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Zeng XT, Liang X, Hong ZL, Chen S, Yang JC, Lin YC, Wu SS. Initial investigation on ultrasound-guided percutaneous biopsy of lesions in the first hepatic hilum with fusion of ultrasound and multimodal imaging cognitive guidance. Front Oncol 2024; 14:1297153. [PMID: 38720805 PMCID: PMC11077297 DOI: 10.3389/fonc.2024.1297153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 03/21/2024] [Indexed: 05/12/2024] Open
Abstract
Purpose This study aims to evaluate the efficacy and safety of ultrasound-guided percutaneous biopsy of the first hepatic hilum lesion, and examine its clinical value of diagnosis and treatment. Methods We conducted a retrospective study on patients diagnosed with the first hepatic hilum lesions at Fujian Provincial Hospital between February 2015 and October 2022. We selected patients who had lesions in the first hepatic hilum(including a 2cm surrounding area of the left/right hepatic ducts and upper-middle segment of the common bile duct) and the liver periphery(in the peripheral area of the liver, outside of the above-mentioned first hepatic porta region). These patients underwent percutaneous ultrasound-guided core needle biopsy (PUS-CNB) with cognitive fusion guidance using CT, MRI, or PET-CT. We compared the safety and efficacy of PUS-CNB in the first hepatic hilum and the liver periphery to explore the value of PUS-CNB in optimizing the clinical treatment of the first hepatic hilum lesions. Results The studied includes 38 cases of the first hepatic hilum cases (18 females; 20 males), 23 presented with mass-forming tumors while the remaining 15 exhibited diffuse infiltrative tumors, with an average diameter of 4.65± 2.51 cm. The percutaneous biopsy procedure, conducted under ultrasound guidance, had an average operation time of 14.55 ± 2.73 minutes, and resulted in a postoperative bleeding volume of approximately 10.79 ± 2.79 ml. The diagnostic success rate was noted to be as high as 92.11% among the participants who underwent percutaneous biopsy of the first hepatic hilum. Procedural complications, such as bleeding, bile leakage, intestinal perforation, infection or needle tract seeding, did not occur during or after the biopsy procedure. Affected by biopsy results, 5 altered their clinical treatment plans accordingly, 24patients received non-surgical treatment, 9 underwent surgical treatment, 5 underwent radiofrequency ablation for the lesions. The study comprised a total of 112 cases for percutaneous biopsy of the liver periphery. The safety and effectiveness of the two biopsy techniques were comparable, with diagnostic success rates of 92.11% VS. 94.34%, respectively (p = 0.61). Conclusion Cognitive fusion of ultrasound and multi-modal imaging for the first hepatic hilum lesion puncture biopsy is a safe and effective diagnostic procedure, with better diagnostic rate, may improve clinical value of diagnosis and treatment of various diseases.
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Affiliation(s)
- Xian-Tao Zeng
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Xia Liang
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Zhi-Liang Hong
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Sheng Chen
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Jian-Chuan Yang
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Yu-cheng Lin
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Ultrasonography, Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, China
| | - Song-Song Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
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Zhu Z, Hu K, Zhao F, Liu W, Zhou H, Zhu Z, Li H. Machine learning-based nomogram for 30-day mortality prediction for patients with unresectable malignant biliary obstruction after ERCP with metal stent: a retrospective observational cohort study. BMC Surg 2023; 23:260. [PMID: 37649027 PMCID: PMC10470194 DOI: 10.1186/s12893-023-02158-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 08/17/2023] [Indexed: 09/01/2023] Open
Abstract
BACKGROUND This study aimed to investigate the risk factors for 30-day mortality in patients with malignant biliary obstruction (MBO) after endoscopic retrograde cholangiopancreatography (ERCP) with endobiliary metal stent placement. Furthermore, we aimed to construct and visualize a prediction model based on LASSO-logistic regression. METHODS Data were collected from 245 patients who underwent their first ERCP with endobiliary metal stent placement for unresectable MBO between June 1, 2013, and August 31, 2021. Univariable and multivariable logistic regression analyses were conducted to identify the risk factors for 30-day mortality. We subsequently developed a logistic regression model that incorporated multiple parameters identified by LASSO regression. The model was visualized and the nomogram was plotted. Risk stratification was performed based on nomogram-derived scores. RESULTS The 30-day mortality rate was 10.7% (23/245 patients). Distant metastasis, total bilirubin, post-ERCP complications, and successful drainage were independent risk factors of 30-day mortality. The variables screened by LASSO regression, including distant metastasis, total bilirubin, post-ERCP complications, and successful drainage, were incorporated into the logistic model. The results were visualized through a nomogram based on the model. To assess the model's performance, discrimination was evaluated using the area-under-the-curve values obtained from receiver operating characteristic analyses with 10-fold cross-validation in the training group and validated in the testing group. The calibration curve showed the good predictive ability of the model. Decision curve analysis is used to evaluate the clinical application of nomogram. Finally, we performed risk stratification based on the risk calculated using the nomogram. Patients were assigned to the low-, moderate-, and high-risk groups based on their probability scores. The Kaplan-Meier survival curves for the different nomogram-based groups were significantly different (p < 0.001). CONCLUSIONS We developed a nomogram using the LASSO-logistic regression model to forecast the 30-day mortality rate in patients who had undergone ERCP with endobiliary metal stent placement due to MBO. This nomogram can assist in identifying individuals at high-risk of 30-day mortality following ERCP.
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Affiliation(s)
- Zongdong Zhu
- Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Jiaxing, Zhejiang, China
- Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
| | - Kaixin Hu
- Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Jiaxing, Zhejiang, China
- Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
| | - Fengqing Zhao
- Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
| | - Wen Liu
- Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
| | - Hongkun Zhou
- Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
| | - Zongliang Zhu
- Henan University of Science and Technology, Luoyang, Henan, China
| | - Huangbao Li
- Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Jiaxing, Zhejiang, China.
- Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.
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A tissue attached to self-expandable metal stents for biliary stricture could be useful to find malignancy. Sci Rep 2022; 12:19659. [PMID: 36385278 PMCID: PMC9668975 DOI: 10.1038/s41598-022-24115-7] [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: 05/26/2022] [Accepted: 11/10/2022] [Indexed: 11/17/2022] Open
Abstract
Biliary strictures can have several benign or malignant causes. We attempted to determine the usefulness of establishing a diagnosis using self-expandable metal stents (SEMS) in a prospective series of patients with suspected malignant biliary obstruction. Data of patients who underwent SEMS removal from August 2016 to December 2019 were collected. During this period, 55 patients underwent endobiliary biopsy and SEMS insertion and removal. Fifty-five consecutive patients (mean age, 69 years; range 53-90 years) were enrolled, and of these, 37 were male and 18 were female. A final diagnosis was established using biopsy specimens in 37 cases (67.3%) and surgical specimens in 6 cases (10.9%), with 12 cases (21.8%) diagnosed on radiological follow-up. The final diagnoses included malignancy in 34 cases (61.8%) and benign stricture in 21 cases (38.2%). Endobiliary biopsy had a sensitivity and specificity of 44.1% and 95.2%, whereas SEMS cytology had a sensitivity and specificity of 52.9% and 100%, respectively. Combining endobiliary biopsy and/or SEMS cytology yielded a sensitivity and specificity of 73.5% and 95.2%, respectively. (1) The use of biopsy results alone as a diagnostic tool yielded an area under the receiver operating characteristic curve (AUC) of 0.70 (0.60-0.79). (2) The addition of SEMS to the biopsy results yielded an AUC of 0.86 (0.78-0.94). (3) The addition of CA 19-9 levels to the biopsy results yielded an AUC of 0.81 (0.71-0.94). (4) Combining the endobiliary biopsy results, SEMS tissues, and CA 19-9 levels yielded the best diagnostic accuracy, with an AUC of 0.90 (0.83-0.98). Detection of biliary obstruction using the combination strategy was better than the diagnostic results based on biopsy alone according to recent 3-year data. Our study suggested that SEMS removal could help establish a diagnosis of suspected malignant biliary obstruction.
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Sasaki M, Sato Y. An immunohistochemical panel of insulin-like growth factor II mRNA-binding protein 3 (IMP3), enhancer of zeste homolog 2 (EZH2), and p53 is useful for a diagnosis in bile duct biopsy. Virchows Arch 2021; 479:697-703. [PMID: 34115196 DOI: 10.1007/s00428-021-03132-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 05/07/2021] [Accepted: 05/30/2021] [Indexed: 11/29/2022]
Abstract
Bile duct biopsy is being increasingly performed in number for a definite diagnosis of cholangiocarcinoma. However, difficulties are associated with a histopathological diagnosis because of the limited small amount of specimen obtained and crash artifact. The aim of the present study was to identify useful diagnostic immunohistochemical markers in bile duct biopsy that support a histological diagnosis. Fifty-one bile duct biopsy samples, including 26 samples taken from patients with cholangiocarcinoma, 11 with intraductal papillary neoplasm of the bile duct (IPNB), and 14 with benign bile duct lesions, were examined. Histology and the immunohistochemical expression of insulin-like growth factor II mRNA-binding protein 3 (IMP3), enhancer of zeste homolog 2 (EZH2), and p53 were assessed. They were then evaluated for their usefulness as diagnostic markers of malignancy. The diagnostic sensitivity and accuracy of the institutional histological diagnosis were 53.8% and 70.0%, respectively. The diagnostic sensitivity and accuracy of IMP3, EZH2, and p53 were 69.2% and 80.0%, 76.9% and 85.0%, and 50.0% and 67.5%, respectively. Immunohistochemical staining for EZH2; the combination of either 2 of IMP3, EZH2, and p53; or the combination of IMP3, EZH2, and p53 significantly increased sensitivity and accuracy over those of the institutional histological diagnosis (p<0.05). In conclusion, an immunohistochemical panel consisting of IMP3, EZH2, and p53 increases the diagnostic sensitivity and accuracy of bile duct biopsy for the diagnosis of cholangiocarcinoma.
