Pancreatic cancer

What do the terms tumour and cancer mean?

What do the terms tumour and cancer mean?

Carcinoma cells in a bile<br />sample taken at ERCP
Carcinoma cells in a bile
sample taken at ERCP

Every cancer starts off as a microscopic cluster of cells. These cells break free of the control mechanisms that prevent normal cells from multiplying endlessly. They keep multiplying, and then break out from their original source and grow into surrounding organs. They can also travel to other organs, to form colonies, which are called secondary tumours or metastases. Cancer cells can get into the blood circulation and spread to the liver, lungs, bones and nearly any other part of the body. Cancer cells can also travel along the lymph vessels to the lymph glands (lymph nodes).

If we say the cancer is multifocal, it means there are several cancer nodules present within the organ. We do not know if this is because it starts off as one tumour that then spreads within the organ via local blood vessels, or if several separate tumours start to grow at the same time.

The term tumour means a lump or a swelling, and can be used to describe cancerous and non-cancerous (benign) swellings. When a cancer is large enough to form a visible lump, the lump is called a cancerous or malignant tumour. Doctors may use the terms cancer, malignancy, neoplasm, growth and tumour interchangeably, to refer to the same entity or the same process.

The bulk of the pancreas is composed of exocrine cells. These make digestive juice that drains into the pancreatic duct. There are also some endocrine cells. These make hormones, and are clustered into little balls called the Islets of Langerhans. In discussing pancreatic tumours, it may be useful to break up the discussion into three headings:

  • Endocrine tumours (these are described here)
  • Cystic tumours (these are described here)
  • Carcinoma of the pancreas (Pancreatic cancer) (see below)
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How common is cancer of the pancreas (adenocarcinoma of the pancreas) and what causes it?

How common is cancer of the pancreas (adenocarcinoma of the pancreas) and what causes it?

This is now the sixth most common cause of cancer death in the UK, with around 7000 new patients diagnosed every year in this country alone. It is common in older people, with a peak incidence in the 65-75 years age-group. It is slightly more common in males, and in black people. Tobacco smoking increases the risk. Certain genetic factors and medical conditions can increase the risk of developing pancreatic cancer:

  • 5-10% of patients with pancreatic cancer have a family history of the disease. If one has two first-degree relatives with this cancer, one is at a higher risk of getting this disease, compared to the average population.
  • Some rare high-risk families may have a mutation of the BRCA2 gene.
  • The condition hereditary pancreatitis can increase the risk of cancer significantly (70-100 fold increased risk compared to the average)
  • Patients with chronic pancreatitis are at a15-25 fold increased risk
  • Certain other syndromes such as HNPCC, Ataxia telangiectasia, Peutz-Jeghers syndrome, Familial breast cancer and Familial atypical multiple mole melanoma
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Where in the pancreas does cancer commonly arise?

Where in the pancreas does cancer commonly arise?

Most of the cancers that arise in the pancreas start off from the lining of the ducts, and are called ductal adenocarcinoma. Interestingly 80-90% of these are in the head of the gland.

Other tumours that can arise here are cancers of the lower end of the bile duct, and cancers of the ampulla (that point in the bowel where the bile duct and pancreatic duct empty). While the treatment may be identical, their behaviour is quite distinct from pancreatic adenocarcinoma. Adenomas (largely benign tumours) of the ampulla show up at endoscopy as polyps. But they can harbour areas of invasive carcinoma; the larger the adenoma, the greater the risk. Biopsies taken at endoscopy may not always include the malignant focus. Endoscopic surveillance, endoscopic resection or even surgical removal should be considered, and the entire lump should be carefully examined by the pathologist. Patients with familial adenomatous polyposis (FAP), an inherited condition, can present with multiple duodenal polyps. Ampullary cancers often present with bile duct obstruction, and compared to pancreatic ductal adenocarcinomas, are relatively small when diagnosed, which may account for their better prognosis.

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What are the symptoms and signs of pancreatic cancer?

What are the symptoms and signs of pancreatic cancer?

Pancreatic cancer has a nasty habit of growing silently and showing itself when it has already gone past the operable stage. The symptoms are:

  • Obstructive jaundice i.e. yellow colour of the eyes and skin, itching of the skin, and passing dark urine
  • Weight loss with back pain
  • Recent-onset diabetes mellitus
  • Diarrhea with pale, greasy bulky stools
  • Unexplained attack of pancreatitis

On physical examination, especially if the disease has progressed a lot, one may find:

  • An abdominal mass
  • Ascites (fluid within the abdominal cavity)
  • Enlarged lymph nodes in the neck
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What tests are done to diagnose pancreatic cancer?

What tests are done to diagnose pancreatic cancer?

CT scan showing a tumour of the pancreatic head

Blood tests generally include liver function tests and the blood level of the tumour marker CA 19-9. The latter is a substance released by some pancreatic cancers. It can be raised in other conditions too, so it is not a foolproof way of diagnosing this cancer, but it is useful to know if the levels are high to begin with, as it can help us monitor progress later on.

Ultrasound is often the first scan carried out in these patients, and is useful in picking out those who have other causes for their obstructive jaundice, especially gallstones.

CT is the current “gold standard” test in most centres. It should be done with intravenous contrast given at the time of the scan.

In some centres, MRI and MRCP scans are used in lieu of CT, and the information obtained is very similar.

