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Surgery for Neuroendocrine Tumours

Although many types of NET are slow growing, in general terms they are malignant (i.e. cancerous) tumours Therefore in common with the vast majority of other types of solid cancer it makes sense to surgically remove the whole of the tumour if it is possible and the benefits outweigh the risks.

Primary NETs can arise in many different organs, as they grow they may also spread as secondary tumours (also called metastases) to other organs or parts of the body. This section will divide the surgery up into operations for primary tumours and operations for secondary tumours. This is only meant as a guide to some of the procedures that can be done, it is not comprehensive and does not cover every possible clinical scenario or individuals set of circumstances. Our intention is to provide individually tailored treatments for patients; sometimes using just a single treatment such as surgery, but often involving combinations of treatments to try and get the best results for the individual’s pattern of disease.

The aims of surgery vary from individual to individual according to the site and size of primary disease, the tumours rate of growth and the pattern of any secondary disease. There are 4 sets of reasons for operating on a patient with NET:

  • Cure
  • Symptom control
  • Prolong life
  • Cyto-reduction (reducing the total quantity of living tumour cells in the body)

Cure. Whereby we are aiming to remove the entire visible tumour in the hope that it will never come back. This is most likely with primary tumours without spread, but can also sometimes occur with secondary liver or lymph gland involvement.

Symptom Control (or Palliation). If a tumour is causing symptoms either by releasing hormones or by pressing on another organ causing pain or an internal blockage or if it is bleeding causing anaemia (low blood count) then it is often helpful to remove the tumour (or tumours) that is causing the symptoms.

Prolong Life. If a tumour is pressing on a critical structure causing a blockage in the stomach or intestine or one of the important blood vessels then even if we cannot cure you with the operation it may be worth considering surgery to clear the mechanical problem if this will remove the immediately life threatening problem.

Cyto-reduction. This is when we do an operation to get rid of as much tumour as possible, even though we know we cannot cure it all. This is usually done in slower growing forms of the disease where the tumour has already spread extensively, but by removing larger lumps of the disease we can keep the disease under control and sometimes make other treatments such as radio-isotope treatment more effective.

Surgery for Primary NETS

Pancreatic NETs

NETs that start in the pancreas are often called Pancreatic Endocrine Tumours however the terms are interchangeable. Pancreatic surgery can be quite complex as the pancreas is an awkward organ to get at, being tucked away behind the stomach, colon and duodenum. The pancreas is also close to some very important blood vessels that supply blood to the liver, pancreas, stomach, spleen, kidneys and intestines.

Small pancreatic tumours (Less than 5cm diameter) seldom have major involvement of the blood vessels so their treatment is more straight forward.

In general if there is only one pancreatic tumour of less than 5cm diameter and it has not spread then if you are fit enough for surgery you should have an operation to remove the tumour intact along with that part of the pancreas that it has come from. Under these circumstances there is a high chance that the surgery will be curative and you will not require any further treatment in the future once you have recovered from the surgery.

Small tumours on the left side of the pancreas (the body and tail of the pancreas) are usually removed as a keyhole operation (distal pancreatectomy); sometimes this also involves removal of the spleen which is closely joined to this part of the pancreas.

Small tumours on the right side of the pancreas (head and neck of the pancreas) need an operation called a Whipple’s procedure or pancreatico-duodenectomy. This is a more complex open operation, that involves taking away the head and neck of the pancreas as well as the duodenum and part of the bile duct. The organs then need to be re connected to enable full recovery and long term return to normal function.

Further detailed information about pancreatic surgery performed here in Southampton can be found on www.allps.co.uk

Multiple pancreatic tumours can occur in a very rare genetic form of NET called MEN1 (multiple endocrine neoplasia) where lots of small, slow growing tumours arise dotted around the pancreas and duodenum. They often produce hormones and can cause symptoms such as high or low blood sugars. We tend to monitor very small tumours with scans unless the symptoms they cause cannot be controlled without removing them. If there are several small tumours (less than 2cm) that require surgery then they are often enucleated, which means they are surgically removed from the pancreas with a very small rim of normal pancreatic tissue around them. Larger tumours causing symptoms are usually managed the same way as solitary tumours (see above and below). Very occasionally if there are multiple active tumours involving several parts of the pancreas that are too big or too deep to enucleate then we remove the whole pancreas (total pancreatectomy).

Large pancreatic tumours over 5cm in diameter or involving the major blood vessels or other adjacent organs can be much more difficult to manage. Again each case must be assessed on it’s merits, weighing up the likely behaviour of the tumour, the presence of any secondary spread, symptoms, the patients fitness, the risks of surgery and the merits of other treatments.

If the disease has not spread and is slow growing then very complex surgery can still be potentially curative even if the operation involves removing parts of several other organs to get clearance of the tumour.

Pancreatic primary with secondary spread. If the disease has spread then the role of surgery for the primary is more controversial. When we assess primary pancreatic tumours in metastatic NET then we have to assess how treatable the secondary disease is and also the likelihood of life threatening symptoms from the primary tumour compared with the likelihood of life threatening symptoms from the secondary tumours.

If the secondary disease is easy to treat then it makes sense to treat the primary as well.

Similarly if the primary disease is significantly more life threatening than the secondary disease, then it may be worth tackling the primary disease first if possible.

