The poor outcome of pancreatic cancer (PC) is reflected by the overall less than 5% five year survival. Eighteen hundred people are diagnosed with PC every year in Australia. Approximately 33,730 new cases were expected to be diagnosed in USA in 2006 with 32,300 expected deaths. Mortality closely follows incidence as demonstrated in the 2002 Australian graph (page 2). However, appropriate attention to certain risk factors has the potential to reduce mortality by early diagnosis. Pancreatic cancer is rare before the age of 45 and slightly more common in the male than in the female (1.3:1).
Hereditary factors: Family history is found in 7-8 % of patients and increases the risk by 13 fold in the relatives. Hereditary chronic pancreatitis , associated with abnormal tripsinogen gene, carries 40% risk of developing PC by the age of 70. Other familial cancer syndromes include (BRCA1 and BRCA2 gene mutations) in hereditary breast and ovarian syndromes, familial atypical multiple mole melano- ma syndrome (DKN2A mutation), Peutz Jeghers syndrome, Ataxia-telengiectasia syndrome and Lynch II syndrome (non-site specific hereditary colorectal cancer syndrome).
Diabetes: Diagnosis of type 2 diabetes often precedes diagnosis of PC by 2 years and such diabetes is believed to be induced by PC rather than the other way round. Hence it is important to image pancreas when type 2 diabetes is diagnosed after the age of 50.
Environmental factors: The relative risk of developing PC is 2.5 for smokers. Increased risk is also associated with a BMI of 30 or greater and decreased physi- cal activity. The role of alcohol, coffee, diet, aspirin and NSAID remains undecided. Partial gastrectomy could precede diagnosis of PC by 15-20 years and increases risk by 2.5 fold. Role of previous cholecystectomy and H.Pylori is uncertain.
Clinical features: Jaundice associated with pain is usually seen with unresectable PC. Painless jaundice is often seen in resectable cancer. Other features include steatorrhoea, weight loss, palpable mass and ascites. The differential diagnosis of pancreatic mass includes chronic pancreatitis and autoimmune pancreatitis which requires endoscopic ultrasound (EUS) guided biopsy to differentiate.
Diagnosis and staging: Jaundice is obvious in some cases, LFTs are often abnormal and Ca 19.9 is elevated. Ca 19.9 has a sensitivity and specificity of 80-90 %. Ultrasound (US) is often done first which may demonstrate a pancreatic mass depending on the amount of gas in the bowel and intestine. CT scan is a superior investigation of pancreas than US. Helical triple phase CT angiography is specifically useful in determining involvement of mesenteric artery and vein in addition to determining encasement of the portal vein, coeliac axis and hepatic artery. More than 25% encasement of these vessels precludes surgery. While some surgeons prefer not to obtain CT guided biopsy of the pancreatic mass, endoscopic ultrasound (EUS) has high sensitivity and specificity for fine needle aspiration of the primary pancreatic tumour as well as staging information for peripancreatic lymph nodes. While MRCP (magnetic resonance cholangiopancreatography) could give non-invasive information regarding the pancreatic and biliary ducts, ERCP provides the same information with the additional therapeutic capability to relieve exclude peritoneal metastasis not uncommonly missed by CT scan. Laparoscopy does not exclude vascular involvement but aids staging.
Surgery: Curative resection is attempted in 14% of patients. If at surgery, the lesion is found to be unresectable, then the surgeon may choose to palliate with anastomosis of the GB or the bile duct to a loop of jejunum for drainage. Palliative: If the tumour is deemed to be unresectable preoperatively, gastroenterologist could drain the bile duct and relieve jaundice with a self-expanding metal stent placed in the bile duct across the tumour in the pancreatic head at ERCP. In case of impending obstruction of the pylorus or duodenum, gastroenterologist could also prevent gastric outlet obstruction by placing a further metal stent in the duodenum or across the pylorus.
Pain control: Chemical intraoperative splanchnicectomy or percutaneous coeliac axis block are better options than narcotic analgesics which have various side effects.
Exocrine pancreatic insufficiency: is treated with pancreatic enzyme supplementation with meals.
Chemoradiation: 5 Flurouracil and radiation or Gemcitabine for adjuvant or palliative therapy has been used.
Screening tests for persons at risk: American Gastroenterology Association AGA) recommends screening should be initiated for persons at risk 10 years before the diagnosis of PC in the index relative and after 35 yr of age in patients with hereditary chronic pancreatitis. Although no clear benefit has been estab- lished, helical CT followed by endoscopic ultrasound supplemented with Ca19.9 and CEA has been recommended. The role of islet amyloid polypeptide found in plasma in increased concentrations is being investigated for early detection of pancreatic cancer.
Recommended further reading:
1.M.Steer:Clinical manifestations ,diagnosis and surgical staging of exocrine pancreatic cancer:Uptodate(14.2):www.uptodate.com:1-16,April 2006.
2.AGA guideline:epidemiology diagnosis and treatment of pancreatic ductal adenocarcinoma: Gastroenterology 1999:117:1463.
3.AGA technical review:epidemiology, diagnosis and treatment of pancreatic ductal adenocarcinoma:gastroenterology 1999:117:1464.