Hilar and distal cholangiocarcinoma

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Cholangiocarcinoma is anatomically heterogeneous. Perihilar tumours grow at the hepatic duct confluence, where millimetres determine which sectors communicate and which liver remnant can be preserved. Distal tumours obstruct the common bile duct nearer the pancreas and ampulla. Both may cause painless jaundice and pruritus, but their imaging, sampling, drainage and curative operations differ.

Primary sclerosing cholangitis is an important risk state, while choledochal cysts, hepatolithiasis and chronic biliary inflammation also increase risk. Most cases still occur without a known precursor. Serum CA19-9 is confounded by obstruction, infection and Lewis-antigen status. Diagnosis therefore integrates high-quality cross-sectional imaging, cholangiographic morphology, cytology or biopsy when appropriate, and MDT judgement.

Treatment begins with resectability, not with automatic stenting. Perihilar surgery requires assessment of duct length, lobar atrophy, portal-vein and hepatic-artery involvement, future liver-remnant volume and occult metastasis. Distal resection generally uses pancreaticoduodenectomy. Advanced disease care combines systemic treatment, molecular profiling, durable biliary decompression, nutrition and early symptom support.

BSG recognises transplantation for narrowly selected perihilar CCA with background chronic liver disease, usually PSC, a tumour under 3 cm and no extrahepatic disease under a specialist protocol. This is not routine transplantation for all CCA, and transplantation without background chronic liver disease remains investigational rather than an established general indication.

Key points

Perihilar cholangiocarcinoma lies between second-order ducts and the cystic-duct insertion; distal cholangiocarcinoma lies below the cystic-duct insertion and is treated surgically like a pancreatic-head region cancer.
Obtain multiphasic CT of chest, abdomen and pelvis for all suspected cholangiocarcinoma; add contrast MRI/MRCP to map proximal duct and satellite liver disease in perihilar presentations.
For operable distal malignant obstruction, BSG recommends EUS and ERCP to seek histology; if jaundice is absent, perform EUS first and avoid ERCP-related complications unless drainage is needed.
Do not instrument suspected perihilar disease before HPB review. If preoperative drainage is chosen, target the future liver remnant and add sectors only for persistent bilirubin or cholangitis in an obstructed system.
R0 resection is the main curative route: distal disease usually needs pancreaticoduodenectomy and perihilar disease an anatomically planned liver/duct resection. Selected pCCA with chronic liver disease, often PSC, tumour under 3 cm and no extrahepatic spread may enter a specialist transplant protocol.
For unresectable or metastatic biliary tract cancer, NICE recommends durvalumab with gemcitabine and cisplatin within its marketing authorisation; profile tumour tissue early for actionable alterations and later-line choices.
Give every stented patient a blockage plan: recurrent pain, fever, jaundice or worsening liver tests requires cross-sectional imaging and on-demand drainage review.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Chronic duct inflammation

PSC, choledochal cysts, hepatolithiasis and selected chronic infections promote epithelial injury, dysplasia and malignant transformation, although most UK cases are sporadic.

Anatomical cell of origin

Malignancy arising at the confluence produces perihilar disease; tumour below the cystic-duct insertion produces distal cholangiocarcinoma with different surgery.

Molecular heterogeneity

Actionable alterations differ by site and biology, making early adequate tissue and broad profiling important once systemic treatment is relevant.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Longitudinal duct spread
Tumour infiltrates along bile-duct epithelium and periductal tissue, so visible wall thickening may underestimate the length needed for a clear margin.
2
Segmental isolation
Perihilar growth separates right and left sectors, allowing one lobe to drain while another remains pressurised and susceptible to infection.
3
Vascular encasement
Close portal and arterial relationships permit local invasion that can determine resectability and the safe future liver remnant.
4
Metastatic dissemination
Regional lymphatic, liver, peritoneal and distant spread commonly precedes diagnosis and changes treatment from radical surgery to systemic control.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Perihilar anatomy

Intrahepatic duct dilatation above a hilar narrowing with a relatively normal distal common duct suggests pCCA and demands right-left sector mapping.

