Tumours are usually adenocarcinomas and have prominent desmoplastic stroma. However, except in cases where there is co-existing biliary dysplasia, it may not be possible, even with immunohistochemistry, to differentiate between CC and metastatic tumour. Examples of this include intraductal papillary neoplasm with associated invasive neoplasia, and mucinous cystic neoplasm with associated invasive neoplasia.
Endoscopic ultrasound EUS allows good views of the distal extrahepatic biliary tree, hilar lesions, gall bladder, regional lymph nodes and vasculature. However, the negative predictive value is low, which does not permit exclusion of malignancy following a negative biopsy.
However, this is not the case in most centres. Given the disappointing accuracy of current diagnostic techniques, interest in cholangioscopy has renewed following technical improvements in endoscopes. Invasive cholangiography should be reserved for histological diagnosis, or therapeutic decompression where there is cholangitis, or stent insertion in irresectable cases Grade B. The above techniques are complementary and may all be necessary as part of a surgical assessment Grade B.
CC staging is based on the tumour-node-metastasis TNM system. The 7th edition of the TNM classification introduced a specific staging system for intrahepatic CC, separate from HCC, providing better prognostic information. Unlike HCC, tumour size is not considered important. A positive resection margin non-R0 resection is a very poor prognostic factor. Although distant spread is late and uncommon in CC, comprehensive staging must be carried out to screen for metastatic disease.
CT provides more accurate information for this purpose than MRI. Most centres consider a staging laparoscopy to exclude local metastatic disease in those considered resectable on imaging. In a study of patients with suspected perihilar CC who underwent staging laparoscopy during the past decade, the overall yield and accuracy of staging laparoscopy decreased compared with earlier reports, possibly due to improved imaging techniques during this time period.
Metastatic adenocarcinoma mimicking CC may arise from several organs, particularly the pancreas, stomach, breast, lung and colon. CC is difficult to differentiate from metastatic adenocarcinoma, particularly if the pathological sample is obtained from outside the biliary tree.
Thorough clinical assessment and other investigations are necessary to exclude a primary from elsewhere. Studies obtained for the initial diagnosis may also provide staging information. However, to rule out metastatic disease, contrast CT of the abdomen, chest and pelvis should be carried out on all patients, particularly if resection is being considered Grade B.
However, due to the risk of tumour seeding, surgical assessment of resectability should be established prior to EUS-guided or percutaneous biopsy attempted Recommendation Grade B. Nevertheless, most experts agree that early detection of CC in PSC is important to identify cases amenable to curative surgery and to avoid inappropriate liver transplantation. This is unproven and based on expert opinion. Suggested algorithm for cholangiocarcinoma screening in primary sclerosing cholangitis Recommendation Grade D.
Surgery is the only curative treatment for patients with CC; however, fewer than one-third of patients are resectable at diagnosis. In a multivariate analysis, post-resection prognosis correlated most strongly with clinical stage and multiplicity of lesions. Resection, which should be guided by medical risk rather than age, involves a major operative procedure and requires appropriate surgical and anaesthetic experience. Surgical treatment depends on the site and extent of bile duct involvement by tumour.
Intrahepatic CCs are usually treated by resection of the involved segments or lobe of the liver. Distal CCs are managed by pancreatoduodenectomy, as with ampullary or pancreatic head cancers. Major hepatectomy for hilar CCs carries a considerable risk of hepatic insufficiency if there is a small future liver remnant.
Portal vein embolisation of the liver lobe to be removed is a safe method for increasing the future liver remnant and permits potentially curative hepatic resection to be carried out. However, a recent study analysed data from 12 transplant centres in the USA. Each had treated at least three patients with perihilar CC using varying protocols of neoadjuvant chemoradiation followed by liver transplantation between and Two hundred and eighty-seven patients were treated and 71 dropped out before transplantation.
Surgical treatment is principally as follows Grade B :. For types I and II: en bloc resection of the extrahepatic bile ducts and gall bladder, regional lymphadenectomy and Roux-en-Y hepaticojejunostomy. For type IV: not usually resectable but extended right or left hepatectomy may be feasible, dependent on biliary anatomy.
Segment 1 of the liver may preferentially harbour metastatic disease from hilar CC and removal should be considered with stages II—IV. Increasing data suggest that liver transplantation for CC can be successful in rigorously selected patients undergoing neoadjuvant therapy in highly specialised centres. There is no current evidence to support the use of adjuvant chemotherapy or radiotherapy.
