Pancreatic cancer

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

Pancreatic ductal adenocarcinoma is an aggressive exocrine malignancy that commonly presents after vascular, nodal or metastatic spread; treatment depends on whether specialist imaging classifies disease as resectable, borderline, locally advanced or metastatic. Cigarette exposure, increasing age, obesity and long-standing diabetes increase pancreatic ductal adenocarcinoma risk, although many affected people have no modifiable cause. Hereditary, tropical and other chronic pancreatitis increases risk through repeated inflammation and genomic damage; ordinary acute pancreatitis is not equivalent. KRAS activation with loss of CDKN2A, TP53 and SMAD4 drives progression from microscopic precursor epithelium to invasive adenocarcinoma. A dense fibrotic and immune-suppressive microenvironment impairs perfusion, promotes invasion and contributes to resistance to systemic treatment.

Recognition depends on the tempo, host context and anatomical pattern rather than one isolated result. Painless jaundice with pale stool, dark urine and pruritus is typical of a pancreatic-head tumour and requires an urgent cancer pathway. Persistent epigastric pain radiating to the back, anorexia and sarcopenic weight loss often indicate locally advanced or systemic disease. New-onset diabetes or unexpectedly worsening control can precede diagnosis, but is not specific enough for isolated cancer testing. Investigation should answer immediate safety, diagnostic confirmation and extent in that order. Pancreatic-protocol contrast CT This is the first-line staging examination in suspected pancreatic cancer; specialist MDT review, not the report phrase alone, determines resectability. MRI with MRCP Use selectively for problem solving and staging; it complements rather than routinely replaces high-quality pancreatic-protocol CT. Endoscopic ultrasound-guided core biopsy Acquire core material for histology and molecular testing; do not delay clearly resectable surgery solely for biopsy when MDT considers tissue unnecessary.

Management is determined by physiological urgency, disease extent, treatment intent and the person's priorities. The pathway moves through stage before disturbing anatomy, then relieve biliary obstruction selectively, then sequence curative-intent treatment; each transition requires named multidisciplinary ownership. Follow-up must anticipate biliary sepsis, malnutrition and sarcopenia, venous thromboembolism while measuring function and treatment toxicity.

Key points

Obstructive jaundice is a pivotal clue in Pancreatic cancer: Painless jaundice with pale stool, dark urine and pruritus is typical of a pancreatic-head tumour and requires an urgent cancer pathway.
Immediate priority in unstable Pancreatic cancer: Resuscitate and give antibiotics for sepsis, obtain urgent biliary and pancreatic specialist input, and arrange source control with endoscopic or percutaneous drainage without delaying for a complete elective staging sequence.
Pancreatic-protocol contrast CT is used early to define tumour, arterial and venous relations, liver and peritoneal metastases and resectability before biliary intervention where stable. This is the first-line staging examination in suspected pancreatic cancer; specialist MDT review, not the report phrase alone, determines resectability.
MRI with MRCP refines the next decision because use selectively for problem solving and staging; it complements rather than routinely replaces high-quality pancreatic-protocol CT.
Stage before disturbing anatomy: Obtain pancreatic-protocol CT before biliary drainage when clinically safe, then review resectability at a specialist hepatopancreatobiliary MDT.
Relieve biliary obstruction selectively: Prefer a self-expanding metal stent when durable palliation or neoadjuvant treatment is expected, using MDT-specific device planning.
A major avoidable harm is biliary sepsis; Obstructed or instrumented ducts can become infected, causing septic shock and requiring antibiotics plus urgent drainage.
A common diagnostic trap is distal cholangiocarcinoma: Both cause painless obstructive jaundice; duct-centred imaging, endoscopy and histopathology distinguish treatment pathways.

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

Smoking and age

Cigarette exposure, increasing age, obesity and long-standing diabetes increase pancreatic ductal adenocarcinoma risk, although many affected people have no modifiable cause.

Chronic pancreatic injury

Hereditary, tropical and other chronic pancreatitis increases risk through repeated inflammation and genomic damage; ordinary acute pancreatitis is not equivalent.