Distal anatomy

Extrahepatic and intrahepatic dilatation to a lower common-duct stricture resembles pancreatic or ampullary obstruction and is accessible to EUS and ERCP.

PSC-associated change

A new dominant or relevant stricture, worsening cholestasis, weight loss or recurrent cholangitis in PSC requires cancer assessment beyond routine disease monitoring.

Advanced spread

Peritoneal disease, distant nodes, lung or liver metastases redirect care from radical resection to systemic and symptom-focused treatment.

Drainage-related infectionRed flag

Fever and rigors after contrast or stent placement can represent an infected undrained segment and requires urgent re-imaging and source control.

Red flags requiring action

Do not undertake endotherapy for a suspected perihilar cholangiocarcinoma before discussion with the regional HPB centre unless emergency source control makes delay unsafe.
Contrast injected into a hilar segment that is not subsequently drained can precipitate cholangitis; define which liver sectors require decompression before ERCP or PTC.
A negative brushing does not exclude cholangiocarcinoma, and a resectable distal or perihilar lesion should not undergo an unplanned percutaneous tumour biopsy.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Multiphasic CT chest, abdomen and pelvisFirst step
Why
Stage the primary lesion, vascular involvement, nodes, liver, peritoneum and distant organs before endoscopic intervention.
Interpretation and limitations
For pCCA, read portal-vein and hepatic-artery contact, lobar atrophy and metastatic disease with future-remnant planning; for dCCA, assess pancreaticoduodenectomy anatomy.
02
Contrast MRI with MRCP
Why
Map longitudinal duct involvement, intrahepatic satellites and separated sectors in proximal disease.
Interpretation and limitations
MRI/MRCP is particularly important for perihilar and intrahepatic CCA; BSG notes that it adds little beyond CT for many distal tumours.
03
EUS with tissue sampling
Why
Assess distal lesions and selected nodes and obtain histology when it will change management.
Interpretation and limitations
For operable distal malignant obstruction, combine EUS with planned ERCP; without jaundice, EUS first may avoid unnecessary ERCP. In potentially operable perihilar disease, EUS may assess and selectively sample suspicious nodes, but do not needle-sample the ductal/hilar primary transperitoneally because tumour seeding can compromise resection or transplant eligibility.
04
ERCP brushings or intraductal sampling
Why
Acquire ductal cytology or biopsy while treating a distal obstruction or investigating a planned stricture.
Interpretation and limitations
Specificity of malignant cytology is useful but sensitivity is limited; a negative result requires correlation and sometimes repeat or alternative sampling.
05
Molecular tumour profile
Why
Identify actionable changes and immune biomarkers before or during initial systemic treatment.
Interpretation and limitations
Profile adequate tissue early because FGFR2 fusions are enriched in intrahepatic disease, while IDH1, HER2, BRAF, NTRK and mismatch-repair findings can direct later therapy.
06
Bilirubin, ALP, INR, renal function and cultures
Why
Measure obstruction, procedural risk and organ dysfunction and diagnose superimposed infection.
Interpretation and limitations
Biochemical improvement after drainage should match the intended sectors; persistent cholestasis may mean an undrained lobe, stent failure or extensive hepatic disease.
07
FDG-PET/CT for cholangiocarcinoma staging
Why
Detect nodal or distant metastatic disease that could change treatment intent.
Interpretation and limitations
BSG recommendation 10 includes FDG-PET/CT in CCA staging. This complements anatomical CT/MRI/MRCP and is a CCA recommendation distinct from the NICE pancreatic-cancer staging pathway.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Benign postoperative stricture

Previous cholecystectomy or anastomosis can cause fibrotic narrowing; progression, shouldering and tissue findings help distinguish malignancy.

IgG4-related cholangitis

Autoimmune pancreatic or bile-duct inflammation can mimic hilar or distal cancer and needs integrated serology, imaging, histology and organ context.

