Clinical FeaturesOncology

Pancreatic Cancer: A Public Health Burden

The global incidence and mortality of pancreatic cancer are increasing annually. Worldwide, the incidence is projected to rise to 18.6 per 100,000 by 2050, with the average annual growth of 1.1%, indicating that pancreatic cancer will pose a significant public health burden.

Theresa Lowry Lehnen, Clinical Nurse Practitioner and Associate Lecturer South East Technological University told us more about the 12th most common cancer worldwide.

Pancreatic cancer is the 11th most common cancer in women, and the 12th most common in men. Theresa notes, “Globally there were more than 495,000 new cases of pancreatic cancer in 2020, and it affects over 600 people in Ireland annually. Despite rapid advances in modern medicine and significant improvements in survival rates of many cancers, pancreatic cancer is still a highly fatal gastrointestinal cancer with difficulty in early detection, and a low 5-year survival rate.

“Pancreatic cancer 5-year survival rates range from 2% to 9%, with little difference between high and low-income, and middle-income countries. The 5-year survival rate varies globally in different regions and countries, but does not exceed 10%. It is predicted that patients with non-operative pancreatic cancer have a lower 5-year survival rate.

“The estimated global, 5-year survival rate for pancreatic cancer is about 5%. Approximately 90% of all cases are among people over 55 years of age, and the incidence rates for both genders increases with age. Surgical resection is the only current option for a cure, however, only 20% of pancreatic cancer is surgically resectable at the time of diagnosis.”

Aetiology and Risk Factors

The aetiology of pancreatic cancer is poorly understood, Theresa says. 95% of tumours carry mutations in the K-RAS2 proto-oncogene, the activation of which leads to increased cell proliferation, loss of the normal response to apoptotic signals, dysplasia and ultimately cancer. In the pancreas, K-RAS mutations tend to cause the development of precancerous lesions called pancreatic intraepithelial neoplasia (PIN), which are present in up to a third of older people, but will only lead to cancer in about 1% of cases. It is estimated that it takes up to 20 years from the time of the first mutation to develop the fullblown disease.

Many non-modifiable and modifiable risk factors are associated with pancreatic cancer.

• Age older than 55 years

• Smoking

• Diabetes

• Obesity

• Chronic pancreatitis

• Cirrhosis of the liver

• Helicobacter pylori infection

• Work exposure to chemicals in the dry cleaning and metalworking industry

• Gender-more common in males than females

• Ethnicity-more common in African Americans than Caucasians

• Family history

• Blood group A patients have a 40% higher risk than those with other blood types

• Pancreatic microbiota

Presentation and Diagnosis

Theresa explains, “Symptoms of pancreatic cancer include; pain or discomfort in the abdomen, which may spread to the back; unexplained weight loss; indigestion; jaundice; loss of appetite; nausea; feeling full very quickly; a lasting change in bowel habits-steatorrhea; a new diagnosis of diabetes without weight gain; and tiredness.

“Sometimes there may be no signs or symptoms in the early stages of pancreatic cancer. Diagnostic tests include, history, examination, laboratory tests, transabdominal ultrasound, abdominal CT scan, PTC (percutaneous transhepatic cholangiography), MRCP scan (magnetic resonance cholangiopancreatography), Endoscopic Ultrasound (EUS), Laparoscopy and Biospy.

“General examination may reveal jaundice, pallor, skin excoriations or weight loss/cachexia. Abdominal examination may reveal epigastric tenderness; an upper abdominal mass; nodular hepatomegaly; ascites; and a palpable gallbladder. Courvoisier’s law states that the presence of a non-tender enlarged gallbladder means that jaundice is unlikely to be due to gallstones, as chronic cholecystitis causes the gallbladder to become shrunken and fibrotic. A palpable gallbladder is, therefore, a worrying sign. There may also be cervical lymphadenopathy.

“Patients with adenocarcinoma of pancreas typically present with painless jaundice (70%) usually due to obstruction of the common bile duct from the pancreatic head tumour. Weight loss occurs in about 90% of patients and abdominal pain in about 75%.

Weakness, pruritus from bile salts in the skin, anorexia, palpable, non-tender, distended gallbladder, acholic stools, and dark urine may be present. Patients may present with recent-onset diabetes, and sometimes may present with recurrent deep vein thrombosis (DVT) due to hypercoagulability that prompts clinicians to suspect cancer and a full workup.

“Blood tests include, FBC, U+E, LFTs, coagulation-studies, glucose, and lipid-profile.”

Staging investigations for patients with confirmed pancreatic cancer include:

• Triple-phase “pancreas protocol” CT scan is the gold standard for assessment of pancreatic cancer. By taking images at different times after IV contrast administration, it provides detailed imaging of the tumour itself, its invasion into surrounding tissues, the degree of vascular infiltration and biliary tree dilatation, and presence of lymphatic or liver metastasis. It can be used to accurately predict surgical resectability in up to 90% of cases.

• Bone scan or PET scan can accurately detect distant metastases.

• Diagnostic laparoscopy is used to rule out intraperitoneal spread in high-risk patients.

• Biopsies for histopathology can be obtained percutaneously, endoscopically via EUS/ERCP, or laparoscopically and in some cases through an open procedure. Endoscopic biopsy is considered to be the safest and most appropriate approach. 8 Differential diagnosis includes acute pancreatitis, chronic pancreatitis, cholangitis, cholecystitis, choledochal cyst, peptic ulcer disease, cholangiocarcinoma, and gastric cancer.

