Pancreatic cancer

Pancreatic cancer, of which pancreatic adenocarcinoma is the most common histological type, is a malignancy with one of the highest mortality rates. It’s aggressive, causes no early symptoms, and is difficult to treat. It mostly affects elderly men.

Pancreatic cancer is the 10th most common cancer, but the fourth leading cause of cancer mortality. About 85% of cases are irresectable at the time of diagnosis due to being metastatic or locally advanced. It responds poorly to chemotherapy and grows quickly. The overall 5-year survival for all patients (regardless of stage) is < 5%, and even in the early stages the median survival is 2 years.

Etiology

• Smoking
• Chronic pancreatitis
• Alcoholism
• Obesity

Pathology

Pancreatic adenocarcinoma accounts for almost all malignant exocrine pancreatic cancer (the remaining being acinar adenocarcinoma and mucinous cystadenocarcinoma). Adenocarcinomas originate from epithelial cells of the pancreatic tubules.

60% of cases are located in the head of the pancreas, with the remaining 40% being spread evenly throughout the body and tail.

Stages

• Resectable disease
  • 15% present in this stage
  • Median survival of 20 – 24 months
• Locally advanced (unresectable) disease
  • 25% present in this stage
  • Median survival of 8 – 12 months
• Metastatic disease
  • 50% present in this stage
  • Median survival of 6 – 12 months

Clinical features

Pancreatic cancer generally causes no symptoms in the early stage, which contributes to the late diagnosis. Tumours in the pancreatic head cause symptoms earlier than tumours in the body or tail.

When symptoms do occur, jaundice, weight loss, anorexia, abdominal pain, vomiting, and constitutional symptoms may occur. Delayed gastric emptying occurs in up to 60% of people with pancreatic cancer and may contribute to the symptoms of anorexia and vomiting. Obstruction of the biliary tract is what leads to jaundice.

Invasion of nearby structures can cause chronic severe abdominal pain, usually belt-like and located to the epigastrium.

Courvoisier sign may be present. It refers to an enlarged, nontender gallbladder with painless jaundice. This contrasts with cholelithiasis, in which the gallbladder is tender.

Trousseau syndrome may also be present. It refers to a migratory, superficial thrombophlebitis.

Diagnosis and evaluation

Abdominal ultrasound is often the first investigation used in patients presenting with jaundice or epigastric pain. US is highly sensitive for pancreatic masses, and will show an echopoor lesion.

Contrast CT or MRI is required for proper staging and to determine whether it’s resectable or not. Pancreatic cancer is hypodense on CT. It will also show any distant metastases. CT of the thoracic cavity is also indicated to look for metastases.The tumour marker CA 19-9 may be elevated; if it is, it may be used for follow-up. Liver enzymes may be elevated if cholestasis has occurred.

The diagnosis requires histological confirmation, which is acquired by biopsy in most cases. However, if the suspicion is high and the mass appears to be resectable, the patient may skip biopsy and proceeds directly to surgery, where the diagnosis is made by intraoperative frozen sections.

Treatment

Even with curative treatment, the survival rate of pancreatic cancer is poor. Few patients have resectable disease at the time of diagnosis. Surgery is the only potentially curative treatment.

Curative modalities

There are two options for surgical treatment of pancreatic head tumours, conventional pancreaticoduodenctomy (Whipple procedure), and pylorus-preserving pancreaticoduodenectomy. Both should be combined with regional lymphadenectomy.

For resectable tumours in the body or tail of the pancreas, an extended distal pancreatectomy is performed, usually with splenectomy.

If the tumour is borderline resectable, neoadjuvant chemotherapy may be used in an attempt to achieve resectability. Adjuvant chemotherapy is frequently used, usually with gemcitabine or 5-FU, combined with erlotinib. Radiotherapy is not frequently used.

Palliative surgery for pancreatic and periampullary tumours

Many cases of pancreatic and periampullary cancer are irresectable and therefore incurable. Palliative surgery is therefore common.

Palliative surgery may be indicated for jaundice or gastric outlet obstruction in people with irresectable pancreatic cancer. These are usually managed with the placement of stents into the obstructed biliary tree or obstructed duodenum with ERCP. In case stent placement is impossible or insufficient, a bypass operation may be necessary.

Palliative double bypass operation involves hepaticojejunostomy and gastrojejunostomy, i.e., diverting biliary flow to the jejunum rather than the duodenum, and diverting food passage to the jejunum as well.

Non-surgical palliative treatment

Pancreatic cancer pain usually requires opioid analgesics. Because the tumour may be close to the coeliac plexus, drugs effective against neuropathic pain may be used as adjuvants.

A permanent coeliac ganglion block (coeliac plexus neurolysis) can be used for pain management in case pharmacological therapy is insufficient. This involves radiographically guided puncture of the coeliac ganglion, followed by installation of ethanol, which destroys the nerve tissue permanently. Injection of a local anaesthetic instead produces temporary pain relief (and is mostly used for chronic pancreatitis).

Chemotherapy (with gemcitabine and erlotinib) may also be used for palliative therapy.

Prognosis

Pancreatic adenocarcinoma is very aggressive. Metastases are often present upon diagnosis. It frequently invades local structures and can even invade the portal vein itself. If the tumor invades other structures locally is it frequently considered inoperable. The 5-year survival rate is less than 5%. ‎