Pancreatic cancer

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

Most pancreatic ductal adenocarcinomas present after local invasion or dissemination. A small head lesion may declare itself earlier through jaundice, pale stools and dark urine, whereas body or tail lesions more often cause weight loss, epigastric-to-back pain or incidental metastatic findings.

The initial clinical job is simultaneous: recognise an urgent cancer signal, detect sepsis or organ dysfunction, obtain high-quality staging, preserve tissue options and establish whether treatment intent could be curative. Early pancreatic multidisciplinary discussion prevents poorly sequenced drainage, biopsy or surgery.

Care remains useful at every stage. Enzyme replacement, diabetes management, analgesia, relief of gastric or biliary obstruction, venous thromboembolism treatment, psychological support and anticipatory palliative care can materially improve function while oncology decisions evolve.

Key points

New obstructive jaundice in a person aged 40 or over warrants an urgent suspected-cancer pathway; fever, hypotension or confusion additionally suggests cholangitis requiring emergency care.
Pancreas-protocol contrast CT of chest, abdomen and pelvis usually defines the primary lesion, vascular relationships and distant spread before any planned biliary drainage.
A normal CA 19-9 does not exclude cancer, while cholestasis can raise it substantially; the marker supports assessment and follow-up but never establishes the diagnosis alone.
Resectability is an anatomical and biological multidisciplinary judgement, not a radiology phrase in isolation; arterial contact, venous reconstructability, metastases, performance status and patient priorities matter.
Obtain histology before systemic anticancer treatment, usually with endoscopic ultrasound-guided sampling; clearly resectable disease may proceed directly to surgery after specialist review.
Do not drain every jaundiced patient before surgery: cholangitis, severe symptomatic obstruction, delayed surgery or planned neoadjuvant treatment are common reasons to intervene.
Offer pancreatic enzyme replacement and dietetic review for resected disease and consider it early in unresectable disease, because maldigestion may be present without classic steatorrhoea.
Discuss germline and tumour genomic testing according to the current NHS genomic directory because inherited risk and actionable findings may affect relatives or treatment selection.

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

Age and tobacco exposure

Incidence rises with age, and smoking is an important modifiable risk factor, although many affected people lack smoking exposure.

Chronic pancreatic injury

Chronic pancreatitis, selected inherited pancreatitis syndromes and longstanding metabolic dysfunction increase risk through repeated inflammation and cellular turnover.

Inherited cancer susceptibility

Pathogenic germline variants and a strong pancreatic or related cancer family history identify a minority needing genetics-led assessment and surveillance.

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

1
Precursor clonal evolution
Pancreatic ductal precursor lesions acquire sequential molecular changes that permit uncontrolled growth and escape from normal epithelial constraints.
2
Desmoplastic invasive growth
Cancer infiltrates pancreatic tissue within a dense stromal response, invading nerves, bile ducts and adjacent vessels early.
3
Lymphatic and haematogenous spread
Tumour disseminates to regional nodes, liver, peritoneum and lungs, often before the primary lesion causes distinctive symptoms.

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

Obstructive jaundice

Progressive scleral icterus, dark urine, pale stools and pruritus with a cholestatic blood pattern are typical of a pancreatic-head or periampullary obstruction.

Pain and weight loss

Persistent epigastric pain radiating to the back, anorexia, early satiety and unintentional weight loss should prompt pancreatic imaging, especially when symptoms are new.

Metabolic clue

New or rapidly worsening diabetes in an older adult, particularly alongside weight loss rather than weight gain, can accompany pancreatic cancer but is not diagnostic.

Pancreatitis presentation

Unexplained acute pancreatitis, recurrent pancreatitis or a new duct cut-off may be the first manifestation of an obstructing small tumour.

Thrombotic presentation

An apparently unprovoked venous thromboembolism, migratory thrombophlebitis or recurrent thrombosis can accompany pancreatic malignancy and should sharpen attention to systemic symptoms.

Advanced disease

Ascites, palpable nodes, hepatomegaly, peritoneal symptoms or profound functional decline suggest dissemination, but imaging and tissue remain necessary before labelling stage.

Red flags requiring action

Jaundice with fever, rigors, hypotension or altered consciousness suggests acute cholangitis and demands immediate sepsis management plus urgent biliary-source control advice.
Persistent vomiting, a succussion splash or inability to tolerate liquids may indicate malignant gastric outlet obstruction and requires urgent fluid correction and specialist decompression planning.
Sudden dyspnoea, pleuritic pain, syncope or unilateral limb swelling should trigger immediate assessment for cancer-associated venous thromboembolism.
Escalating back pain with weakness, sensory change or sphincter disturbance requires emergency investigation for spinal metastatic compression rather than routine analgesic adjustment.
Oliguria, severe thirst, confusion or postural collapse in a jaundiced patient indicates important dehydration, sepsis or renal injury and should not wait for an outpatient cancer appointment.