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Affiliation(s)
- Motoko Sasaki
- Department of Human Pathology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.
| | - Yasunori Sato
- Department of Human Pathology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan
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Mao X, Wen F, Liang H, Sun W, Lu Z. A preliminary single-center investigation of percutaneous biliary stenting in malignant hilar biliary obstruction: what impacts the clinical success and the long-term outcomes? Support Care Cancer 2021; 29:6781-6792. [PMID: 33990879 DOI: 10.1007/s00520-021-06271-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 05/04/2021] [Indexed: 11/27/2022]
Abstract
PURPOSE The purpose of this study is to investigate the influencing factors that may impact the clinical success, jaundice-free time, and overall survival in patients of malignant hilar biliary obstruction (MHBO) treated with a self-expanding metallic stent (SEMS). MATERIALS AND METHODS Patients diagnosed with MHBO and treated with SEMS through percutaneous access from 1 Jul. 2013 to 1 Jul. 2018 were enrolled in this monocentric study. Demographic information, disease baseline measurements, and interventional strategies were collected and examined. Bilirubin was measured 1-3 days before and 3-7 days after stenting using the unit of "μmol/L." The bilirubin reduction ratio was compared between different study groups, which were separated by specific characteristics. Univariate and multivariate analyses were performed to evaluate each characteristic's impact on jaundice-free time (JF) and overall survival time (OS). Statistical analyses were conducted using SPSS 14.0, p < 0.05 indicated significance. RESULTS Eighty patients were enrolled. Direct bilirubin (DB) and indirect bilirubin (IB) both significantly decreased after stenting (U = 1575.0, p < 0.001; U = 1541.0, p < 0.001). The DB reduction ratio of the "nearby lymph metastases" group was significantly higher (U = 566.0, p = 0.037). The IB reduction ratio in the "single stent" group was significantly higher (U = 554.0, p = 0.018). Sixty-six cases reached jaundice recurrence, the median JF was 6 months, and the 95% confidence interval was 4.411 ~ 7.589 months. Fifty-eight cases ended in death, the median OS was 7 months, and the 95% confidence interval was 5.759 ~ 8.241 months. "Nearby lymph metastases" and "distant metastases" independently impacted OS (OR = 2.344, p = 0.013; OR = 3.239, p = 0.042). "IB reduction ratio" independently impacted both JF and OS (OR = 0.422, p = 0.021; OR = 0.315, p = 0.001). CONCLUSION The goal of treatment in patients with MHBO is to recover liver function. However, the overall survival is greatly impacted by the presence of metastases. Managing to obtain adequate liver function recovery may improve the long-term outcomes in affected patients.
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Affiliation(s)
- Xiaonan Mao
- Department of Radiology, Shengjing Hospital of China Medical University, Huaxiang Road 39, Shenyang City, 110004, Liaoning Province, China
| | - Feng Wen
- Department of Radiology, Shengjing Hospital of China Medical University, Huaxiang Road 39, Shenyang City, 110004, Liaoning Province, China
| | - Hongyuan Liang
- Department of Radiology, Shengjing Hospital of China Medical University, Huaxiang Road 39, Shenyang City, 110004, Liaoning Province, China
| | - Wei Sun
- Department of Radiology, Shengjing Hospital of China Medical University, Huaxiang Road 39, Shenyang City, 110004, Liaoning Province, China
| | - Zaiming Lu
- Department of Radiology, Shengjing Hospital of China Medical University, Huaxiang Road 39, Shenyang City, 110004, Liaoning Province, China.
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Kamp EJCA, Dinjens WNM, Doukas M, Bruno MJ, de Jonge PJF, Peppelenbosch MP, de Vries AC. Optimal tissue sampling during ERCP and emerging molecular techniques for the differentiation of benign and malignant biliary strictures. Therap Adv Gastroenterol 2021; 14:17562848211002023. [PMID: 33948111 PMCID: PMC8053835 DOI: 10.1177/17562848211002023] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 02/15/2021] [Indexed: 02/04/2023] Open
Abstract
Patients with cholangiocarcinoma have poor survival since the majority of patients are diagnosed at a stage precluding surgical resection, due to locally irresectable tumors and/or metastases. Optimization of diagnostic strategies, with a principal role for tissue diagnosis, is essential to detect cancers at an earlier stage amenable to curative treatment. Current barriers for a tissue diagnosis include both insufficient tissue sampling and a difficult cyto- or histopathological assessment. During endoscopic retrograde cholangiopancreatography, optimal brush sampling includes obtaining more than one brush within an individual patient to increase its diagnostic value. Currently, no significant increase of the diagnostic accuracy for the new cytology brush devices aiming to enhance the cellularity of brushings versus standard biliary brush devices has been demonstrated. Peroral cholangioscopy with bile duct biopsies appears to be a valuable tool in the diagnostic work-up of indeterminate biliary strictures, and may overcome current technical difficulties of fluoroscopic-guided biopsies. Over the past years, molecular techniques to detect chromosomal instability, mutations and methylation profiling of tumors have revolutionized, and implementation of these techniques on biliary tissue during diagnostic work-up of biliary strictures may be awaited in the near future. Fluorescence in situ hybridization has already been implemented in routine diagnostic evaluation of biliary strictures in several centers. Next-generation sequencing is promising for standard diagnostic care in biliary strictures, and recent studies have shown adequate detection of prevalent genomic alterations in KRAS, TP53, CDKN2A, SMAD4, PIK3CA, and GNAS on biliary brush material. Detection of DNA methylation of tumor suppressor genes and microRNAs may evolve over the coming years to a valuable diagnostic tool for cholangiocarcinoma. This review summarizes optimal strategies for biliary tissue sampling during endoscopic retrograde cholangiopancreatography and focuses on the evolving molecular techniques on biliary tissue to improve the differentiation of benign and malignant biliary strictures.
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Affiliation(s)
- Eline J. C. A. Kamp
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Winand N. M. Dinjens
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands
| | - Michail Doukas
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands
| | - Marco J. Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Pieter Jan F. de Jonge
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Maikel P. Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Annemarie C. de Vries
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, Room Na-609, Rotterdam, 3015 GD, The Netherlands
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Yang CM, Shu J. Cholangiocarcinoma Evaluation via Imaging and Artificial Intelligence. Oncology 2020; 99:72-83. [PMID: 33147583 DOI: 10.1159/000507449] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 03/23/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is a relatively rare malignant biliary system tumor, and yet it represents the second most common primary hepatic neoplasm, following hepatocellular carcinoma. Regardless of the type, location, or etiology, the survival prognosis of these tumors remains poor. The only method of cure for CCA is complete surgical resection, but part of patients with complete resection are still subject to local recurrence or distant metastasis. SUMMARY Over the last several decades, our understanding of the molecular biology of CCA has increased tremendously, diagnostic and evaluative techniques have evolved, and novel therapeutic approaches have been established. Key Messages: This review provides an overview of preoperative imaging evaluations of CCA. Furthermore, relevant information about artificial intelligence (AI) in medical imaging is discussed, as well as the development of AI in CCA treatment.
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Affiliation(s)
- Chun Mei Yang
- Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jian Shu
- Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China,
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Vugts JJA, Gaspersz MP, Roos E, Franken LC, Olthof PB, Coelen RJS, van Vugt JLA, Labeur TA, Brouwer L, Besselink MGH, IJzermans JNM, Darwish Murad S, van Gulik TM, de Jonge J, Polak WG, Busch ORC, Erdmann JL, Groot Koerkamp B, Buettner S. Eligibility for Liver Transplantation in Patients with Perihilar Cholangiocarcinoma. Ann Surg Oncol 2020; 28:1483-1492. [PMID: 32901308 PMCID: PMC7892510 DOI: 10.1245/s10434-020-09001-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 07/22/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Liver transplantation (LT) has been performed in a select group of patients presenting with unresectable or primary sclerosing cholangitis (PSC)-associated perihilar cholangiocarcinoma (pCCA) in the Mayo Clinic with a reported 5-year overall survival (OS) of 53% on intention-to-treat analysis. The objective of this study was to estimate eligibility for LT in a cohort of pCCA patients in two tertiary referral centers. METHODS Patients diagnosed with pCCA between 2002 and 2014 were included from two tertiary referral centers in the Netherlands. The selection criteria used by the Mayo Clinic were retrospectively applied to determine the proportion of patients that would have been eligible for LT. RESULTS A total of 732 consecutive patients with pCCA were identified, of whom 24 (4%) had PSC-associated pCCA. Overall, 154 patients had resectable disease on imaging and 335 patients were ineligible for LT because of lymph node or distant metastases. An age limit of 70 years led to the exclusion of 50 patients who would otherwise be eligible for LT. After applying the Mayo Clinic criteria, only 34 patients (5%) were potentially eligible for LT. Median survival from diagnosis for these 34 patients was 13 months (95% CI 3-23). CONCLUSION Only 5% of all patients presenting with pCCA were potentially eligible for LT under the Mayo criteria. Without transplantation, a median OS of about 1 year was observed.
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Affiliation(s)
- Jaynee J A Vugts
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Marcia P Gaspersz
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Eva Roos
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Lotte C Franken
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Pim B Olthof
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Robert J S Coelen
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jeroen L A van Vugt
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Tim A Labeur
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Lieke Brouwer
- Department of Gastroenterology, Maasstad Ziekenhuis, Rotterdam, The Netherlands
| | - Marc G H Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jan N M IJzermans
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Sarwa Darwish Murad
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Wojciech G Polak
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Olivier R C Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Joris L Erdmann
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
| | - Stefan Buettner
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
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Thomaidis T, Kallimanis G, May G, Zhou P, Sivanathan V, Mosko J, Triantafillidis JK, Teshima C, Moehler M. Advances in the endoscopic management of malignant biliary obstruction. Ann Gastroenterol 2020; 33:338-347. [PMID: 32624653 PMCID: PMC7315700 DOI: 10.20524/aog.2020.0497] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 04/28/2020] [Indexed: 12/11/2022] Open
Abstract
Biliary obstruction is common in pancreatobiliary malignancies and has a negative impact on the patient's quality of life, postoperative complications, and survival rates. Particularly in the last decade, there has been enormous progress regarding the diagnostic and therapeutic options in patients with malignant biliary obstruction. Endoscopy has given a new insight in this direction and novel techniques have been developed for the better characterization and treatment of malignant strictures. We herein summarize the available data on the different endoscopic techniques, and clarify their role in the diagnosis and treatment of malignant biliary obstructive disease. Finally, we propose an algorithm that can facilitate management decisions in these patients.
