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Sunday November 6, 2011

Pancreatic cancer: A silent killer

It only hits about one person in 100,000, but when it does, it develops so quietly that many don’t stand a good chance of survival at all.

IT is a relatively rare form of cancer, but when it strikes, it infiltrates the body silently, and quietly siphons off the resources of the pancreas without triggering any alarm bells until it is usually too late.

Not only does pancreatic cancer usually only shows symptoms at a late stage in the disease, but the symptoms that are commonly presented are also very vague, leading to the patient going on a merry-go-round of doctor visits before finally receiving the correct diagnosis.

According to consultant gastroenterologist Dr Sharmila Sachithanandan, most patients are usually only diagnosed accurately around five to seven years after they first see a doctor with their symptoms.

In addition, consultant oncologist and radiotherapist Dr Matin Mellor Abdullah says that pancreatic cancers are “quite aggressive cancers”.

Dr Sharmila points out the position of the pancreas in the human digestive system. The pancreas is responsible for producing certain hormones and our digestive juices. – IBRAHIM MOHTAR/The Star

“For those with metastasised pancreatic cancer (where the cancer cells have spread beyond the pancreas), most patients are dead within two years.

“Very, very few survive to five years. Even two years is quite optimistic,” he says.

The good news is that pancreatic cancer is quite rare, compared to other types of cancers. According to the Malaysian Cancer Registry’s latest report in 2006, there was a total of 253 cases of pancreatic cancer diagnosed in that year. This is in comparison to the total of 21,773 cancer cases.

And while cancer is likely to strike approximately 109.8 people per 100,000, only 1.3 of those people are likely to get pancreatic cancer.

According to Dr Matin, there is no typical profile of a pancreatic cancer patient. “I’ve seen people who are very physically well get it,” he says.

An endoscopic ultrasound-guided biopsy of a pancreatic mass. The EUS is the best imaging tool to pick up and stage cancer of the pancreas .

But the disease is generally one of old age. In Selayang Hospital, Selangor, which is the national referral centre for hepatopancreatobiliary (liver, pancreas and bile duct) surgery, the most common age group of pancreatic cancer patients is that of 60-69 years.

The hospital, which has seen an average of about 250 cases a year for the past decade, has also treated two times more men than women for the disease. There does not, however, appear to be any difference in the ethnicity of the patients.

Different cells, different cancers

There are two main types of pancreatic cancer. The most common type, accounting for about 95% of cases, are those arising from the exocrine cells of the pancreas, and are mostly comprised of adenocarcinomas.

Pancreatic exocrine cells are the most common type of pancreatic cell, and serve to produce pancreatic juices filled with enzymes that help digest the food we eat.

Dr Matin says: “Depending on the location (of the tumour), the symptoms are different. If it is at the body or the tail of the pancreas, it may be asymptomatic. If it is at the head of the pancreas, it may block the common bile duct, and cause jaundice.”

Jaundice is a condition where patients develop a yellow tinge to their skin, and even the whites of their eyeballs, when there is too much bilirubin in the body.

In cases that do not present with jaundice, symptoms usually only start appearing after the tumour has grown large enough to break through the cover of the pancreas, says Dr Matin.

Dr Matin... There is no typical profile for a pancreatic cancer patient, although it mostly hits older people. - RAJA FAISAL HISHAN/The Star

“The presentation is usually pain; most of the time, abdominal pain associated with loss of weight and loss of appetite,” he says.

Abdominal pain is associated with many other medical conditions, although loss of weight and loss of appetite are generally symptoms of cancer.

The other rarer form of pancreatic cancer is that arising from the endocrine cells of the pancreas.

These cells are found in small clusters, or islets, also called islets of Langerhans, throughout the pancreas. Their main function is to produce various hormones like insulin and glucagon.

Tumours arising from these cells are called neuroendocrine tumours (NETs), or islet cell tumours. They can be further divided into functional and non-functional tumours.

Functional tumours continue to produce hormones, whereas non-functional tumours do not.

While most cases – like the pancreatic adenocarcinomas – usually don’t show any symptoms until the cancer is already at an advanced stage, functional NETs present with symptoms from hormonal excess.

According to Dr Sharmila, patients with NETs can also display symptoms like flushing, wheezing, breathlessness and diarrhoea, among others, which – as with abdominal pain – are also common symptoms of other medical conditions. (See Misleading signs)

She adds that there is also another type of pancreatic tumour that arises from fluid-filled cells called cysts. These are called cystic neoplasms of the pancreas.

“Simple cysts and serous cysts are benign, but there are a group of cysts filled with mucin – a jelly-like substance – that have the potential to become malignant in 10-20 years’ time.”

She says that these cysts, if detected, need to be operated on and removed if they exceed three centimetres in diameter, because of this cancerous potential.

Looking for the problem

With such vague symptoms, Dr Matin explains that most patients get picked up through screening tests that form a part of their medical work-up when they go to the doctor with their symptoms.

There are a few blood tests that can point the way to pancreatic cancer, like the liver function test (LFT), and tumour markers CA (cancer antigen) 19-9 and CEA (carcinoembryonic antigen).

However, Dr Sharmila cautions that they are not sure-fire indicators of pancreatic cancer.

“Tumour markers can be elevated in patients with pancreatic cancer, but even patients with pancreatic cancer may have normal tumour marker levels, and the converse is also true – normal patients can have high tumour markers.”

