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Miller LJ, Holmes IM, Chen-Yost HI, Smola B, Lew M, Pang J. Detecting Cholangiocarcinoma in the Setting of Primary Sclerosing Cholangitis: Is Biliary Tract Fluorescence In Situ Hybridization Helpful? Cytopathology 2025; 36:150-155. [PMID: 39366926 DOI: 10.1111/cyt.13452] [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: 12/15/2023] [Revised: 02/27/2024] [Accepted: 09/19/2024] [Indexed: 10/06/2024]
Abstract
INTRODUCTION/OBJECTIVE Biliary brushing cytology (BB) to detect cholangiocarcinoma (CCA) is integral in the surveillance of patients with primary sclerosing cholangitis (PSC). Since reactive changes can mimic carcinoma, indeterminant results are frequent. Fluorescence in situ hybridization (FISH) using the UroVysion probe set has been advocated to enhance the detection of CCA. This study evaluates the performance of FISH for detecting CCA in patients with and without PSC. MATERIALS AND METHODS A query of our pathology database for atypical and suspicious BB with concurrent FISH results was performed from 2014 to 2021. FISH (using UroVysion probe set containing centromere enumeration probes to chromosomes 3, 7, and 17) was positive if at least 5 cells demonstrated polysomy. Electronic medical records were reviewed to identify patients with PSC and CCA. CCA was confirmed by pathology or clinical impression. RESULTS Of the 65 patients (103 BB) in the PSC cohort, 59 patients (94 BB) without CCA and 6 patients (9 BB) with CCA were identified. 33 non-PSC patients (41 BB) with CCA were included for comparison. Positive FISH was highest in non-PSC patients with CCA (10/41 BB, 24%). Positive FISH was seen in both PSC with (1/9 BB, 11%) and without (2/94 BB, 2%) CCA. CONCLUSIONS FISH positivity was lower than expected and was positive in PSC patients without CCA. These results question the clinical utility of FISH for CCA surveillance in PSC patients.
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Affiliation(s)
- Lauren J Miller
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Isabella M Holmes
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan, USA
| | | | - Brian Smola
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Madelyn Lew
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Judy Pang
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan, USA
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2
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Dunleavy KA, Santiago P, Forde G, Harmsen WS, McKenna NP, Coelho-Prabhu N, Shawki S, Raffals L. Total Proctocolectomy vs Subtotal/total Colectomy for Neoplasia in Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis. Inflamm Bowel Dis 2024; 30:1935-1945. [PMID: 38142126 DOI: 10.1093/ibd/izad278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Indexed: 12/25/2023]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) frequently undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for medically refractory disease or colonic dysplasia/neoplasia. Subtotal colectomy with ileosigmoid or ileorectal anastomosis may have improved outcomes but is not well studied. Due to increased risk for colorectal cancer in PSC-IBD, there is hesitancy to perform subtotal colectomy. We aim to describe the frequency of colorectal dysplasia/neoplasia following IPAA vs subtotal colectomy in PSC-IBD patients. METHODS We completed a retrospective study from 1972 to 2022 of patients with PSC-IBD who had undergone total proctocolectomy with IPAA or subtotal colectomy. We abstracted demographics, disease characteristics, and endoscopic surveillance data from the EMR. RESULTS Of 125 patients (99 IPAA; 26 subtotal), the indication for surgery was rectal sparing medically refractory disease (51% vs 42%), dysplasia (37% vs 30%) and neoplasia (11% vs 26%) in IPAA vs subtotal colectomy patients, respectively. On endoscopic surveillance of IPAA patients, 2 (2%) had low-grade dysplasia (LGD) in the ileal pouch and 2 (2%) had LGD in the rectal cuff after an average of 8.4 years and 12.3 years of follow-up, respectively. One (1%) IPAA patient developed neoplasia of the rectal cuff after 17.8 years of surgical continuity. No subtotal colectomy patients had dysplasia/neoplasia in the residual colon or rectum. CONCLUSIONS In patients with PSC-IBD, there was no dysplasia or neoplasia in those who underwent subtotal colectomy as opposed to the IPAA group. Subtotal colectomy may be considered a viable surgical option in patients with rectal sparing PSC-IBD if adequate endoscopic surveillance is implemented.
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Affiliation(s)
- Katie Ann Dunleavy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Priscila Santiago
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Gerard Forde
- Department of Gastroenterology, Galway University Hospital, Galway, Ireland
| | - W Scott Harmsen
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA
| | | | | | - Sherief Shawki
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA
| | - Laura Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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3
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Miyazu T, Ishida N, Asai Y, Tamura S, Tani S, Yamade M, Iwaizumi M, Hamaya Y, Osawa S, Baba S, Sugimoto K. Intrahepatic cholangiocarcinoma in patients with primary sclerosing cholangitis and ulcerative colitis: Two case reports. World J Gastrointest Surg 2023; 15:1224-1231. [PMID: 37405109 PMCID: PMC10315124 DOI: 10.4240/wjgs.v15.i6.1224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 03/10/2023] [Accepted: 04/12/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is an extraintestinal manifestation of ulcerative colitis (UC). PSC is a well-known risk factor for intrahepatic cholangiocarcinoma (ICC), and ICC is known to have a poor prognosis. CASE SUMMARY We present two cases of ICC in patients with PSC associated with UC. In the first case, a tumor was found by magnetic resonance imaging (MRI) in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain. The second patient was asymptomatic, but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC. ICC was strongly suspected by computed tomography and MRI in both cases, and surgery was performed, but unfortunately, the first patient died of ICC recurrence 16 mo postoperatively, and the second patient died of liver failure 14 mo postoperatively. CONCLUSION Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.
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Affiliation(s)
- Takahiro Miyazu
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Natsuki Ishida
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Yusuke Asai
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Satoshi Tamura
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Shinya Tani
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Moriya Iwaizumi
- Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Yasushi Hamaya
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Satoshi Osawa
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Satoshi Baba
- Department of Diagnostic Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
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Pery R, Smoot RL, Thiels CA, Cleary SP, Vierkant RA, Ilyas SI, Gores GJ, Nagorney DM. Hepatobiliary and pancreatic resection for cholangiocarcinoma in patients with primary sclerosing cholangitis. Br J Surg 2022; 109:1032-1035. [DOI: 10.1093/bjs/znac229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/09/2022] [Accepted: 06/09/2022] [Indexed: 11/14/2022]
Affiliation(s)
- Ron Pery
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic , Rochester, Minnesota , USA
- Department of Surgery and Transplantation, Sheba Medical Center, Tel Hashomer, affiliated with the Faculty of Medicine, Tel Aviv University , Tel Aviv , Israel
| | - Rory L Smoot
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic , Rochester, Minnesota , USA
| | - Cornelius A Thiels
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic , Rochester, Minnesota , USA
| | - Sean P Cleary
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic , Rochester, Minnesota , USA
| | - Robert A Vierkant
- Department of Quantitative Health Sciences, Mayo Clinic , Rochester, Minnesota , USA
| | - Sumera I Ilyas
- Division of Gastroenterology and Hepatology, Mayo Clinic , Rochester, Minnesota , USA
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic , Rochester, Minnesota , USA
| | - David M Nagorney
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic , Rochester, Minnesota , USA
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5
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Jansson H, Olthof PB, Bergquist A, Ligthart MAP, Nadalin S, Troisi RI, Groot Koerkamp B, Alikhanov R, Lang H, Guglielmi A, Cescon M, Jarnagin WR, Aldrighetti L, van Gulik TM, Sparrelid E. Outcome after resection for perihilar cholangiocarcinoma in patients with primary sclerosing cholangitis: an international multicentre study. HPB (Oxford) 2021; 23:1751-1758. [PMID: 33975797 PMCID: PMC8720371 DOI: 10.1016/j.hpb.2021.04.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 03/14/2021] [Accepted: 04/03/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Resection for perihilar cholangiocarcinoma (pCCA) in primary sclerosing cholangitis (PSC) has been reported to lead to worse outcomes than resection for non-PSC pCCA. The aim of this study was to compare prognostic factors and outcomes after resection in patients with PSC-associated pCCA and non-PSC pCCA. METHODS The international retrospective cohort comprised patients resected for pCCA from 21 centres (2000-2020). Patients operated with hepatobiliary resection, with pCCA verified by histology and with data on PSC status, were included. The primary outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications. RESULTS Of 1128 pCCA patients, 34 (3.0%) had underlying PSC. Median overall survival after resection was 33 months for PSC patients and 29 months for non-PSC patients (p = .630). Complications (Clavien-Dindo grade ≥ 3) were more frequent in PSC pCCA (71% versus 44%, p = .003). The rate of posthepatectomy liver failure (21% versus 17%, p = .530) and 90-day mortality (12% versus 13%, p = 1.000) was similar for PSC and non-PSC patients. CONCLUSION Median overall survival after resection for pCCA was similar in patients with underlying PSC and non-PSC patients. Complications were more frequent after resection for PSC-associated pCCA, with no difference in postoperative mortality.
