Pancreatic ductal adenocarcinoma

Introduction

Pancreatic Ductal Adenocarcinoma (PDAC) is the most common type of pancreatic cancer, accounting for approximately 90–95% of all pancreatic neoplasms. It arises from the epithelial cells lining the pancreatic ducts—the network of tubes responsible for transporting digestive enzymes from the pancreas to the duodenum (the first part of the small intestine).

Despite advances in oncology, PDAC remains one of the most lethal solid malignancies. It is currently the 4th leading cause of cancer-related death in Western countries (7th globally) and is projected to become the 2nd leading cause by 2030. The high mortality rate is primarily driven by late presentation—over 80% of patients are diagnosed at an unresectable (locally advanced or metastatic) stage—and an inherent resistance to conventional chemotherapy and radiotherapy.

This article provides a detailed, patient-centered, and clinically accurate resource covering epidemiology, pathology, clinical presentation, diagnostics, staging, treatment paradigms, and survivorship.

Epidemiology and Risk Factors

Incidence and Demographics

• Annual Incidence: ~13–15 per 100,000 people in Europe and North America.
• Median Age at Diagnosis: 70–71 years. It is rare before age 45.
• Sex Distribution: Slight male predominance (Male:Female ratio ~1.3:1), likely reflecting historical smoking patterns.
• Geographic Variation: Highest rates in Western Europe, North America, Australia/New Zealand; lowest in Middle Africa and South-Central Asia.

Established Risk Factors

Clinical Pearl: Approximately 10% of PDAC cases have a hereditary component. Current guidelines (NCCN, ESMO) recommend germline genetic testing for all patients diagnosed with PDAC**, regardless of family history, to guide therapy (e.g., PARP inhibitors for BRCA mutations) and cascade testing for relatives.

Pathophysiology: The Molecular Landscape

PDAC does not arise de novo; it progresses through a well-defined sequence of Pancreatic Intraepithelial Neoplasia (PanIN) lesions: PanIN-1 (low grade) → PanIN-2 (intermediate) → PanIN-3 (high grade/carcinoma in situ) → Invasive Carcinoma.

The “Core” Driver Mutations (The “Big Four”)

These mutations are found in the vast majority of sporadic PDACs and define the disease biology.

Molecular Subtyping (Transcriptomic)

Beyond histology, PDAC is classified into subtypes with prognostic and predictive implications:

1. Classical (Progenitor/Classical): High GATA6, epithelial markers, better differentiation, better prognosis, higher response to adjuvant FOLFIRINOX.
2. Basal-like (Quasi-mesenchymal/Squamous): Low GATA6, squamous differentiation, immune evasion, poor prognosis, relative resistance to standard chemo, potential sensitivity to immunotherapy/ADCs (clinical trial context).
3. Hybrid/Intermediate: Features of both.

How Does It Look? (Pathology, Gross Anatomy & Imaging Appearance)

This section details the visual characteristics of PDAC across macroscopic (gross), microscopic (histologic), and radiological domains.

1. Gross Pathology (Macroscopic Appearance)

Upon surgical resection (e.g., Whipple specimen) or autopsy, PDAC presents distinct physical features:

• Location: 60–70% in the pancreatic head (often obstructing the common bile duct), 20–25% in the body/tail, remainder diffuse/multicentric.
• Texture: Characteristically firm, gritty, scirrhous (rock-hard) due to an intense desmoplastic stromal reaction (dense fibrosis). This distinguishes it from the soft, friable texture of neuroendocrine tumors or metastases.
• Color: Grey-white to yellow-tan on cut section (fibrosis + necrosis). Lacks the bright yellow/tan of normal pancreas or the cystic fluid of IPMNs.
• Margins: Infiltrative and ill-defined. The tumor blends imperceptibly into the surrounding parenchyma, making “enucleation” impossible and clear surgical margins difficult to achieve.
• Ductal Obstruction: The main pancreatic duct (Wirsung) and Common Bile Duct (CBD) are frequently stenosed or occluded proximal to the mass. Upstream pancreatic atrophy (fatty replacement) is common.
• Vascular Involvement: Gross adherence to or encasement of the Superior Mesenteric Vein (SMV), Portal Vein (PV), Superior Mesenteric Artery (SMA), or Celiac Axis is a hallmark of local advancement.

2. Microscopic Pathology (Histology)

Diagnosis is confirmed via Core Needle Biopsy (preferred over FNA for architecture) or surgical specimen.