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Affiliation(s)
- Thomas Thomaidis
- 2 Gastroenterology Clinic, Hygeia Hospital, Athens, Greece (Thomas Thomaidis, George Kallimanis)
- Johannes Gutenberg University, Mainz, Germany (Thomas Thomaidis, Visvakanth Sivanathan, Markus Moehler)
| | - George Kallimanis
- 2 Gastroenterology Clinic, Hygeia Hospital, Athens, Greece (Thomas Thomaidis, George Kallimanis)
| | - Gary May
- Division of Therapeutic Endoscopy, St. Michael’s Hospital, University of Toronto, Toronto, Canada (Gary May, Jeff Mosko, Christopher Teshima)
| | - Pinghong Zhou
- Interventional endoscopy, Zhongshan Hospital, Fudan University, Shanghai, China (Pinghong Zhou)
| | - Visvakanth Sivanathan
- Johannes Gutenberg University, Mainz, Germany (Thomas Thomaidis, Visvakanth Sivanathan, Markus Moehler)
| | - Jeff Mosko
- Division of Therapeutic Endoscopy, St. Michael’s Hospital, University of Toronto, Toronto, Canada (Gary May, Jeff Mosko, Christopher Teshima)
| | | | - Christopher Teshima
- Division of Therapeutic Endoscopy, St. Michael’s Hospital, University of Toronto, Toronto, Canada (Gary May, Jeff Mosko, Christopher Teshima)
| | - Markus Moehler
- Johannes Gutenberg University, Mainz, Germany (Thomas Thomaidis, Visvakanth Sivanathan, Markus Moehler)
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Wang CC, Yang TW, Sung WW, Tsai MC. Current Endoscopic Management of Malignant Biliary Stricture. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:114. [PMID: 32151099 PMCID: PMC7143433 DOI: 10.3390/medicina56030114] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Revised: 03/02/2020] [Accepted: 03/02/2020] [Indexed: 02/07/2023]
Abstract
Biliary and pancreatic cancers occur silently in the initial stage and become unresectable within a short time. When these diseases become symptomatic, biliary obstruction, either with or without infection, occurs frequently due to the anatomy associated with these cancers. The endoscopic management of these patients has changed, both with time and with improvements in medical devices. In this review, we present updated and integrated concepts for the endoscopic management of malignant biliary stricture. Endoscopic biliary drainage had been indicated in malignant biliary obstruction, but the concept of endoscopic management has changed with time. Although routine endoscopic stenting should not be performed in resectable malignant distal biliary obstruction (MDBO) patients, endoscopic biliary drainage is the treatment of choice for palliation in unresectable MDBO patients. Self-expanding metal stents (SEMS) have better stent patency and lower costs compared with plastic stents (PS). For malignant hilum obstruction, PS and uncovered SEMS yield similar short-term outcomes, while a covered stent is not usually used due to a potential unintentional obstruction of contralateral ducts.
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Affiliation(s)
- Chi-Chih Wang
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (C.-C.W.); (W.-W.S.)
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Tzu-Wei Yang
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- Institute and Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan
| | - Wen-Wei Sung
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (C.-C.W.); (W.-W.S.)
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
- Department of Urology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Ming-Chang Tsai
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (C.-C.W.); (W.-W.S.)
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
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11
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Fernandez Y Viesca M, Arvanitakis M. Early Diagnosis And Management Of Malignant Distal Biliary Obstruction: A Review On Current Recommendations And Guidelines. Clin Exp Gastroenterol 2019; 12:415-432. [PMID: 31807048 PMCID: PMC6842280 DOI: 10.2147/ceg.s195714] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Accepted: 10/23/2019] [Indexed: 12/13/2022] Open
Abstract
Malignant biliary obstruction is a challenging condition, requiring a multimodal approach for both diagnosis and treatment. Pancreatic adenocarcinoma and cholangiocarcinoma are the leading causes of malignant distal biliary obstruction. Early diagnosis is difficult to establish as biliary obstruction can be the first presentation of the underlying disease, which can already be at an advanced stage. Consequently, the majority of patients (70%) with malignant distal biliary obstruction are unresectable at the time of diagnosis. The association of clinical findings, laboratory tests, imaging, and endoscopic modalities may help in identifying the underlying cause. Novel endoscopic techniques such as cholangioscopy, intraductal ultrasonography, or confocal laser endomicroscopy have been developed with promising results, but are not used in routine clinical practice. As the number of patients with malignant distal biliary obstruction who will undergo curative surgery is limited, endoscopy has a crucial role in palliation, to relieve biliary obstruction. According to the last European guidelines published in the management of biliary obstruction, self-expandable metal stents have a central place in biliary drainage compared to plastic stents. Endoscopic ultrasound has evolved impressively in the last decades. When standard techniques of biliary cannulation by endoscopic retrograde cholangiopancreatography fail, endoscopic ultrasound-guided biliary drainage is a good option compared to percutaneous drainage.
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Affiliation(s)
- Michael Fernandez Y Viesca
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Univertié Libre de Bruxelles (ULB), Brussels, Belgium
| | - Marianna Arvanitakis
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Univertié Libre de Bruxelles (ULB), Brussels, Belgium
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12
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Salerno R, Mezzina N, Ardizzone S. Endoscopic retrograde cholangiopancreatography, lights and shadows: Handle with care. World J Gastrointest Endosc 2019; 11:219-230. [PMID: 30918587 PMCID: PMC6425281 DOI: 10.4253/wjge.v11.i3.219] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 02/21/2019] [Accepted: 03/11/2019] [Indexed: 02/06/2023] Open
Abstract
The role of endoscopic retrograde cholangiopancreatography (ERCP) has dramatically changed in the last years, mainly into that of a therapeutic procedure. The treatment of benign biliary disease, like “difficult” choledocolithiasis, with endoscopic papillary large balloon dilation combined with endoscopic sphinterotomy has proven an effective and safe technique. Moreover, safety in ERCP has improved as well, with the prevention of post-ERCP pancreatitis and patient-to-patient transmission of infections. The advent of self-expandable metal stenting has radically changed the management of biliopancreatic malignant strictures, while the role for therapy of benign strictures is still controversial. In addition, cholangioscopy (though the direct visualization of the biliopancreatic ductal system) has allowed for characterization of indeterminate biliary strictures and facilitated rescue therapy of large biliary stones deemed removable. Encouraging data from tissue ablation techniques, such as photodynamic therapy and radiofrequency ablation, need to be confirmed by large sample size clinical controlled trials. On the other hand, we have no drug-coated stents yet available to implant and evidence for the use of biodegradable stents is still weak. The competency and privileging of ERCP and endoscopic ultrasonography have been analyzed longer but the switch between the two procedures, at the same time, is becoming ordinary; as such, the endoscopist interested in this field should undergo parallel edification through training plans. Finally, the American Society for Gastrointestinal Endoscopy’s statement on non-anesthesiologist administration of propofol for gastrointestinal endoscopy is not actually endorsed by the European Society of Anaesthesiology, having many medical-legal implications in some European countries.
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Affiliation(s)
- Raffaele Salerno
- Gastroenterology and Digestive Endoscopy Unit, ASST Fatebenefratelli Sacco, Milan 20121, Italy
| | - Nicolò Mezzina
- Gastrointestinal Unit, ASST Fatebenefratelli Sacco-Department of Biochemical and Clinical Sciences "L. Sacco", University of Milan, Milano 20100, Italy
| | - Sandro Ardizzone
- Gastrointestinal Unit, ASST Fatebenefratelli Sacco - Department of Biochemical and Clinical Sciences "L. Sacco", University of Milan, Milano 20100, Italy
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13
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Kim HS, Moon JH, Lee YN, Choi HJ, Lee HW, Kim HK, Lee TH, Choi MH, Cha SW, Cho YD, Park SH. Prospective Comparison of Intraductal Ultrasonography-Guided Transpapillary Biopsy and Conventional Biopsy on Fluoroscopy in Suspected Malignant Biliary Strictures. Gut Liver 2018; 12:463-470. [PMID: 29409305 PMCID: PMC6027842 DOI: 10.5009/gnl17205] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 07/27/2017] [Accepted: 09/29/2017] [Indexed: 12/12/2022] Open
Abstract
Background/Aims In suspected malignant biliary strictures (MBSs), the diagnostic yield of endoscopic retrograde cholangiopancreatography (ERCP)-based tissue sampling is limited. Transpapillary forceps biopsy (TPB) under intraductal ultrasonography (IDUS) guidance is expected to improve the diagnostic accuracy in patients with indeterminate biliary strictures. We evaluated the usefulness of IDUS-guided TPB in patients with suspected MBS. Methods Consecutive patients with suspected MBS were prospectively enrolled in the study. ERCP with IDUS was performed in all patients. Both conventional TPB and IDUS-guided TPB on fluoroscopy were performed in each patient. The primary outcome was the diagnostic accuracy of conventional TPB and IDUS-guided TPB. Results The technical success rate of IDUS-guided TPB was 97.0% (65/67 patients). Of these 65 patients, the final diagnosis was malignancy in 61 patients (93.8%). On IDUS, the most common finding of IDUS was an intraductal infiltrating lesion in 29 patients (47.5%). The overall diagnostic accuracy was significantly higher using IDUS-guided TPB than that using conventional TPB (90.8% vs 76.9%, p=0.027). According to the subgroup analysis based on the tumor morphology, IDUS-guided TPB had a significantly higher cancer detection rate than conventional TPB for intraductal infiltrating lesions (89.6% vs 65.5%, p=0.028). Conclusions IDUS-guided TPB appears to improve the accuracy of histological diagnosis in patients with MBS.
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Affiliation(s)
- Hyun Su Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Jong Ho Moon
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Yun Nah Lee
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Hyun Jong Choi
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Hyun Woo Lee
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Hee Kyung Kim
- Department of Pathology, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Tae Hoon Lee
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Moon Han Choi
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Sang-Woo Cha
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Young Deok Cho
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Sang-Heum Park
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
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14
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Moura DTH, de Moura EGH, Matuguma SE, dos Santos ME, Moura ETH, Baracat FI, Artifon ELA, Cheng S, Bernardo WM, Chacon D, Tanigawa R, Jukemura J. EUS-FNA versus ERCP for tissue diagnosis of suspect malignant biliary strictures: a prospective comparative study. Endosc Int Open 2018; 6:E769-E777. [PMID: 29876515 PMCID: PMC5988546 DOI: 10.1055/s-0043-123186] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Accepted: 10/27/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND AND STUDY AIMS Biliary strictures are frequently a challenging clinical scenario and the anatomopathological diagnosis is essential in the therapeutic management, whether for curative or palliative purposes. The acquisition of specimens is necessary since many benign diseases mimic biliopancreatic neoplasms. Endscopic retrograde cholangiopancreatography (ERCP) is the traditionally used method despite the low sensitivity of biliary brush cytology and forceps biopsy. On the other hand, several studies reported good accuracy rates using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The aim of this prospective study was to compare, the accuracy of EUS-FNA and ERCP for tissue sampling of biliary strictures. PATIENTS AND METHODS After performing the sample size calculation, 50 consecutive patients with indeterminate biliary strictures were included to undergo ERCP and EUS on the same sedation.The gold-standard was surgery or 6 months' follow-up. Evaluation of the diagnostic indices (sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio), concordance and adverse events among the methods were performed. Also, subtype analyses of the techniques, anatomical localization and size of the lesion were included. RESULTS The final diagnoses reported in 50 patients were 47 malignant, 1 suspicious and 2 benign lesions. 31 lesions were extraductal and 19 intraductal, 35 were distal and 15 proximal strictures. In the intention-to-treat analysis, the sensitivity and accuracy of EUS-FNA were superior than ERCP tissue sampling (93,8 %, 94 % vs. 60,4 %, 62 %, respectively) ( P = 0.034), with similar adverse events. There was no concordance between the methods and combining both methods improved the sensitivity and accuracy for 97.9 % and 98 %, respectively. In the subtype analyses, the EUS-FNA was superior, with a higher accuracy than ERCP tissue sampling in evaluating extraductal lesions (100 % vs. 54.8 %, P = 0.019) and in those larger than 1.5 cm (95.8 % vs. 61.9 %, P = 0.031), but were similar in evaluating intraductal lesions and lesions smaller than 1.5 cm. There was no significant difference between the methods in the analyzes of proximal, distal and pancreatic lesions. CONCLUSION EUS-FNA is better than ERCP with brush cytology and intraductal forceps biopsy in diagnosing malignant biliary strictures, mainly in the assessment of extraductal lesions and in those larger than 1.5 cm. Combining ERCP with tissue sampling and EUS-FNA is feasible, the techniques have similar complication rates, and the combination greatly improves diagnostic accuracy.