PSC dominant stricture

Inflammatory stricturing may be benign yet carries cancer risk; a new relevant stricture requires cytological and multidisciplinary assessment.

Pancreatic or ampullary cancer

Both cause distal obstruction; EUS, pancreatic imaging and histological origin distinguish them from primary distal bile-duct carcinoma.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Resectable perihilar diseasePlan the future liver remnantFirst stepCT and MRCP show a hilar tumour extending into the right duct, with a potentially preservable left liver and no metastasis.

1Review ductal, portal and arterial anatomy in the HPB MDT before elective ERCP or percutaneous access. Avoid transperitoneal needle biopsy of a potentially operable hilar primary; if EUS sampling is needed, distinguish suspicious nodes from the primary and agree the target with the resection/transplant team.
2Estimate future left-liver volume and function and decide whether portal-vein embolisation or selective drainage is needed before surgery.
3If decompression is indicated, drain the future left remnant; do not automatically opacify and stent every right-sided segment scheduled for resection.
4Proceed to an R0-intent bile-duct and liver resection in a high-volume unit after verifying bilirubin response, remnant adequacy and absence of interval spread.

02Distal obstructing lesionCouple tissue with necessary drainageA stable jaundiced adult has a distal common-bile-duct stricture on CT and appears operable.

1Review pancreatic, ampullary and bile-duct origins and confirm staging at the HPB MDT.
2Use EUS to characterise the lesion and nodes, with ERCP for duct sampling and decompression when clinically indicated.
3If brushings are negative but imaging remains malignant, do not reclassify the stricture as benign; agree further tissue or operative strategy.
4DefinitiveFor confirmed resectable dCCA, prepare for pancreaticoduodenectomy and verify that any stent plan will not delay definitive surgery.

03Advanced diseaseWorked case: drainage before first-line systemic treatmentFirst lineA fictional 64-year-old with biopsy-confirmed metastatic distal CCA has jaundice and pruritus, no fever and ECOG performance status 1. She wishes to pursue systemic treatment; no previous anticancer therapy has been given.

1The MDT confirms non-curative stage, retains tissue for molecular profiling and discusses expected benefit, toxicity and supportive care. She chooses durvalumab with gemcitabine/cisplatin if the obstruction and treatment-safety checks permit it.
2At ERCP, a fully covered SEMS is placed across the confirmed malignant distal stricture. Bile drains freely; after ten days bilirubin has fallen from 142 to 19 micromol/L and pruritus has eased without cholangitis. This distal device choice is not transferred automatically to separated hilar ducts.
3Oncology documents weight 68 kg, recorded BSA 1.80 m², CrCl 68 mL/min, neutrophils 3.1 ×10^9/L, platelets 224 ×10^9/L, normal potassium/magnesium and ALT 1.2×ULN. With no hearing loss, neuropathy or fluid-overload concern, she receives the selected SWAG schedule: durvalumab 1,500 mg first, then day-1 cisplatin 45 mg and gemcitabine 1,800 mg with the hydration/infusion plan in the medicine card.
4The day-8 assessment finds preserved renal function and counts, so the scheduled cisplatin/gemcitabine doses are given. At the first planned response review she remains jaundice-free, imaging shows no progression and no grade ≥2 toxicity has emerged; she elects to continue. New fever or jaundice would trigger urgent stent/infection assessment, and new respiratory symptoms would trigger treatment withholding and immune-toxicity assessment rather than assuming ordinary fatigue.

Key medicines and prescribing safety1 treatment · regimens, roles and cautions

NICE TA944 supports the durvalumab combination within its marketing authorisation. This card names a local NHS delivery example so that its split cisplatin dose, short hydration schedule and dose-modification thresholds are not mistaken for universal product-label instructions. Relieve significant obstruction and treat infection before systemic therapy; obtain a patient-specific SACT prescription, antiemetic plan and informed consent.