Appropriate trials are needed to address this issue. Surgical resection with palliative rather than curative intent is unproven. Symptoms from biliary obstruction in irresectable disease may be palliated by biliary stenting rather than a surgical bypass. Stent placement resulting in adequate biliary drainage improves survival.
Surgical bypass has not been demonstrated to be superior to stenting. Close liaison between oncological, palliative care and surgical teams is essential. These must be adequately sampled because local recurrence is related to involvement of the margins.
To stage lymph nodes accurately, the node groups must be specifically identified. Peripancreatic nodes located along the body and tail of the pancreas are considered sites of distant metastasis. Preoperative biliary drainage is controversial. It has been associated with bacteriobilia and fungal colonisation, higher rates of postoperative sepsis, wound infection, longer hospital stay and increased cost. One of the included studies found that preoperative endoscopic biliary drainage prolonged hospital stay and increased cost.
However, the overall strength of evidence was deemed low due to the poor quality of the included trials. Mortality and the length of hospital stay did not differ between the groups. In patients who are severely malnourished or have acute suppurative cholangitis and in those in whom major hepatic resection is planned, preoperative drainage may be beneficial. Routine biliary drainage before assessing resectability or preoperatively should be avoided except for certain situations such as acute cholangitis, with modification of antibiotic prophylaxis according to patient characteristics and local microbiological specialist advice Grade B.
Most patients with CC have unresectable disease. In such patients, a study from the USA found that endoscopic stenting cost significantly less and was associated with longer survival than surgical treatment 19 vs Narrower stents have lower patency rates and should not be used routinely. Covered removable self-expanding metal stents SEMS may also be used and some specialists prefer SEMS in patients who are candidates for neoadjuvant therapies.
Biliary drainage by the percutaneous route can be effective, particularly for high strictures involving segmental ducts. A multicentre retrospective Korean study of 85 patients with newly diagnosed advanced hilar CC who did not undergo surgery, chemotherapy or radiotherapy compared percutaneous versus endoscopic SEMS insertion. Procedure-related complications, median survival and stent patency duration were similar in both groups. Bilateral versus unilateral stent insertion for hilar strictures is controversial.
Early small studies reported that day mortality and cholangitis were lower in patients who underwent bilateral compared with unilateral drainage for hilar strictures.
Post-stent cholangitis can be reduced by minimising the amount of contrast injected. Careful imaging with MRCP to plan endoscopic stent placement in complex hilar tumours may guide optimum stent placement. In particular, non-atrophic areas of the liver with a likelihood of providing viable bile production should be considered for drainage. If contemplated, it should be performed in expert centres. Most patients with malignant biliary obstruction treated by plastic stents will require at least one stent change.
Metal stents have several advantages over plastic stents. Plastic stents may be satisfactory for patients surviving less time than this. Disadvantages of uncovered metal stents include being difficult to remove endoscopically and potentially making surgery more technically challenging. Metal stents should not be deployed for biliary strictures prior to a multidisciplinary team decision on resectability.
Tumour growth through the mesh of metal stents may lead to further problems with biliary obstruction and sepsis. This may be overcome by inserting plastic stents through the lumen of the metal stent, or placement of a further mesh metal stent where technically possible.
Covered biliary metal stents have recently been developed to prevent tumour ingrowth. Patency was higher in pancreatic cancer and in lymphadenopathy-associated obstruction compared with biliary malignancy, but numbers of the latter were small. Patients were randomised to ERCP with insertion of a covered or uncovered metal nitinol stent.
However, covered stents migrated significantly more often than uncovered stents and tumour ingrowth was more frequent with uncovered stents. Complications of stents include complications of endoscopy and sedation. Following palliative stenting, patients can die from recurrent sepsis, biliary obstruction and stent occlusion, as well as disease progression.
Acute cholecystitis from covered stents is another recognised complication. In an early prospective open-label trial, 39 patients with unresectable CC were randomised to stenting alone or stenting and photodynamic therapy PDT. Although overall survival was significantly improved among those who had chemotherapy compared with those who did not Initial stent insertion for biliary obstruction should be plastic or covered SEMS, particularly if the diagnosis and resectability are undecided Grade C.