Inherited susceptibility

Pathogenic variants involving BRCA1, BRCA2, PALB2, ATM, mismatch repair and syndromes such as Peutz–Jeghers can alter risk, family counselling and treatment.

Precursor lesions

Pancreatic intraepithelial neoplasia and selected mucinous cystic or intraductal papillary mucinous lesions can accumulate driver mutations and become invasive.

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

1
Ductal transformation
KRAS activation with loss of CDKN2A, TP53 and SMAD4 drives progression from microscopic precursor epithelium to invasive adenocarcinoma.
2
Desmoplastic stroma
A dense fibrotic and immune-suppressive microenvironment impairs perfusion, promotes invasion and contributes to resistance to systemic treatment.
3
Early neural and vascular invasion
Perineural spread causes back pain, while close relation to portal, mesenteric and coeliac vessels determines surgical resectability.
4
Biliary and exocrine obstruction
A head lesion compresses the distal bile duct and pancreatic duct, producing cholestasis, malabsorption, steatorrhoea and weight loss.
5
Early dissemination
Liver and peritoneal metastases are frequent, so apparently local symptoms require complete specialist staging before major surgery.

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

Obstructive jaundice

Painless jaundice with pale stool, dark urine and pruritus is typical of a pancreatic-head tumour and requires an urgent cancer pathway.

Pain and weight loss

Persistent epigastric pain radiating to the back, anorexia and sarcopenic weight loss often indicate locally advanced or systemic disease.

New metabolic change

New-onset diabetes or unexpectedly worsening control can precede diagnosis, but is not specific enough for isolated cancer testing.

Exocrine insufficiency

Steatorrhoea, bloating, urgency and weight loss reflect reduced pancreatic enzyme delivery and can continue after resection.

CholangitisRed flag

Fever, rigors, jaundice, hypotension or confusion with obstruction is a source-control emergency rather than routine outpatient staging.

Thromboembolism

Cancer-associated venous thrombosis or migratory superficial thrombophlebitis may occur before or during pancreatic treatment.

Red flags requiring action

Painless progressive jaundice, dark urine, pale stool and pruritus suggest distal malignant biliary obstruction.
Unexplained weight loss, epigastric pain radiating to the back or new anorexia persists in an older adult.
New diabetes, rapidly worsening glycaemia or pancreatitis occurs without another clear explanation.
Fever, rigors, hypotension or confusion accompanies jaundice and indicates possible acute cholangitis.
Persistent vomiting, early satiety or inability to tolerate intake suggests gastric outlet obstruction.
A tender calf, pulmonary embolus or migratory thrombophlebitis may be a thrombotic presentation of occult cancer.

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
Pancreatic-protocol contrast CTFirst step
Why
Define tumour, arterial and venous relations, liver and peritoneal metastases and resectability before biliary intervention where stable.
Interpretation and limitations
This is the first-line staging examination in suspected pancreatic cancer; specialist MDT review, not the report phrase alone, determines resectability.
02
MRI with MRCP
Why
Clarify liver lesions, duct anatomy or a pancreatic abnormality that remains uncertain on CT.
Interpretation and limitations
Use selectively for problem solving and staging; it complements rather than routinely replaces high-quality pancreatic-protocol CT.
03
Endoscopic ultrasound-guided core biopsy
Why
Obtain tissue when systemic, neoadjuvant or non-surgical treatment is planned or imaging is diagnostically uncertain.
Interpretation and limitations
Acquire core material for histology and molecular testing; do not delay clearly resectable surgery solely for biopsy when MDT considers tissue unnecessary.
04
Tissue from an accessible metastasis
Why
Confirm metastatic pancreatic cancer by the safest route before systemic anticancer therapy.
Interpretation and limitations
Image-guided liver or other metastatic-site core may be safer and stages disease simultaneously; radiological probability alone is not histological confirmation.
05
Liver tests, coagulation and renal profile
Why
Quantify cholestasis, vitamin-K-related coagulopathy, infection and organ function before contrast, drainage or treatment.
Interpretation and limitations
A rising bilirubin affects procedure urgency and systemic dosing; correct sepsis and clinically important coagulopathy without reflexive preoperative drainage.
06
CA 19-9
Why
Provide a baseline adjunct after cholestasis is relieved and follow selected treated disease.
Interpretation and limitations
It is neither a screening nor diagnostic test; Lewis-antigen non-secretors may have a low value, while obstruction and infection can cause false elevation.
07
Diagnostic laparoscopy
Why
Detect occult peritoneal or small-volume liver spread in selected high-risk apparently localised disease.
Interpretation and limitations
Use according to specialist surgical policy when finding metastasis would prevent a non-beneficial laparotomy.