• Architecture: Gland-forming (tubular) structures infiltrating between normal pancreatic acini, nerves, and vessels. “Gland-within-gland” pattern is common.
• Cellular Features:
• Nuclei: Enlarged, hyperchromatic, pleomorphic, prominent nucleoli.
• Mitoses: Frequent atypical mitoses.
• Cytoplasm: Scant to moderate, eosinophilic (pink) or clear (mucinous).
• Apical Mucin: Mucin vacuoles often seen at the apical surface of malignant ductal cells (PAS-Diastase positive, Mucicarmine positive).
• Stroma (The Microenvironment): Desmoplasia is the histologic hallmark. Dense, hypocellular collagen (Type I/III) deposited by Cancer-Associated Fibroblasts (CAFs). This stroma creates high interstitial fluid pressure, compressing vasculature → hypoxia and poor drug delivery.
• Invasion Patterns (Prognostic):
• Perineural Invasion (PNI): Present in >90% of resections. The primary route of local spread and pain generation.
• Lymphovascular Invasion (LVI): Predictor of nodal recurrence.
• Venous/Arterial Invasion: Defines borderline resectability.

Histologic Variants (WHO Classification)

3. Radiological Appearance (Imaging “Look”)

Imaging is the cornerstone of diagnosis, staging, and resectability assessment. Contrast-Enhanced Multi-Detector CT (MDCT) with Pancreas Protocol is the gold standard initial modality.

A. Computed Tomography (MDCT) – Pancreas Protocol

• Phases: Non-contrast → Late Arterial (25–35s) → Portal Venous (60–70s) – Most Critical → Delayed (3–5 min).
• Classic PDAC Appearance:
• Hypoattenuating (Hypodense) Mass: Poorly enhancing relative to normal pancreatic parenchyma in the arterial and portal venous phases (due to hypovascularity/fibrosis).
• “Double Duct Sign”: Simultaneous dilation of the Common Bile Duct (CBD) and Main Pancreatic Duct (MPD). Highly specific for peri-ampullary malignancy.
• Pancreatic Atrophy: Upstream fatty replacement/volume loss distal to the obstruction.
• Vascular Interface (Resectability Criteria):
• Contact < 180°: Resectable.
• Contact ≥ 180° or contour irregularity: Borderline Resectable (Venous) / Locally Advanced (Arterial).
• Encasement/occlusion: Unresectable (Locally Advanced/Metastatic).
• Metastases: Hypodense liver lesions (portal venous phase), peritoneal nodules, ascites, lung nodules (chest CT).

B. Magnetic Resonance Imaging (MRI/MRCP)

• Superior Soft Tissue Contrast: Better detection of small lesions (<1 cm), characterization of cystic lesions (IPMN vs. MCN), and assessment of bile/pancreatic duct anatomy (MRCP).
• Sequences: T1-weighted (fat-suppressed), T2-weighted (heavily T2 for MRCP), Diffusion-Weighted Imaging (DWI – restricted diffusion in PDAC), Dynamic Contrast-Enhanced (DCE) with Gadolinium (gadoxetate disodium/Eovist preferred for hepatobiliary phase).
• Role: Problem-solving for indeterminate CT lesions; baseline for locally advanced disease prior to chemoradiation; patients with iodinated contrast allergy/renal failure.

C. Endoscopic Ultrasound (EUS)

• Highest Sensitivity: Detects tumors < 1 cm (T1a) missed by CT/MRI.
• Appearance: Hypoechoic, heterogeneous mass with irregular borders, disrupting the normal “three-layer” ductal/parenchymal architecture.
• EUS-FNA/FNB (Fine Needle Aspiration/Biopsy): Gold standard for tissue diagnosis (Sensitivity 85–95%, Specificity ~100%). Allows simultaneous celiac plexus neurolysis (pain management) and molecular profiling.

D. PET-CT (FDG-PET)

• Not routine for primary diagnosis.
• Indications: Staging equivocal findings on CT (e.g., indeterminate liver lesions, lymph nodes); restaging after neoadjuvant therapy; detecting occult metastatic disease before major surgery. PDAC is typically FDG-avid (SUVmax often > 5–10), though inflammation (pancreatitis) causes false positives.

Symptoms: Clinical Presentation

PDAC is notoriously asymptomatic in early stages. Symptoms usually arise only when the tumor invades adjacent structures, obstructs ducts, or metastasizes. The median duration of symptoms before diagnosis is 3–6 months.

