Guideline sources The following summarized guidelines for the evaluation and management of klatskin tumor are prepared by our editorial team based on guidelines from the American Society for Gastrointestinal Endoscopy (ASGE 2021; 2013), the American College of Radiology (ACR 2019), the American Society of Clinical Oncology (ASCO 2019), the European Society of Medical Oncology (ESMO 2016), and the American Association for the Study of Liver Diseases (AASLD 2014). 1 2 3 4 5 6 Guidelines 1. Screening and diagnosis Indications for screening: consider obtaining screening for biliary cancer only in at-risk patients, such as patients with PSC. E https://web.pathway.md/diseases/recsg4euWMOmNpwbs 1/5 6/29/23, 5:44 AM Klatskin tumor Pathway 2. Classification and risk stratification Staging: use the AJCC/UICC (7th edition) staging system for biliary tract cancer with subclassifications for intrahepatic, perihilar and distal cholangiocarcinomas. E Show 5 more 3. Diagnostic investigations Diagnostic imaging: As per ESMO 2016 guidelines, obtain initial radiological imaging in patients presenting with jaundice before ERCP or percutaneous transhepatic cholangiography, as the inserted drains/stents obscure the diagnosis and assessment of the extent of disease. B Show 3 more As per ASGE 2013 guidelines: Perform MRCP to assess for resectability if CT suggests cholangiocarcinoma, particularly of the bifurcation. A Perform ERCP to obtain tissue or facilitate further evaluation of indeterminate strictures. B Cancer antigen 19-9: consider obtaining serum CA 19-9 with cut-off > 129 U/mL. C Interpret baseline CA 19-9 with caution and use it to guide treatment and follow-up. Recognize that it may have a prognostic role in the absence of biliary obstruction. E 4. Diagnostic procedures Biopsy: perform ERCP-guided biopsy whenever possible over biliary brush cytology. B Show 4 more 5. Medical management General principles: provide patients with biliary tract cancer a designated point of contact within the multidisciplinary team for advice and support (such as nurse specialist). E Show 2 more Management of local/locoregional disease: As per ASCO 2019 guidelines: Offer adjuvant capecitabine chemotherapy for 6 months in patients with resected biliary tract cancer. B Consider offering chemoradiotherapy in patients with extrahepatic cholangiocarcinoma with a microscopically positive surgical margin resection (R1). C As per ESMO 2016 guidelines, insufficient evidence to support the use of neoadjuvant therapy in patients with early-stage hilar cholangiocarcinoma. Encourage participating in clinical trials. I https://web.pathway.md/diseases/recsg4euWMOmNpwbs 2/5 6/29/23, 5:44 AM Klatskin tumor Pathway Show 2 more Management of advanced/metastatic disease: offer chemotherapy as the treatment of choice in patients with locally advanced or inoperable disease. Offer combination chemotherapy in patients with performance status 0-1 and monotherapy in patients with performance status 2. E Show 5 more Enrollment in clinical trials: Encourage patients participating in clinical trials and/or tissue biobanking aiming to define specific disease subgroups with a view to future risk stratification or selection for specific therapies. E Provide patients with all information (including potential risks and benefits) required to make an informed decision to give consent before participating in clinical trials and support them and their carers in making such decisions. E 6. Therapeutic procedures Biliary stenting: As per ASGE 2021 guidelines, consider performing either endoscopic or percutaneous transhepatic biliary drainage in patients with unresectable malignant hilar obstruction undergoing palliative drainage. Make the final decision based on patient preferences, disease characteristics, and local expertise. C Show 3 more As per ACR 2019 guidelines: Place a percutaneous internal/external biliary catheter as an initial therapeutic procedure in patients with malignant hilar obstruction. B Place an endoscopic internal biliary catheter with a removable plastic stent as an initial therapeutic procedure in patients with dilated bile ducts and coagulopathy (INR > 2.0 or platelet count < 60, 000) or moderate-to-massive ascites. B As per ESMO 2016 guidelines, perform biliary stenting by ERCP to relieve bile duct obstruction in patients with biliary tract cancer. E Show 3 more As per ASGE 2013 guidelines, perform endoscopic palliation of jaundice using MRCP as a guide for unilateral drainage, if the lesion is unresectable on MRCP, to minimize the risk of cholangitis. A 7. Surgical interventions Surgical resection: perform radical surgery with lymphadenectomy as the only curative treatment in patients with biliary tract cancer. Decide the exact nature and extent of surgery depending on tumor subtype/location agreed with specialist hepatobiliary multidisciplinary tumor board. E Show 3 more https://web.pathway.md/diseases/recsg4euWMOmNpwbs 3/5 6/29/23, 5:44 AM Klatskin tumor Pathway Liver transplantation: As per ESMO 2016 guidelines, insufficient evidence to recommend liver transplantation in patients with early-stage hilar cholangiocarcinoma. I As per AASLD 2014 guidelines: Consider performing liver transplantation in combination with neoadjuvant chemoradiation in patients with early-stage cholangiocarcinoma deemed unresectable due to parenchymal liver disease or anatomic location. B Refer patients with cholangiocarcinoma being potential transplant candidates to centers having established protocols for oncologic assessment and treatment. B 8. Patient education Patient education: inform patients about the likely duration of stent patency. Educate patients about symptoms and signs indicative of biliary obstruction or infection and instruct what they need to do in such an event. E 9. Follow-up and surveillance Reassessment after good treatment response: reassess patients in the multidisciplinary team in the event of a good response to any treatment. B Follow-up: Recognize that there is no universal standard follow-up schedule. Consider obtaining the following with a schedule depending on the stage of disease and agreed with the patient: clinical examination blood tests (including tumor markers) CT. E Show 3 more Clinical findings Symptoms Integument exam Abdominal pain Jaundice Dark urine Imaging findings Epigastric pain Fatigue Bile duct stricture Fever Dilated bile ducts Generalized pruritus Loss of appetite Nausea Pale stools RUQ pain https://web.pathway.md/diseases/recsg4euWMOmNpwbs 4/5 6/29/23, 5:44 AM Klatskin tumor Pathway Vomiting Weight loss Lab findings serum AFP serum ALP serum CA 19-9 serum CEA serum TBIL serum gamma- glutamyltransferase References 1. Bashar J Qumseya, Laith H Jamil, Badih Joseph Elmunzer et al. ASGE guideline on the role of endoscopy in the management of malignant hilar obstruction. Gastrointest Endosc. 2021 Aug;94 2 222 234.e22. Open 2. J W Valle, I Borbath, S A Khan et al. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep;27(suppl 5):v28-v37. Open 3. Anderson MA, Appalaneni V, Ben-Menachem T et al. The role of endoscopy in the evaluation and treatment of patients with biliary neoplasia. Gastrointest Endosc. 2013 Feb;77 2 167 74. Open 4. Expert Panel on Interventional Radiology:, Alexandra H Fairchild, Eric J Hohenwalter et al. ACR Appropriateness Criteria Radiologic Management of Biliary Obstruction. J Am Coll Radiol. 2019 May;16 5S S196 S213. Open 5. Rachna T Shroff, Erin B Kennedy, Melinda Bachini et al. Adjuvant Therapy for Resected Biliary Tract Cancer: ASCO Clinical Practice Guideline. J Clin Oncol. 2019 Apr 20;37 12 1015 1027. Open 6. Paul Martin, Andrea DiMartini, Sandy Feng et al. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014 Mar;59 3 1144 65. Open https://web.pathway.md/diseases/recsg4euWMOmNpwbs 5/5