Covered stents cannot be recommended for routine use based on current evidence Grade B. Surgical bypass should be reconsidered in patients with a good estimated life expectancy where stenting has failed Grade C. Photodynamic therapy cannot be recommended for routine use based on the most recent data Grade A. Given that most patients present with unresectable disease and at least half have lymph node metastases, oncological approaches could potentially have a beneficial impact on many patients.
The performance status PS is a major prognostic factor. Even achieving stable disease in patients on therapy correlates with length and quality of life. This is particularly important because of the frequent difficulty in confirming objective radiological responses, particularly in the perihilar area.
Good symptom control is paramount and requires multidisciplinary team input and, for many patients, palliative care is immediately appropriate. Until recently, chemotherapy for CC had poor results and studies were small and disparate.
The median progression-free survival was 8. Patients in the CisGem group also had a significantly improved tumour control rate Overall toxicity was similar between the arms, with a slight excess in clinically non-significant haematological toxicities for the CisGem group.
Similarly, there was no clear advantage for the small subset of patients with ampullary cancer. The efficacy of CisGem has been validated in the Japanese equivalent of the ABC study, which reported similar outcomes. There are encouraging reports of several patients being successfully downstaged with neoadjuvant chemotherapy and converted to operability in phase II studies, with occasional long-term survivors. Regimens combining chemotherapy with newer targeted biological agents are now being tested.
There is currently no evidence to support postoperative adjuvant therapy for CC outside a trial setting. A phase III RCT evaluated postoperative adjuvant therapy with mitomycin C and 5-fluorouracil versus surgery alone in resected pancreatobiliary carcinoma. However, the trial was underpowered to show a survival advantage in CC and there was no significant survival advantage for patients with BTC overall.
The trial is expected to report in There is currently no evidence to support the routine use of radiotherapy postoperatively or for unresectable disease. Radiotherapy may have important palliative value—for example, for localised metastases or uncontrolled bleeding. A small non-randomised retrospective study of metal stent insertion combined with external beam radiotherapy versus stent insertion alone showed a longer survival in the combination group The prognosis for any treated patient with progressing, recurring or relapsing bile duct cancer is poor.
Further treatment depends on several factors including prior treatment, site of recurrence, specific symptoms and PS. Relief of recurrent jaundice usually improves quality of life. Clinical trials should be considered if appropriate. Recent literature suggests an emerging role for locoregional therapies in intrahepatic CC, including transcatheter arterial chemoembolisation, radiofrequency ablation and transarterial hepatic yttrium 90 Y radioembolisation, which have previously been successfully used for the treatment of HCC and colorectal liver metastases.
TACE had no effect on survival in patients without poor prognostic factors. Several recent small studies have suggested that percutaneous US-guided thermal ablation for unresectable intrahepatic CC is safe and potentially effective, particularly for primary and relatively smaller tumours.
There were no treatment-associated deaths. Radioembolisation using 90 Y microspheres was assessed in 33 patients with unresectable intrahepatic CC and appeared safe. The emerging data for locoregional therapies in unresectable CC are encouraging, but larger studies are required to determine their efficacy.
Gemcitabine and Cisplatin combination chemotherapy is recommended for locally advanced or metastatic unresectable CC Grade A. Further data on specific disease subsets such as perihilar CC are warranted to identify the best treatment combination options for different subcategories of CC Grade B.
All operable patients should be offered adjuvant treatment trials. Locoregional therapies such as radioembolisation and TACE need prospective randomised data to assess their true value. We recommend that these guidelines are regularly audited and we request feedback from all users.
These guidelines should be revised in the light of new evidence that is likely to improve management. Provenance and peer review Not commissioned; externally peer reviewed. You will be able to get a quick price and instant permission to reuse the content in many different ways. Skip to main content.
Log in via OpenAthens. Log in using your username and password For personal accounts OR managers of institutional accounts. Forgot your log in details?
Register a new account? Forgot your user name or password? Search for this keyword. Advanced search. Log in via Institution. You are here Home Archive Volume 61, Issue 12 Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Email alerts. Article Text. Article menu. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Abstract The British Society of Gastroenterology guidelines on the management of cholangiocarcinoma were originally published in Statistics from Altmetric.
Cholangiocarcinoma guidelines cholangiocarcinoma hepatocellular carcinoma endoscopic retrograde pancreatography pancreatic cancer gall bladder cancer hepatic encephalopathy liver imaging brain imaging MRI nuclear magnetic resonance Background Development of guidelines These guidelines on the management of cholangiocarcinoma CC were originally published in Intent These guidelines are intended to bring consistency and improvement in the management from first suspicion of CC through to diagnosis and subsequent treatment.
