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Pancreatic cancer: Can it be cured?

Posted Mar 28 2012 10:13am

This article overviews the symptoms and latest treatments for pancreaticRelating to the pancreas. cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. and discusses why screeningA way to identify people who may have a certain condition, among a group of people who may or may not seem to for this life-threatening disease may not be an option.

Pancreatic cancer is the fifth leading cause of cancer-related death in the United Kingdom with more than 8000 new cases diagnosed every year. The prognosis of pancreatic cancer has historically been very poor with approximately 3% of patients alive five years after diagnosis. Surgical resection remains the only potentially curative option and is associated with a 5-year overall survival rate of between 10 and 15%, but can only be performed in less than 20% of cases. This is primarily because the cancer is either too advanced locally, or it has already spread to other organs, particularly to the liverA large abdominal organ that has many important roles including the production of bile and clotting factors, detoxification, and the metabolism of proteins, carbohydrates and fats. with metastasesSecondary tumours’ that result from the spread of a malignant tumour to other parts of the body..

The reason for such a low operability rate is related to the very menacing nature of this cancer which frequently becomes manifest when it is too late to intervene surgically. The symptoms are often non-specificHaving a general effect. and include stomach and back pain, lack of appetite and weight loss; but late onset of diabetesA disorder caused by insufficient or absent production of the hormone insulin by the pancreas, or because the tissues are resistant to the effects. and acuteHas a sudden onset. pancreatitisInflammation of the pancreas, a gland behind the stomach that produces digestive enzymes and the hormones insulin and glucagon. can also be caused by pancreatic cancer. When the tumourAn abnormal swelling. is located in the head of the pancreas it can narrow the bile duct and cause jaundiceA term used to describe a yellow tinge to the skin and a yellowing of the whites of the eyes. It is caused by a build up of bilirubin in the blood., with yellow discoloration of the skin, dark urine pale stools and itching.

Several risk factors have been identified in cancer of the pancreas, and smoking remains the strongest link. A recent study demonstrated that approximately one third of pancreatic cancers in the UK in 2010 were caused by smoking. Other risk factors include diabetes, obesityExcess accumulation of fat in the body. and chronicA disease of long duration generally involving slow changes. pancreatitis (frequently caused by excessive alcohol consumption). A weaker association has also been found with Crohn’s Disease, periodontal diseaseGum disease., a diet rich in processed meat and in people with a history of gastric ulcers. People with at least one first-degree relative diagnosed with pancreatic cancer have almost double the risk of someone without a family history of pancreatic cancer.

Early diagnosis is vital as demonstrated by the correlation between stage of the tumour and survival in the table below. Unfortunately screening is not a feasible option as the incidenceThe number of new episodes of a condition arising in a certain group of people over a specified period of time. of pancreatic cancer is very low compared to other cancers, like breast or bowelA common name for the large and/or small intestines. cancer. Screening would not be cost effective and it would also require invasive diagnostic modalities, which in themselves carry a risk. To date there is not a national screening programme for pancreatic cancer and prompt investigation of suspicious symptoms remains the best chance for an early diagnosis.

Stage Classification 5-year survival
IA Tumour ≤ 2 cm limited to the pancreas 16%
IB Tumour > 2 cm limited to the pancreas 14%
IIA Tumour ≤ 2 cm limited to the pancreas
Regional lymphA watery or milky bodily fluid containing lymphocytes, proteins and fats. Lymph accumulates outside the blood vessels in the intercellular spaces of the body tiisues and is collected by the vessels of the lymphatic system. node metastasisThe spread of a malignant tumour to other parts of the body.
8%
IIB Tumour limited to the pancreas or spread beyond without involving bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. vessels
Regional lymph node metastasis
6%
III Tumour spread beyond pancreas involving blood vessels
With or without regional lymph node metastasis
3%
IV Tumour limited to pancreas or spread beyond, with or without involvement of blood vessels
With or without regional lymph node metastasis
Distant metastasis

1%

In general, those patients treated with surgery survived longer, while those not treated with surgery fared worse. However, only about one of every six patients can be treated with surgery.