She adds: “Seventy percent of patients with pancreatic cancer may have high CA19-9 and CEA. It’s really about putting the whole jigsaw puzzle together – the patient’s medical history, physical examination, diagnostic tests, etc.”

Imaging studies, like a CT scan or ultrasound, is likely to follow blood tests, especially when a patient complains of abdominal pain.

Says Dr Matin: “For tummy pain, we usually pop a scope in to look for the problem.”

However, as an endoscope only visualises the throat, stomach and duodenum (first part of the small intestine), or the rectum and large intestines, depending on which way it goes in, it cannot pick up any lesions in the pancreas.

Even a CT scan might not be able pick up any signs of tumours in the pancreas, says Dr Matin. “You must be looking for pancreatic cancer, otherwise, you might miss it.”

The best imaging tool in picking up cancers of the pancreas is endoscopic ultrasonography (EUS).

“What is new for pancreatic cancer is endoscopic ultrasound, which is basically a combination of a stomach endoscope, which has an ultrasound transducer on its tip.

“The beauty of it is it can go very close to the pancreas (while in the stomach or duodenum), and visualise it through ultrasound,” says Dr Sharmila.

She adds: “We can also pass a needle through the scope and biopsy any pancreatic lesions, so that we can stage the cancer and get tissue samples.”

This is important, she says, as sometimes patients might have pancreatic lesions that appear to be cancer, but are actually something else, like tuberculosis, lymphoma or autoimmune pancreatitis.

There are also certain tests that are used when the patients is suspected of having a NET. This includes serum chromogranin A (CgA) and the Gallium-68 DOTATATE PET/CT scan.

According to Dr Sharmila, a high CgA can indicate the presence of a NET, but she cautions that the biomarker is also high in patients with liver or kidney problems.

Meanwhile, she says that the DOTATATE scan, which only become available in Malaysia in the past year, is now considered the gold standard imaging study for NETs, replacing the octreoscan.

“It can pick up an NET anywhere in the body, which the Gallium-68 isotope will cause to ‘light up’ in the PET/CT scan,” she explains.

Treatment options

As mentioned earlier, most patients are diagnosed too late into the disease for curative treatment to be an option.

For the lucky few who are caught early enough that their tumour is still confined to the pancreas, surgery is their first and best option.

Known as the Whipple procedure, this surgery removes the head of the pancreas, parts of the bile duct, duodenum and gallbladder, and usually, part of the stomach as well.

“With cancer, the most important thing is the first treatment. All other treatments after that are not as important.

“The first treatment is the one where the cure is tried — you must hit it, and hit it hard,” says Dr Matin.

He cautions, however, that while surgery is meant to be curative, “in real life, what you see on the scan might not reflect what is actually there, so when the surgeon goes in, it might be more extensive than they thought”.

He adds that even if all the cancer is removed, there might still be micrometastases, which are too small to be detected with the naked eye.

If surgery is not a viable option, then patients will be started on palliative treatment such as radiotherapy and chemotherapy.

Says Dr Matin: “What chemotherapy and radiotherapy hope to achieve is to extend the patient’s time from months to years, and to delay the symptoms from happening.

“We want to shrink the tumour as much as possible, and keep it as small as possible for as long as possible.”

Other supportive therapies include pain control and stenting the bile duct or duodenum, if necessary.

Dr Matin explains: “Because the pancreas is located retroperitoneally (at the back of the abdominal cavity), the cancer can erode into the back where the celiac nerve plexus lies, and cause a lot of pain.”

Therefore, patients who experience this require effective pain therapy by anaesthetists or pain experts.

For those whose jaundice is severe, an operation to insert a stent into the blocked common bile duct can relieve the jaundice and the symptoms, like itchiness, that come with it.

Those suffering from a blocked duodenum would benefit from the insertion of an enteral stent to open up the passageway between the stomach and the rest of the small intestine, so that they are able to eat.

If the stent does not work, they can opt for surgery to bypass the blockage in the duodenum.

Because the outlook for NETs is better than the exocrine tumours, doctors are much more aggressive in treating it, says Dr Sharmila.

“Even with metastases, surgeons remove as much of the primary tumour as possible,” she says.

This is because NETs are generally slow-growing, therefore, debulking the tumour gives more time to the patient. They also metastasise more slowly than the adenocarcinomas.

Other treatments include control of any hormonal imbalances and drug therapy.

According to Dr Sharmila, while patients with pancreatic adenocarcinomas are usually given a life expectancy of six months to two years, patients with NETs can live much longer than that.

Famous examples of those statistics would be actor Patrick Swayze, who lived up to 20 months after being diagnosed with pancreatic adenocarcinoma, whereas Apple Inc co-founder Steve Jobs survived his NET for about eight years, despite first trying alternative therapies.

However, doctors themselves must also keep in mind the possible differential diagnosis of pancreatic cancer.

That is why Dr Sharmila and a group of her colleagues from various related specialities, and public and private institutions, formed the NET Alliance Interest Group.

The group has worked over the past two years to come up with a booklet for doctors, outlining how to diagnose and treat NETs.

“The booklet is to alert doctors if their patients have unusual symptoms, for example, diarrhoea at night, or symptoms that are triggered by the consumption of alcohol or certain cheeses.”

> Worldwide NET Cancer Awareness Day will be celebrated this Thursday with the theme “Early detection for NET cancer”.

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