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
Liver profile and baseline bloodsFirst step
Why
Define cholestasis, organ reserve and immediate complications before contrast imaging or intervention.
Interpretation and limitations
Conjugated hyperbilirubinaemia with raised alkaline phosphatase supports obstruction; anaemia, low albumin, renal impairment or high inflammatory markers alter urgency and procedural risk.
02
Pancreas-protocol CT chest abdomen pelvis
Why
Stage the tumour and map arterial, venous, nodal and metastatic involvement.
Interpretation and limitations
A pancreatic mass, abrupt duct cut-off, double-duct sign or upstream atrophy supports suspicion; a negative scan does not exclude a small lesion when jaundice or duct dilatation persists.
03
Endoscopic ultrasound with tissue acquisition
Why
Sample a suspected lesion and clarify small or indeterminate abnormalities after cross-sectional imaging.
Interpretation and limitations
Cytology or histology should be reviewed in the pancreatic pathway; a non-diagnostic sample may require repeat targeted sampling rather than reassurance when imaging remains concerning.
04
MRI pancreas and MRCP
Why
Characterise ducts, liver lesions or cystic components when CT leaves uncertainty.
Interpretation and limitations
Use it as a problem-solving and staging study, not as an automatic substitute for properly acquired CT or required tissue.
05
CA 19-9
Why
Provide a contextual baseline and sometimes support longitudinal assessment after biliary decompression.
Interpretation and limitations
Interpret with bilirubin and imaging: obstruction causes false elevation, Lewis-antigen non-secretors may not produce it, and benign pancreatobiliary inflammation can also raise it.
06
Germline and tumour genomic tests
Why
Identify inherited predisposition and selected treatment-relevant alterations under the current NHS directory.
Interpretation and limitations
Eligibility, tissue requirements and consequences for relatives change over time; obtain consent and route results through oncology and clinical genetics rather than ordering an uncurated panel.

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

Autoimmune pancreatitis

Diffuse or focal enlargement, IgG4-related organ disease and a specialist-confirmed treatment response support autoimmune disease, but elevated IgG4 alone cannot exclude cancer.

Chronic pancreatitis

Calcification, longstanding recurrent inflammation and diffuse duct change favour chronic pancreatitis; a new focal cut-off, jaundice or weight loss still requires cancer evaluation.

Choledocholithiasis or cholangiocarcinoma

A visible duct stone or bile-duct-centred stricture may explain jaundice, distinguished through pancreas-protocol and biliary imaging plus planned tissue acquisition.

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

01JAUNDICENew suspected malignant obstructionFirst stepJaundice or cholestatic symptoms without an established benign explanation.

1Assess immediately for cholangitis, dehydration, coagulopathy and renal injury; admit and treat urgently when systemic illness is present.
2Arrange pancreas-protocol CT before elective biliary drainage whenever the patient is stable enough, preserving accurate staging information.
3Refer through the urgent pancreatic cancer route and discuss drainage, endoscopic sampling and resectability with the hepatopancreatobiliary multidisciplinary team.
4AlternativeUse ERCP or alternative drainage when clinically indicated, with antibiotics and stent strategy governed by infection, anatomy and the anticipated treatment sequence.

02RESECTPotentially curable diseaseNo distant metastasis and anatomy that may permit complete resection.

1Confirm specialist radiology review, physiological fitness, nutritional status and whether histology is required before the planned treatment.
2Discuss upfront surgery versus neoadjuvant treatment for borderline or selected high-risk disease within the regional pancreatic MDT.
3Provide prehabilitation, enzyme replacement, diabetes review and honest consent about operative morbidity, recurrence and likely adjuvant treatment.
4After resection, coordinate pathology staging, adjuvant oncology assessment and surveillance using the current regional protocol.

03ADVANCEDUnresectable or metastatic pathwayMetastatic spread, locally unresectable anatomy or fitness incompatible with major surgery.

1Secure adequate tissue and document performance status, comorbidity, organ function, disease burden and the patient's goals.
2Select systemic therapy only through oncology using current NICE commissioning and local protocols; include supportive care from diagnosis.
3Treat pain, maldigestion, obstruction, nausea, thrombosis, diabetes and psychological distress proactively rather than waiting for anticancer treatment to help.
4Reassess benefit and toxicity at defined intervals, and change emphasis toward symptom-led care when burdens outweigh realistic tumour control.

04DECLINEAcute deterioration during the pathwayFever, jaundice, vomiting, bleeding, new thrombosis or rapid functional loss.