Levels of evidence Studies used as a basis for these guidelines are graded according to the quality of evidence using the Oxford Centre for Evidence-based Medicine levels of evidence table 1.
B: consistent level 2 or 3 studies or extrapolations from level 1 studies. C: level 4 studies or extrapolations from level 2 or 3 studies. D: level 5 evidence or inconsistent or inconclusive studies of any level. View this table: View inline View popup. Table 1 Levels of evidence.
Epidemiology CC is the second commonest primary liver tumour worldwide, after hepatocellular carcinoma HCC. Table 2 Established risk factors for cholangiocarcinoma CC. Likely risk factors Less established but likely risk factors for CC include cirrhosis of any cause and chronic viral hepatitis B or C.
Type II: reaching confluence but not involving left or right hepatic ducts. Figure 1 Bismuth—Corlette classification of biliary strictures. Pathology Histological classifications There are separate histological classifications of intrahepatic and extrahepatic CC.
Table 3 WHO classification of biliary malignancies 22— Table 4 Main macroscopic types of cholangiocarcinoma CC. Molecular diagnosis CC is often associated with inactivation of tumour suppressor genes, for example, p53, Smad-4, bcl -2 and p Distinction from other tumours Distinguishing intrahepatic CC from metastatic adenocarcinoma and other primary liver tumours can be difficult.
Diagnosis Clinical features Perihilar or extrahepatic CCs typically present with features of biliary obstruction jaundice, pale stool, dark urine and pruritus. Blood tests No blood tests are diagnostic for CC.
Immunoglobulin G4 IgG4 cholangiopathy Immunoglobulin Ig G4-associated cholangiopathy, the biliary presentation of a multisystem inflammatory disorder in which affected organs have a lymphoplasmacytic infiltrate rich in IgG4-positive cells, can mimic CC. Recent findings: Cholangiocarcinoma has seen significant increase in incidence rates over the last several decades. Most patients do not carry the documented risk factors, which include infections and inflammatory conditions, but cholangiocarcinoma typically forms in the setting of cholestasis and chronic inflammation.
Management strategies include multispecialty treatments, with consideration of surgical resection, systemic chemotherapy, and targeted radiation therapy.
Surgically resectable disease is the only curable treatment option, which may involve liver transplantation in certain selected cases. Referrals to centers of excellence, along with enrollment in novel clinical trials are recommended for patients with unresectable or recurrent disease.
Cholangiocarcinoma bile duct cancer care at Mayo Clinic. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press.
This content does not have an English version. This content does not have an Arabic version. Diagnosis Endoscopic retrograde cholangiopancreatography Open pop-up dialog box Close. Endoscopic retrograde cholangiopancreatography Endoscopic retrograde cholangiopancreatography ERCP uses a dye to highlight the bile ducts and pancreatic duct on X-ray images.
Endoscopic ultrasound Open pop-up dialog box Close. Endoscopic ultrasound During an endoscopic ultrasound, your doctor inserts a long, flexible tube endoscope down your throat and into your abdomen. Care at Mayo Clinic Our caring team of Mayo Clinic experts can help you with your cholangiocarcinoma bile duct cancer -related health concerns Start Here.
Email address. First Name let us know your preferred name. Last Name. Thank you for subscribing Your in-depth coping with cancer guide will be in your inbox shortly. Sorry something went wrong with your subscription Please, try again in a couple of minutes Retry. Request an Appointment at Mayo Clinic. Share on: Facebook Twitter. Show references AskMayoExpert. Cholangiocarcinoma adult. Mayo Clinic; Feldman M, et al. Tumors of the bile ducts, gallbladder and ampulla. Elsevier; Accessed Jan.
Bile duct cancer cholangiocarcinoma. Accessed April 6, Hepatobiliary cancers. National Comprehensive Cancer Network. Choi J, et al. Aspirin use and the risk of cholangiocarcinoma. Banales JM, et al. Cholangiocarcinoma The next horizon in mechanisms and management. Bile duct cancer cholangiocarcinoma treatment — Health professional version PDQ. National Cancer Institute. Lowe RC, et al. Clinical manifestations and diagnosis of cholangiocarcinoma. Anderson CD.
0コメント