 

An abdominalRelating to the abdomen, which is the region of the body between the chest and the pelvis. ultrasoundA diagnostic method in which very high frequency sound waves are passed into the body and the reflective echoes analysed to build a picture of the internal organs – or of the foetus in the uterus. and baseline blood tests are usually the first tests requested by GPs but their sensitivity is low. A special blood tumour marker known as CA 19-9, is high in two thirds of patients with pancreatic cancer. A contrast enhanced CTThe abbreviation for computed tomography, a scan that generates a series of cross-sectional x-ray images scan is the gold standard pancreatic screening test if a reasonable suspicion exists.

Figure 1. An ERCP showing stricture of the lower part of the bile duct; a mesh metal stent has been inserted endoscopically to relieve the jaundice in a patient with locally advanced pancreatic cancer

In jaundiced patients, a special MRIAn abbreviation for magnetic resonance imaging, a technique for imaging the body that uses electromagnetic waves and a strong magnetic field. scan called Magnetic Resonance Cholangiopancreatography (MRCP) can demonstrate the level of the bile duct obstruction. Most of these patients will require a camera test, called Endoscopic Retrograde Cholangiopancreatography (ERCPAn abbreviation for endoscopic retrograde cholangiopancreaticogram.), to stentA tube placed inside a tubular structure in the body, to keep it patent, that is, open. the bile duct (with a plastic or a mesh metal stent) and relieve the jaundice, either as a preliminary step prior to surgery or as definitive treatment in inoperable patients (Figure 1). Cellular material can also be obtained to confirm a cancer diagnosis (known as brushing cytologyThe study of cells, in medicine used to mean examination of cell samples under a microscope.). There are cases, however, where the diagnosis is uncertain, either because a definite mass cannot be identified on a CT scan or because the features of the lesiona general term to cover any abnormality such as a wound, infection, abscess or tumour. are not entirely typical for pancreatic cancer. In these cases a biopsyThe removal of a small sample of cells or tissue so that it may be examined under a microscope. The term may also refer to the tissue sample itself. is recommended and commonly done by Endoscopic Ultrasound (EUS). In this procedure, an endoscopic probe is deployed in the stomach and the tumour is visualised and biopsied. A percutaneousUsually related to medical procedures; entering the body through the skin. biopsy, usually done by the radiologists under CT or ultrasound scanThe process of using high-frequency sound waves to produce internal images of the body., should be performed only in patients with clearly inoperable or metastatic disease because of the potential risk of needle track seedingA complication arising from a biopsy whereby the tumour cells are released into the surrounding tissues.. A Positron Emission Tomography (PET) scan, a nuclear medicine, can be used in selected cases, mainly to clarify metastatic disease such as dubious liver and lung lesions or enlarged lymph nodesSmall, rounded organs of the immune system that are distributed along the lymphatic system that filter lymph, a fluid derived from the blood, and produce antibodies and a type of white blood cells, lymphocytes..

Figure 2. Anatomy of the liver and pancreas

The pancreas is located behind the stomach and is attached to the duodenumThe first part of the small intestine., the first part of the intestineThe section of gut, or gastrointestinal tract, from the stomach to the anus. in continuity with the stomach, as well as with the bile duct which carries the bile from the liver to the duodenum (Figure 2). The pancreas sits on the two largest blood vessels in the body, the inferior vena cavaThe large vein that carries de-oxygenated blood from the lower half of the body to the heart. and the aortaThe body's main artery, which arises out of the heart and supplies blood to all other parts of the body., and the neck of the pancreas is traversed by two important vessels, the superior mesentericrelating to the mesentery. arteryA blood vessel that carries blood away from the heart. Apart from the pulmonary artery and umbilical artery, all arteries carry oxygenated blood. and the portal veinA blood vessel that carries blood towards the heart. (Figure 3).

Figure 3. Anatomy of the pancreas showing its relation to major vascular structures

The pancreas is a glandAn organ with the ability to make and secrete certain fluids. which produces digestive enzymes (exocrine pancreas) as well as hormones, primarily insulinA hormone produced by the beta cells of the pancreas that acts to lower blood glucose levels. and glucagonA hormone produced by the pancreas that broadly opposes the actions of insulin and so increases the blood sugar (glucose) level., essential to metaboliseTo break down or process substances in the body. sugars (endocrine pancreas). Pancreatic cancer derives from the more common exocrine component. The cells which produce the hormones are scattered throughout the pancreas gland and if they replicate abnormally they can cause a different type of neoplasia An abnormal proliferation of cells. called a neuroendocrine tumour. The behaviour of neuroendocrine tumours can be aggressive but very often they are quite benignNot dangerous, usually applied to a tumour that is not malignant. or even indolentCausing little or no pain, slow to develop..