1. The “Classic Triad” (Head of Pancreas Tumors)

Tumors in the head (majority) present earlier due to mechanical obstruction.

2. Symptoms by Tumor Location

Body & Tail Tumors (20–25%) – “Silent Killers”

• Later Presentation: No bile duct obstruction → no jaundice.
• Dominant Symptoms: Vague epigastric/back pain, significant weight loss, new-onset diabetes.
• Physical Exam: Palpable epigastric mass (late), Courvoisier’s Sign (palpable, non-tender gallbladder) rare here (more common in head tumors), Virchow’s Node (Left supraclavicular node – Troisier sign), Sister Mary Joseph Nodule (periumbilical metastasis), Blumer’s Shelf (rectal shelf on DRE – peritoneal carcinomatosis).

Metastatic Symptoms (Stage IV – ~50-55% at diagnosis)

• Liver: Right upper quadrant pain, hepatomegaly, ascites, liver failure (late), elevated ALP/GGT/Bilirubin.
• Peritoneum: Ascites (malignant), bowel obstruction, abdominal distension.
• Lungs: Dyspnea, pleural effusion, cough.
• Bone: Pathologic fractures, bone pain.

3. Paraneoplastic & Metabolic Manifestations

These can precede radiologic detection by months.

4. “Red Flag” Symptom Combinations Requiring Urgent Imaging

Clinicians should have a low threshold for CT abdomen in patients >50 with:

1. Weight loss + New-onset Diabetes + Abdominal/Back Pain.
2. Painless Jaundice + Weight Loss.
3. Unprovoked VTE + Vague Abdominal Symptoms.
4. Persistent Epigastric Pain unresponsive to PPIs + Weight Loss.

Diagnostic Workup: Step-by-Step Algorithm

1. Initial Laboratory Evaluation

• Liver Function Tests (LFTs): Obstructive pattern – ↑ Total/Direct Bilirubin, ↑ ALP, ↑ GGT, mild-moderate ↑ AST/ALT.
• Tumor Markers:
• CA 19-9 (Carbohydrate Antigen 19-9): Only validated serum marker. Sensitivity ~80%, Specificity ~90% (cutoff >37 U/mL).
• Caveats: False negative in Lewis antigen-negative individuals (5–10% population, cannot synthesize CA 19-9). False positive in cholangitis, biliary obstruction (stent), benign biliary disease, other GI cancers.
• Utility: Baseline for monitoring response, prognostic stratification (very high >1000 = occult mets likely), detecting recurrence.
• CEA (Carcinoembryonic Antigen): Lower sensitivity/specificity; adjunctive.
• Metabolic Panel: Glucose (screen for diabetes), Electrolytes, Renal function (cisplatin/chemo eligibility), Albumin (nutritional status).
• Coagulation: PT/INR, PTT (pre-procedure, VTE risk).

2. Imaging Strategy (The “Pancreas Protocol” CT is Step 1)

1. CT Abdomen/Pelvis + Chest (Contrast, Pancreas Protocol): Diagnosis, local staging (vascular contact), distant mets.
2. If Resectable/Borderline on CT: Proceed to EUS-FNA/FNB for tissue confirmation + molecular profiling (germline/somatic).
3. If Locally Advanced/Metastatic on CT: EUS-FNA/FNB mandatory for tissue diagnosis before systemic therapy.
4. MRI/MRCP: If CT indeterminate, cystic lesion, contrast allergy, renal impairment.
5. PET-CT: Equivocal mets on CT; restaging post-neoadjuvant.

3. Tissue Acquisition: EUS-FNA vs. FNB

• FNB (Franseen/Reverse Bevel needles): Preferred. Yields core tissue → allows histology (architecture), IHC staining, and comprehensive NGS (Next-Gen Sequencing) for BRCA, MSI, TMB, KRAS, NRG1 fusions, NTRK.
• FNA: Cytology only; limited molecular yield.
• Safety: No significant tumor seeding risk with modern needles; prophylactic antibiotics for cystic lesions.

4. Staging Systems

TNM 8th Edition (AJCC/UICC) – Anatomic Staging

Critical Distinction: Anatomic TNM staging does not equal Resectability. Resectable: No arterial contact (SMA, CHA, Celiac), venous contact <180° no contour irregularity. Borderline Resectable: Venous contact ≥180°/irregularity (reconstructible), limited arterial contact (CHA short segment, hepatic artery). Locally Advanced: Unreconstructible venous occlusion, significant arterial contact/encasement (>180° SMA/Celiac). Metastatic:** Distant mets (Liver, Peritoneum, Lung, Bone, Non-regional nodes).