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Affiliation(s)
- Hannes Jansson
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
| | - Pim B Olthof
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Annika Bergquist
- Unit of Gastroenterology and Rheumatology, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Marjolein A P Ligthart
- Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Silvio Nadalin
- Department of General and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Roberto I Troisi
- Department of Human Structure and Repair, Faculty of Medicine, Ghent University, Ghent, Belgium; Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Federico II University Naples, Naples, Italy
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Ruslan Alikhanov
- Department of Hepato-Pancreato-Biliary Surgery, Moscow Clinical Scientific Center, Moscow, Russia
| | - Hauke Lang
- Department of General, Visceral and Transplantation Surgery, University Hospital of Mainz, Mainz, Germany
| | - Alfredo Guglielmi
- Department of Surgery, Unit of Hepato-Pancreato-Biliary Surgery, University of Verona Medical School, Verona, Italy
| | - Matteo Cescon
- General Surgery and Transplantation Unit, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - William R Jarnagin
- Division of Hepatopancreatobiliary Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
| | - Luca Aldrighetti
- Hepato-biliary Surgery Division, Ospedale San Raffaele-IRCCS, Milan, Italy
| | - Thomas M van Gulik
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Ernesto Sparrelid
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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Han S, Kahaleh M, Sharaiha RZ, Tarnasky PR, Kedia P, Slivka A, Chennat JS, Joshi V, Sejpal DV, Sethi A, Shah RJ. Probe-based confocal laser endomicroscopy in the evaluation of dominant strictures in patients with primary sclerosing cholangitis: results of a U.S. multicenter prospective trial. Gastrointest Endosc 2021; 94:569-576.e1. [PMID: 33798541 DOI: 10.1016/j.gie.2021.03.027] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 03/21/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Patients with primary sclerosing cholangitis (PSC) and dominant biliary strictures carry increased risk for the development of cholangiocarcinoma. Although ERCP-based techniques including brush cytology and intraductal biopsy sampling represent first-line tissue sampling methods for dominant strictures, sensitivity is low. Probe-based confocal laser endomicroscopy (pCLE) offers microscopic-level imaging of subepithelial biliary mucosa. Because data regarding the use of pCLE in PSC are limited, we aimed to investigate its diagnostic performance in dominant strictures. METHODS This was a multicenter prospective study involving PSC patients with dominant strictures. ERCP with pCLE was performed with use of the Miami classification (2+ criteria for malignant diagnosis) and Paris classification. Final malignant diagnoses required histopathologic confirmation, and benign diagnoses required a minimum of 1 year of follow-up without development of cancer. RESULTS Fifty-nine patients (mean age, 49 years; 59% men) with 63 strictures were included in the study. Stricture locations included the common bile duct (31.7%), bifurcation (22.2%), and common hepatic duct (19%). Seven patients (11.9%) were found to have cholangiocarcinoma. The sensitivity and specificity of pCLE was 85.7% (95% confidence interval [CI], 42.1-99.6) and 73.1% (95% CI, 58.9-84.4), respectively. Within specific stricture locations, the highest sensitivity was seen at the bifurcation (100%; 95% CI, 2.5-100) and the right hepatic duct (100%; 95% CI, 29.2-100). The lowest sensitivities were seen at the common bile duct (25%; 95% CI, 5.5-57.2) and the left hepatic duct (28.6%; 95% CI, 3.7-70.9). CONCLUSIONS In this prospective multicenter study, pCLE had a high sensitivity in detecting cholangiocarcinoma, but technical aspects of the probe may limit evaluation in the common bile duct and left hepatic duct. Further evaluation is needed to elucidate the role of pCLE in the algorithm of excluding neoplasia in biliary strictures associated with PSC. (Clinical trial registration number: NCT02736708.).
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Affiliation(s)
- Samuel Han
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Michel Kahaleh
- Division of Gastroenterology, Rutgers Robert Wood Johnson University Hospital, New Brunswick, New Jersey, USA
| | - Reem Z Sharaiha
- Division of Gastroenterology, Weill Cornell Medical Center, New York, New York, USA
| | - Paul R Tarnasky
- Division of Gastroenterology, Dallas Methodist Medical Center, Dallas, Texas, USA
| | - Prashant Kedia
- Division of Gastroenterology, Dallas Methodist Medical Center, Dallas, Texas, USA
| | - Adam Slivka
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jennifer S Chennat
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Virendra Joshi
- Division of Gastroenterology, Louisiana State University Health Center, New Orleans, Louisiana, USA
| | - Divyesh V Sejpal
- Division of Gastroenterology, Northwell Health, Manhasset, New York, USA
| | - Amrita Sethi
- Division of Gastroenterology, Columbia University Medical Center, New York, New York, USA
| | - Raj J Shah
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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7
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Abstract
Biliary strictures have several etiologies that can broadly be classified into benign and malignant causes. The clinical presentation is variable with strictures identified incidentally on imaging or during the evaluation of routine laboratory abnormalities. Symptoms and cholangitis lead to imaging that can diagnose biliary strictures. The diagnosis and medical management of biliary strictures will be discussed in this article.
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Affiliation(s)
- Terrance Rodrigues
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Justin R Boike
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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8
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Yang JD, Ghoz H, Aboelsoud MM, Taylor WR, Yab TC, Berger CK, Cao X, Foote PH, Giama NH, Barr Fritcher EG, Mahoney DW, Moser CD, Smyrk TC, Kipp BR, Gores GJ, Roberts LR, Kisiel JB. DNA Methylation Markers for Detection of Cholangiocarcinoma: Discovery, Validation, and Clinical Testing in Biliary Brushings and Plasma. Hepatol Commun 2021; 5:1448-1459. [PMID: 34430788 PMCID: PMC8369938 DOI: 10.1002/hep4.1730] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 03/03/2021] [Accepted: 03/22/2021] [Indexed: 02/04/2023] Open
Abstract
Cholangiocarcinoma (CCA) has poor prognosis due to late-stage, symptomatic presentation. Altered DNA methylation markers may improve diagnosis of CCA. Reduced-representation bisulfite sequencing was performed on DNA extracted from frozen CCA tissues and matched to adjacent benign biliary epithelia or liver parenchyma. Methylated DNA markers (MDMs) identified from sequenced differentially methylated regions were selected for biological validation on DNA from independent formalin-fixed, paraffin-embedded CCA tumors and adjacent hepatobiliary control tissues using methylation-specific polymerase chain reaction. Selected MDMs were then blindly assayed on DNA extracted from independent archival biliary brushing specimens, including 12 perihilar cholangiocarcinoma, 4 distal cholangiocarcinoma cases, and 18 controls. Next, MDMs were blindly assayed on plasma DNA from patients with extrahepatic CCA (eCCA), including 54 perihilar CCA and 5 distal CCA cases and 95 healthy and 22 primary sclerosing cholangitis controls, balanced for age and sex. From more than 3,600 MDMs discovered in frozen tissues, 39 were tested in independent samples. In the clinical pilot of 16 MDMs on cytology brushings, methylated EMX1 (empty spiracles homeobox 1) had an area under the curve (AUC) of 0.98 (95% confidence interval [CI], 0.95-1.0). In the clinical pilot on plasma, a cross-validated recursive partitioning tree prediction model from nine MDMs was accurate for de novo eCCA (AUC, 0.88 [0.81-0.95]) but not for primary sclerosing cholangitis-associated eCCA (AUC, 0.54 [0.35-0.73]). Conclusion: Next-generation DNA sequencing yielded highly discriminant methylation markers for CCA. Confirmation of these findings in independent tissues, cytology brushings, and plasma supports further development of DNA methylation to augment diagnosis of CCA.
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Affiliation(s)
- Ju Dong Yang
- Division of Gastroenterology and HepatologyCedars‐Sinai Medical CenterLos AngelesCAUSA
| | - Hassan Ghoz
- Division of Gastroenterology and HepatologyMayo ClinicJacksonvilleFLUSA
| | | | - William R. Taylor
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Tracy C. Yab
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Calise K. Berger
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Xiaoming Cao
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Patrick H. Foote
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Nasra H. Giama
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | | | - Douglas W. Mahoney
- Department of Biomedical Statistics and InformaticsMayo ClinicRochesterMNUSA
| | - Catherine D. Moser
- Department of Pathology and Laboratory MedicineChildren’s Healthcare of AtlantaAtlantaGAUSA
| | | | | | - Gregory J. Gores
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Lewis R. Roberts
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - John B. Kisiel
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
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9
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Fong ZV, Brownlee SA, Qadan M, Tanabe KK. The Clinical Management of Cholangiocarcinoma in the United States and Europe: A Comprehensive and Evidence-Based Comparison of Guidelines. Ann Surg Oncol 2021; 28:2660-2674. [PMID: 33646431 DOI: 10.1245/s10434-021-09671-y] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 01/18/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND The incidence of cholangiocarcinoma has doubled over the last 15 years with a similar rise in mortality, which provides the impetus for standardization of evidence-based care through the establishment of guidelines. METHODS We compared available guidelines on the clinical management of cholangiocarcinoma in the United States and Europe, which included the National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO), British Society of Gastroenterology (BSG) and the International Liver Cancer Association (ILCA) guidelines. RESULTS There is discordance in the recommendation for biopsy in patients with potentially resectable cholangiocarcinoma and in the recommendation for use of fluorodeoxyglucose positron emission tomography scans. Similarly, the recommendation for preoperative biliary drainage for extrahepatic and perihilar cholangiocarcinoma in the setting of jaundice is inconsistent across all four guidelines. The BILCAP (capecitabine) and ABC-02 trials (gemcitabine with cisplatin) have provided the strongest evidence for systemic therapy in the adjuvant and palliative settings, respectively, but all guidelines have refrained from setting them as standard of care, given heterogeneity in the study cohorts and ABC-02's negative intention-to-treat results. CONCLUSIONS Future progress in enhancing survivorship of patients with cholangiocarcinoma would likely entail improvements in diagnostic biomarkers and novel systemic therapies. Based on recent results from studies of targeted therapy, future iterations of the guidelines will likely incorporate molecular profiling.
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Affiliation(s)
- Zhi Ven Fong
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Sarah A Brownlee
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Motaz Qadan
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kenneth K Tanabe
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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10
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Kingham TP, Aveson VG, Wei AC, Castellanos JA, Allen PJ, Nussbaum DP, Hu Y, D'Angelica MI. Surgical management of biliary malignancy. Curr Probl Surg 2021; 58:100854. [PMID: 33531120 PMCID: PMC8022290 DOI: 10.1016/j.cpsurg.2020.100854] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 06/12/2020] [Indexed: 02/07/2023]
Affiliation(s)
| | - Victoria G Aveson
- New York Presbyterian Hospital-Weill Cornel Medical Center, New York, NY
| | - Alice C Wei
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Peter J Allen
- Duke Cancer Center, Chief, Division of Surgical Oncology, Duke University School of Medicine, Durham, NC
| | | | - Yinin Hu
- Division of Surgical Oncology, University of Maryland, Baltimore, MD
| | - Michael I D'Angelica
- Memorial Sloan Kettering Cancer Center, Professor of Surgery, Weill Medical College of Cornell University, New York, NY..
