Diagnosis

Pancreatic cancer

Etiology

Cause [mmq]

1. Sporadic DNA mutation --> cancer

2. Genetic mutations or association with syndromes: Lynch syndrome, Peutz-Jeghers syndrome, Von Hippel-Lindau syndrome, and MEN1

Classification of pancreatic cancer

1. Exocrine Pancreatic Cancer: 95% of all pancreatic cancer cases

   • Adenocarcinoma: 90%

   • Acinar cell carcinoma: 1-2%

   • Squamous cell carcinoma: Extremely rare

   • Adenosquamous carcinoma: 1-4%

   • Colloid carcinoma: 1-3%

2. Neuroendocrine Pancreatic Tumors/NET (Endocrine/islet cell tumors): <5%

3. Other rare types include:

   • Pancreatoblastoma: Mainly occurs in children

   • Sarcomas of the pancreas: Extremely rare cancers of the connective tissue

   • Lymphoma: Cancer of the lymphatic system that can develop in the pancreas

   • Benign/Precancerous: Mucinous pancreatic cysts

Pathophysiology [mmq]

1. Growing tumor in the pancreatic parenchyma

   • Two-thirds arise in the pancreatic head

   • One-third arise in the rest (body and tail)

2. Compression of the common bile duct --> Painless jaundice (50%)

3. Late symptoms:

   Weight loss, pain, weakness, pruritus, distended gallbladder, pale stools, dark urine, DVT

4. Metastasis pattern: 52% have distant metastasis at the time of diagnosis

   Regional lymph nodes, surrounding visceral organs such as the duodenum, stomach, colon, peritoneum, and the liver (less commonly to the lungs)

Risk Factors [cu7][mmq]

• Age > 55 years

• Male gender

• Tobacco

• Diabetes mellitus

• Obesity

• Diet (red meat, animal fat)

• Alcohol abuse

• Liver cirrhosis

• Helicobacter pylori infection

• Chronic pancreatitis

• Physical inactivity

• Work exposure to chemicals (dry cleaning and metalworking)

Complications [mmq]

• After surgery:

  Pancreatic fistula, ileus, anastomotic leak, bleeding, and infection

Epidemiology

Incidence per 100.000 [neb][a82][w5r][7ek]

Approach

• Blood test

• CT abdomen

• ERCP

• PTC

• Angiography

Staging

1. Stage I:  Tumor is located in the pancreas and does not extend elsewhere

2. Stage II: Tumor infiltrates bile duct and other near structures; however, lymph nodes are negative

3. Stage III:  Any positive lymph nodes

4. Stage IVA:  Metastases into nearby organs such as stomach, liver, diaphragm, adrenals

5. Stage IVB: Tumor infiltrates distant organs

Inoperability is decided on imaging by superior mesenteric artery encasement, liver metastases, peritoneal implants, distal lymph node metastases, and distant metastases.

Treatment

1. Surgical options: [xqf]

   • Pancreaticoduodenectomy (Whipple procedure), with/without pylorus

   • Total pancreatectomy

   • Distal pancreatectomy

2. Chemotherapy: if locally advanced unresectable tumor

   • FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin): Neadjuvant and and adjuvant

   • Albumin-bound paclitaxel plus gemcitabine

   • Irinotecan liposome with oxaliplatin, 5-FU, and leucovorin: metastatic disease

   • Gemcitabine monotherapy: palliative setting

   • Gemcitabine + capecitabine (GemCap): adjuvant with FOLFIRINOX-intolerance

   • Erlotinib plus gemcitabine: Third-line therapy

   • OFF (oxaliplatin, folinic acid, 5-FU): 2nd/3rd-line therapy

   • CapeOx (capecitabine, oxaliplatin): 2nd/3rd-line therapy

   • Larotrectinib or entrectinib: Tumors with NTRK fusions

   • Pembrolizumab (+/- ipilimumab): MSI-H or deficient mismatch repair or Lynch syndrome

   • Gemcitabine + cisplatin: BRCA1/2 or PALB2 mutations

3. Maintenance therapy:

   • Olaparib: deleterious germline BRCA-mutated metastatic pancreatic adenocarcinoma

4. Supportive care:

   • Pain relief: Non-opioid and opioid analgesics, celiac plexus lysis

5. Endoscopic interventions for biliary or duodenal obstruction

6. Dietary support: Management of pancreatic insufficiency

7. Behavioral support: Coping mechanisms, anxiety, depression

Differential diagnoses

Abdominal aortic aneurysm, Acute pancreatitis, Ampullary carcinoma, Benign bile duct tumor, Bile duct stricture, Cholangiocarcinoma, Cholangitis, Cholecystitis, Choledochal cysts, Choledocholithiasis, Cholelithiasis, Chronic mesenteric ischemia, Chronic pancreatitis, Cirrhosis, Gallbladder cancer, Gastric cancer, Gastric lymphoma, Gastrinoma, Glucagonoma, Hepatocellular carcinoma, Insulinoma, Pancreatic lymphoma, Primary biliary cirrhosis, Primary sclerosing cholangitis, Ulcer disease, VIPoma