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Affiliation(s)
- Diogo Turiani Hourneaux Moura
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Gastrointestinal Endoscopy Unit, São Paulo, Brazil
| | | | - Sergio Eiji Matuguma
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Gastrointestinal Endoscopy Unit, São Paulo, Brazil
| | - Marcos Eduardo dos Santos
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Gastrointestinal Endoscopy Unit, São Paulo, Brazil
| | - Eduardo Turiani Hourneaux Moura
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Gastrointestinal Endoscopy Unit, São Paulo, Brazil
| | - Felipe Iankelevich Baracat
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Gastrointestinal Endoscopy Unit, São Paulo, Brazil
| | - Everson LA Artifon
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Gastrointestinal Endoscopy Unit, São Paulo, Brazil
| | - Spencer Cheng
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Gastrointestinal Endoscopy Unit, São Paulo, Brazil
| | - Wanderley Marque Bernardo
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Gastrointestinal Endoscopy Unit, São Paulo, Brazil
| | - Danielle Chacon
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Gastrointestinal Endoscopy Unit, São Paulo, Brazil
| | - Ryan Tanigawa
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Gastrointestinal Endoscopy Unit, São Paulo, Brazil
| | - José Jukemura
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Gastrointestinal Endoscopy Unit, São Paulo, Brazil
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15
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Tanaka H, Matsusaki S, Baba Y, Isono Y, Sase T, Okano H, Saito T, Mukai K, Murata T, Taoka H. Usefulness of Endoscopic Transpapillary Tissue Sampling for Malignant Biliary Strictures and Predictive Factors of Diagnostic Accuracy. Clin Endosc 2018; 51:174-180. [PMID: 28854772 PMCID: PMC5903074 DOI: 10.5946/ce.2017.082] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 07/14/2017] [Accepted: 07/14/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND/AIMS It is sometimes difficult to distinguish between malignant and benign biliary strictures using imaging studies alone, and pathological diagnosis is necessary. The aim of this study was to determine the usefulness of endoscopic transpapillary tissue sampling and factors predictive of diagnostic accuracy. METHODS From April 2008 to December 2014, 136 patients underwent endoscopic transpapillary tissue sampling for malignant biliary strictures. The cytological and histological findings were reported as negative, suspicious, or positive. Suspicious and positive findings were defined as pathologically positive. RESULTS The sensitivity was 65.0% for forceps biopsy, 49.5% for brush cytology, 46.2% for bile aspiration cytology, and 21.9% for endoscopic nasobiliary drainage cytology. The combination of these procedures improved the sensitivity (72.8%). Endoscopic transpapillary tissue sampling was more sensitive for lesions of biliary origin (91.4%) than for extrabiliary lesions (66.3%). In surgical cases, the sensitivity for tumors with an infiltrative growth pattern (53.3%) was significantly lower than for a tumor with an expanding or intermediate growth pattern (87.5%). CONCLUSIONS Combining procedures can improve diagnostic accuracy. It may be possible to predict the sensitivity of endoscopic transpapillary tissue sampling by evaluating the etiology and tumor growth pattern using preoperative imaging studies.
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Affiliation(s)
- Hiroki Tanaka
- Department of Gastroenterology, Suzuka General Hospital, Suzuka, Japan
| | - Shimpei Matsusaki
- Department of Gastroenterology, Suzuka General Hospital, Suzuka, Japan
| | - Youichirou Baba
- Department of Pathology, Suzuka General Hospital, Suzuka, Japan
| | - Yoshiaki Isono
- Department of Gastroenterology, Suzuka General Hospital, Suzuka, Japan
| | - Tomohiro Sase
- Department of Gastroenterology, Suzuka General Hospital, Suzuka, Japan
| | - Hiroshi Okano
- Department of Gastroenterology, Suzuka General Hospital, Suzuka, Japan
| | - Tomonori Saito
- Department of Gastroenterology, Suzuka General Hospital, Suzuka, Japan
| | - Katsumi Mukai
- Department of Gastroenterology, Suzuka General Hospital, Suzuka, Japan
| | - Tetsuya Murata
- Department of Pathology, Suzuka General Hospital, Suzuka, Japan
| | - Hiroki Taoka
- Department of Surgery, Suzuka General Hospital, Suzuka, Japan
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16
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Capobianco I, Rolinger J, Nadalin S. Resection for Klatskin tumors: technical complexities and results. Transl Gastroenterol Hepatol 2018; 3:69. [PMID: 30363698 PMCID: PMC6182019 DOI: 10.21037/tgh.2018.09.01] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 08/27/2018] [Indexed: 12/18/2022] Open
Abstract
Klatskin's tumors, actually-redefined as perihilar cholangiocarcinoma (phCCA) do represent 50-70% of all CCAs and develop in a context of chronic inflammation and cholestasis of bile ducts. Surgical resection provides the only chance of cure for this disease but is technically challenging because of the complex, intimate and variable relationship between biliary and vascular structures at this location. Five years survival rates range between 25-45% (median 27-58 months) in case of R0 resection and 0-23% (median 12-21 months) in case of R1 resection respectively. It should be noted that the major costs of high radicality are represented by relative high morbidity and mortality rates (i.e., 20-66% and 0-9% respectively). Considering the fact that radical resection may represent the only curative treatment of phCCA, we focused our review on surgical planning and techniques that may improve resectability rates and outcomes for locally advanced phCCA. The surgical treatment of phCCA can be successful when following aspects have been fulfilled: (I) accurate preoperative diagnostic aimed to identify the tumor in all its details (localization and extension) and to study all the risk factors influencing a posthepatectomy liver failure (PHLF): i.e., liver volume, liver function, liver quality, haemodynamics and patient characteristics; (II) High end surgical skills taking in consideration the local extension of the tumor and the vascular invasion which usually require an extended hepatic resection and often a vascular resection; (III) adequate postoperative management aimed to avoid major complications (i.e., PHLF and biliary complications). These are technically challenging operations and must be performed in a high volume centres by hepato-biliary-pancreas (HBP)-surgeons with experience in microsurgical vascular techniques.
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Affiliation(s)
- Ivan Capobianco
- Department of General, Visceral and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany
| | - Jens Rolinger
- Department of General, Visceral and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany
| | - Silvio Nadalin
- Department of General, Visceral and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany
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17
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Yamamoto K, Tsuchiya T, Itoi T, Tsuji S, Tanaka R, Tonozuka R, Honjo M, Mukai S, Kamada K, Fujita M, Asai Y, Matsunami Y, Nagakawa Y, Yamaguchi H, Sofuni A. Evaluation of novel slim biopsy forceps for diagnosis of biliary strictures: Single-institutional study of consecutive 360 cases (with video). World J Gastroenterol 2017; 23:6429-6436. [PMID: 29085192 PMCID: PMC5643268 DOI: 10.3748/wjg.v23.i35.6429] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Revised: 07/16/2017] [Accepted: 08/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the feasibility and reliability of endoscopic transpapillary bile duct biopsy for the diagnosis of biliary strictures.
METHODS A total of 360 patients (241 men) who underwent endoscopic retrograde cholangiopancreatography for biliary strictures with biopsy from April 2012 to March 2016 at Tokyo Medical University Hospital were retrospectively reviewed. This study was approved by our Institutional Review Board (No. 3516). Informed consent was obtained from all individual participants included in this study. The biopsy specimens were obtained using a novel slim biopsy forceps (Radial Jaw 4P, Boston Scientific, Boston, MA, United States).
RESULTS The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 69.6%, 100%, 100%, 59.1%, and 78.8%, respectively. The sensitivity was 75.6% in bile duct cancer, 64% in pancreatic cancer, 61.1% in gallbladder cancer, and 57.1% in metastasis. In bile duct cancer, a lower sensitivity was observed for perihilar bile duct stricture (68.7%) than for distal bile duct stricture (83.1%). In terms of the stricture lengths of pancreatic cancer, gallbladder cancer, and metastasis, a longer stenosis resulted in a better sensitivity. In particular, there was a significant difference between pancreatic cancer and gallbladder cancer (P < 0.05). One major complication was perforation of the extrahepatic bile duct with bile leakage.
CONCLUSION Endoscopic transpapillary biopsy alone using novel slim biopsy forceps is feasible and reliable, but restrictive. Biopsy should be performed in consideration of the stricture level, stricture length, and cancer type.
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Affiliation(s)
- Kenjiro Yamamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Takayoshi Tsuchiya
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Takao Itoi
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Shujiro Tsuji
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Reina Tanaka
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Ryosuke Tonozuka
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Mitsuyoshi Honjo
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Shuntaro Mukai
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Kentaro Kamada
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Mitsuru Fujita
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Yasutsugu Asai
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Yukitoshi Matsunami
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Yuichi Nagakawa
- Third Department of Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Hiroshi Yamaguchi
- Department of Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Atsushi Sofuni
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
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18
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Keane MG, Shah A, Pereira SP, Joshi D. Novel biomarkers and endoscopic techniques for diagnosing pancreaticobiliary malignancy. F1000Res 2017; 6:1643. [PMID: 28944047 PMCID: PMC5585877 DOI: 10.12688/f1000research.11371.1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/06/2017] [Indexed: 12/12/2022] Open
Abstract
The UK incidence of pancreatic ductal adenocarcinoma is 9 per 100,000 population, and biliary tract cancer occurs at a rate of 1–2 per 100,000. The incidence of both cancers is increasing annually and these tumours continue to be diagnosed late and at an advanced stage, limiting options for curative treatment. Population-based screening programmes do not exist for these cancers, and diagnosis currently is dependent on symptom recognition, but often symptoms are not present until the disease is advanced. Recently, a number of promising blood and urine biomarkers have been described for pancreaticobiliary malignancy and are summarised in this review. Novel endoscopic techniques such as single-operator cholangioscopy and confocal endomicroscopy have been used in some centres to enhance standard endoscopic diagnostic techniques and are also evaluated in this review.