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11
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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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Zhang C, Hussaini T, Yoshida EM. Review of pharmacotherapeutic treatments for primary sclerosing cholangitis. CANADIAN LIVER JOURNAL 2019; 2:58-70. [PMID: 35990218 PMCID: PMC9202752 DOI: 10.3138/canlivj-2018-0016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 08/15/2018] [Indexed: 11/13/2023]
Abstract
BACKGROUND The objective of this review was to evaluate pharmacotherapeutic treatments for primary sclerosing cholangitis (PSC) through a literature search of current published data. A review of the current clinical data for each treatment is discussed. METHODS We conducted a systematic literature search for articles using EMBASE (1980 to April 1, 2018), and MEDLINE (1948 to April 1, 2018) using Ovid, to identify studies investigating various therapies in PSC. Search terms included the following: primary sclerosing cholangitis, cholangitis, sclerosing cholangitis; ursodeoxycholic acid, glucocorticoids, cyclosporine, tacrolimus, methotrexate, azathioprine, 6-mercaptopurine, penicillamine, anti-TNF, antibiotics, and probiotics. We also performed a review of current clinical trials using ClinicalTrials.gov. We considered for review relevant studies published in English, pilot studies, and randomized controlled trials involving human subjects. RESULTS Therapies that have been investigated in the management of PSC include those used in search terms and others that were not included in our search parameters. Analysis of published data involving each therapy was explored and none have shown any sustained, significant benefit in the treatment of PSC. In terms of relevance to patient care and clinical practice, this review evaluates and compares various pharmacotherapeutic treatments for PSC where liver transplantation remains the only definitive treatment. CONCLUSIONS To date, no clinical study of any drug has demonstrated effectiveness in terms of survival benefit or a decreased need for liver transplantation. More clinical studies are needed, and patients need to be adequately informed before any medical therapy for PSC is undertaken.
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Affiliation(s)
- Chaoran Zhang
- Internal Medicine Residency Training Program, Department of Medicine, University of British Columbia, Vancouver, British Columbia;
| | - Trana Hussaini
- Department of Pharmaceutical Sciences Medicine, Vancouver General Hospital, Vancouver, British Columbia;
| | - Eric M Yoshida
- Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia
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13
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Moris D, Kostakis ID, Machairas N, Prodromidou A, Tsilimigras DI, Ravindra KV, Sudan DL, Knechtle SJ, Barbas AS. Comparison between liver transplantation and resection for hilar cholangiocarcinoma: A systematic review and meta-analysis. PLoS One 2019; 14:e0220527. [PMID: 31365594 PMCID: PMC6668826 DOI: 10.1371/journal.pone.0220527] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Accepted: 07/17/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Hilar cholangiocarcinoma (hCCA) is a rare and aggressive malignancy with R0 resection being currently the only option for long-term survival. With the improvement in the outcomes of liver transplantation (LT), the indications for LT have expanded to include other malignant tumors, such as hCCA. The aim of the present analysis is to demonstrate and critically evaluate the outcomes of LT compared to resection with curative intent in patients with hCCA. METHODS We systematically searched the literature for articles published up to May 2018. The following algorithm was applied ((hilar cholangiocarcinoma) OR (perihilar cholangiocarcinoma) OR klatskin$ OR (bile duct neoplasm) OR cholangiocarcinoma) AND (transplant$ OR graft$). RESULTS Neoadjuvant treatment with chemotherapy and radiation therapy was far more common in the LT group, with very few patients having received preoperative therapy in the resection group (p = 0.0005). Moreover, length of hospital stay was shorter after LT than after resection (p<0.00001). In contrast, no difference was found between the two treatment methods concerning postoperative mortality (p = 0.57). There was a trend towards longer overall survival after LT in comparison with resection. This was not obvious in the first year postoperatively, however, the advantage of LT over resection became obvious at 3 years after the operation (p = 0.02). CONCLUSIONS In non-disseminated unresectable tumors, LT seems to have a non-inferior survival. In the same patients, neoadjuvant chemoradiotherapy and/or strict selection criteria may contribute to superior survival outcomes compared to curative-intent resection. Due to the scarcity of level 1 evidence, it remains unclear whether LT should be increasingly considered for technically resectable early stage hCCA.
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Affiliation(s)
- Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
| | - Ioannis D. Kostakis
- Department of Transplantation, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
| | - Nikolaos Machairas
- Third Department of Surgery, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Prodromidou
- Third Department of Surgery, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Diamantis I. Tsilimigras
- Third Department of Surgery, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Kadiyala V. Ravindra
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
| | - Debra L. Sudan
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
| | - Stuart J. Knechtle
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
| | - Andrew S. Barbas
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
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Menon S, Holt A. Large-duct cholangiopathies: aetiology, diagnosis and treatment. Frontline Gastroenterol 2019; 10:284-291. [PMID: 31288256 PMCID: PMC6583582 DOI: 10.1136/flgastro-2018-101098] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 12/06/2018] [Accepted: 12/09/2018] [Indexed: 02/04/2023] Open
Abstract
Cholangiopathies describe a group of conditions affecting the intrahepatic and extrahepatic biliary tree. Impairment to bile flow and chronic cholestasis cause biliary inflammation, which leads to more permanent damage such as destruction of the small bile ducts (ductopaenia) and biliary cirrhosis. Most cholangiopathies are progressive and cause end-stage liver disease unless the physical obstruction to biliary flow can be reversed. This review considers large-duct cholangiopathies, such as primary sclerosing cholangitis, ischaemic cholangiopathy, portal biliopathy, recurrent pyogenic cholangitis and Caroli disease.
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Affiliation(s)
- Shyam Menon
- Department of Hepatology and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK,Department of Gastroenterology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK
| | - Andrew Holt
- Department of Hepatology and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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15
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Chamadol N, Khuntikeo N, Thinkhamrop B, Thinkhamrop K, Suwannatrai AT, Kelly M, Promthet S. Association between periductal fibrosis and bile duct dilatation among a population at high risk of cholangiocarcinoma: a cross-sectional study of cholangiocarcinoma screening in Northeast Thailand. BMJ Open 2019; 9:e023217. [PMID: 30898798 PMCID: PMC6475358 DOI: 10.1136/bmjopen-2018-023217] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES To assess associations between periductal fibrosis (PDF) and bile duct dilatation (BDD) in ultrasonography (US) screening of population at risk of cholangiocarcinoma (CCA) due to residence in an endemic area for Opisthorchis viverrini. CCA survival rates are low, and early identification of risk factors is essential. BDD is one symptom that can identify patients at risk of CCA. Detection of PDF by US can also identify at-risk patients, at an earlier stage of CCA development. Identification of association between PDF and BDD will inform screening practices for CCA risk, by increasing the viability of PDF screening for CCA risk. SETTING Nine tertiary care hospitals in Northeast Thailand. DESIGN Cross-sectional study. PARTICIPANTS Study subjects in the Cholangiocarcinoma Screening and Care Program (CASCAP) in Northeast Thailand. CASCAP inclusion criteria are all residents of Northeast Thailand aged ≥40 years. Participants are recruited through CCA screening centres and through primary healthcare units. So far, 394 026 have been enrolled. METHODS PDF and BDD were identified through US. PDF was categorised into three groups, PDF1, 2 and 3, depending on their high echo locality in the peripheral, segmental and main bile duct, respectively. Associations between PDF and BDD were determined by adjusted OR and 95% CI using multiple logistic regression. RESULTS BDD was found in 6.6% of PDF3, 1.7% of PDF2 and 1.4% of PDF1 cases. Among PDF cases, especially in PDF3, BDD was found in men more than in women (8.9% and 4.6%, respectively). Compared with non-PDF, the association between PDF3 and BDD was highly significant (adjusted OR=5.74, 95% CI 4.57 to 7.21, p<0.001). CONCLUSIONS Our findings reveal that there is a relationship between PDF and BDD, which is associated with CCA. Therefore, PDF can also be an indicator for suspected CCA diagnosis through US.
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Affiliation(s)
- Nittaya Chamadol
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Narong Khuntikeo
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Bandit Thinkhamrop
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Epidemiology and Biostatistics Section, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand
- Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand
| | - Kavin Thinkhamrop
- Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand
| | - Apiporn T Suwannatrai
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Matthew Kelly
- Department of Global Health, Research School of Population Health, Australian National University, Canberra, Australia
| | - Supannee Promthet
- Epidemiology and Biostatistics Section, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand
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Marya NB, Tabibian JH. Role of endoscopy in the management of primary sclerosing cholangitis. World J Gastrointest Endosc 2019; 11:84-94. [PMID: 30788027 PMCID: PMC6379747 DOI: 10.4253/wjge.v11.i2.84] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 01/15/2019] [Accepted: 01/30/2019] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare but prominent fibroinflammatory cholangiopathy which can affect individuals of essentially any age. It carries a median survival of 15-20 years, regardless of age at diagnosis, and is a foremost risk factor for cholangiocarcinoma. Given the chronic and progressive nature of PSC, its inherent risk for biliary tract and other complications, and the paucity of effective pharmacotherapies, endoscopy plays a major role in the care of many patients with this disorder. In this review, we discuss the endoscopic management of PSC, including established and evolving approaches to the diagnosis and treatment of its benign as well as malignant sequelae. Owing to the rarity of PSC and dearth of high-quality evidence, we propose pragmatic approaches based on both currently available data and expert opinion.