Treatment Paradigms: A Multidisciplinary Approach

Treatment decisions are made in a Multidisciplinary Tumor Board (MDT) comprising Surgical Oncology, Medical Oncology, Radiation Oncology, Radiology, Pathology, Palliative Care, Nutrition, and Genetics.

1. Resectable Disease (Upfront Surgery → Adjuvant Therapy)

• Surgery:
• Head/Uncinate: Pancreaticoduodenectomy (Whipple Procedure). Standard: Pylorus-preserving (PPPD) vs. Classic. Radical antegrade modular pancreatosplenectomy (RAMPS) for body/tail.
• Lymphadenectomy: Standard (≥15 nodes examined for accurate staging).
• Vascular Resection: SMV/PV resection with primary anastomosis or graft is standard for borderline venous involvement; arterial resection (SMA/CHA/Celiac) is generally NOT recommended upfront (high morbidity, no survival benefit proven).
• Adjuvant Therapy (Start within 8–12 weeks post-op):
• Standard (Fit Patients): mFOLFIRINOX (Modified FOLFIRINOX) – PRODIGE 24 / ACCORD 24 Trial. Median OS: 54.4 months vs 35.0 months (Gemcitabine). 6 months (12 cycles).
• Alternative (Less Fit/Frail): Gemcitabine + Capecitabine (ESPAC-4) – Median OS 28.0 vs 25.5 mo (Gem alone). Or Gemcitabine monotherapy.
• Adjuvant Radiotherapy? Controversial. ESPAC-1: No benefit for chemoradiation. LAP07/RTOG 0848: Role unclear. Generally reserved for R1 margins or positive nodes in clinical trials or select MDT decisions.

2. Borderline Resectable (BRPC) – Neoadjuvant Therapy First

Standard of Care: Neoadjuvant Chemotherapy ± Radiotherapy → Re-staging → Surgery.

• Goal: Downstage tumor, treat micrometastases early, select patients with favorable biology for surgery (avoid futile laparotomy in rapid progressors).
• Regimens: FOLFIRINOX (preferred for fit), GnP (Gemcitabine + nab-Paclitaxel), or Gem/Cape.
• Radiation: Often added (SBRT or conventional) for local control/sterilization of margins.
• Surgery: Proceed if no progression on imaging, CA 19-9 normalization, good PS. R0 resection rate higher than upfront surgery.

3. Locally Advanced (LAPC) – Non-Metastatic, Unresectable

• Primary: Systemic Chemotherapy (FOLFIRINOX or GnP) for 4–6 months.
• Consolidation: If stable/responding → Chemoradiation (CRT) or SBRT (Stereotactic Body Radiation Therapy).
• Re-assessment: 10–20% may convert to resectable (“Conversion Surgery”).
• Maintenance: Continue systemic therapy (de-escalated) or Olaparib (if gBRCA mutant – POLO trial paradigm).

4. Metastatic Disease (Stage IV) – Palliative Systemic Therapy

Goals: Prolong survival, maintain/improve Quality of Life (QoL), symptom control.

First-Line Options (Performance Status Dependent)

Biomarker-Directed Therapy (Precision Oncology)

• Germline BRCA1/2 / PALB2 Mutation (~5-7% PDAC):
• 1st Line: Platinum-based chemo (FOLFIRINOX or Gem/Cis) preferred.
• Maintenance: Olaparib (PARP inhibitor) after ≥16 weeks 1st line platinum without progression (POLO Trial: PFS benefit 7.4 vs 3.8 mo; OS trend).
• MSI-H / dMMR (~1-2%):
• Pembrolizumab (Anti-PD-1) approved tissue-agnostic. High response rates, durable.
• NTRK Fusions (<1%):
• Larotrectinib / Entrectinib (TRK inhibitors). Dramatic responses.
• KRAS G12C (~1-2%):
• Sotorasib / Adagrasib (KRAS G12C inhibitors) + chemo/immunotherapy combos in trials.
• NRG1 Fusions (<1%):
• Zenocutuzumab (MCLA-128 / Bispecific HER2/HER3) – Breakthrough Therapy Designation.

Second Line & Beyond

• Post-FOLFIRINOX: Gemcitabine-based (GnP or Gem/Cape).
• Post-GnP: 5-FU based (FOLFOX, FOLFIRI, Nal-IRI + 5-FU/LV – NAPOLI-1 approved).
• Clinical Trials: Strongly recommended at every line.