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Affiliation(s)
| | - Amar Shah
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Stephen P Pereira
- UCL Institute for Liver and Digestive Health, Royal Free Campus, London, UK
| | - Deepak Joshi
- Institute of Liver Studies, King's College Hospital, London, UK
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19
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Voigtländer T, Metzger J, Schönemeier B, Jäger M, Mischak H, Manns MP, Lankisch TO. A combined bile and urine proteomic test for cholangiocarcinoma diagnosis in patients with biliary strictures of unknown origin. United European Gastroenterol J 2017; 5:668-676. [PMID: 28815030 PMCID: PMC5548357 DOI: 10.1177/2050640616687836] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 11/24/2016] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Detection of cholangiocarcinoma (CC) remains a diagnostic challenge particularly in patients with primary sclerosing cholangitis (PSC). We recently established diagnostic peptide marker models in bile and urine to detect CC. Our aim was to combine both models to reach a higher diagnostic accuracy of CC diagnosis. METHODS Bile (BPA) and urine (UPA) proteome analysis by capillary electrophoresis mass spectrometry was performed in a case-control phase II study on 87 patients (36 CC including 13 with CC on top of PSC, 33 PSC and 18 other benign disorders). A logistic regression model with both analyses was developed and subsequently validated in a prospective cohort of 45 patients. RESULTS In the retrospective study, single BPA and UPA showed sensitivities of 83 and 89 % and specificities of 80 and 86 % with an area under the curve (AUC) value of 0.85 and 0.93. If CC was defined as positive UPA and BPA the combination resulted in a sensitivity of 72 % and a specificity of 96 %. The logistic regression model resulted in an increase in sensitivity to 92 % at 84 % specificity with an AUC of 0.96. Applied to the prospective study cohort, the logistic regression model was superior in its sensitivity (94%) and specificity (76%) over single BPA (63% sensitivity, 69% specificity) and UPA (81% sensitivity, 72% specificity) with an AUC of 0.84. CONCLUSION Our logistic regression model enables CC diagnosis with a higher accuracy than currently available diagnostic tools leading potentially to an earlier diagnosis.
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Affiliation(s)
- Torsten Voigtländer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Integrated Research and Treatment Center – Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany
| | | | - Bastian Schönemeier
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Mark Jäger
- Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany
| | | | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Integrated Research and Treatment Center – Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany
| | - Tim O Lankisch
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Integrated Research and Treatment Center – Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany
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Lee YN, Moon JH, Choi HJ, Kim HK, Choi SY, Choi MH, Lee TH, Lee TH, Cha SW, Park SH. Diagnostic approach using ERCP-guided transpapillary forceps biopsy or EUS-guided fine-needle aspiration biopsy according to the nature of stricture segment for patients with suspected malignant biliary stricture. Cancer Med 2017; 6:582-590. [PMID: 28220692 PMCID: PMC5345615 DOI: 10.1002/cam4.1034] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 01/02/2017] [Accepted: 01/17/2017] [Indexed: 12/21/2022] Open
Abstract
In malignant biliary stricture (MBS), the diagnostic accuracy of ERCP‐based tissue sampling is insufficient. EUS‐guided fine needle aspiration biopsy (EUS‐FNAB) is emerging as a reliable diagnostic procedure. This study aimed to evaluate the usefulness of a diagnostic approach using ERCP‐guided transpapillary forceps biopsy (TPB) or EUS‐FNAB according to the characteristics of suspected MBS. Consecutive patients diagnosed with suspected MBS with obstructive jaundice and/or cholangitis were enrolled prospectively. ERCP with intraductal ultrasonography (IDUS) and TPB were performed as initial diagnostic procedures. Based on the results of imaging studies and IDUS, all MBS were classified as extrinsic or intrinsic type. If the malignancy was not confirmed by TPB, EUS‐FNAB for extrinsic type or second TPB for intrinsic type was performed. Among a total of 178 patients, intrinsic and extrinsic types were detected in 88 and 90 patients, respectively. The diagnostic accuracy of first TPB was significantly higher in the intrinsic than in the extrinsic type (81.8% vs. 67.8, P = 0.023). In 33 patients with extrinsic type and negative for malignancy on first TPB, the diagnostic accuracy of EUS‐FNAB was 90.9%. In 19 patients with intrinsic type and negative for malignancy on first TPB, the diagnostic accuracy of second TPB was 84.2%. The diagnostic accuracies of the combination of initial TPB with EUS‐FNAB and second TPB were 96.7% and 96.6%, respectively. A diagnostic approach using EUS‐FNAB or TPB according to the origin of MBS is considered effective to improve the diagnostic accuracy of MBS with negative for malignancy on first TPB. (Clinical trial registration number: UMIN000016886).
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Affiliation(s)
- Yun Nah Lee
- Department of Internal Medicine, Digestive Disease Center and Research Institute, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea
| | - Jong Ho Moon
- Department of Internal Medicine, Digestive Disease Center and Research Institute, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea
| | - Hyun Jong Choi
- Department of Internal Medicine, Digestive Disease Center and Research Institute, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea
| | - Hee Kyung Kim
- Department of Pathology, SoonChunHyang University School of Medicine, Bucheon, Korea
| | - Seo-Youn Choi
- Department of Radiology, SoonChunHyang University School of Medicine, Bucheon, Korea
| | - Moon Han Choi
- Department of Internal Medicine, Digestive Disease Center and Research Institute, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea
| | - Tae Hee Lee
- Department of Internal Medicine, Digestive Disease Center and Research Institute, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea
| | - Tae Hoon Lee
- Department of Internal Medicine, Digestive Disease Center and Research Institute, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea
| | - Sang-Woo Cha
- Department of Internal Medicine, Digestive Disease Center and Research Institute, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea
| | - Sang-Heum Park
- Department of Internal Medicine, Digestive Disease Center and Research Institute, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea
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Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in biliary brush cytology. Br J Cancer 2017; 116:349-355. [PMID: 28081547 PMCID: PMC5294492 DOI: 10.1038/bjc.2016.447] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 10/16/2016] [Accepted: 12/14/2016] [Indexed: 12/18/2022] Open
Abstract
Background: Biliary brush cytology is the standard method of evaluating biliary strictures, but is insensitive at detecting malignancy. In pancreaticobiliary cancer minichromosome maintenance replication proteins (MCM 2–7) are dysregulated in the biliary epithelium and MCM5 levels are elevated in bile samples. This study aimed to validate an immunocolorimetric ELISA assay for MCM5 as a pancreaticobiliary cancer biomarker in biliary brush samples. Methods: Biliary brush specimens were collected prospectively at ERCP from patients with a biliary stricture. Collected samples were frozen at −80 °C. The supernatant was washed and lysed cells incubated with HRP-labelled anti-MCM5 mouse monoclonal antibody. Test positivity was determined by optical density absorbance. Patients underwent biliary brush cytology or additional investigations as per clinical routine. Results: Ninety-seven patients were included in the study; 50 had malignant strictures. Median age was 65 years (range 21–94) and 51 were male. Compared with final diagnosis the MCM5 assay had a sensitivity for malignancy of 65.4% compared with 25.0% for cytology. In the 72 patients with paired MCM5 assay and biliary brush cytology, MCM5 demonstrated an improved sensitivity (55.6% vs 25.0% P=0.0002) for the detection of malignancy. Conclusions: Minichromosome maintenance replication protein5 is a more sensitive indicator of pancreaticobiliary malignancy than standard biliary brush cytology.
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Waghray A, Sobotka A, Marrero CR, Estfan B, Aucejo F, Narayanan Menon KV. Serum albumin predicts survival in patients with hilar cholangiocarcinoma. Gastroenterol Rep (Oxf) 2016; 5:62-66. [PMID: 27389416 PMCID: PMC5444265 DOI: 10.1093/gastro/gow021] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2016] [Accepted: 05/04/2016] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND AND AIMS Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma. METHODS All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation. RESULTS A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P < 0.01), cancer antigen 19-9 ≤200 U/mL (P = 0.03), carcinoembryonic antigen ≤10 ìg/L (P < 0.01) or patients without a history of cirrhosis (P < 0.01) or diabetes (P = 0.02) were associated with a greater length of overall survival. A serum albumin level >3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14-0.70) with a survival benefit of 44 weeks. CONCLUSION This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival.
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Affiliation(s)
- Abhijeet Waghray
- Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio, USA
| | - Anastasia Sobotka
- Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Carlos Romero Marrero
- Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Bassam Estfan
- Department of Hepatobiliary and Transplant Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Federico Aucejo
- Department of Hepatobiliary and Transplant Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - K V Narayanan Menon
- Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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Abstract
Peroral cholangioscopy has become an important tool in the diagnosis and treatment of a variety of biliary diseases, ranging from indeterminate biliary strictures to bile duct stones. Although the first cholangioscopy was performed in the 1970s, recent technological advances have provided us with cholangioscopes that yield high-resolution images, possess single-operator capability, and have ultrathin design to allow easier maneuverability and detailed imaging of the biliary tract. We review here the currently available devices for peroral cholangioscopy, their clinical applications, limitations, and complications.
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Affiliation(s)
- Ming-Ming Xu
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, Cornell University, New York, NY, USA
| | - Michel Kahaleh
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, Cornell University, New York, NY, USA
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Fugazza A, Gaiani F, Carra MC, Brunetti F, Lévy M, Sobhani I, Azoulay D, Catena F, de'Angelis GL, de'Angelis N. Confocal Laser Endomicroscopy in Gastrointestinal and Pancreatobiliary Diseases: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2016; 2016:4638683. [PMID: 26989684 PMCID: PMC4773527 DOI: 10.1155/2016/4638683] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2015] [Accepted: 12/31/2015] [Indexed: 12/15/2022]
Abstract
Confocal laser endomicroscopy (CLE) is an endoscopic-assisted technique developed to obtain histopathological diagnoses of gastrointestinal and pancreatobiliary diseases in real time. The objective of this systematic review is to analyze the current literature on CLE and to evaluate the applicability and diagnostic yield of CLE in patients with gastrointestinal and pancreatobiliary diseases. A literature search was performed on MEDLINE, EMBASE, Scopus, and Cochrane Oral Health Group Specialized Register, using pertinent keywords without time limitations. Both prospective and retrospective clinical studies that evaluated the sensitivity, specificity, or accuracy of CLE were eligible for inclusion. Of 662 articles identified, 102 studies were included in the systematic review. The studies were conducted between 2004 and 2015 in 16 different countries. CLE demonstrated high sensitivity and specificity in the detection of dysplasia in Barrett's esophagus, gastric neoplasms and polyps, colorectal cancers in inflammatory bowel disease, malignant pancreatobiliary strictures, and pancreatic cysts. Although CLE has several promising applications, its use has been limited by its low availability, high cost, and need of specific operator training. Further clinical trials with a particular focus on cost-effectiveness and medicoeconomic analyses, as well as standardized institutional training, are advocated to implement CLE in routine clinical practice.