Because of its close proximity with vital vascularRelating to blood vessels. structures, surgery of the pancreas is particularly delicate and is prohibited in locally advanced tumours which invade some of these vessels.

Pancreato-duodenectomy is the standard operation for cancer of the pancreatic head. In this procedure, known as the Whipple’s operation, the head of the pancreas is removed together with the duodenum, the bile duct, the gallbladderSmall pear-shaped organ that sits under the liver and that stores bile. and the distal part of the stomach. A variant of this procedure adopted by many surgeons is the PPPD, or pylorus preserving pancreato-duodencetomy, where the whole stomach is preserved (Figure 4). Clinical trials have clearly demonstrated no difference in the short- or long-term outcome between the two techniques, though patients undergoing PPPD are more likely to have difficulty in emptying the stomach as the pyloric sphincterA ring of muscle around a natural opening or passage that acts as a valve, regulating inflow or outflow. is maintained but becomes more proneLying face-downwards. to developing gastric ulcerationThe presence or formation of an ulcer - an abnormal break in epithelium, the outer layer of cells covering the open surfaces of the body. and refluxBackflow of a bodily fluid in the wrong direction of bile into the stomach.

Figure 4a. Before resection of a pancreatic tumour Figure 4b. After resection of a pancreatic tumour. Notice that the whole stomach has been preserved (PPPD variant of pancreatoduodenectomy)

Figure 5. Pancreato-gastrostomy: the pancreatic stump is tunnelled on the back of the stomach

The continuity of the stomach and bile duct is restored by joining them with a loop of intestine. The pancreatic stump can be joined to the intestine (pancreato-jejunostomy) or to the back of the stomach (pancreato-gastrostomy – Figure 5). Again, there is good clinical evidence that neither of the two techniques is superior to the other and this is purely down to personal preference and experience of the operating surgeon.

On the other hand, if the cancer is located in the body or tail of the pancreas, the standard operation is a distal pancreatectomySurgical removal of the pancreas. with splenectomyThe surgical removal of the spleen, an organ on the left side of the abdomen that filters out worn-out red blood cells and other foreign bodies from the bloodstream., as the spleenAn organ situated on the left side of the abdomen that filters out worn-out red blood cells and other foreign bodies from the bloodstream. will need to be removed as well for oncological reasons. Laparoscopic or keyhole surgeryA type of minimally invasive surgery., sometimes performed for benign or neuroendocrine tumours in the tail of the pancreas, is very rarely considered for cancer, although a few laparoscopicA keyhole surgical procedure. Whipple’s have been reported in specialised centres.

Resection of pancreatic cancer involves major surgery, especially for tumours in the head of the pancreas, as the Whipple’s operation is one of the most invasive and complex surgical procedures. There is a clearly demonstrated correlation between large workload and good results at hospitals and clinics and is a convincing reason to choose high volume centres for this type of surgery.

Patients have to be generally fit to undergo major surgery and will routinely undergo a full pre-operative check-up to assess their cardiorespiratoryRelating to the heart and lungs., renalRelating to the kidney. and nutritional status. Advanced age is not an absolute contraindicationA condition which may make a medical treatment or procedure inadvisable. to surgery per se and a large number of elderly people are routinely operated on in our unit.

If surgery is uncomplicated patients are expected to be discharged approximately one to two weeks later, although complete recovery can take as long as three months. Improvement in peri-operativeThe entire duration of a surgical procedure, from pre-operative steps to post-operative recovery. care, including anaesthesia and intensive care support, as well as technical progress in surgical and radiological equipment, have led to a drastic decrease in post-operative mortality, with very few patients dying as a result of pancreatic surgery. This improvement is also associated with a better management of the complications, which occur in approximately 30% of cases. The most serious side effects of pancreatic surgery include bleeding, infectionInvasion by organisms that may be harmful, for example bacteria or parasites. and leakage from the pancreas (pancreatic fistulaAn abnormal channel between two parts of the body, for example between a hollow organ and another hollow organ, or between the inside and the outside of the body.). In some cases where a pancreatic fistula occurs or the gastric function is impaired, a period of intravenousWithin a vein. feeding might be necessary to provide nutritional support.