EUS (Endoscopic ultrasound) is used in situations where there is some doubt after a CT and/or MR. It provides close-up ultrasound pictures of the tumour and one can also take a biopsy at the same

ERCP and biliary stenting relieves the jaundice, and also can provide a brush cytology or biopsy specimen to confirm the diagnosis. ERCP and biliary stenting prior to surgery is not always necessary if the patient is going to have an operation very soon to remove the tumour. But it should be carried out if the tumour looks inoperable, if there is any suggestion of cholangitis (infection in the bile duct), if there is diagnostic doubt (small tumours of the ampulla may not be seen on CT, and ERCP is the best way to identify them) or if there is likely to be a delay between diagnosis and surgery and the patient is deeply jaundiced with distressing itching.

Diagnostic laparoscopy can pick up small peritoneal and liver deposits. It can be combined with laparoscopic ultrasonography.

FDG PET scans are not routinely used in the diagnosis of pancreatic cancers

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What is the treatment of pancreatic cancer?

What is the treatment of pancreatic cancer?

For the majority of patients with pancreatic cancer, by the time they develop symptoms and the diagnosis is made, their disease is too advanced to be cured by surgery. If scans shows that the tumour is potentially operable, then the patient should be considered for surgical resection, as that offers a chance of a cure. Age, other illnesses and overall fitness have to be taken into account. If a cystic tumour is encountered, no matter how large, surgical resection should be considered, as it carries a reasonable chance of cure. Tumours of the ampulla have a good prognosis and should, if at all possible, be resected. Some of the rare tumours and the neuroendocrine lesions should also be resected if at all possible. For those patients who have inoperable disease, palliative treatments are offered. These include chemotherapy and radiation (or occasionally both), and measures to relieve symptoms

Surgical resection
The standard resection for a tumour of the pancreatic head or the ampulla is a Pancreatoduodenectomy. Originally known as the Whipple operation (but now slightly modified), this involves removal of the pancreatic head, along with the duodenum and the lower part of the bile duct. Total pancreatectomy (removal of the entire gland) is warranted only in rare situations where one is dealing with multiple tumours within the gland, or the body and tail of the gland are very inflamed or friable. For tumours of the body and tail, distal pancreatectomy with splenectomy is the standard. This involves removal of the body and tail of the gland along with the spleen. When resecting the pancreatic tail for a benign lesion, the surgeon may attempt to preserve the spleen if possible. See below for more information on these operations.

Attempts to shrink down inoperable disease with chemotherapy or chemoradiation and render it operable are rarely successful.

Resectional surgery for pancreatic cancer should be carried out in specialist units. There is a clear correlation between higher caseload volume and lower hospital mortality and morbidity. The operation should carry a mortality rate of no more than 3-5%. But around a third of patients develop a complication in the postoperative period. These complications are usually infective, but a leak from the anastomosis between the pancreas and the bowel is known to occur in at least 10% of patients, and this can give rise to major complications. Mean in-patient stays range from 12 to 16 days.

Adjuvant treatment after surgery
With surgery alone, the 5-year survival following resection of a pancreatic adenocarcinoma ranges around 10-20%, and figures of upto 25% have been reported. Patients with resected ampullary tumours have 5-year survivals of 40-50%, and cystic tumours and neuroendocrine tumours can often be cured by surgical resection.

The high recurrence rate following resection has inevitably led to the consideration of additional (adjuvant) treatments to try and improve the outcome after surgery. The role of adjuvant radiotherapy and chemotherapy after resection has been addressed in several studies, with conflicting results. Most patients with resected ductal adenocarcinoma are now offered adjuvant chemotherapy, on the basis of the ESPAC1 trial that showed improved survival. Some centres continue to offer chemoradiotherapy, particularly in patients who may have had a small part of the tumour left behind, and further trials of adjuvant chemoradiation are in progress.

If inoperable disease is found in the course of an operation that was commenced with the intent to remove the tumour, a choledocho-enterostomy (diversion of the bile flow into the gut) and a gastro-enterostomy (diversion of the flow of food, bypassing the duodenum) can be carried out, to relieve jaundice and duodenal obstruction.

In patients found to have unresectable disease on scans, jaundice is relieved by stenting at ERCP. Plastic stents tend to block faster, and if the patient is likely to have a longer life-expectancy, a self-expanding mesh metal stent can be used. If the patient is not a suitable candidate for endoscopic stenting, a percutaneous transhepatic stent can be placed. This involves puncturing the skin and placing a stent through the liver substance, and is done in the X-ray department.

Obstruction of the duodenum occurs in approximately 15% of cases; if this occurs early in the course of the disease, surgical bypass by gastrojejunostomy is appropriate, but if it is late in the course of the disease then the use of expanding metal stents inserted endoscopically should be considered.

If no operative procedure is undertaken, biopsy of the tumour should be performed before consideration of chemotherapy or chemoradiation. The role of chemotherapy in the management of pancreatic cancer remains ill-defined. For the patients with ductal adenocarcinoma, 5-FU or gemcitabine will produce a remission in 15-25% of patients. No long-term cures have been described with chemotherapy or radiotherapy.

Steatorrhoea (diarrhea due to enzyme deficiency) is treated with enzyme supplements. Diabetes mellitus, if it develops, is treated with tablets or insulin as appropriate, and pain with analgesics or an appropriate nerve block.

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These treatment options are described here in a very general sense, and individual patients should discuss their treatment with their own medical team.
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