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Affiliation(s)
- Neil Bharat Marya
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Gastroenterology Fellowship Training Program, Los Angeles, CA 90095, United States
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
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18
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19
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Abstract
Liver transplant (LT) for perihilar cholangiocarcinoma (CCA) offers an opportunity for survival among patients with early-stage but anatomically unresectable disease. The 5-year survival rate after LT is 65% to 70%, higher among patients with primary sclerosing cholangitis, who are often diagnosed earlier, and lower among patients with de novo CCA. The results of LT for hilar CCA, along with recent limited data suggesting favorable survival among patients with very early intrahepatic CCA (ICC), have reignited interest in the subject. This article discusses LT following neoadjuvant therapy for CCA and the early data on LT alone for ICC.
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Affiliation(s)
- Daniel Zamora-Valdes
- Division of Transplantation Surgery, Mayo Clinic, 200 First Street, Rochester, MN 55905, USA
| | - Julie K Heimbach
- Division of Transplantation Surgery, Mayo Clinic, 200 First Street, Rochester, MN 55905, USA.
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20
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Ali AH, Tabibian JH, Nasser-Ghodsi N, Lennon RJ, DeLeon T, Borad MJ, Hilscher M, Silveira MG, Carey EJ, Lindor KD. Surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis. Hepatology 2018; 67:2338-2351. [PMID: 29244227 DOI: 10.1002/hep.29730] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 10/25/2017] [Accepted: 12/08/2017] [Indexed: 12/19/2022]
Abstract
UNLABELLED Primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma (CCA) and gallbladder carcinoma (GBCa). Surveillance for GBCa is recommended, but the clinical utility of surveillance for other hepatobiliary cancers (HBCa) in PSC, namely CCA and hepatocellular carcinoma (HCC), remains unclear. We aimed to determine whether surveillance is associated with better survival after diagnosis of HBCa in patients with PSC. Medical records of PSC patients seen at the Mayo Clinic Rochester from 1995 to 2015 were reviewed. Patients were included if they had ≥1 year of follow-up and developed HBCa. Patients were categorized according to their surveillance status (abdominal imaging, carbohydrate antigen 19-9, and alpha-fetoprotein). The primary endpoints were HBCa recurrence, HBCa-related death, and all-cause mortality. Overall survival was assessed by the Kaplan-Meier survival method; HBCa-related survival was assessed using competing risk regression. Tests of significance were two-tailed, and a P value <0.05 was considered statistically significant. From 1995 to 2015, a total of 79 of 830 PSC patients were diagnosed with HBCa. Cumulative follow-up was 712 and 283 person-years pre- and post-HBCa diagnosis, respectively. Seventy-eight percent of patients (54/79) developed CCA, 21% (17/79) HCC, 6% (5/79) GBCa, 3% (2/79) both CCA and HCC, and 1% (1/79) both HCC and GBCa. Fifty-one percent (40/79) were under HBCa surveillance, and 49% (39/79) were not. Patients in the surveillance group had significantly higher 5-year overall survival (68% versus 20%, respectively; P < 0.001) and significantly lower 5-year probability of experiencing an HBCa-related adverse event (32% versus 75%, respectively; P < 0.001) compared with the no-surveillance group. CONCLUSION This study demonstrates that HBCa surveillance significantly improves outcomes, including survival, in patients with PSC. (Hepatology 2018;67:2338-2351).
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Affiliation(s)
- Ahmad Hassan Ali
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ
- Texas Tech University Health Sciences Center, Amarillo, TX
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | | | - Ryan J Lennon
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | | | | | - Moira Hilscher
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Marina G Silveira
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT
| | - Elizabeth J Carey
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ
| | - Keith D Lindor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ
- Arizona State University, Phoenix, AZ
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Bragazzi MC, Ridola L, Safarikia S, Matteo SD, Costantini D, Nevi L, Cardinale V. New insights into cholangiocarcinoma: multiple stems and related cell lineages of origin. Ann Gastroenterol 2017; 31:42-55. [PMID: 29333066 PMCID: PMC5759612 DOI: 10.20524/aog.2017.0209] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 09/14/2017] [Indexed: 12/12/2022] Open
Abstract
Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that may develop at any level of the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) on the basis of its anatomical location. Notably, although these three CCA subtypes have common features, they also have important inter- and intra-tumor differences that can affect their pathogenesis and outcome. A unique feature of CCA is that it manifests in the hepatic parenchyma or large intrahepatic and extrahepatic bile ducts, furnished by two distinct stem cell niches: the canals of Hering and the peribiliary glands, respectively. The complexity of CCA pathogenesis highlights the need for a multidisciplinary, translational, and systemic approach to this malignancy. This review focuses on advances in the knowledge of CCA histomorphology, risk factors, molecular pathogenesis, and subsets of CCA.
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Affiliation(s)
- Maria Consiglia Bragazzi
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Ridola
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Samira Safarikia
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Sabina Di Matteo
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Daniele Costantini
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Nevi
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
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Abstract
PURPOSE OF REVIEW Liver transplantation for unresectable hilar cholangiocarcinoma is a highly controversial issue. This review will summarize results with transplantation alone and a new strategy of high-dose neoadjuvant chemoradiotherapy and subsequent liver transplantation. The review will address controversies regarding this novel approach to the treatment of hilar cholangiocarcinoma, including prioritization of patients with cholangiocarcinoma awaiting scarce deceased donor livers. RECENT FINDINGS Results with liver transplantation alone for patients with unresectable cholangiocarcinoma are poor and do not justify use of scarce donor livers for these patients. Several centers have recently reported excellent results combining high-dose neoadjuvant chemoradiotherapy and liver transplantation for patients with early stage disease. Patient selection, operative staging, timely transplantation, and strict adherence to protocol are keys to success. SUMMARY Hilar cholangiocarcinoma - once a contraindication for transplantation - has reemerged as an indication for transplantation when combined with neoadjuvant therapy. Results are comparable to results achieved with liver transplantation for other indications and exceed results with standard resection.
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Vardevanyan H, Holzinger J, Forstner R. Hepatoduodenal lymph node metastasis mimicking Klatskin tumor in a patient with sigmoid colon mucinous cancer. Radiol Case Rep 2017; 12:494-499. [PMID: 28828110 PMCID: PMC5551956 DOI: 10.1016/j.radcr.2017.04.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 03/19/2017] [Accepted: 04/11/2017] [Indexed: 12/25/2022] Open
Abstract
We report a case of a 48-year-old female patient, who presented with abdominal pain, jaundice, and lack of appetite. Ultrasound showed intrahepatic biliary dilatation with retroperitoneal lymphadenopathy. Further magnetic resonance cholangiopancreatography detected Klatskin tumor. Computed tomography (CT) confirmed the Klatskin tumor with liver metastases and retroperitoneal lymphadenopathy. Biopsy from the hepatic lesion identified mucinous adenocarcinoma, likely originating from bile ducts. Endoscopic retrograde cholangiopancreatography was performed 3 times with stents placed in the left and right hepatic bile ducts. Later the patient had hematochezia and was referred to colonoscopy. Tubulovillous adenoma with dysplasia was diagnosed with signs of in situ cancer. Preoperative CT was done for further staging: new pulmonary metastases were discovered. Sigmoid colon was resected. Histopathology verified a poorly differentiated mucinous adenocarcinoma within the tubulovillous adenoma. Intraoperative biopsies of porta hepatis mass resembled metastatic lymph nodes in hepatoduodenal ligament, mimicking Klatskin tumor. Retrospective analysis of CT data demonstrated presence of sigmoid colon tumor.
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Affiliation(s)
- Hovhannes Vardevanyan
- Department of Diagnostic Imaging, Armenian-American Wellness Center, Sayat-Nova 6, Apartment 11, Yerevan 0001, Armenia
| | - Josef Holzinger
- Department of Endoscopic Surgery, University Hospital of Salzburg, PMU, Salzburg, Austria
| | - Rosemarie Forstner
- Department of Radiology, University Hospital of Salzburg, PMU, Salzburg, Austria
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Cost utility of ERCP-based modalities for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Gastrointest Endosc 2017; 85:773-781.e10. [PMID: 27590963 DOI: 10.1016/j.gie.2016.08.020] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 08/17/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Cholangiocarcinoma (CCA) is a leading cause of morbidity and mortality in patients with primary sclerosing cholangitis (PSC). Although several ERCP-based diagnostic modalities are available for diagnosing CCA, it is unclear whether one modality is more cost-effective than the others. The primary aim of this study was to compare the cost-effectiveness of ERCP-based techniques for diagnosing CCA in patients with PSC-induced biliary strictures. METHODS We performed a cost utility analysis to assess the net monetary benefit for accurately diagnosing CCA using 5 different diagnostic strategies: (1) ERCP with bile duct brushing for cytology, (2) ERCP with brushings for cytology and fluorescence in situ hybridization (FISH)-trisomy, (3) ERCP with brushings for cytology and FISH-polysomy, (4) ERCP with intraductal biopsy sampling, and (5) single-operator cholangioscopy (SOC) with targeted biopsy sampling. A Monte Carlo simulation assessed outcomes including quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were also performed. RESULTS SOC with targeted biopsy sampling, as compared with ERCP with brushing for FISH-polysomy, produced an incremental QALY gain of .22 at an additional cost of $8562.44, resulting in a base case ICER of $39,277.25. Deterministic and probabilistic sensitivity analyses demonstrated that diagnosis with SOC was cost-effective at conventional willingness-to-pay thresholds of $50,000 and $100,000. SOC was the most cost-effective diagnostic strategy. CONCLUSIONS SOC with biopsy sampling is the most cost-effective diagnostic modality for CCA in PSC strictures.