Supportive Care & Symptom Management (Integral to Treatment)

1. Exocrine Pancreatic Insufficiency (EPI)

• Prevalence: >80% unresectable; >50% post-Whipple.
• Diagnosis: Clinical (steatorrhea, weight loss, low fecal elastase <200 µg/g).
• Treatment: Pancreatic Enzyme Replacement Therapy (PERT) – Enteric-coated microspheres (e.g., Creon, Pancreaze, Zenpep).
• Dosing: Start high (40,000–50,000 lipase units/meal; 25,000/snack). Titrate to symptoms. Take with first bite and mid-meal.
• Adjunct: PPI (Omeprazole/Pantoprazole) to protect enzymes from gastric acid. Fat-soluble vitamins (A, D, E, K) supplementation.

2. Diabetes Management (Pancreatogenic / Type 3c Diabetes)

• Pathophysiology: Loss of insulin (beta cells) + glucagon (alpha cells) + incretin deficiency. Brittle glucose control, high hypoglycemia risk.
• Management: Insulin is mainstay. Avoid Sulfonylureas (hypoglycemia risk). GLP-1 agonists/SGLT2i used cautiously (weight loss/GI side effects). Continuous Glucose Monitoring (CGM) highly beneficial.

3. Pain Management

• Mechanism: Perineural invasion, celiac plexus infiltration, capsular stretch, biliary obstruction.
• WHO Analgesic Ladder: Opioids (Morphine, Oxycodone, Fentanyl patch) + Adjuvants (Gabapentin/Pregabalin for neuropathic component, Corticosteroids for inflammatory/visceral pain).
• Celiac Plexus Neurolysis (CPN): EUS-guided or CT-guided alcohol injection. Best evidence for somatic/visceral pain reduction and opioid sparing. Perform early (before intractable pain/opioid tolerance). Duration: 3–6 months.

4. Biliary & Gastric Outlet Obstruction

• Biliary: Endoscopic stenting (Metal SEMS preferred over plastic for >3 mo survival) via ERCP (or EUS-guided hepaticogastrostomy if failed). PTBD if endoscopic failure.
• Gastric (Duodenal): Duodenal SEMS (EUS-guided or fluoroscopic) or Surgical Gastrojejunostomy (if fit for surgery/at laparotomy).

5. Venous Thromboembolism (VTE) Prophylaxis & Treatment

• High Risk: PDAC = highest VTE risk of all cancers (Khorana Score usually ≥3).
• Inpatient: Pharmacologic prophylaxis (LMWH) mandatory.
• Outpatient: Primary prophylaxis with LMWH (Enoxaparin 40mg daily) or DOAC (Apixaban/Rivaroxaban – CASSINI/AVERT trials) during active chemo for high-risk ambulatory patients (Khorana ≥2).
• Treatment of established VTE: LMWH preferred over DOACs/Warfarin for first 3-6 months (lower GI bleed risk in GI cancers), then transition to DOAC if stable.

6. Nutrition & Sarcopenia

• Prehabilitation: High-protein, high-calorie oral nutritional supplements (ONS) pre/post-op and during chemo.
• Sarcopenia: CT-assessed (L3 Skeletal Muscle Index). Predicts chemo toxicity, post-op complications, mortality. Resistance exercise + protein + Leucine/HMB supplementation.

7. Palliative Care Integration

• Early Integration (Diagnosis of Stage IV): ASCO/ESMO guidelines mandate early palliative care referral.
• Benefits: Improved QoL, mood, symptom burden, survival (Temel et al., NEJM 2010 – lung cancer; extrapolation supported in GI), reduced aggressive end-of-life care, improved caregiver outcomes.
• Advance Care Planning: Goals of care discussions, code status, hospice referral timing.

Prognosis, Survival Statistics & Follow-Up

Survival by Stage (Modern Era Data – Adjuvant FOLFIRINOX / Neoadjuvant Era)

Statistics are population averages (median); individual outcomes vary significantly based on biology, performance status, treatment access, and comorbidities.

Surveillance After Resection (High Recurrence Risk: ~70-80%)

• Frequency: Every 3–6 months for 2 years, then every 6–12 months up to 5 years.
• Modality: CA 19-9 (every visit) + CT Chest/Abdomen/Pelvis (every 3–6 mo x 2yr, then 6–12 mo).
• PET-CT: Not routine; reserved for rising CA 19-9 with negative CT.
• Recurrence Patterns: Liver (40%), Peritoneum (30%), Local (20%), Lung (15%), Distant Nodes.
• Treatment of Recurrence: Systemic therapy (re-challenge or new line), SBRT for oligometastases/oligorecurrence (emerging data), clinical trials.