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Affiliation(s)
- Alessandro Fugazza
- Unit of Gastroenterology and Digestive Endoscopy, University of Parma, 43100 Parma, Italy
| | - Federica Gaiani
- Unit of Gastroenterology and Digestive Endoscopy, University of Parma, 43100 Parma, Italy
| | | | - Francesco Brunetti
- Unit of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
| | - Michaël Lévy
- Department of Gastroenterology and Digestive Endoscopy, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
| | - Iradj Sobhani
- Department of Gastroenterology and Digestive Endoscopy, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Cancer Research Lab. EC2M3, Université Paris-Est, Val de Marne UPEC, 94010 Créteil, France
| | - Daniel Azoulay
- Unit of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
| | - Fausto Catena
- Emergency Surgery Department, University of Parma, 43100 Parma, Italy
| | - Gian Luigi de'Angelis
- Unit of Gastroenterology and Digestive Endoscopy, University of Parma, 43100 Parma, Italy
| | - Nicola de'Angelis
- Unit of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Cancer Research Lab. EC2M3, Université Paris-Est, Val de Marne UPEC, 94010 Créteil, France
- Department of Advanced Biomedical Sciences, University Federico II of Naples, 80138 Naples, Italy
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Tabibian JH, Visrodia KH, Levy MJ, Gostout CJ. Advanced endoscopic imaging of indeterminate biliary strictures. World J Gastrointest Endosc 2015; 7:1268-1278. [PMID: 26675379 PMCID: PMC4673389 DOI: 10.4253/wjge.v7.i18.1268] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Revised: 08/05/2015] [Accepted: 10/27/2015] [Indexed: 02/05/2023] Open
Abstract
Endoscopic evaluation of indeterminate biliary strictures (IDBSs) has evolved considerably since the development of flexible fiberoptic endoscopes over 50 years ago. Endoscopic retrograde cholangiography pancreatography (ERCP) was introduced nearly a decade later and has since become the mainstay of therapy for relieving obstruction of the biliary tract. However, longstanding methods of ERCP-guided tissue acquisition (i.e., biliary brushings for cytology and intraductal forceps biopsy for histology) have demonstrated disappointing performance characteristics in distinguishing malignant from benign etiologies of IDBSs. The limitations of these methods have thus helped drive the search for novel techniques to enhance the evaluation of IDBSs and thereby improve diagnosis and clinical care. These modalities include, but are not limited to, endoscopic ultrasound, intraductal ultrasound, cholangioscopy, confocal endomicroscopy, and optical coherence tomography. In this review, we discuss established and emerging options in the evaluation of IDBSs.
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Abstract
Benign biliary strictures are a common indication for endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic management has evolved over the last 2 decades as the current standard of care. The most common etiologies of strictures encountered are following surgery and those related to chronic pancreatitis. High-quality cross-sectional imaging provides a road map for endoscopic management. Currently, sequential placement of multiple plastic biliary stents represents the preferred approach. There is an increasing role for the treatment of these strictures using covered metal stents, but due to conflicting reports of efficacies as well as cost and complications, this approach should only be entertained following careful consideration. Optimal management of strictures is best achieved using a team approach with the surgeon and interventional radiologist playing an important role.
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The diagnostic value of brush cytology alone and in combination with tumor markers in pancreaticobiliary strictures. Gastroenterol Res Pract 2015; 2015:580254. [PMID: 25883643 PMCID: PMC4391493 DOI: 10.1155/2015/580254] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Accepted: 03/18/2015] [Indexed: 12/18/2022] Open
Abstract
Aim. Differentiation of malignant and benign strictures constitutes a problem despite the increasing experience of the endoscopists, radiologists, and pathologists. The aim of our study is to determine the factors that affect the efficacy of the ERCP guided brush cytology in PBS and to evaluate its diagnostic success when used alone and together with tumor markers. Method. The data from brush cytologies of 301 PBS patients were collected retrospectively and analyzed. The final diagnosis was approved based on the histological examination of the tissue taken surgically or by other methods. In the absence of a histological diagnosis, the final diagnosis was based on radiological studies or the results of a 12-month clinical follow up. Results. A total of 28 patients were excluded from the study. From the remaining 273 patients 299 samples were analyzed. The sensitivity and the specificity of brush cytology in diagnosing malignancy are 62.4% and 97.7, respectively. The sensitivity of brush cytology increased to 94.1% when combined with CA-19.9 and CA-125. Conclusion. Brush cytology is a useful method in diagnosing pancreaticobiliary strictures. Advanced age, stricture dilatation before sampling, the presence of a mass identified by radiological studies, high levels of CA-19.9, ALT, and total bilirubin increase the sensitivity of brush cytology.
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Singla S, Piraka C. Endoscopic retrograde cholangiopancreatography. Clin Liver Dis (Hoboken) 2015; 4:133-137. [PMID: 30992940 PMCID: PMC6448759 DOI: 10.1002/cld.441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Sumit Singla
- Division of GastroenterologyHenry Ford Health SystemDetroitMI
| | - Cyrus Piraka
- Section of Advanced Therapeutic Endoscopy, Division of GastroenterologyHenry Ford Health SystemDetroitMI
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Evaluation of pCLE in the bile duct: final results of EMID study : pCLE: impact in the management of bile duct strictures. Surg Endosc 2014; 29:2661-8. [PMID: 25492449 DOI: 10.1007/s00464-014-3986-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Accepted: 11/04/2014] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Pre-operative histology of bile duct stenosis is associated with low accuracy. Probe confocal laser endomicroscopy (pCLE) enables optical biopsy or in vivo histology. The definitive results of the EMID study are presented here, comparing optical biopsies with definitive histology. AIMS AND METHODS Sixty one patients with a biliary stricture without any previous histology were included (July 2007-May 2012). An endoscopic ultrasound (EUS) had to be conducted before the ERCP procedure. pCLE was done using CholangioFlex during the ERCP procedure. Results were compared to those of definitive histology obtained by biopsy or surgery in case of malignant lesions, and by surgery or 1-year follow-up in case of benign lesions. RESULTS Six patients were excluded because no definitive histology was available. There were 41 malignant lesions and 14 benign lesions. Sensitivity, specificity, PPV, NPV, and accuracy with combination of pCLE with endobiliary and EUS biopsies were 100, 71, 91, 100, and 93%, respectively (with a significant increase of accuracy compared with endobiliary and EUS biopsies without pCLE, p = 0.03). 19 patients had a biliary stricture without individualized mass (6 malignant lesions, 13 benign lesions). Sensitivity, specificity, PPV, NPV, and accuracy for pCLE were 83, 77, 62, 91, and 79%, respectively. Sensitivity, specificity, PPV, NPV, and accuracy for combination of pCLE with endobiliary and EUS biopsies were 100, 69, 60, 100, and 79%, respectively. CONCLUSION The addition of a pCLE procedure in the diagnostic histologic examination of a biliary stricture permits a significant increase in diagnostic reliability and allows for a VPN of 100%.
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30
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Lee SJ, Lee YS, Lee MG, Lee SH, Shin E, Hwang JH. Triple-tissue sampling during endoscopic retrograde cholangiopancreatography increases the overall diagnostic sensitivity for cholangiocarcinoma. Gut Liver 2014; 8:669-73. [PMID: 25368755 PMCID: PMC4215455 DOI: 10.5009/gnl13292] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Revised: 11/29/2013] [Accepted: 12/19/2013] [Indexed: 12/12/2022] Open
Abstract
Background/Aims There are several methods for obtaining tissue samples to diagnose malignant biliary strictures during endoscopic retrograde cholangiopancreatography (ERCP). However, each method has only limited sensitivity. This study aimed to evaluate the diagnostic accuracy of a combined triple-tissue sampling (TTS) method (on-site bile aspiration cytology, brush cytology, and forceps biopsy). Methods We retrospectively reviewed 168 patients with suspicious malignant biliary strictures who underwent double-tissue sampling (DTS; n=121) or TTS (n=47) via ERCP at our institution from 2004 to 2011. Results Among the 168 patients reviewed, 117 patients (69.6%) were eventually diagnosed with malignancies. The diagnostic sensitivity for cancer was significantly higher in the TTS group than the DTS group (85.0% vs 64.9%, respectively; p=0.022). Furthermore, the combination of brush cytology and forceps biopsy was superior to the other method combinations in the DTS group. With respect to cancer type (cholangiocarcinoma vs noncholangiocarcinoma), interestingly, the diagnostic sensitivity was higher for cholangiocarcinoma in the TTS group than the DTS group (100% vs 69.4%, respectively; p<0.001) but not for the non-cholangiocarcinoma patients (57.1% vs 57.1%, respectively). Conclusions TTS can provide an improved diagnostic accuracy in suspicious malignant biliary strictures, particularly for cholangiocarcinoma.
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Affiliation(s)
- Seung June Lee
- Department of Internal Medicine and, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yoon Suk Lee
- Department of Internal Medicine and, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Min Geun Lee
- Department of Internal Medicine and, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Eun Shin
- Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine and, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Caillol F, Bories E, Poizat F, Pesenti C, Esterni B, Monges G, Giovannini M. Endomicroscopy in bile duct: Inflammation interferes with pCLE applied in the bile duct: A prospective study of 54 patients. United European Gastroenterol J 2014; 1:120-7. [PMID: 24917949 DOI: 10.1177/2050640613483462] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2012] [Accepted: 02/23/2013] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The preoperative diagnosis of biliary stenosis is associated with low accuracy. As a consequence, probe-based confocal laser endomicroscopy (pCLE), an in-vivo histological imaging technique, was applied in the bile duct. The aim of this study was to establish whether previous inflammation of the bile duct affects confocal interpretation. The findings from pCLE were compared in two groups of patients: those in whom there had been no cholangitis nor stenting and those in whom stents had been used and subsequently retrieved or who had suffered cholangitis. PATIENTS AND METHODS pCLE was performed on 54 patients (mean age 66 years; 31 men, 23 women) from September 2008 to July 2011. Patients were divided in two groups: group 1: 39 patients who had not undergone a biliary procedure in the month preceding the pCLE procedure; and group 2: 15 patients who had undergone stent placement or presented with cholangitis in the month preceding the pCLE procedure. Endoscopic and pCLE data were collected prospectively. pCLE results were compared to benchmark histology (surgery, endoultrasonography, percutaneous biopsy). Patients with a benign stricture who did not undergo operation were followed for 1 year. pCLE images of the bile duct were obtained during endoscopic retrograde cholangiopancreatography procedures. pCLE images were interpreted prospectively using the Miami classification in vivo and in real time. RESULTS In group 1, sensitivity, specificity, and accuracy were 88, 83, and 87%, respectively. In group 2, sensitivity, specificity, and accuracy were 75, 71, and 73%, respectively. Diagnostic accuracy of pCLE was lower when applied to group 2 (p < 0,001). The investigation is less reliable in bile ducts affected by inflammation from cholangitis or previous stenting. CONCLUSIONS Inflammatory lesions of the bile duct interfere with interpretation of pCLE. A refined pCLE description of inflammatory lesions should improve accuracy of pCLE in bile duct stenosis.