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25
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Tsuchiya K, Nanashima A, Ikeda T, Minami S, Nagano M, Hamada T, Yano K, Fujii Y. A case of concomitant colitic cancer and intrahepatic cholangiocarcinoma during follow-up for ulcerative colitis. Clin J Gastroenterol 2017; 10:157-162. [PMID: 28138905 DOI: 10.1007/s12328-017-0715-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 01/17/2017] [Indexed: 02/08/2023]
Abstract
Colitis-associated colorectal cancer (CAC) is known to occur in long-standing and extensive ulcerative colitis (UC). Furthermore, UC is known to complicate primary sclerosing cholangitis (PSC), which subsequently results in an increased risk of developing cholangiocarcinoma. We report a case of colitis-associated rectal cancer (CARC) accompanied by intrahepatic cholangiocarcinoma (ICC) based on UC and PSC. A 73-year-old man had suffered from UC for 19 years. During surveillance colonoscopy, a tumor was found in the rectum that was pathologically diagnosed as CARC from the resected specimen. Abdominal computed tomography also revealed a localized dilation of the intrahepatic bile duct, and endoscopic retrograde cholangiography revealed a band-like stricture. This remarkable tumor lesion was not observed in the hepatic duct. Left hepatectomy was performed because of the suspicion of possible ICC at the stenosis of the hepatic duct. The presence of ICC was confirmed at the lesion causing the stricture. The pathological diagnosis from the resected specimen was ICC based on PSC. Adjuvant chemotherapy for ICC was performed for 6 months. Neither cancer has recurred for 2.5 years after hepatectomy. Patients with PSC concomitant with UC should be considered a high-risk group for CAC and ICC.
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Affiliation(s)
- Kazuyo Tsuchiya
- Division of Gastrointestinal, Endocrine and Pediatric Surgery, Department of Surgery, University of Miyazaki Faculty of Medicine, Miyazaki, Japan
| | - Atsushi Nanashima
- Division of Hepato-Biliary-Pancreas Surgery, Department of Surgery, University of Miyazaki Faculty of Medicine, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
| | - Takuto Ikeda
- Division of Gastrointestinal, Endocrine and Pediatric Surgery, Department of Surgery, University of Miyazaki Faculty of Medicine, Miyazaki, Japan
| | | | | | - Takeomi Hamada
- Division of Hepato-Biliary-Pancreas Surgery, Department of Surgery, University of Miyazaki Faculty of Medicine, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Koichi Yano
- Division of Hepato-Biliary-Pancreas Surgery, Department of Surgery, University of Miyazaki Faculty of Medicine, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Yoshiro Fujii
- Division of Hepato-Biliary-Pancreas Surgery, Department of Surgery, University of Miyazaki Faculty of Medicine, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
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Primary sclerosing cholangitis in the Swiss Inflammatory Bowel Disease Cohort Study: prevalence, risk factors, and long-term follow-up. Eur J Gastroenterol Hepatol 2017; 29:91-97. [PMID: 27622999 DOI: 10.1097/meg.0000000000000747] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM Primary sclerosing cholangitis (PSC) represents the most common hepatobiliary extraintestinal manifestation of inflammatory bowel disease (IBD). We aimed to assess the prevalence of PSC in the Swiss Inflammatory Bowel Disease Cohort Study, to identify associated risk factors, and to describe the long-term evolution. PATIENTS AND METHODS Data of patients enrolled into the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. Logistic regression modeling was performed to identify risk factors for PSC. RESULTS Among 2744 patients [1188 ulcerative colitis (UC); 1556 Crohn's disease (CD)], 57 had PSC (48 UC-PSC, nine CD-PSC). The prevalence of PSC was higher in UC compared with CD (4.04 vs. 0.58%, P<0.001). We identified the following significant independent risk factors for PSC in patients with UC: male sex [odds ratio (OR) 2.771, P=0.022], pancolitis (OR 2.855, P=0.011), nonsmoker at diagnosis (OR 9.253, P=0.030), and a history of appendicectomy (OR 4.114, P=0.019). During a median follow-up time of 74.8 months, four (7.0%) of PSC patients developed cholangiocarcinoma, six (10.5%) underwent liver transplantation, and five (8.8%) died. Survival of IBD-PSC patients was significantly worse compared with IBD patients without PSC (P=0.001). UC-PSC patients developed significantly more frequently colorectal cancer compared with UC patients without PSC (2/48 vs. 9/1440, P=0.017). CONCLUSION Approximately 4% of UC patients and 0.6% of CD patients had PSC. Male sex, pancolitis, nonsmoker status, and a history of appendicectomy were significantly associated with PSC. PSC is associated with considerable morbidity and mortality in the long term.
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Njei B, McCarty TR, Varadarajulu S, Navaneethan U. Systematic review with meta-analysis: endoscopic retrograde cholangiopancreatography-based modalities for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Aliment Pharmacol Ther 2016; 44:1139-1151. [PMID: 27696456 DOI: 10.1111/apt.13817] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Revised: 05/18/2016] [Accepted: 09/13/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND The accuracy of current endoscopic modalities for diagnosing cholangiocarcinoma in primary sclerosing cholangitis (PSC) is suboptimal. AIM To evaluate the comparative effectiveness of endoscopic retrograde cholangiopancreatography (ERCP)-based modalities, independently or in combination, for the diagnosis of cholangiocarcinoma in patients with PSC-induced biliary strictures. METHODS Searches of PubMed, EMBASE, Web of Science and the Cochrane Library databases were performed through December 2015. Measured outcomes included sensitivity and specificity of all diagnostic modalities independently or in combination. A bivariate model was used to compute the pooled sensitivity and specificity, and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI). A logistic regression model was used to impute the incremental performance of combining two diagnostic tests. RESULTS Twenty-one studies met inclusion criteria: 13 on bile duct brushing for cytology, 7 on fluorescence in situ hybridisation (FISH), 2 on probe-based confocal laser endomicroscopy, and 4 on single-operator cholangioscopy with targeted biopsies. Single-operator cholangioscopy with targeted biopsies was the most accurate diagnostic modality at 96% (95% CI, 94-97%). The pooled sensitivity and specificity of single-operator cholangioscopy for diagnosis of cholangiocarcinoma in patients with PSC was 65% (95% CI, 35-87%) and 97% (95% CI, 87-99%), respectively. The pooled diagnostic odds ratio to detect cholangiocarcinoma was 59 (95% CI, 10-341). CONCLUSIONS Single-operator cholangioscopy with targeted biopsies appears to be the most accurate ERCP-based modality for diagnosing cholangiocarcinoma in primary sclerosing cholangitis. However, future large, well-designed comparative diagnostic studies are warranted to validate these findings.
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Affiliation(s)
- B Njei
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.,Investigative Medicine Program, Yale Center of Clinical Investigation, New Haven, CT, USA
| | - T R McCarty
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - S Varadarajulu
- Center for Interventional Endoscopy, Florida Hospital, Orlando, FL, USA
| | - U Navaneethan
- Center for Interventional Endoscopy, Florida Hospital, Orlando, FL, USA
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Benlice C, Gorgun E. Is ileal pouch-anal anastomosis after Whipple procedure doable? Tech Coloproctol 2016; 20:501-4. [PMID: 27142854 DOI: 10.1007/s10151-016-1472-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Accepted: 04/24/2016] [Indexed: 10/21/2022]
Affiliation(s)
- C Benlice
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Ave. A-30, Cleveland, OH, 44195, USA
| | - E Gorgun
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Ave. A-30, Cleveland, OH, 44195, USA.
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Geramizadeh B, Ghavvas R, Kazemi K, Shamsaeefar A, Nikeghbalian S, Malekhosseini SA. Cholangiocarcinoma Secondary to Primary Sclerosing Cholangitis in Explanted Livers: A Single-Center Study in the South of Iran. HEPATITIS MONTHLY 2015; 15:e33626. [PMID: 26977169 PMCID: PMC4779251 DOI: 10.5812/hepatmon.33626] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 11/24/2015] [Accepted: 11/28/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic disease, characterized by chronic inflammation and fibrosis of bile duct epithelial cells. This is a significant contributory factor to the development of malignancy, most commonly cholangiocarcinoma (CCA), which is the second most common malignant liver tumor. OBJECTIVES For the first time in Iran, we intend to describe our experience with cases of PSC, with and without CCA, in explanted livers, and compare our results with those found in other areas of the world. PATIENTS AND METHODS The study population comprised 181 individuals with a diagnosis of PSC who had undergone liver transplantation in the main liver transplant center of Iran, the largest center of hepatobiliary surgery in the south of that country, over a 3-year period between 2012 and 2014. All explanted livers, with and without CCA, were evaluated. RESULTS Of the 181 patients, 16 were found to have CCA, two of whom had been diagnosed after pathologic study of the explanted livers. Therefore it appeared that 8.8% of the patients with PSC in our center had developed CCA before liver transplantation. CONCLUSIONS A comparison of our results with those obtained from other centers in both Western and Asian countries (which reported CCA in 3.6% - 36.5% of patients with PSC), shows that the incidence of CCA in the patients we studied is intermediate.
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Affiliation(s)
- Bita Geramizadeh
- Department of Pathology, Shiraz University of Medical Sciences, Shiraz, IR Iran
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Roshanak Ghavvas
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Kurosh Kazemi
- Department of Hepatobiliary and Liver Transplant Surgery, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Alireza Shamsaeefar
- Department of Hepatobiliary and Liver Transplant Surgery, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Saman Nikeghbalian
- Department of Hepatobiliary and Liver Transplant Surgery, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Seyed-Ali Malekhosseini
- Department of Hepatobiliary and Liver Transplant Surgery, Shiraz University of Medical Sciences, Shiraz, IR Iran
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Abstract
Primary sclerosing cholangitis (PSC) is a frequently progressive and fatal disease. Death from cancer occurs in a significant subset of patients with PSC. Patients with PSC have a 10 to 15 % lifetime risk of developing cholangiocarcinoma (CCA). About one third of CCAs are present in the first year after a diagnosis of PSC; the remainder are present with a frequency of about 1.5 % each year. Patients with concomitant PSC and inflammatory bowel disease (IBD) have a 4-fold higher risk of colorectal cancer (CRC) than patients with IBD alone and a 10-fold higher risk of CRC than the general population. The risk does not diminish with liver transplantation. This patient population also has a high frequency of carcinoma in gallbladder mass lesions. The risk for hepatocellular carcinoma (HCC) in the presence of cirrhosis is uncertain-two large cohort studies suggest that HCC is not as common as in other causes of cirrhosis. Although AASLD guidelines do not recommend routine screening for liver tumors in patients with PSC, we recommend MRI/MRCP and serum CA 19-9 levels in patients with PSC every 6 months to screen for CCA, HCC, pancreatic cancer, and gallbladder cancer. Screening colonoscopy at the diagnosis of PSC and surveillance colonoscopies every 1-2 years should be performed in those with PSC and IBD.
