biliary tract cytology in specimens obtained by direct cholangiographic procedures: a study of 74 cases. Diagn Cytopathol 1996; 14:334-48. [PMID: 8725136 DOI: 10.1002/(sici)1097-0339(199605)14:4<334::aid-dc12>3.0.co;2-l] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
A retrospective review of bile (BL) and biliary tract brushings (Br) obtained by endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) was undertaken to determine the sensitivity and specificity of cytology in the diagnosis of pancreaticobiliary malignancies. A total of 104 cytologic specimens (PTC-BL 15, PTC-Br 13, ERCP-BL 8, ERCP-Br 68) received between 1990 and mid-1994 from 77 patients who had undergone ERCP and/or PTC primarily for biliary stricture were reviewed. Specimens were unsatisfactory/ inadequate in 11 (10.6%), benign in 41 (39.4%), suspicious in 25 (24%), and positive for malignant cells in 27 (26%). Follow-up was available in 74/77 patients; 46 (59.7%) had tissue confirmation while 28 (32.5%) had adequate clinical follow-up based on chart review. Of those with histologic confirmation, there were 32 malignant and 14 benign cases. The overall sensitivity and specificity of PTC- and ERCP-obtained cytologic specimens were 88.9 and 95.7% respectively. There was only one false positive case (ERCP-Br). Overall positive predictive value was 96% negative predictive value 88%, and accuracy 96%. PTC had a significantly lower sensitivity rate (42.8%) and higher rate for unsatisfactory specimens (21%) compared with ERCP-obtained material (100 and 1.9%). Bile obtained by PTC or ERCP appeared less sensitive in detecting malignancies compared with endoscopic brushing using either technique (BL 50% vs. Br 100%). All three false negative cases were PTC-BL specimens. Of the 17 suspicious cases, eight were confirmed histologically as malignant, four were clinically consistent with malignancy, and five showed marked inflammatory atypia on biopsy. Positive predictive value and accuracy rate of a "suspicious cytology" diagnosis were 69 and 80.5%, respectively. Inadequate specimen, poor cellular preservation, and cells obscured by bile all interfere with proper cytologic evaluation. Experience is necessary to appreciate subtle malignant changes in well differentiated carcinomas. Communication between the cytopathologist and the clinician is critical in the accurate interpretation and proper management of the patients.
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Jones RS. The Biopsy of Hepatobiliary and Pancreatic Masses. Surg Oncol Clin N Am 1995. [DOI: 10.1016/s1055-3207(18)30468-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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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; 40:150-4. [PMID: 8013812 DOI: 10.1016/s0016-5107(94)70157-1] [Citation(s) in RCA: 58] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The disruption of malignant biliary strictures by dilation could enhance the results of bile cytology. To test this hypothesis, we studied the results of bile cytology in 64 consecutive patients undergoing endoscopic biliary drainage for malignant biliary strictures. Patients included 36 men and 28 women, ages 29 to 79 years. In the control group (n = 15), bile was obtained by aspiration without dilating the biliary stricture. In the dilated group (n = 49), bile was aspirated after dilating the biliary stricture to 10F gauge. The bile was centrifuged, and smears were prepared, stained, and interpreted as malignant, suggestive of malignancy, or not malignant. The biliary obstruction was caused by gallbladder cancer in 33, primary bile duct cancer in 14, pancreatic cancer in 11, and metastasis in 6 patients. Forty patients had obstruction at the bifurcation of the hepatic duct. Malignancy was confirmed by surgery in 14, fine-needle aspiration cytology in 9, presence of metastasis in 19, and a combination of clinical and radiologic studies, endoscopic cholangiopancreatography findings, elevated tumor markers, and follow-up in 22 patients. Bile cytology was positive for malignancy in 4 (26.6%) and 31 (63.3%), suggestive in 1 (6.7%) and 6 (12.2%), and negative in 10 (66.7%) and 12 (24.5%) patients in the control group and the dilated group, respectively (p = 0.028, 95% CI 1.15 and 21.03). Cytology was positive in 73% of gallbladder cancers, 62.5% of bile duct cancers, 40% of pancreatic cancers, and 60% of metastasized cancers after dilation. Two patients had hemobilia, 8 had cholangitis, and 2 had pancreatitis after biliary drainage.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- K M Mohandas
- Division of Gastroenterology, Tata Memorial Hospital, Bombay, India
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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. [PMID: 8244264 DOI: 10.1002/hep.1840180618] [Citation(s) in RCA: 100] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In patients with obstructive jaundice due to biliary tract stricture a tissue diagnosis is essential because of the varied treatment options available. Radiological imaging of a biliary stricture may suggest that it is malignant, but only a tissue diagnosis can be conclusive. The difficulty of obtaining biopsy tissue has encouraged the use of cytology in this field. This study prospectively analyzed the diagnostic value of exfoliative bile and brush cytology methods. One hundred consecutive patients with biliary strictures diagnosed at endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography (60 men and 40 women; median age = 71 yr, range = 31 to 91 yr) underwent biliary cytology and were divided into two groups. Group 1 comprised the first 47 patients, who were studied by means of bile cytology alone; and group 2 comprised the subsequent 46 patients, who were studied by means of bile and brush cytology techniques. Seven patients were excluded from analysis because of inadequate follow-up information. A single experienced cytologist examined all samples to determine whether they were neoplastic. Eighty-one patients had malignant strictures and 12 had benign strictures. Combined bile and brush cytology (group 2) was more sensitive than bile cytology alone (group 1) (69% [27 of 39] vs. 33% [16 of 42], p < 0.01). In the patients studied by means of bile and brush cytology methods (group 2), cytologic study of brushings was more sensitive (69% vs. 26%, p < 0.01). No false-positive results were reported in either group (specificity = 100%).(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- T R Kurzawinski
- Hepatobiliary and Liver Transplantation Unit, Royal Free Hospital, London, United Kingdom
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Affiliation(s)
- B R Davidson
- Hepatobiliary and Liver Transplantation Unit, Royal Free Hospital Medical School, London
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Abstract
Over the past 20 years, bile aspiration at endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography has been developed for cytological diagnosis of biliary tract stricture. This safe and specific test has allowed a diagnosis to be reached before or without operation in about one-third of malignancies of the pancreas or biliary tree. The recent development of biliary brush cytology has produced better results. An endobiliary biopsy forceps is now available that may allow safe sampling of lesions causing extrinsic compression of the biliary tract. An endobiliary aspiration cytology needle has been produced that may permit non-ulcerating lesions to be diagnosed. A safe alternative to endobiliary methods is percutaneous fine-needle aspiration cytology; this yields a diagnosis in about half of patients presenting with obstructive jaundice and an imaged mass lesion.
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Affiliation(s)
- T Kurzawinski
- Department of Surgery, Royal Free Hospital and Medical School, London, UK
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