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Victor DW, Sherman S, Karakan T, Khashab MA. Current endoscopic approach to indeterminate biliary strictures. World J Gastroenterol 2012; 18:6197-6205. [PMID: 23180939 PMCID: PMC3501767 DOI: 10.3748/wjg.v18.i43.6197] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Biliary strictures are considered indeterminate when basic work-up, including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing, are non-diagnostic. Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patient’s outcome. Early and accurate diagnosis of malignancy impacts not only a patient’s candidacy for surgery, but also potential timely targeted chemotherapies. A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is, thus, paramount to avoid unnecessary surgery. Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy. Emerging data on other diagnostic modalities, such as ancillary cytology techniques, single operator cholangioscopy, and endoscopic ultrasonography-guided fine needle aspiration, revealed promising results with much improved sensitivity.
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Nagino M. Perihilar cholangiocarcinoma: a surgeon's viewpoint on current topics. J Gastroenterol 2012; 47:1165-76. [PMID: 22847554 DOI: 10.1007/s00535-012-0628-6] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2012] [Accepted: 06/09/2012] [Indexed: 02/07/2023]
Abstract
Perihilar cholangiocarcinomas are defined anatomically as "tumors that are located in the extrahepatic biliary tree proximal to the origin of the cystic duct". However, as the boundary between the extrahepatic and intrahepatic bile ducts is not well defined, perihilar cholangiocarcinomas potentially include two types of tumors: one is the "extrahepatic" type, which arises from the large hilar bile duct, and the other is the "intrahepatic" type, which has an intrahepatic component with the invasion of the hepatic hilus. The new TNM staging system published by the International Union Against Cancer (UICC) has been well revised with regard to perihilar cholangiocarcinoma, but it still lacks stratification of patient prognosis and has little applicability for assessing the feasibility of surgical treatment; therefore, further refinement is essential. Most patients with perihilar cholangiocarcinomas present with jaundice, and preoperative biliary drainage is mandatory. Previously, percutaneous transhepatic biliary drainage was used in many centers; however, it is accepted that endoscopic naso-biliary drainage is the most suitable method of preoperative drainage. Portal vein embolization is now widely used as a presurgical treatment for patients undergoing an extended hepatectomy to minimize postoperative liver dysfunction. The surgical resection of a perihilar cholangiocarcinoma is technically demanding and continues to be the most difficult challenge for hepatobiliary surgeons. Because of advances in diagnostic and surgical techniques, surgical outcomes and survival rates after resection have steadily improved. However, survival, especially for patients with lymph node metastasis, is still unsatisfactory, and the establishment of adjuvant chemotherapy is necessary. Further synergy of endoscopists, radiologists, oncologists, and surgeons is required to conquer this intractable disease.
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Affiliation(s)
- 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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Nischalke HD, Schmitz V, Luda C, Aldenhoff K, Berger C, Feldmann G, Sauerbruch T, Spengler U, Nattermann J. Detection of IGF2BP3, HOXB7, and NEK2 mRNA expression in brush cytology specimens as a new diagnostic tool in patients with biliary strictures. PLoS One 2012; 7:e42141. [PMID: 22879911 PMCID: PMC3413695 DOI: 10.1371/journal.pone.0042141] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Accepted: 07/02/2012] [Indexed: 01/02/2023] Open
Abstract
Introduction It is a challenging task to distinguish between benign and malignant lesions in patients with biliary strictures. Here we analyze whether determination of target gene mRNA levels in intraductal brush cytology specimens may be used to improve the diagnosis of bile duct carcinoma. Materials and Methods Brush cytology specimens from 119 patients with biliary strictures (malignant: n = 72; benign: n = 47) were analyzed in a retrospective cohort study. mRNA of IGF-II mRNA-binding protein 3 (IGF2BP3), homeobox B7 (HOXB7), Forkhead box M1 (FOXM1), kinesin family member 2C (KIF2C) and serine/threonine kinase NEK2 was determined by semi-quantitative RT-PCR using the ΔCt method. Results IGF2BP3 (p<0.0001), HOXB7 (p<0.0001), and NEK2 (p<0.0001) mRNA expression levels were significantly increased in patients with cholangiocarcinoma or pancreatic cancer. Median ΔCt values differed by 3.5 cycles (IGF2BP3), 2.8 cycles (HOXB7) and 1.3 cycles (NEK2) corresponding to 11-fold, 7-fold and 2.5-fold increased mRNA levels in malignant versus benign samples. Sensitivity to detect biliary cancer was 76.4% for IGF2BP3 (80.9% specificity); 72.2% for HOXB7 (78.7% specificity) and 65.3% for NEK2 (72.3% specificity), whereas routine cytology reached only 43.1% sensitivity (85.4% specificity). Diagnostic precision was further improved, when all three molecular markers were assessed in combination (77.8% sensitivity, 87.2% specificity) and achieved 87.5% sensitivity and 87.2% specificity when molecular markers were combined with routine cytology. Conclusions Our data suggest that measuring IGF2BP3, HOXB7 and NEK2 mRNA levels by RT-PCR in addition to cytology has the potential to improve detection of malignant biliary disorders from brush cytology specimens.
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Affiliation(s)
| | - Volker Schmitz
- Department of Internal Medicine 1, University of Bonn, Bonn, Germany
| | - Carolin Luda
- Department of Internal Medicine 1, University of Bonn, Bonn, Germany
| | | | - Cordula Berger
- Department of Internal Medicine 1, University of Bonn, Bonn, Germany
| | - Georg Feldmann
- Center of Integrated Oncology Cologne-Bonn, Department of Internal Medicine 3, University of Bonn, Bonn, Germany
| | - Tilman Sauerbruch
- Department of Internal Medicine 1, University of Bonn, Bonn, Germany
| | - Ulrich Spengler
- Department of Internal Medicine 1, University of Bonn, Bonn, Germany
| | - Jacob Nattermann
- Department of Internal Medicine 1, University of Bonn, Bonn, Germany
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Malignant biliary stenosis: conventional cytology versus DNA image cytometry. Surg Endosc 2010; 25:1808-13. [PMID: 21170660 DOI: 10.1007/s00464-010-1469-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2010] [Accepted: 10/29/2010] [Indexed: 01/20/2023]
Abstract
BACKGROUND The aim of this study is to evaluate the utility of image cytometry (ICM)-DNA analysis on cytological brush specimens in improving the sensitivity and diagnostic accuracy for biliary neoplasias. METHODS A total of 71 patients with 89 samples of biliary tree brushing from a stenosis were included in this prospective study. Conventional cytology (CC) and DNA ploidy using ICM of the brushing were performed. Benign or malignant findings were confirmed by surgical exploration or a clinical follow-up of at least 12 months. RESULTS Diagnosis was confirmed by clinical follow-up in 44 cases and surgical investigation or histology in 41 cases. A definitive diagnosis of the smears resulted in 40 malignant and 49 benign diagnoses. The sensitivity was 0.666 for CC and 0.658 for ICM, and the specificity was 0.920 and 0.937, respectively. The positive predictive value (PPV) was 0.866 for CC and 0.900 for ICM. McNemar's test did not reveal a significant difference between CC and ICM (P=0.803). Agreement of the two methods was found in 73 samples, raising specificity to 0.998 but not sensitivity (0.725). CONCLUSIONS ICM-DNA seems not to improve significantly the PPV and NPV for detecting neoplasias of the biliary tract compared to CC. Nevertheless a clinical advantage can be seen in the agreement of the two methods in diagnosing dysplasia or cancer, since it did not show false positive results.
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Levy MJ, Baron TH, Clayton AC, Enders FB, Gostout CJ, Halling KC, Kipp BR, Petersen BT, Roberts LR, Rumalla A, Sebo TJ, Topazian MD, Wiersema MJ, Gores GJ. Prospective evaluation of advanced molecular markers and imaging techniques in patients with indeterminate bile duct strictures. Am J Gastroenterol 2008; 103:1263-73. [PMID: 18477350 PMCID: PMC2911775 DOI: 10.1111/j.1572-0241.2007.01776.x] [Citation(s) in RCA: 128] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Standard techniques for evaluating bile duct strictures have poor sensitivity for detection of malignancy. Newer imaging modalities, such as intraductal ultrasound (IDUS), and advanced cytologic techniques, such as digital image analysis (DIA) and fluorescence in situ hybridization (FISH), identify chromosomal abnormalities, and may improve sensitivity while maintaining high specificity. Our aim was to prospectively evaluate the accuracy of these techniques in patients with indeterminate biliary strictures. METHODS Cholangiography, routine cytology (RC), intraductal biopsy, DIA, FISH, and IDUS were performed in 86 patients with indeterminate biliary strictures. Patients were stratified based on the presence or absence of primary sclerosing cholangitis (PSC). RESULTS RC provided low sensitivity (7-33%) but high specificity (95-100%) for PSC and non-PSC patients. The composite DIA/FISH results (when considering trisomy-7 [Tri-7] as a marker of benign disease) yielded a 100% specificity and increased sensitivity one- to fivefold in PSC patients versus RC, and two- to fivefold in patients without PSC, depending on how suspicious cytology results were interpreted. For the most difficult-to-manage patients with negative cytology and histology who were later proven to have malignancy (N = 21), DIA, FISH, composite DIA/FISH, and IDUS were able to predict malignant diagnoses in 14%, 62%, 67%, and 86%, respectively. CONCLUSIONS DIA, FISH, and IDUS enhance the accuracy of standard techniques in evaluation of indeterminate bile duct strictures, allowing diagnosis of malignancy in a substantial number of patients with false-negative cytology and histology. These findings support the routine use of these newer diagnostic modalities in patients with indeterminate biliary strictures.