Prevention & Screening

General Population

• No screening recommended. Low prevalence, lack of cost-effective test, harm from false positives (invasive procedures).

High-Risk Individuals (Screening Recommended – CAPS Consortium / NCCN / IAP Guidelines)

Criteria (Any One):

1. Genetic: BRCA1/2, PALB2, ATM, CDKN2A, MLH1/MSH2/MSH6, STK11, PRSS1 pathogenic variant + 1 FDR with PDAC.
2. Familial Pancreatic Cancer (FPC): ≥2 FDRs with PDAC (regardless of gene).
3. Peutz-Jeghers Syndrome (STK11).
4. Hereditary Pancreatitis (PRSS1/SPINK1/CFTR).

Protocol:

• Age to Start: 50 years old (or 10 years younger than earliest diagnosis in family).
• Modality: Annual MRI/MRCP (no radiation, excellent duct visualization) alternating with or combined with EUS.
• Center: High-volume expert center (CAPS Center of Excellence).

Living with PDAC: Psychosocial & Practical Support

• Financial Toxicity: High cost of care (oral chemo parity laws, copay assistance foundations: PanCAN, Patient Advocate Foundation, HealthWell).
• Caregiver Burden: High intensity (stoma care, PERT management, pain pumps, frequent visits). Respite care, caregiver support groups essential.
• Mental Health: High rates of depression, anxiety, existential distress. Screening (PHQ-9, GAD-7) + psycho-oncology referral.
• Fertility Preservation: Discuss before chemotherapy (sperm banking, oocyte/embryo cryopreservation) for patients of reproductive age.
• Patient Advocacy Organizations:
• PanCAN (Pancreatic Cancer Action Network): Patient Central (free 1:1 case managers, clinical trial finder, molecular profiling “Know Your Tumor”).
• Lustgarten Foundation: Research funding, patient resources.
• NCCN Guidelines for Patients: Free plain-language treatment guides.

Summary of Key Takeaways

1. PDAC is aggressive but treatable. Early detection (Stage I) offers >40% 5-year survival.
2. Jaundice + Weight Loss + New Diabetes in >50yo = CT Pancreas Protocol immediately.
3. Tissue is the issue. EUS-FNB for histology + Mandatory Germline/Somatic Genetic Testing for every patient.
4. Resectability ≠ TNM Stage. Vascular involvement defines operability. Borderline = Neoadjuvant First.
5. mFOLFIRINOX is the adjuvant standard for fit patients post-resection.
6. Supportive Care IS Treatment. PERT, Pain Control (CPN), VTE Prophylaxis, Nutrition, Early Palliative Care improve survival and quality of life.
7. Clinical Trials are the engine of progress. Ask your oncologist about trial options at every decision point.

Glossary of Common Terms

• Adjuvant Therapy: Treatment given after surgery to kill micrometastases.
• Neoadjuvant Therapy: Treatment given before surgery to shrink tumor.
• Borderline Resectable: Tumor technically removable but high risk of positive margins; needs neoadjuvant therapy first.
• Desmoplasia: Dense fibrous stroma characteristic of PDAC.
• ECOG Performance Status: 0=Fully active, 1=Restricted strenuous, 2=Up >50% day, 3=Bed >50% day, 4=Bedbound.
• FOLFIRINOX: Combination: Folinic acid (Leucovorin), Fluorouracil (5-FU), Irinotecan, Oxaliplatin.
• GnP: Gemcitabine + nab-Paclitaxel (Abraxane).
• GERD: Gastroesophageal Reflux Disease.
• IPMN: Intraductal Papillary Mucinous Neoplasm (precursor cyst).
• MDT: Multidisciplinary Team / Tumor Board.
• MRCP: Magnetic Resonance Cholangiopancreatography.
• Olaparib: PARP Inhibitor (maintenance for gBRCA).
• PERT: Pancreatic Enzyme Replacement Therapy.
• PNI: Perineural Invasion.
• R0/R1/R2 Resection: R0=Negative margins (>1mm), R1=Microscopic positive, R2=Macroscopic residual.
• SBRT: Stereotactic Body Radiation Therapy (high dose, few fractions).
• SEMS: Self-Expanding Metal Stent.
• Whipple (PD): Pancreaticoduodenectomy.

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