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Ilyas SI, Eaton JE, Gores GJ. Primary Sclerosing Cholangitis as a Premalignant Biliary Tract Disease: Surveillance and Management. Clin Gastroenterol Hepatol 2015; 13:2152-65. [PMID: 26051390 PMCID: PMC4618039 DOI: 10.1016/j.cgh.2015.05.035] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2015] [Revised: 05/20/2015] [Accepted: 05/22/2015] [Indexed: 02/07/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a premalignant biliary tract disease that confers a significant risk for the development of cholangiocarcinoma (CCA). The chronic biliary tract inflammation of PSC promotes pro-oncogenic processes such as cellular proliferation, induction of DNA damage, alterations of the extracellular matrix, and cholestasis. The diagnosis of malignancy in PSC can be challenging because inflammation-related changes in PSC may produce dominant biliary tract strictures mimicking CCA. Biomarkers such as detection of methylated genes in biliary specimens represent noninvasive techniques that may discriminate malignant biliary ductal changes from PSC strictures. However, conventional cytology and advanced cytologic techniques such as fluorescence in situ hybridization for polysomy remain the practice standard for diagnosing CCA in PSC. Curative treatment options of malignancy arising in PSC are limited. For a subset of patients selected by using stringent criteria, liver transplantation after neoadjuvant chemoradiation is a potential curative therapy. However, most patients have advanced malignancy at the time of diagnosis. Advances directed at identifying high-risk patients, early cancer detection, and development of chemopreventive strategies will be essential to better manage the cancer risk in this premalignant disease. A better understanding of dysplasia definition and especially its natural history is also needed in this disease. Herein, we review recent developments in our understanding of the risk factors, pathogenic mechanisms of PSC associated with CCA, as well as advances in early detection and therapies.
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Affiliation(s)
- Sumera I Ilyas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - John E Eaton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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Sapisochín G, Fernández de Sevilla E, Echeverri J, Charco R. Liver transplantation for cholangiocarcinoma: Current status and new insights. World J Hepatol 2015; 7:2396-2403. [PMID: 26464755 PMCID: PMC4598610 DOI: 10.4254/wjh.v7.i22.2396] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 08/12/2015] [Accepted: 09/18/2015] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma is a malignant tumor of the biliary system that can be classified into intrahepatic (iCCA), perihiliar (phCCA) and distal. Initial experiences with orthotopic liver transplantation (OLT) for patients with iCCA and phCCA had very poor results and this treatment strategy was abandoned. In the last decade, thanks to a strict selection process and a neoadjuvant chemoradiation protocol, the results of OLT for patients with non-resectable phCCA have been shown to be excellent and this strategy has been extended worldwide in selected transplant centers. Intrahepatic cholangiocarcinoma is a growing disease in most countries and can be diagnosed both in cirrhotic and in non-cirrhotic livers. Even though OLT is contraindicated in most centers, recent investigations analyzing patients that were transplanted with a misdiagnosis of HCC and were found to have an iCCA have shown encouraging results. There is some information suggesting that patients with early stages of the disease could benefit from OLT. In this review we analyze the current state-of-the-art of OLT for cholangiocarcinoma as well as the new insights and future perspectives.
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Poruk KE, Pawlik TM, Weiss MJ. Perioperative Management of Hilar Cholangiocarcinoma. J Gastrointest Surg 2015; 19:1889-99. [PMID: 26022776 PMCID: PMC4858933 DOI: 10.1007/s11605-015-2854-8] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Accepted: 05/04/2015] [Indexed: 01/31/2023]
Abstract
BACKGROUND Cholangiocarcinoma is the most common primary tumor of the biliary tract although it accounts for only 2 % of all human malignancies. We herein review hilar cholangiocarcinoma including its risk factors, the main classification systems for tumors, current surgical management of the disease, and the role chemotherapy and liver transplantation may play in selected patients. METHODS We performed a comprehensive literature search using PubMed, Medline, and the Cochrane library for the period 1980-2015 using the following MeSH terms: "hilar cholangiocarcinoma", "biliary cancer", and "cholangiocarcinoma". Only recent studies that were published in English and in peer reviewed journals were included. FINDINGS Hilar cholangiocarcinoma is a disease of advanced age with an unclear etiology, most frequently found in Southeast Asia and relatively rare in Western countries. The best chance of long-term survival and potential cure is surgical resection with negative surgical margins, but many patients are unresectable due to locally advanced or metastatic disease at diagnosis. As a result of recent efforts, new methods of management have been identified for these patients, including preoperative portal vein embolism and biliary drainage, neoadjuvant chemotherapy with subsequent transplantation, and chemoradiation therapy. CONCLUSION Current management of hilar cholangiocarcinoma depends on extent of the tumor at presentation and includes surgical resection, liver transplantation, portal vein embolization, and chemoradiation therapy. Our understanding of hilar cholangiocarcinoma has improved in recent years and further research offers hope to improve the outcome in patients with these rare tumors.
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Affiliation(s)
- Katherine E Poruk
- Department of Surgery, The Johns Hopkins University School of Medicine, Halsted 614 600 N. Wolfe Street, Baltimore, MD, 21287, USA
| | - Timothy M Pawlik
- Department of Surgery, The Johns Hopkins University School of Medicine, Halsted 614 600 N. Wolfe Street, Baltimore, MD, 21287, USA
| | - Matthew J Weiss
- Department of Surgery, The Johns Hopkins University School of Medicine, Halsted 614 600 N. Wolfe Street, Baltimore, MD, 21287, USA.
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Modha K, Navaneethan U. Diagnosis and management of primary sclerosing cholangitis-perspectives from a therapeutic endoscopist. World J Hepatol 2015; 7:799-805. [PMID: 25914780 PMCID: PMC4404385 DOI: 10.4254/wjh.v7.i5.799] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Revised: 01/04/2015] [Accepted: 01/20/2015] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver condition characterized by inflammation, fibrosis, and destruction of the intra- and extrahepatic bile ducts. The therapeutic endoscopist plays a key role in the diagnosis and management of PSC. In patients presenting with a cholestatic profile, endoscopic retrograde cholangiopancreatography (ERCP) is warranted for a definite diagnosis of PSC. Dominant strictures of the bile duct occur in 36%-57% of PSC patients. Endoscopic balloon dilatation with or without stenting have been employed in the management of dominant strictures. In addition, PSC patients are at increased risk of developing cholangiocarcinoma with a 20% lifetime risk. Brush cytology obtained during ERCP and use of fluorescence in situ hybridization forms the initial diagnostic step in the investigation of patients with dominant biliary strictures. Our review aims to summarize the current evidence supporting the role of a therapeutic endoscopist in the management of PSC patients.
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Plentz RR, Malek NP. Clinical presentation, risk factors and staging systems of cholangiocarcinoma. Best Pract Res Clin Gastroenterol 2015; 29:245-52. [PMID: 25966425 DOI: 10.1016/j.bpg.2015.02.001] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Revised: 01/18/2015] [Accepted: 02/07/2015] [Indexed: 01/31/2023]
Abstract
Cholangiocarcinoma (CCA) is the second most common primary liver tumour. Intra-hepatic CCA develops within the liver parenchyma while extrahepatic CCA involves the biliary tree within the hepatoduodenal ligament. Hilar CCA are also called Klatskin tumour. The CCA incidence has increased worldwide over the last years, but there are also geographic differences, with focus in Asian countries. Known risk factors are primary sclerosing cholangitis (PSC), hepatolithiasis, Caroli's disease, hepatitis B and C infection, liver flukes, cirrhosis, diabetes, obesity, alcohol consumption and probably tobacco smoking. Patients with early CCA have only little discomfort, but can later show episodes with jaundice and other non-specific tumour symptoms. For the staging of the disease different classifications are available, which consider various factors like tumour size, location, regional lymph nodes, metastasis, vascular involvement and tumour marker.
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Affiliation(s)
- Ruben R Plentz
- Department of Internal Medicine I, Medical University Hospital, Otfried-Müller-Str. 10, 72076 Tübingen, Germany.
| | - Nisar P Malek
- Department of Internal Medicine I, Medical University Hospital, Otfried-Müller-Str. 10, 72076 Tübingen, Germany
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Croome KP, Rosen CB, Heimbach JK, Nagorney DM. Is Liver Transplantation Appropriate for Patients with Potentially Resectable De Novo Hilar Cholangiocarcinoma? J Am Coll Surg 2015; 221:130-9. [PMID: 25872685 DOI: 10.1016/j.jamcollsurg.2015.01.064] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 01/28/2015] [Accepted: 01/28/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND Liver transplantation (LTX) is curative for selected patients with hilar cholangiocarcinoma (HC) in the setting of sclerosing cholangitis. However, the outcome of LTX vs liver resection (RTX) for patients with de novo HC remains unclear. STUDY DESIGN Patients with de novo HC treated by protocol LTX (n = 90) or RTX (n = 124) between 1993 and 2013 were reviewed. Based on preoperative imaging, RTX was pursued for Bismuth type III HC and LTX for unresectable Bismuth type IV. RESULTS Unadjusted analysis showed that overall survival after operation was greater for LTX than RTX (p = 0.003). One-, 3-, and 5-year overall survival rates, respectively, were 90%, 71%, and 59% for LTX and 81%, 53%, and 36% for RTX. Survival was not different between LTX and RTX after adjusting for patient age, lymph node metastases, and tumor size. After postoperative pathologic review, HC after RTX was reclassified as Bismuth-Corlette (B-C) IV, based on the necessity of multiple biliary anastomoses in 40 patients to more accurately compare treatment outcomes. Overall survival was greater after LTX than RTX (p = 0.039) for patients with Bismuth-Corlette IV HC. CONCLUSIONS Patients with clearly resectable de novo HC should be treated with resection because there is no evidence that they would fare better with LTX. Patients with locally unresectable de novo HC, meeting criteria for our protocol, should be treated with LTX. The decision to proceed with RTX or LTX for patients with borderline resectable de novo HC remains difficult, but our results suggest that patients with B-C type IV HC might be best treated with transplantation, if they are excellent transplant candidates.