Results from the largest randomised controlled trialA study comparing the outcomes between one or more different treatments for a disease (or in some instances, preventive measures against that disease) and no active treatment at all (the placebo group). Study participants are allocated to the various groups on a random basis. May be abbreviated to RCT., ESPAC-1, have demonstrated a clear benefit in adjuvant chemotherapyThe use of chemical substances to treat disease, particularly cancer. after surgery to reduce the chance of recurrence and improve survival. Today the majority of patients are recommended to have gemcitabine post-operatively. The ongoing ESPAC-4 trial is currently recruiting and enrolling patients to compare adjuvant gemcitabine alone versus combination chemotherapy with gemcitabine and capecitabine.

As surgical resection remains the gold standard treatment and the only one to confer potential long-term survival, all efforts should be made to make these patients operable, although several studies have suggested that the long-term survival of patients with residual tumour left behind microscopically (so called R1 resection) can be similar to patients who undergo a curative resection with clear margins (R0 resection), the intention is quite clearly to eradicate the tumour completely. For this reason any intention to debulkTo remove a tumour. a clearly inoperable tumour is not acceptable.

There are other ways to make locally advanced disease operable. Standard downstaging or neo-adjuvant chemotherapy with gemcitabine can shrink the tumour in a relatively small number of cases. However, recently, a new chemotherapy regimen with 5-Fluorouracil, irinotecan and oxaliplatin (folfirinox) has been associated with a response rate as high as 30%. In responsive patients a short course of chemoradiotherapyTreatment of cancer with both chemotherapy and radiation therapy. is usually administered to further decrease the size of the tumour and to reconsider surgical intervention if possible.

Figure 6. The portal vein has been removed with the tumour and replaced with a segment of internal jugular vein

In the absence of metastatic spread, the most common contraindication to operate is the encasement of the arterial vessels. In this case, the tumour is involved in, or even wraps around, the main arterial structures, precluding any surgical treatment, as arterial reconstruction is not a feasible option. On the contrary, if the portal vein is involved, surgery is possible by removing the vein together with the cancer and joining the two ends of the vein together. In cases where the gap is too large to approximate the two ends, the missing part of the portal vein is replaced with a graft, commonly taken from the jugular vein (Figure 6). Several studies have demonstrated that overall survival after portal vein reconstruction is similar to the survival of patients undergoing standard pancreatic surgery and is better than after palliative A therapy that gives relief from the symptoms of a disease rather than impacting on its course. Often known as 'end of life' care. bypass or other forms of non-surgical palliation. In our Institution, we have extensive experience in treating patients with locally advanced disease and to date we have not recorded any post-operative death after vascular reconstruction of the portal vein in patients undergoing pancreatic surgery.

However, even with the most aggressive and sophisticated techniques, the majority of patients with locally advanced pancreatic cancer remain inoperable. Various treatment modalities have been described in patients with locally advanced and inoperable pancreatic cancer including Cyberknife®, radiofrequency ablation and photodynamic therapy. These techniques utilise different forms of energy in the attempt to locally destroy the tumour but none of them has been proven to be curative and should be regarded as palliative therapies. Cyberknife®, the most promising of these, has been used with some success in selected cases of localised recurrence after surgical resection. In patients with inoperable or recurrent disease, attention should be concentrated on the quality of life, pain relief and the nutritional status of these unfortunate patients, which can be improved with palliative chemotherapy.

Soon after surgery, patients are usually transferred to Intensive or High Dependency Care, where they can be closely monitored for the first 24 hours before they go back to the surgical ward. An epiduralOn or over the dura mater, the outermost of the three membranes covering the brain and spinal cord. The epidural space is used for anaesthetising spinal nerve roots, for example during pregnancy., a small anaestheticA medication that reduces sensation. pipe inserted on the back of the spine, provides excellent pain relief and is frequently used but some patients prefer to use PCA (patient controlled analgesia), a special device connected to the patient which releases a standard dose of morphine by pressing a button.

Patients are mobilised a few hours after their operation and frequently sit on a chair on the first post-operative day. Although they can usually have some sips of water, proper oral intake is not allowed for the first four or five days.

Not at all. On the contrary very few patients need surgery to correct a complication. In the majority of the cases complications can be resolved with radiological or simple medical intervention, such as intravenous feeding and antibioticsMedication to treat infections caused by microbes (organisms that can't be seen with the naked eye), such as bacteria..
 

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