Durvalumab with gemcitabine and cisplatin for advanced biliary tract cancer

For first-line, locally advanced unresectable or metastatic biliary tract cancer, an eligible adult over 36 kg receives durvalumab 1,500 mg IV over 60 minutes on day 1, BEFORE chemotherapy. Give gemcitabine 1,000 mg/m² IV over 30 minutes and cisplatin 25 mg/m² IV on days 1 and 8, repeating every 21 days for up to eight cycles; continue durvalumab 1,500 mg IV every 28 days until progression or unacceptable toxicity. At 36 kg or less, durvalumab is 20 mg/kg on the same three-week combination/four-week maintenance intervals until weight exceeds 36 kg. Durvalumab’s label licenses the combination; the cited Hospira gemcitabine/cisplatin labels do not individually list BTC. The following delivery is the SWAG local BTC protocol, including off-label short cisplatin infusion, not the general cisplatin SmPC schedule: gemcitabine in 250–500 mL sodium chloride 0.9%; cisplatin in 500 mL sodium chloride 0.9% over 60 minutes. For a patient tolerating this fluid plan with normal potassium/magnesium, prehydrate with 1 litre sodium chloride 0.9% plus magnesium sulfate 2 g and potassium chloride 20 mmol over one hour, verify urine output above 100 mL/hour before cisplatin, then give 500 mL sodium chloride 0.9% over 30 minutes afterward. If output is inadequate, withhold cisplatin and assess volume status/renal function. If potassium or magnesium is low, SWAG instead uses a 1-litre post-hydration bag containing magnesium sulfate 2 g and potassium chloride 20 mmol over two hours. Reassess for overload and plan adequate oral fluid afterward; the standard SWAG oral target is at least 2 litres over 24 hours for someone able to tolerate it.

Specialist oncology/pharmacy supervision is essential. Check FBC, creatinine/CrCl, liver tests, magnesium, calcium, glucose, thyroid function and baseline cortisol, plus hearing, neuropathy, volume status and performance status. Repeat counts before each treatment day, with day-8 FBC within 24 hours; check renal/liver/electrolyte results and symptoms before dosing. SWAG local full-dose limits are neutrophils >1.0 ×10^9/L, platelets >100 ×10^9/L, bilirubin <1.5×ULN, ALT/AST <3×ULN and CrCl ≥45 mL/min; the gemcitabine label’s general cycle-initiation neutrophil threshold is ≥1.5, so a lower starting count requires explicit specialist protocol authorisation. Outside these limits, hold for prescriber review. If neutrophils are <0.5 or platelets <50, omit both cytotoxics. Otherwise, at neutrophils 0.5–1.0 or platelets 50–100, SWAG uses gemcitabine at 75% and unchanged cisplatin if its other eligibility criteria are met. At CrCl 30–44 omit cisplatin; below 30 omit cisplatin and reconsider gemcitabine dose. Bilirubin >1.5×ULN prompts consultant consideration of gemcitabine at 80%. The cited cisplatin label contraindicates pre-existing renal impairment: a local protocol decision to treat outside that restriction must be documented by the responsible oncologist and pharmacist as an off-label departure, not inferred automatically from CrCl ≥45. Stop cisplatin for grade ≥2 hearing or neurological toxicity. Review nephrotoxic drugs, platinum allergy, dehydration and marrow suppression; avoid live vaccines. SWAG advises replacing warfarin through the anticoagulation team; if it continues pending that review, check INR closely. Before durvalumab, systemic immunosuppression is not recommended apart from physiological corticosteroid doses (≤10 mg/day prednisone-equivalent); obtain oncology review rather than abruptly stopping necessary treatment. Steroids used to treat an immune reaction are a separate indication. Durvalumab needs no adjustment for mild/moderate renal impairment; severe renal data are limited. Its label recommends no hepatic adjustment but severe hepatic experience remains limited. New breathlessness, diarrhoea, marked fatigue, headache or glucose disturbance needs urgent acute-oncology assessment for immune toxicity. Do not reduce its dose for immune toxicity: for grade 2 immune pneumonitis, withhold durvalumab, investigate competing causes and start systemic corticosteroid treatment at prednisone-equivalent 1–2 mg/kg/day under the acute oncology team; after improvement to grade ≤1, taper over at least a month. Grade 3–4 pneumonitis requires permanent discontinuation and urgent specialist treatment. In a jaundiced patient with a biliary stent, investigate cholangitis and obstruction urgently before attributing the change to immune hepatitis or giving reflex steroids. Pregnancy requires urgent specialist assessment: this combination is not a routine pregnancy treatment. Discuss fertility preservation. Effective contraception continues through treatment and the applicable component intervals: women at least 3 months after durvalumab, 6 months after gemcitabine and 29 weeks (at least 7 months) after the cited cisplatin; men 3 months after gemcitabine and 17 weeks (at least 4 months) after cisplatin. Calculate these from each drug’s last dose. No breastfeeding during cytotoxic treatment or for four weeks after cisplatin; continuing durvalumab requires a separate breastfeeding-versus-treatment decision.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Acute cholangitis