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Affiliation(s)
- Kristopher P Croome
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, FL; Division of Subspecialty General Surgery, Mayo Clinic College of Medicine, Rochester, MN
| | - Charles B Rosen
- Division of Transplantation Surgery and Mayo Clinic William J von Liebig Transplant Center, Mayo Clinic College of Medicine, Rochester, MN
| | - Julie K Heimbach
- Division of Transplantation Surgery and Mayo Clinic William J von Liebig Transplant Center, Mayo Clinic College of Medicine, Rochester, MN
| | - David M Nagorney
- Division of Subspecialty General Surgery, Mayo Clinic College of Medicine, Rochester, MN; Division of Transplantation Surgery and Mayo Clinic William J von Liebig Transplant Center, Mayo Clinic College of Medicine, Rochester, MN.
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Bonato G, Cristoferi L, Strazzabosco M, Fabris L. Malignancies in Primary Sclerosing Cholangitis--A Continuing Threat. Dig Dis 2015; 33 Suppl 2:140-8. [PMID: 26641079 PMCID: PMC4939833 DOI: 10.1159/000440826] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
UNLABELLED Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease of unknown etiology, primarily targeting cholangiocytes at any portion of the biliary tree. No effective medical treatments are currently available. A unique feature of PSC is its close association (about 80%) with inflammatory bowel disease (IBD), mainly ulcerative colitis (UC). As in many chronic inflammatory conditions, cancer development can complicate PSC, accounting for >40% of deaths. Cholangiocarcinoma (CCA), gallbladder carcinoma (GBC) and colorectal carcinoma (CRC) have been variably associated to PSC, with a prevalence up to 13-14%. The risk of cancer is one of the most challenging issues in the management of PSC; it raises several questions about cancer surveillance, early diagnosis, prevention and treatment. KEY MESSAGES Among the different cancers complicating PSC, CCA is the most relevant, because it is more frequent (incidence of 0.5-1.5%) and because the prognosis is poor (5-year survival <10%). Early diagnosis of CCA in PSC can be difficult because lesions may not be evident in radiological studies. Surgical resection provides disappointing results; liver transplantation combined with neoadjuvant chemoradiotherapy is being proposed, but this approach is limited to a highly selected group of patients and is available only in a few specialized centers. Similar to CCA, GBC carries a dismal prognosis. Since it is difficult to discriminate GBC from other gallbladder abnormalities, cholecystectomy has been proposed in all gallbladder lesions detected in PSC, regardless of their size. CRC is a frequent complication of PSC associated to UC; its incidence steadily increases with time of colitis, reaching up to 20-30% of the patients after 20 years. Colonoscopy with extensive histologic sampling at an annual/biannual interval is an effective surveillance strategy. However, when dysplastic lesions are detected, preemptive proctocolectomy should be considered. CONCLUSIONS PSC may be regarded as paradigmatic of the sequence leading from chronic inflammatory epithelial damage to neoplastic transformation. Understanding the molecular mechanisms regulating this pathogenetic sequence, may improve strategies of disease surveillance and cancer prevention and treatment. PSC is a chronic inflammatory cholangiopathy of unknown etiology but likely immune-mediated, characterized by peribiliary inflammation and fibrosis leading to strictures in any portion (intra- and/or extrahepatic) of the bile duct system. No effective medical treatments are currently available. A unique feature of PSC is the close association (about 80%) with IBD, mainly UC, often diagnosed before PSC (PSC/UC). As in other chronic inflammatory diseases, development of malignancies is a feared complication of PSC.
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Affiliation(s)
- Giulia Bonato
- Department of Surgery and Translational Medicine, University of Milan-Bicocca, Milan
| | - Laura Cristoferi
- Department of Surgery and Translational Medicine, University of Milan-Bicocca, Milan
| | - Mario Strazzabosco
- Department of Surgery and Translational Medicine, University of Milan-Bicocca, Milan,Section of Digestive Diseases, Yale University, New Haven, Conn., USA
| | - Luca Fabris
- Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy,Section of Digestive Diseases, Yale University, New Haven, Conn., USA
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Abstract
Optimal treatment of hilar cholangiocarcinoma depends on location of the cancer and extent of biliary and vascular involvement. Candidates for resection or transplantation must be evaluated and managed by a multidisciplinary team at a high-volume hepatobiliary center. Success requires absence of distant nodal or extrahepatic metastases and an adequate functional liver remnant with a negative ductal margin. Ipsilateral portal vein resection and reconstruction should be performed in patients with venous involvement. Neoadjuvant chemoradiation and liver transplantation is the best treatment option for patients with unresectable hilar cholangiocarcinoma without nodal or distant metastases and for patients with underlying chronic liver disease.
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Affiliation(s)
- Victor M Zaydfudim
- Department of Surgery, University of Virginia, 1300 Jefferson Park Avenue, Charlottesville, VA 22908, USA
| | - Charles B Rosen
- Division of Transplantation Surgery, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA
| | - David M Nagorney
- Department of Surgery, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA.
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Liu R, Cox K, Guthery SL, Book L, Witt B, Chadwick B, Adler DG. Cholangiocarcinoma and high-grade dysplasia in young patients with primary sclerosing cholangitis. Dig Dis Sci 2014; 59:2320-4. [PMID: 24748183 DOI: 10.1007/s10620-014-3152-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2014] [Accepted: 04/01/2014] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Cholangiocarcinoma (CCA) is very often an adulthood disease with primary sclerosing cholangitis (PSC) as one of the risk factors. It is rarely seen in the pediatric population, and when it is diagnosed before adulthood, it can be associated with PSC as well as HIV infection, biliary atresia, radiation therapy, and choledochal cyst. Although there have been some case reports of pediatric CCA, cases of childhood CCA associated with PSC are still relatively rare. AIM To describe the clinical and pathologic features of CCA in pediatric patients with previously diagnosed PSC. METHODS Retrospective study RESULTS Four patients with PSC (age range 15-18, mean 17 years) were included in this study. All patients underwent ERCP for diagnosis. Tissue samples obtained included routine cytology and FISH. ERCP was used to target sites for tissue acquisition in all patients. 3/4 of patients have inflammatory bowel disease (two Crohn's disease and one ulcerative colitis). Alkaline phosphatase was elevated in 3/4 patients, aspartate aminotransferase/alanine aminotransferase were elevated in 2/4 patients, and total bilirubin/direct bilirubin were elevated in 2/4 patients. 4/4 patients had positive FISH studies, and 3/4 patients had brush cytology concerning for CCA. 2/4 patients received chemotherapy, one patient underwent orthotopic liver transplant, and one patient underwent Whipple procedure. Two patients died soon after being diagnosed. CONCLUSIONS Young patients with PSC can develop CCA. This finding has implications for both screening and surveillance for cancer in pediatric patients with PSC.
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Affiliation(s)
- Roy Liu
- Gastroenterology and Hepatology, Huntsman Cancer Center, University of Utah School of Medicine, 30 N 1900E 4R118, Salt Lake City, UT, 84312, USA
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Aspirin may prevent cholangiocarcinoma: a case-control study from the United kingdom. Dig Dis Sci 2014; 59:1567-72. [PMID: 24535250 DOI: 10.1007/s10620-014-3056-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Accepted: 01/31/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND The proliferation of cholangiocarcinoma cells is suppressed in cell culture by nonsteroidal antiinflammatory drugs (NSAIDs) through the inhibition of cyclo-oxygenase-2 enzyme and also by statins which decrease the production of mediators of the cell cycle. AIMS To investigate whether there is an inverse association between NSAIDs, including aspirin, and the development of cholangiocarcinoma and, for the first time in a Western population, between statin use and the development of cholangiocarcinoma. METHODS This epidemiological study had a case-control design in which cases of cholangiocarcinoma diagnosed in Norwich between 2004 and 2010 and in Leicester in 2007 were identified from clinical databases. Controls were patients with basal cell carcinomas treated in the respective dermatology departments. The case notes of all subjects were reviewed to confirm diagnoses and obtain information on medication use. The data were analyzed using unconditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI). RESULTS In total, 81 cases of cholangiocarcinoma and 275 controls were identified. For all cases there was radiological evidence of cancer and 86 % of the cases involved the extrahepatic biliary system. Aspirin use was inversely associated with the development of cholangiocarcinoma (OR 0.45, 95 % CI 0.22-0.92), but there were no significant associations between the development of cholangiocarcinoma and NSAIDs (OR 0.39; 95 % CI 0.11-1.42) or statins (OR 0.58; 95 % CI 0.28-1.19). CONCLUSIONS The epidemiological data from this study support the biological evidence for aspirin having a protective effect against the development of cholangiocarcinoma. Aspirin use should be measured in future etiological studies and assessed as a chemoprevention agent in those at high risk of developing this type of cancer.