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

Distal cholangiocarcinoma

Both cause painless obstructive jaundice; duct-centred imaging, endoscopy and histopathology distinguish treatment pathways. In Pancreatic cancer, this distinction materially changes diagnostic assessment.

Autoimmune pancreatitis

Diffuse or focal inflammatory enlargement, raised IgG4 and other organ involvement can mimic cancer, but steroid trial before adequate exclusion is unsafe.

Chronic pancreatitis mass

Fibrosis and duct change can resemble carcinoma; new focal mass, progressive obstruction or vascular invasion requires tissue and specialist review.

Ampullary cancer

Earlier jaundice and an ampullary lesion on endoscopy may indicate a different periampullary primary with distinct pathology and prognosis.

Pancreatic neuroendocrine tumour

Hypervascular imaging, hormone syndrome or neuroendocrine histology separates this biologically different pancreatic neoplasm. In Pancreatic cancer, this distinction materially changes diagnostic assessment.

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

01DiagnoseStage before disturbing anatomyFirst stepPancreatic cancer is suspected in a stable patient with jaundice, pain, weight loss or a pancreatic lesion.

1Obtain pancreatic-protocol CT before biliary drainage when clinically safe, then review resectability at a specialist hepatopancreatobiliary MDT.
2Use MRI for liver or duct uncertainty and endoscopic ultrasound core biopsy when neoadjuvant, systemic or non-operative treatment is planned.
3Assess performance, nutrition, diabetes, exocrine insufficiency, thrombosis and hereditary features alongside anatomical staging.

02DrainRelieve biliary obstruction selectivelyJaundice causes cholangitis, severe symptoms, renal dysfunction or delay before planned surgery or systemic treatment.

1Treat cholangitis with sepsis care and urgent endoscopic biliary drainage; use percutaneous access when endoscopic drainage fails or anatomy prevents it.
2Prefer a self-expanding metal stent when durable palliation or neoadjuvant treatment is expected, using MDT-specific device planning.
3Avoid routine preoperative drainage of every stable resectable jaundice because instrumentation can add infection and procedural harm.

03LocalisedSequence curative-intent treatmentDisease is resectable or borderline resectable without distant metastasis and the person is fit for active treatment.

1For resectable disease, offer specialist pancreatic resection followed by adjuvant chemotherapy when recovery and pathology permit.
2For borderline vascular involvement, consider neoadjuvant systemic therapy through the specialist MDT and restage before exploration.
3Report margin, nodes, tumour regression, mismatch repair and other indicated pathology, then provide enzyme, glycaemic, nutritional and surgical follow-up.

04AdvancedConfirm tissue and control systemic diseaseImaging shows locally advanced unresectable or metastatic disease, or recurrence after surgery.

1Obtain adequate histological tissue before systemic anticancer treatment, preferably from a safe metastatic site when this also confirms stage.
2Select modified FOLFIRINOX, gemcitabine-based or biomarker-directed therapy by performance, organ function, pathology, germline findings and patient priorities.
3Treat pain, exocrine failure, diabetes, obstruction, nausea, thrombosis and nutrition concurrently and involve palliative care early.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Treats pancreatic exocrine insufficiency before and after surgery, improving absorption, weight and gastrointestinal symptoms.

Pancreatin replacement

Start a high-strength preparation with all meals and snacks; a common adult starting dose supplies at least 50,000 units of lipase with a main meal and 25,000 units with a snack, titrated to stool, weight and intake.

Take during food and spread capsules through longer meals; increase to dietary fat and consider acid suppression if response remains poor, while checking adherence and alternative diarrhoea causes.

Provides active systemic treatment for fit patients in adjuvant or advanced settings selected by the pancreatic cancer MDT.

