Pancreatic Cancer

Definition
Malignant cells are found in the tissue of the pancreas. Also called pancreatic exocrine cancer.

Epidemiology

• 5th most common cause of cancer death
• Risk: African descent, male:female= 1.7:1, age (50-70)

Aetiology
Risk factors

• Smoking: RR = 2.5 for current smokers.
• Diabetes: RR = 2.1
• History of partial gastrectomy or cholecystectomy: 2- to 5-fold increased risk 15–20 years after partial gastrectomy.
• Familial aggregation/genetic factors: 5–10% of patients have a 1st-degree relative with the disease.
• Hereditary chronic pancreatitis: Cumulative risk by age 50 and 75 years is 10% and 54%.
• Chronic pancreatitis: Tropical and nontropical
• Coffee and alcohol consumption
• Diets high in red meat, soft drink (risk ratio 1.87)
• H. pylori infection

Genetics

Multifactorial	Activation of oncogenes (e.g., K-ras mutation 90%); inactivation of tumor suppressor genes (e.g., CDKN2A [95%], p53 [50-60%], DPC4 [55%], and BRCA2 genes[10%]); and defects in DNA mismatch repair genes (e.g., MLH1 and MSH2 [5% of pancreatic tumors])
Hereditary pancreatitis	lifetime risk of 40%. Related with DNA mismatch repair genes PRSS1 and SPINK1
Inherited cancer syndromes	Peutz-Jeghers syndrome: Related genes: LKB1/STK 11; lifetime risk is as high as 36%. Hereditary breast/ovarian cancer: 5% lifetime risk for pancreas cancer. Related genes: BRCA2 and BRCA1 Familial atypical multiple-mole melanoma (FAMMM) syndrome: 19% lifetime risk. Related gene: CDKN2A Ataxia-telangiectasia: Related gene: ATM Li-Fraumeni syndrome: Related Gene: p53

Presentation

Head of the pancreas (70%)

weight loss, obstructive jaundice abdominal pain- dull ache in midepigastrium, progressive, often worse at night, may radiate to back painless jaundice(70%) occurs more often with ampullary or primary bile duct tumours, and is not common in pancreatic cancers palpable tumour mass=incurable Trousseau sign, in which blood clots form spontaneously in the portal blood vessels, the deep veins of the extremities, or the superficial veins anywhere on the body Courvoisier sign (33%) defines the presence of jaundice and a painlessly distended gallbladder Virchow node (left supraclavicular) and Sister Mary Joseph node (umbilical) in metastatic disease; palpable rectal shelf

Body/head of pancreas (30%)

tends to present later and usually inoperable <10% jaundiced weight loss, vague midepigastric pain sudden onset diabetes mellitus

Pathology

• ductal adenocarcinoma –commonest (75-80%)
• giant cell carcinoma (4%), adenosquamous carcinoma (3%)
• other: mucinous, cystadenocarcinoma, acinar cell carcinoma

Investigation

FBC	anameia of chronic disease, thrombocytosis
LFT	↑ALP, GGT bilirubin (>18)
amylase/ lipase	↑ in less than half of pt with resectable cancer
CA 19-9	↑ >37 U/mL (80%) ↑ >37 U/mL (80%) individuals with Lewis-negative blood group antigen phenoptype (5–10%) are unable to synthesize CA 19-9.
Imaging	Abdominal US 75–89% sensitivity and 90–99% specificity; dilated bile ducts or the presence of a mass in the head of the pancreas. CT and CT angiography 85–90% sensitivity and 90–95% specificity ERCP 90% sensitivity and 95% specificity MRI no significant diagnostic advantage over contrast-enhaced CT MRCP 90% sensitivity and 95% specificity; does not require contrast material to be administered into the ductal system
Procedures	Percutaneous FNA biopsy using either US or CT guidance: 80–90% sensitivity and 98–100% specificity Endoscopic US most sensitive noninvasive test to diagnose vascular invasion: 90% specificity and 73% sensitivity. Endoscopic US–guided biopsy 85–90% sensitivity and virtually 100% specificity for pancreatic mass Staging laparoscopy and US 92% sensitivity, 88% specificity, and 89% accuracy peritoneal cytology positive predictive value of 94%, specificity of 98%, and sensitivity of 25% for determining unresectability PET scan 90% sensitivity but 70% specificity; limited anatomic information
Staging	TNM Staging AJCC, 2002. Tumor (T) TX - Primary tumor cannot be assessed T0 - No evidence of primary tumor Tis - Carcinoma in situ T1 - Tumor limited to the pancreas, 2 cm or smaller in greatest dimension T2 - Tumor limited to the pancreas, larger than 2 cm in greatest dimension T3 - Tumor extension beyond the pancreas (eg, duodenum, bile duct, portal or superior mesenteric vein) but not involving the celiac axis or superior mesenteric artery T4 - Tumor involves the celiac axis or superior mesenteric arteries Regional lymph nodes (N) NX - Regional lymph nodes cannot be assessed N0 - No regional lymph node metastasis N1 - Regional lymph node metastasis Distant metastasis (M) MX - Distant metastasis cannot be assessed M0 - No distant metastasis M1 - Distant metastasis Stage grouping for pancreatic cancer is as follows: Stage 0 - Tis, N0, M0 Stage IA - T1, N0, M0 Stage IB - T2, N0, M0 Stage IIA - T3, N0, M0 Stage IIB - T1-3, N1, M0 Stage III - T4, Any N, M0 Stage IV - Any T, Any N, M1

Management

Operable	Stage I and III - no metastases outside abdomen, liver, peritoneal structures, and no involvement of hepatic artery, sup. mesenteric artery, portal vein at body of pancreas. Radical pancreatic resection ± postoperative 5-FU chemotherapy and radiation therapy. 20% of head of pancreas cancers can be resected. Options: Whipple’s procedure (pancreatoduodenectomy) for cure – 5% mortality. - removes the head and uncinate process of the pancreas, the duodenum, and the gallbladder. A portion of the stomach is often removed as well. Total pancreatectomy distal pancreatectomy + splenectomy, lymphadenectomy if carcinoma of midbody and tail of pancreas. Click here for surgery details
Inoperable	Stage III and IV -  ie involves liver, vasculature or regional nodes most body and tail cancers not resectable relieve biliary procedure: choledochoenterostomy, gastroenterostomy
Palliative	Goal; Relieve pain, biliary and duodenal obstruction combination chemotherapy(gemcitabine/5-FU)/radiotherapy for palliation, ↑ survival
Pancreatic enzyme replacement	in patients with malabsorption caused by exocrine insufficiency
Follow-up	Physical exams, Blood studies, including CA 19-9 Periodic imaging studies, usually CT scans at 6-month intervals or earlier if needed to assess new symptoms

Complications
Diabetes mellitus, malabsorption
Surgical complications: Intraabdominal abscess, postgastrectomy syndromes, pancreaticojejunostomy, gastric and biliary anastomotic leaks; operative mortality varies from 1–16%.

Prognosis
average survival – 7months
5 year survival 10%
following whipple’s procedure, mean survival – 18 months
most important prognostic indicator is lymph node status.