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Soares KC, Kamel I, Cosgrove DP, Herman JM, Pawlik TM. Hilar cholangiocarcinoma: diagnosis, treatment options, and management. Hepatobiliary Surg Nutr 2014; 3:18-34. [PMID: 24696835 DOI: 10.3978/j.issn.2304-3881.2014.02.05] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 12/30/2013] [Indexed: 12/16/2022]
Abstract
Hilar cholangiocarcinoma (HC) is a rare disease with a poor prognosis which typically presents in the 6(th) decade of life. Of the 3,000 cases seen annually in the United States, less than one half of these tumors are resectable. A variety of risk factors have been associated with HC, most notably primary sclerosing cholangitis (PSC), biliary stone disease and parasitic liver disease. Patients typically present with abdominal pain, pruritis, weight loss, and jaundice. Computed topography (CT), magnetic resonance imaging (MRI), and ultrasound (US) are used to characterize biliary lesions. Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) assess local ductal extent of the tumor while allowing for therapeutic biliary drainage. MRCP has demonstrated similar efficacies to PTC and ERCP in identifying anatomic extension of tumors with less complications. Treatment consists of surgery, radiation, chemotherapy and photodynamic therapy. Biliary drainage of the future liver remnant should be performed to decrease bilirubin levels thereby facilitating future liver hypertrophy. Standard therapy consists of surgical margin-negative (R0) resection with extrahepatic bile duct resection, hepatectomy and en bloc lymphadenectomy. Local resection should not be undertaken. Lymph node invasion, tumor grade and negative margins are important prognostic indicators. In instances where curative resection is not possible, liver transplantation has demonstrated acceptable outcomes in highly selected patients. Despite the limited data, chemotherapy is indicated for patients with unresectable tumors and adequate functional status. Five-year survival after surgical resection of HC ranges from 10% to 40% however, recurrence can be as high as 50-70% even after R0 resection. Due to the complexity of this disease, a multi-disciplinary approach with multimodal treatment is recommended for this complex disease.
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Affiliation(s)
- Kevin C Soares
- 1 Department of Surgery, Division of Surgical Oncology, 2 Department of Radiology, 3 Department of Oncology, 4 Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ihab Kamel
- 1 Department of Surgery, Division of Surgical Oncology, 2 Department of Radiology, 3 Department of Oncology, 4 Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - David P Cosgrove
- 1 Department of Surgery, Division of Surgical Oncology, 2 Department of Radiology, 3 Department of Oncology, 4 Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Joseph M Herman
- 1 Department of Surgery, Division of Surgical Oncology, 2 Department of Radiology, 3 Department of Oncology, 4 Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Timothy M Pawlik
- 1 Department of Surgery, Division of Surgical Oncology, 2 Department of Radiology, 3 Department of Oncology, 4 Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Mertens J. Clinical diagnosis and management of perihilar cholangiocarcinoma. Clin Liver Dis (Hoboken) 2014; 3:60-64. [PMID: 30992887 PMCID: PMC6448701 DOI: 10.1002/cld.328] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Joachim Mertens
- Department of Gastroenterology and HepatologyUniversity Hospital ZurichZurichSwitzerland.
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Singal A, Welling TH, Marrero JA. Role of liver transplantation in the treatment of cholangiocarcinoma. Expert Rev Anticancer Ther 2014; 9:491-502. [DOI: 10.1586/era.09.5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Epidemiology of Cholangiocarcinoma and Gallbladder Carcinoma. BILIARY TRACT AND GALLBLADDER CANCER 2014. [DOI: 10.1007/978-3-642-40558-7_1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Sugita R. Magnetic resonance evaluations of biliary malignancy and condition at high-risk for biliary malignancy: Current status. World J Hepatol 2013; 5:654-665. [PMID: 24432183 PMCID: PMC3888665 DOI: 10.4254/wjh.v5.i12.654] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Revised: 07/26/2013] [Accepted: 12/11/2013] [Indexed: 02/06/2023] Open
Abstract
Tumors of the biliary tree are relatively rare; but their incidence is rising worldwide. There are several known risk factors for bile duct cancers, and these are seem to be associated with chronic inflammation of the biliary epithelium. Herein, 2 risk factors have been discussed, primary sclerosing cholangitis and reflux of pancreatic juice into the bile duct, as seen in such as an abnormal union of the pancreatic-biliary junction because magnetic resonance imaging (MRI) is used widely and effectively in the diagnosis of these diseases. When biliary disease is suspected, MRI can often help differentiate between benignity and malignancy, stage tumors, select surgical candidates and guide surgical planning. MRI has many advantages over other modalities. Therefore, MRI is a reliable noninvasive imaging tool for diagnosis and pre-surgical evaluation of bile duct tumors. Nowadays remarkable technical advances in magnetic resonance technology have expanded the clinical applications of MRI in case of biliary diseases. In this article, it is also discussed how recent developments in MRI contributes to the diagnosis of the bile duct cancer and the evaluation of patients with risk factors affecting bile duct cancer.
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Ishii Y, Sasaki T, Serikawa M, Minami T, Okazaki A, Yukutake M, Ishigaki T, Kosaka K, Mouri T, Yoshimi S, Shimizu A, Tsuboi T, Chayama K. Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: ιmplications for cholangiocarcinogenesis. Int J Oncol 2013; 43:1073-9. [PMID: 23900502 DOI: 10.3892/ijo.2013.2038] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2013] [Accepted: 06/05/2013] [Indexed: 11/05/2022] Open
Abstract
Cholangiocarcinoma (CCA) occurs frequently in primary sclerosing cholangitis (PSC). Cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) induced by inflammation are believed to mediate prostaglandin E2 (PGE2) production thereby promoting carcinogenesis. Their expression in PSC-associated CCA tissues and non-neoplastic bile duct epithelial cells (BDECs) in PSC was investigated. COX-2 and mPGES-1 levels in 15 PSC patients (7 with CCA) were scored using immunohistochemical staining. The results were compared with those obtained in CCA tissues and non-neoplastic BDECs (controls) of 15 sporadic CCA patients. Non-neoplastic BDECs from large and small bile ducts were investigated separately. The mRNA expression levels of COX-2 and mPGES-1 in CCA tissues were analyzed by quantitative polymerase chain reaction. Ki-67 immunostaining was performed to evaluate cell proliferation. COX-2 was strongly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC. This expression was significantly upregulated in both compared with sporadic CCA tissues and non-neoplastic BDECs in sporadic CCA (both P<0.01). mPGES-1 was expressed at moderate to strong levels in PSC. Compared with controls, the expression was significantly higher in non-neoplastic small BDECs (P<0.01). COX-2 mRNA levels were significantly higher in PSC-associated tissues than in sporadic CCA tissues (P<0.01). Conversely, no differences were observed in mPGES-1 mRNA levels. Ki-67 labeling indices were higher in PSC-associated CCA tissues and non-neoplastic BDECs in PSC than in controls. In conclusion, COX-2 and mPGES-1 were highly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC, suggesting the involvement of COX-2 and mPGES-1 in cholangiocarcinogenesis.
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Affiliation(s)
- Yasutaka Ishii
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Minami, Hiroshima 734-8551, Japan
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Pellino G, Sciaudone G, Candilio G, Perna G, Santoriello A, Canonico S, Selvaggi F. Stepwise approach and surgery for gallbladder adenomyomatosis: a mini-review. Hepatobiliary Pancreat Dis Int 2013; 12:136-142. [PMID: 23558066 DOI: 10.1016/s1499-3872(13)60022-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Gallbladder adenomyomatosis (GBA) is a hyperplastic disease affecting the wall of the gallbladder, with some typical features. It has historically been considered a benign condition, nevertheless recent reports highlighted a potential role of GBA in predisposing to malignancies of the gallbladder. DATA SOURCES We reviewed the literature concerning GBA from its identification until July 2012. Owing to the relative rarity of the disease, studies often are case reports or case series. Thus we herein report a summary of the key-points concerning diagnosis and treatment of GBA, easily applicable in everyday practice, rather than a systematic review. Also, results are integrated with our recent experience. RESULTS In our experience, we observed a trend toward an increase of GBA during the last years, probably due to enhanced ultrasonographic technical advancements and physician's expertise. GBA has distinctive imaging features. Several recent reports highlight the potential risk of cancer associated with GBA; however the disease is still classified as a benign condition. Although its correlation with malignancy has not been demonstrated, it is prudent to recommend cholecystectomy in some cases. However, in selected asymptomatic patients, a wait-and-see policy is a viable alternative. We propose an algorithm, based on GBA pathological pattern (diffuse, segmental, localized or fundal), suitable for decision-making. CONCLUSIONS In symptomatic patients and if the diagnosis is doubtful, cholecystectomy is mandatory. Postponing surgery is an option to be offered to asymptomatic patients with low-risk GBA pattern who adhere to scheduled follow-ups.
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Affiliation(s)
- Gianluca Pellino
- Unit of General and Geriatric Surgery, School of Medicine, Second University of Naples, Piazza Miraglia 2, 80138 Naples, Italy
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Lim TS, Park JY, Kim SI, Kang H, Chung MJ. A Case of Rapidly Progressive Primary Sclerosing Cholangitis Requiring Liver Transplantation. KOREAN JOURNAL OF TRANSPLANTATION 2013. [DOI: 10.4285/jkstn.2013.27.1.24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Tae Seop Lim
- Department of Internal Medicine, Yonsei Institute of Gastroenterology, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei Institute of Gastroenterology, Seoul, Korea
| | - Soon Il Kim
- Department of Surgery, Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Huapyong Kang
- Department of Internal Medicine, Yonsei Institute of Gastroenterology, Seoul, Korea
| | - Moon Jae Chung
- Department of Internal Medicine, Yonsei Institute of Gastroenterology, Seoul, Korea
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Patil SA, Cross RK. Update in the management of extraintestinal manifestations of inflammatory bowel disease. Curr Gastroenterol Rep 2013; 15:314. [PMID: 23371321 DOI: 10.1007/s11894-013-0314-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
Inflammatory bowel disease, comprised of Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. Up to 40 % of patients with inflammatory bowel disease can develop inflammation in other organ systems of the body. These extraintestinal manifestations (EIM) can affect the musculoskeletal, ocular, mucocutaneous, and hepatobiliary systems. Symptoms related to EIM can result in impaired quality of life, and complications of EIM can lead to disfigurement, functional deficits, and even life-threatening organ dysfunction. Some EIM parallel the activity of IBD, and respond to treatment of the underlying disease. Others, however, follow an independent course and require targeted treatment.
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Affiliation(s)
- Seema A Patil
- University of Maryland School of Medicine, Baltimore, MD, USA.
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