Special Surgery 15. Malignant Diseases of the Pancreas: Curative and Palliative, Surgical and Interventional Options

I. Types, Risk Factors and Spread

Main Types

1. Exocrine pancreatic tumors

• Pancreatic ductal adenocarcinoma: most common, about 90%, arises from ductal epithelium
• Acinar cell carcinoma: rare
• Undifferentiated carcinoma: rare, aggressive
• Cystic neoplasms / IPMN: malignant potential

2. Endocrine pancreatic tumors = pancreatic neuroendocrine tumors (pNET)

• Can be benign or malignant
• Functional examples: insulinoma, gastrinoma, glucagonoma
• Non-functional pNET often presents late as mass/metastasis

Risk Factors

• Age > 50 years
• Smoking: strongest modifiable risk factor
• Genetic predisposition / family history: BRCA/PALB2, Lynch, Peutz-Jeghers, hereditary pancreatitis
• Chronic pancreatitis
• Alcohol, mainly through chronic pancreatitis
• Obesity
• Diabetes mellitus, especially new-onset diabetes in older patient

Localization and Spread

• Localization: head most common, about 60-70%; body/tail tumors present later
• Direct invasion: duodenum, stomach/colon, portal vein / SMV, SMA, celiac axis
• Lymphatic spread: peripancreatic, hepatoduodenal/celiac/SMA nodes, Virchow node, periumbilical metastasis
• Hematogenous spread: liver most common, then lung/bone
• Peritoneal seeding can occur

II. Clinical Features and Diagnosis

Clinical Features

• Early stage: often asymptomatic
• Head of pancreas tumor:

• Painless progressive jaundice from bile duct obstruction
• Dark urine, acholic/pale stool, pruritus
• Courvoisier sign: palpable painless enlarged gallbladder + obstructive jaundice

• Body/tail tumor:

• Epigastric pain radiating to back, belt-like
• Often late because no early bile duct obstruction

• General symptoms: weight loss, anorexia, fatigue, cachexia, nausea/vomiting
• New-onset diabetes in elderly or worsening diabetes
• Exocrine insufficiency: steatorrhea, malabsorption, weight loss
• Trousseau syndrome: paraneoplastic migratory thrombophlebitis

Laboratory Tests

• Cholestatic pattern if bile duct obstruction: increased direct bilirubin, ALP, GGT
• AST/GOT and ALT/GPT can increase
• Pancreatic enzymes can increase but are not diagnostic for cancer
• Hyperglycemia / new diabetes
• CA 19-9: useful for prognosis and follow-up if elevated, but not diagnostic alone
• CA 19-9 can be falsely high in obstructive jaundice/cholangitis and falsely negative in Lewis antigen-negative patients

Imaging and Tissue Diagnosis

• US: often first in jaundice; shows dilated bile duct ± pancreatic head mass/liver metastasis
• Pancreas-protocol contrast CT: first-line for diagnosis and staging

• Tumor size/location
• Vascular involvement: SMV/PV, SMA, celiac axis, common hepatic artery
• Local invasion, liver/peritoneal metastasis, resectability

• MRI/MRCP: ductal anatomy, liver metastasis, cystic neoplasms/IPMN, CT-equivocal cases
• EUS: local staging and biopsy of small lesions
• EUS-guided FNA/core biopsy: preferred tissue method when needed
• Tissue diagnosis needed before neoadjuvant therapy, chemotherapy or if diagnosis is uncertain
• Tissue diagnosis may be omitted before upfront surgery in classic clearly resectable cancer after MDT decision
• ERCP: mainly therapeutic biliary stenting; brush cytology only selected
• PET-CT or staging laparoscopy: selected cases when occult metastasis is suspected

III. Curative Treatment

Resectability and Treatment Logic

• Curative treatment possible only in about 15-20% of patients at diagnosis
• Goal: R0 resection + regional lymphadenectomy + systemic therapy
• Decision by pancreatic MDT / onco-team
• Resectable tumor: no distant metastasis, no unreconstructable major vascular involvement → radical surgery + adjuvant chemotherapy
• Borderline resectable tumor: limited vascular contact where R0 is uncertain → neoadjuvant therapy → restaging → surgery if no progression
• Locally advanced unresectable: major arterial encasement or unreconstructable venous invasion → systemic therapy ± local palliation
• Metastatic disease: systemic/palliative therapy

Surgical Procedures

1. Pancreaticoduodenectomy / Whipple Procedure

• For tumors in pancreatic head / periampullary region
• Resection: pancreatic head, duodenum, gallbladder, distal common bile duct, regional lymph nodes
• Reconstruction: pancreaticojejunostomy, hepaticojejunostomy, gastrojejunostomy/duodenojejunostomy

2. Distal Pancreatectomy

• For tumors in pancreatic body or tail
• Often includes splenectomy for adenocarcinoma because of lymphatic drainage

3. Total Pancreatectomy

• Rare
• Selected multifocal disease/IPMN, positive margins not otherwise clearable, or special anatomy
• Consequence: complete endocrine and exocrine insufficiency → brittle diabetes + lifelong enzyme replacement

Neoadjuvant and Adjuvant Therapy

• Neoadjuvant therapy: borderline resectable disease; selected high-risk resectable disease
• Purpose: treat micrometastases early, test tumor biology, increase chance of R0 resection
• Adjuvant chemotherapy improves survival after resection
• Examples: modified FOLFIRINOX in fit patients; gemcitabine + capecitabine or other gemcitabine-based treatment if less fit

IV. Palliative and Interventional Treatment

Indications and Systemic Therapy

• Indication: unresectable tumor with major vascular invasion or metastatic disease
• Goals: relieve symptoms, prolong survival, maintain quality of life
• Chemotherapy prolongs survival:

• Fit patient: FOLFIRINOX / modified FOLFIRINOX
• Frail/elderly patient: gemcitabine-based regimen or best supportive care
• Targeted/immunotherapy: limited, selected cases

Jaundice and Obstruction Palliation

• Biliary stent implantation: relieves obstructive jaundice
• ERCP with biliary stent: first-line if endoscopically possible
• Palliative biliary bypass if ERCP/stent is not feasible:

• Hepaticojejunostomy / choledochojejunostomy
• Cholecystojejunostomy: only if cystic duct is patent and anatomy suitable

• Gastric outlet obstruction: endoscopic duodenal stent or palliative gastrojejunostomy

Supportive Care and Prognosis

• Pain management: opioids, celiac plexus block/neurolysis for advanced back-radiating pain
• Nutritional support
• Pancreatic enzyme replacement if pancreatic insufficiency/steatorrhea
• Psychological and palliative care services
• Prognosis of pancreatic ductal adenocarcinoma is poor because most patients present late
• Median survival: resected early-stage ~20-30 months; locally advanced ~6-12 months; metastatic often <6 months without treatment