Treatment and Management

Treatment for pancreatic cancer includes surgery, chemotherapy and radiotherapy. Theresa continues, “The treatment and management of pancreatic cancer is determined by whether the tumour is resectable or not, but other important factors include the patient’s overall health and fitness for major surgery and postoperative chemotherapy.

“There are surgical treatments available for both resectable cancers and palliate unresectable disease, and these are supported by the use of adjuvant medical therapies such as chemoradiotherapy and pain control measures. If the pancreatic adenocarcinoma is considered locally advanced it is unresectable, and neoadjuvant treatment with chemotherapy and/or radiation is typically preferred in this situation.

“There is a role for radiation therapy in combination with chemotherapy to treat locally advanced pancreatic cancer. Radiation therapy was originally used to alleviate the pain, but its use is now more widespread to shrink tumours and increase survival.

“Pylorus-preserving pancreaticoduodenectomy (Modified Whipple): Localised tumours in the head of the pancreas or periampullary region are suitable for pylorus-preserving pancreaticoduodenectomy, more commonly known as the modified Whipple procedure. It involves removal of the head of the pancreas, most of the duodenum, the common bile duct and the gallbladder, with or without extended dissection of additional lymph nodes.

“The traditional Whipple’s procedure also includes removal of the pylorus and antrum of the stomach, which is still occasionally necessary depending on the extent of the tumour. If the portal or superior mesenteric veins are involved, they can also sometimes be resected and reconstructed using vein grafts. Once the above organs have been resected, the functional anatomy of the upper GI tract must be restored so the patient can still digest and absorb food.

“This is done by creating a Roux-en-Y loop from a segment of jejunum, and using end-toside anastamoses to make a pancreaticojejunostomy to drain pancreatic juice into the small bowel; a hepaticojejunostomy to drain bile into the small bowel, and a duodenojejunostomy to restore GI tract continuity. This is normally done via a large abdominal “rooftop” incision, but some centres do it laparoscopically. The Whipple is a high-risk procedure requiring careful pre-operative work-up and intensive post-operative monitoring and management.

“Complications of the Whipple procedure include bleeding, sepsis, bile and pancreatic leakage, anastamotic failure, delayed gastric emptying, and nutritional problems, and patients often remain in hospital for weeks or months while they recover. Patients require long-term pancreatic enzyme replacement in the form of Creon tablets taken with food. Five-year survival for patients with ductal carcinomas is 10-20%, and 40% for patients with other types of pancreatic cancer.

“Distal Pancreatectomy: Patients with localised tumours in the body or tail of the pancreas are suitable for a distal pancreatectomy. This involves removal of the body and tail of the pancreas as well as the spleen. Distal pancreatectomy is a more straightforward procedure than the Whipple and can be done openly or laparoscopically.

“Complications are less frequent but include bleeding, sepsis, pancreatic leakage and pancreatic endocrine insufficiency resulting in diabetes. As the procedure involves a splenectomy, these patients are also at lifelong risk of potentially fatal overwhelming postsplenectomy infections (OPSI).

“Total pancreatectomy: Rarely, patients with localised tumours in or involving the neck of the pancreas, or diffuse cancers such as intraductal papillary mucinous neoplasm (IPMN) may be offered a total pancreatectomy. Complication rates are similar to a Whipple procedure, but with the added risk of post-splenectomy sepsis, and lifelong insulindependent diabetes, which can be difficult to manage.

“Palliative Surgical Treatments: Patients presenting with obstructive symptoms secondary to inoperable pancreatic cancer may be offered palliative surgical treatments to help control their symptoms. Biliary obstruction and jaundice is common in advanced disease. It leads to malaise, abdominal pain and severe pruritis, and can also put patients at risk of death from cholangitis, renal failure and severe coagulopathy.

“Management options include biliary stenting, endoscopically via an ERCP, or percutaneously using radiological transhepatic techniques, and biliary bypass surgery with choledochojejunostomy, hepaticojejunostomy or sometimes a palliative ‘Whipple’ procedure. Duodenal obstruction is common and presents with symptoms of gastric outlet obstruction such as epigastric pain and profuse nonbilious vomiting. It can be treated endoscopically with duodenal stenting, or gastric bypass surgery using a gastrojejunostomy or Roux-en-Y bypass.

“Pancreatic duct obstruction can lead to pain and malabsorption. It can be treated with endoscopic pancreatic stenting or sometimes with pancreaticoduodenectomy.”

Theresa adds that pain is a significant problem in patients with pancreatic cancer and is generally managed with opiate analgesia, neuropathic adjuncts and the management of obstructive symptoms. “Medical therapies for exocrine cancers may be used as adjuncts to surgery, or as a primary palliative treatment in advanced disease. Patients with unresectable disease may be offered palliative chemotherapy. Although most pancreatic tumours are chemoresistant, gemcitabinebased regimes can delay disease progression and improve survival in patients with reasonable performance status.

“Radiotherapy can help with pain control, but does not improve survival. Pancreatic enzyme supplementation with Creon tablets can help with malabsorption and weight loss. Advanced metastatic cancer requires individualised palliative treatment with chemoradiotherapy and symptom control. Unresectable or metastatic functional endocrine tumours except for somatostatinomas can be managed medically with somatostatin analogues, which act to control symptoms by suppressing pancreatic hormone secretion.”

Theresa concludes that, “Despite major scientific and medical advances, mortality rates for pancreatic cancer have not improved much since the 1970s. Pancreatic cancer rates continue to rise, and will cause a major economic burden for all countries and related populations in the next two decades. A global prevention and control strategy for pancreatic cancer must include effective tobacco-control policy, recommendations for healthier lifestyles, increased screening, vaccination programmes, and education to improve public awareness and the need to take precautions.”

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