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Affiliation(s)
- Michael J. Levy
- Division of Gastroenterology and Hepatology, Mayo Clinic Foundation, Rochester, Minnesota
| | - Todd H. Baron
- Division of Gastroenterology and Hepatology, Mayo Clinic Foundation, Rochester, Minnesota
| | - Amy C. Clayton
- Department of Pathology, Mayo Clinic Foundation, Rochester, Minnesota
| | | | - Christopher J. Gostout
- Division of Gastroenterology and Hepatology, Mayo Clinic Foundation, Rochester, Minnesota
| | - Kevin C. Halling
- Department of Pathology, Mayo Clinic Foundation, Rochester, Minnesota
| | - Benjamin R. Kipp
- Department of Pathology, Mayo Clinic Foundation, Rochester, Minnesota
| | - Bret T. Petersen
- Division of Gastroenterology and Hepatology, Mayo Clinic Foundation, Rochester, Minnesota
| | - Lewis R. Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic Foundation, Rochester, Minnesota
| | - Ashwin Rumalla
- Division of Gastroenterology and Hepatology, Mayo Clinic Foundation, Rochester, Minnesota
| | - Thomas J. Sebo
- Department of Pathology, Mayo Clinic Foundation, Rochester, Minnesota
| | - Mark D. Topazian
- Division of Gastroenterology and Hepatology, Mayo Clinic Foundation, Rochester, Minnesota
| | - Maurits J. Wiersema
- Division of Gastroenterology and Hepatology, Mayo Clinic Foundation, Rochester, Minnesota
| | - Gregory J. Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic Foundation, Rochester, Minnesota
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Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in bile aspirates. Br J Cancer 2008; 98:1548-54. [PMID: 18414413 PMCID: PMC2391096 DOI: 10.1038/sj.bjc.6604342] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Biliary brush cytology is the standard method of sampling a biliary stricture but has a low sensitivity for the detection of malignancy. We have previously shown that minichromosome maintenance (MCM) replication proteins (Mcm2–7) are markers of dysplasia and have utilised these novel biomarkers of growth for the diagnosis of cervical and bladder cancer. We aimed to determine if MCM proteins are dysregulated in malignant pancreaticobiliary disease and if levels in bile are a sensitive marker of malignancy. In 30 tissue specimens from patients with malignant/benign biliary strictures, we studied Mcm2 and -5 expression by immunohistochemistry. Bile samples were also collected prospectively at endoscopic retrograde cholangiopancreatography from 102 consecutive patients with biliary strictures of established (n=42) or indeterminate aetiology (n=60). Patients with indeterminate strictures also underwent brush cytology as part of standard practice. Bile sediment Mcm5 levels were analysed using an automated immunofluorometric assay. In benign biliary strictures, Mcm2 and -5 protein expression was confined to the basal epithelial proliferative compartment – in contrast to malignant strictures where expression was seen in all tissue layers. The percentage of nuclei positive for Mcm2 was higher in malignant tissue (median 76.5%, range 42–92%) than in benign tissue (median 5%, range 0–33%) (P<0.0005), with similar results for Mcm5. Minichromosome maintenance protein 5 levels in bile were significantly more sensitive than brush cytology (66 vs 20%; P=0.004) for the detection of malignancy in patients with an indeterminate stricture, with a comparable positive predictive value (97 vs 100%; P=ns). In this study, we demonstrate that Mcm5 in bile detected by a simple automated test is a more sensitive indicator of pancreaticobiliary malignancy than routine brush cytology.
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Abstract
Biliary strictures at the liver hilum are caused by a heterogeneous group of benign and malignant conditions. In the absence of a clear-cut benign etiology, i.e. bile duct damage during surgery, hilar biliary strictures remain a diagnostic and therapeutic challenge for which a multidisciplinary approach is often necessary. A definitive diagnosis can be achieved in only 40-60% of the patients, while in all the other cases strictures are treated as though they are malignant until surgical pathology determines otherwise. Surgical resection is the only treatment that prolongs survival in patients with malignant strictures. Because these tumors frequently extend longitudinally via the hepatic ducts into the liver parenchyma, partial hepatic resection has been gradually added to biliary resection to ensure tumor-free surgical margins. For unresectable cases, endoscopic stenting of biliary obstruction is considered the preferred palliation modality to relieve pruritus, cholangitis, pain and jaundice, while the percutaneous approach has been reserved for cases of failure. Other modalities of treatment such as radiotherapy, chemotherapy, and photodynamic therapy currently remain investigational. For benign post surgical hilar strictures, surgical repair can be difficult and requires specific skills and experience. As an alternative, a multi-stent technique with endoscopic placement of an increasing number of stents over time until complete resolution of the stricture has been proposed.
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Affiliation(s)
- Alberto Larghi
- Digestive Endoscopy Unit, Università Cattolica del Sacro Cuore, Rome, Italy
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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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Chen VK, Arguedas MR, Kilgore ML, Eloubeidi MA. A cost-minimization analysis of alternative strategies in diagnosing pancreatic cancer. Am J Gastroenterol 2004; 99:2223-34. [PMID: 15555006 DOI: 10.1111/j.1572-0241.2004.40042.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Several modalities currently exist for tissue confirmation of suspected pancreatic cancer prior to therapy. Since there is a paucity of cost-minimization studies comparing these different biopsy modalities, we analyzed costs and examined effectiveness of four alternative strategies for diagnosing pancreatic cancer. METHODS A decision analysis model of patients with suspected pancreatic cancer was constructed. We analyzed costs, failure rate, testing characteristics, and complication rates of four commonly employed diagnostic modalities: 1) computerized tomography or ultrasound-guided fine-needle aspiration (CT/US-FNA), 2) endoscopic retrograde cholangiopancreatography with brushings (ERCP-B), 3) Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA), and 4) laparoscopic surgical biopsy. If the first attempt with a particular modality failed, a different modality was employed to identify the most preferable secondary biopsy strategy. RESULTS This analysis identifies EUS-FNA as the preferred initial modality for the diagnosis of pancreatic cancer. Resultant expected costs and strategies in decreasing optimality include: 1) EUS-FNA (1,405 dollars), 2) ERCP-B (1,432 dollars), 3) CT/US-FNA (3,682 dollars), and 4) surgery (17,711 dollars). If a patient presents with obstructive jaundice, decision analysis modeling resulted in a total expected costs of 1,970 dollars if ERCP-B is successful at the time of biliary stent placement. Additional analyses to identify the preferred follow-up modality after a failed alternative method showed that EUS-FNA is the preferred secondary modality if any of the other three modalities failed first, in both the setting of and absence of obstructive jaundice. One- and two-way sensitivity analysis of the variables shows unchanged results over an acceptable range. CONCLUSIONS This cost-minimization study illustrates that EUS-FNA is the best initial and the preferred secondary alternative method for the diagnosis of suspected pancreatic cancer. In addition to local expertise and availability, costs and diagnostic yield should be considered when choosing an optimal diagnostic strategy.
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Affiliation(s)
- Victor K Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Public Health, The University of Alabama at Birmingham, Birmingham, Alabama 35294-0007, USA
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Wamsteker EJ, Anderson MA. Fluorescence in situ hybridization for the detection of malignant bile duct strictures: has FISH found a new pond? Am J Gastroenterol 2004; 99:1682-3. [PMID: 15330901 DOI: 10.1111/j.1572-0241.2004.40744.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Routine cytology for the diagnosis of biliary and pancreatic malignancies has exceptionally poor sensitivity and has spurred a search for new technology in the evaluation of these diseases. The recent study by Kipp et al. in this issue of the Journal, compares one of these novel techniques (fluorescence in situ hybridization to standard cytology) for the detection of malignant biliary strictures. Although larger studies are indicated, the modality shows considerable promise for future clinical use.
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Harewood GC, Baron TH, Stadheim LM, Kipp BR, Sebo TJ, Salomao DR. Prospective, blinded assessment of factors influencing the accuracy of biliary cytology interpretation. Am J Gastroenterol 2004; 99:1464-9. [PMID: 15307861 DOI: 10.1111/j.1572-0241.2004.30845.x] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES There is little published data assessing factors that influence the accuracy of biliary cytology. The aim of this study was to (a) prospectively compare interobserver variability among two blinded pathologists interpreting biliary cytology specimens, (b) to describe the predictors of interpathologist agreement, and (c) to characterize the predictors of accurate cytology interpretation. METHODS In total, 113 consecutive patients undergoing endoscopic retrograde cholangiopancreatography with brushing of suspicious biliary tract strictures were prospectively enrolled to assess routine cytology (RC) accuracy. The initial RC interpretation was performed by the pathologist on duty with the benefit of the patient's clinical information. Subsequent interpretation was performed by two independent pathologists blinded to the patients' clinical details. RESULTS Of the 113 patients, 67 had malignant strictures and 46 had benign strictures. The sensitivity of RC varied from 9% to 24% (p= 0.02), while the specificity varied from 61% to 100% (p < 0.001). Accuracy varied from 43% to 51% (p= n.s.). The rate of equivocal readings was lowest for the initial interpretation (1.7%), p < 0.0001 versus pathologist 1, p= 0.002 versus pathologist 2. Overall correlation of the blinded pathologists' interpretations was moderate, k= 0.66. Neither cytology accuracy nor interpathologist agreement improved with increasing specimen cellularity. CONCLUSIONS There is a high rate of interpathologist variation for the biliary cytology interpretation. The knowledge of the patient's clinical information appears to clarify cytology interpretation resulting in fewer equivocal results. We did not detect any reliable predictors of cytology accuracy.
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Affiliation(s)
- Gavin C Harewood
- Division of Gastroenterology and Hepatology, Department of Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA
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Duggan MA, Brasher P, Medlicott SA. ERCP-directed brush cytology prepared by the ThinprepR method: test performance and morphology of 149 cases. Cytopathology 2004; 15:80-6. [PMID: 15056167 DOI: 10.1111/j.1365-2303.2004.00129.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Conventionally prepared endobiliary brushings are moderately (42%) sensitive and highly (98%) specific in detecting malignancy. The performance and morphological features of brushings prepared by Thinprep, a liquid-based method are mostly unknown. All brushings were retrieved from the laboratory files. Disease was classified as benign or malignant by linkage with the provincial cancer registry and sensitivity, specificity, positive (PPV) and negative predictive values (NPV) calculated. True positives and negatives were reviewed and predictive morphological features analysed by regression tree analysis. Out of 149 brushings, 55 (37%) were positive and 94 (63%) negative. Malignancy was identified in 86 (58%) and benign disease in 63 (42%) of the cases. The sensitivity was 51%, specificity 83%, PPV 80% and NPV 55%. Absolute discriminants of positive and negative brushings were not found, but nuclear cytoplasmic ratio was a useful feature. The performance of Thinprep-prepared brushings from this anatomical site was comparable with conventional preparations.
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Affiliation(s)
- M A Duggan
- Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
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