1Use an ABCDE assessment and identify reversible emergencies such as cholangitis, pulmonary embolism, gastric outlet obstruction or treatment toxicity.
2Contact the responsible surgical or oncology service early because drainage devices, chemotherapy timing and immunosuppression change management.
3EscalationClarify escalation preferences while treating reversible causes, ensuring specialist palliative support is an active layer of care rather than a late referral.

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

Treat tumour-related or postoperative maldigestion and support weight, strength and treatment tolerance.

Pancreatin pancreatic enzyme replacement

Begin with a substantial lipase dose at every meal and a smaller dose with snacks, then titrate to food and symptoms under local guidance.

Take throughout food, swallow granules intact and review adherence, dose, acid suppression and alternative causes when symptoms persist; current supply advice may require brand-strength substitution.

Control pancreatic visceral and neuropathic pain while specialist procedures are considered.

Opioid analgesia with bowel protection

Titrate an immediate-release preparation to effect, then convert to a regular regimen with breakthrough rescue according to local palliative guidance.

Review sedation, driving, falls, renal or hepatic impairment, constipation and nausea; severe focal pain may benefit from coeliac plexus intervention rather than indefinite dose escalation.

Treat confirmed venous thromboembolism and reduce recurrence during active malignancy.

Therapeutic anticoagulation

Use the cancer-associated thrombosis regimen selected from current local guidance after confirming renal function, weight and bleeding risk.

Account for biliary or endoscopic procedures, thrombocytopenia, gastrointestinal bleeding, drug interactions and altered absorption; seek haematology or oncology advice for competing risks.

Treat biliary infection while urgent decompression provides definitive source control.

Antibiotics for acute cholangitis

Give prompt intravenous therapy according to the local biliary-sepsis policy after cultures when this causes no unsafe delay.

Adjust for allergy, renal function and local resistance patterns; antibiotics alone are inadequate when an infected obstructed system remains undrained.

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

Biliary obstruction and cholangitis

A pancreatic-head tumour blocks the distal bile duct, causing jaundice, pruritus and potentially infected obstruction requiring coordinated drainage.

Exocrine, endocrine and nutritional failure

Duct obstruction and tissue loss cause maldigestion, diabetes, weight loss and sarcopenia, reducing fitness for surgery or systemic therapy.

Pain, thrombosis and metastasis

Perineural invasion causes back pain, while cancer-associated thrombosis and distant spread produce organ dysfunction, ascites and progressive cachexia.

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

Record weight trajectory, oral intake, stool features and enzyme use because cachexia and exocrine insufficiency are distinct, overlapping and treatable drivers of decline.
Trend bilirubin, liver enzymes, renal function and inflammatory markers after drainage; recurrent jaundice or sepsis can indicate stent blockage or migration.
Check glucose and diabetes symptoms around surgery, pancreatic loss, steroid exposure and systemic treatment, involving diabetes specialists for unstable control.
During anticancer therapy, monitor blood counts, renal and hepatic function, neuropathy, infection, diarrhoea and performance status according to the exact regimen.
Review pain scores, breakthrough use, bowel function, alertness and daily activity rather than judging analgesic success from a prescription list.
Revisit treatment intent, capacity, advance-care preferences and family support when imaging, toxicity or functional status changes.

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

Sequence protects options

High-quality staging before non-urgent drainage reduces artefact and helps the MDT choose between surgery, tissue sampling, neoadjuvant treatment and palliation.

Marker humility matters

CA 19-9 is neither a screening test nor a diagnostic gate; its most useful interpretation is longitudinal, contextual and often after cholestasis improves.

Resectable is multidisciplinary

Operability incorporates vascular anatomy, occult metastatic risk, biological behaviour, fitness and patient preference, so a single report should not close the decision.

Jaundice is not always cancer

Autoimmune pancreatitis, choledocholithiasis and benign strictures can resemble malignancy, yet steroid response or reassuring serology must never replace adequate cancer exclusion.

Support changes treatment fitness

Early enzymes, nutrition, activity support and symptom control may preserve function sufficiently to widen realistic oncology choices without promising an anticancer effect.

11Common pitfallsFrequent interpretation and management errors.

01
Do not wait for CA 19-9 before urgent referral or interpret a normal value as reassurance against a pancreatic lesion.
02
Do not arrange routine biliary stenting before appropriate staging and specialist discussion when a stable patient may proceed promptly to resection.
03
Do not call a lesion unresectable solely from a non-specialist report; regional pancreatic radiology review can change anatomical classification.
04
Do not prescribe enzymes as one capsule three times daily irrespective of meal size; matching and distributing the dose through food is fundamental.
05
Do not present systemic regimens as timeless standard choices because eligibility, biomarkers, licensing and commissioning alter; use current oncology protocols.
06
Do not equate palliative care with stopping active treatment; concurrent symptom and decision support is appropriate from advanced-disease diagnosis.