Modified FOLFIRINOX

A common 14-day specialist regimen uses oxaliplatin 85 mg/m² IV, irinotecan 150 mg/m² IV, folinic acid 400 mg/m² IV and fluorouracil 2,400 mg/m² by 46-hour continuous infusion, with protocol-led dose modification.

Requires central access and oncology prescribing; monitor marrow, diarrhoea, cholinergic toxicity, mucositis, neuropathy, liver function, DPD status and infection, with dose changes for frailty and organ dysfunction.

Offers systemic therapy when combination treatment is unsuitable and is also combined with other agents in protocol-defined settings.

Gemcitabine

A common single-agent schedule is 1,000 mg/m² intravenously on days 1, 8 and 15 of a 28-day cycle, with count and organ-function criteria before each dose.

Monitor neutropenia, thrombocytopenia, infection, liver and renal function, pulmonary toxicity and rare haemolytic uraemic syndrome; use the current NHS regimen document.

Treats persistent visceral or back pain while tumour-directed, radiotherapy or coeliac-plexus options are assessed.

Morphine for cancer pain

For opioid-naive severe pain, immediate-release oral morphine may start at 2.5–5 mg every 4 hours with the same dose available for breakthrough, then be titrated and converted to sustained release after response assessment.

Individualise for frailty and renal impairment, prescribe stimulant laxative and antiemetic when indicated, review sedation and respiration, and consider an alternative opioid when metabolites accumulate.

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

Biliary sepsis

Obstructed or instrumented ducts can become infected, causing septic shock and requiring antibiotics plus urgent drainage.

Malnutrition and sarcopenia

Anorexia, inflammation, pain, obstruction and exocrine insufficiency reduce strength and treatment tolerance unless actively addressed. In Pancreatic cancer, this distinction materially changes complication assessment.

Venous thromboembolism

Pancreatic adenocarcinoma has a high thrombosis risk, but prophylaxis and treatment must balance bleeding and procedural plans.

Gastric outlet obstruction

Local tumour can narrow duodenum, causing persistent vomiting, dehydration and need for stent, bypass or medical palliation.

Postoperative pancreatic fistula

Pancreatic resection can cause leak, delayed gastric emptying, haemorrhage, infection and later endocrine or exocrine failure.

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

Track bilirubin, fever and stent function after drainage; recurrent jaundice or rigors requires urgent reassessment for occlusion or cholangitis.
Review weight, intake, stool quality, enzyme timing, glucose and sarcopenia at each treatment transition rather than relying on albumin alone.
Before every systemic dose, assess performance, neuropathy, diarrhoea, mucositis, blood count, renal and liver function and infection.
After resection, follow pathology, adjuvant-treatment readiness, fistula or delayed-emptying recovery and new endocrine or exocrine failure.
Use symptom-led and protocolled imaging to assess treatment response, and investigate new thrombotic, pain or obstructive symptoms between scans.
Offer germline testing and genetics pathways according to current eligibility, recording implications for relatives and targeted therapy.

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

CT before stent when stable

Biliary instrumentation can obscure anatomy and add infection; high-quality pancreatic staging is most informative before drainage unless sepsis or clinical need intervenes.

Tissue precedes systemic therapy

Metastatic-looking imaging does not replace histological confirmation before chemotherapy; an accessible liver lesion may be the best target.

CA 19-9 is contextual

Cholangitis and obstruction can elevate it, while Lewis-negative people may not produce it even with substantial cancer.

Enzymes are active treatment

Pancreatic replacement should start when insufficiency is likely rather than waiting for profound weight loss or formal faecal testing.

Resectability is specialist

Venous contact does not automatically preclude surgery, while unsuspected arterial involvement or metastasis can change intent.

11Common pitfallsFrequent interpretation and management errors.

01
Draining every stable jaundiced patient before pancreatic-protocol CT.
02
Starting systemic treatment for presumed metastatic disease without obtaining diagnostic tissue.
03
Using CA 19-9 as a stand-alone cancer test.
04
Calling a vascular-contact tumour unresectable without specialist MDT review.
05
Ignoring pancreatic enzyme insufficiency during weight loss.
06
Delaying cholangitis source control for elective staging completion.