An obstructed or instrumented duct can become infected, leading rapidly to bacteraemia, shock, kidney injury and urgent drainage.

Stent dysfunction

Tumour ingrowth, overgrowth, sludge or migration causes recurrent jaundice and infection and requires imaging-led specialist reintervention.

Post-hepatectomy liver failure

An inadequate or cholestatic future remnant may not meet metabolic demand after major perihilar cancer resection.

Systemic-treatment toxicity

Myelosuppression, renal injury, hearing loss and immune inflammation can interrupt therapy and require prompt cause-specific management.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Before and during systemic treatment, record performance status, FBC, kidney and liver function, magnesium, hearing or neuropathy symptoms and immune adverse-event screening.
For a stent, trend bilirubin and inflammatory markers and give the patient direct instructions for fever, rigors, recurrent jaundice, pale stools or new pain.
Suspected stent dysfunction should prompt cross-sectional imaging to define tumour progression, migration, debris and which sectors remain undrained before another procedure.
After resection, discuss margins, nodes and pathological stage and consider adjuvant capecitabine through specialist oncology.
Review molecular results while the patient remains well enough for later therapy; actionable findings that arrive after rapid decline cannot influence care.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Hilar drainage is volumetric

The clinically useful target is functioning liver volume, especially the future remnant, rather than the simple number of stents inserted.

A negative brush is incomplete evidence

Biliary cytology has limited sensitivity, so malignant imaging and progression require continued specialist evaluation after a non-diagnostic sample.

Avoid unplanned tumour tracks

Percutaneous biopsy of a potentially resectable perihilar or distal primary can affect later strategy; agree tissue route at MDT.

Distal and hilar operations differ

Pancreaticoduodenectomy removes distal duct disease, whereas pCCA resection couples bile-duct excision with an anatomy-driven hepatectomy.

Genomics needs lead time

Obtain adequate material early so targetable alterations can inform later lines before disease or performance status deteriorates.

11Common pitfallsFrequent interpretation and management errors.

01
Treating perihilar and distal CCA as one procedural problem ignores fundamentally different duct anatomy and operations.
02
Performing an elective ERCP before CT and MRCP in suspected hilar disease can introduce infection and erase a clean anatomical baseline.
03
Stenting both liver lobes automatically can expose undrained contrast-filled sectors and may conflict with future-remnant planning.
04
Calling a stricture benign after one negative brush cytology allows a false-negative test to overrule the full malignant phenotype.
05
Starting cisplatin-based treatment without renal, hearing, neurological and hydration assessment can cause avoidable cumulative toxicity.
06
Transperitoneal needle sampling of a potentially operable hilar primary can seed tumour and jeopardise resection or transplant eligibility; EUS assessment or sampling of suspicious nodes is a different decision.

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