Jejunal and ileal NETs

The jejunum and ileum are part of the small intestine, together they are a common site for primary NETs to form. Primary tumours from the small intestine very often secrete the hormone serotonin or 5HT which can give rise to the classic “carcinoid syndrome” of flushing, palpitations, diarrhoea, sweating and abdominal pain. However in the early stages of the disease, which may last for several years there may be no symptoms or there may be mild “irritable bowel” type symptoms.

The evidence with primary tumours in the small intestine is that they should be resected whenever possible, even in the presence of secondary tumours, because patients are more likely to have life threatening complications from the primary as they are from the secondary disease.

Small intestine NETs are also commonly surrounded by a condition called desmoplasia, this is a hard, fibrous reaction around the tumour that appears like sheets of thick white scar tissue on the surface of the bowel and around blood vessels and lymph glands. Desmoplasia grows in response to release of serotonin from the NET cells.

Surgery for Liver Tumours

Liver surgery is most commonly performed for people who have malignant (cancerous) tumours in the liver. Our aim as liver surgeons is to try and pick those people who have the best chance of being cured or at least would have a significantly prolonged life span or improved quality of life after liver surgery. Unfortunately many people with liver cancers would be no better off after an operation therefore we do not operate on everyone with liver cancer. The cancers that we can help most with are outlined above in section 5. Whenever we plan to operate we always weigh up the risks of the operation against the potential benefits for the individual. These risks and benefits are different for each patient and can only be decided after reviewing all the evidence and discussing the pro’s and con’s.

If we do not think that an operation has a good chance of improving the length or quality of your life we will not offer you surgery, but instead will make other suggestions about how to treat or manage your disease.

We rarely operate on benign liver tumours unless any of the following criteria are met:

  •  The tumour is causing pain or discomfort
  •  The tumour may turn cancerous in the future
  •  We cannot be sure from the scans whether this is a benign or malignant tumour

Common Questions before liver surgery:

Is liver surgery safe? Liver surgery has changed faster than any other branch of general surgery in the last twenty years and has now become relatively safe surgery if performed by experts in specialist units such as the Southampton unit. For the majority of operations that we perform the risk of death whilst in hospital after the operation is around 1 or 2 in 100. If we think that your operation is higher risk than this we will estimate this for you so that you can make an informed decision about surgery.

Will I need a blood transfusion after the operation? The vast majority of patients do not require blood transfusion after surgery. For routine surgery we expect the blood loss to be around 200-600ml. Even with complicated operations it is uncommon for blood loss to reach much more than 1000ml (approximately 2 pints).

How long will I be in hospital after open surgery? The average stay for open surgery is around seven to ten days after the operation. Younger, fitter patients often go home a little sooner. If any complications occur we keep you in until they are resolved, how ever long that takes.

How long will I stay in hospital after keyhole liver surgery? The average stay after keyhole surgery is 2 to 4 days although a few fit young patients may be able to go home the day after operation.

Who will do the operation? The vast majority of operations are performed by a consultant liver surgeon (Pearce / Abu Hilal). Some straightforward cases are performed by a specialist registrar (a qualified senior surgical trainee) assisted or supervised by a consultant liver surgeon.

What complications can occur? Any operation has the general risks of the anaesthetic which depend on the over all health of the patient as well as the magnitude of the surgery. There are some risks specific to liver surgery such as a leak of bile from the cut surface of the liver. This occurs in 4 or 5 people in every 100 cases that we operate on, they usually resolve without the requirement for any further surgery. A small number of patients develop collections of infected fluid next to the surface of the liver these are usually managed by drainage of the fluid under local anaesthetic. After major resections it is not unusual to go slightly jaundiced a few days after the operation, this may be accompanied by drowsiness or confusion (see common symptoms above). It usually resolves within a few days.

Does the liver grow back? The liver can regenerate after surgery. The speed of regeneration depends on the quality of the liver as well as how much has been taken. It is possible to remove up to approximately 85% of an otherwise healthy liver in a fit patient.

Would a transplant be better? Most transplants are done for cirrhosis and liver failure. Although the idea of “getting rid of it all” is very attractive for cancer surgery the problem is that the strong drugs that you need to take after a transplant to prevent rejection, weaken the immune system and for most types of tumour make the cancer much more likely to come back else where in the body.

Open Liver Surgery

There are approximately twenty high volume centres in the UK performing open liver surgery. The total number of liver resections per year has gone up drastically in the last few years. The first successful major liver resection (right hemi hepatectomy) was performed in 1952 in Paris. In the 1980’s there were probably fewer than 150 liver resections carried out in the whole of the UK per year. Currently there are closer to 2000 performed annually, for an ever widening array of different diseases. Liver surgery has become very safe if performed by properly trained experts, backed up by specialist anaesthetic, nursing and critical care staff in specialist centres, with the full range of equipment available. It should never be done by non specialist surgeons or outside high volume specialist centres as the risk becomes unacceptably high.

Laparoscopic (keyhole) liver surgery

Laparoscopic surgery has taken off across the world for all kinds of abdominal surgery. However it has been slow to get established in liver surgery because of the technical difficulty of the procedure and the type of training that most traditional liver surgeons have had. The first case was performed in France in 1993 and the first small series of laparoscopic liver resections were reported in the 1990s. The largest series worldwide are from our group in Southampton and from centres in the USA, France and Australia. By 2010 there were still fewer than 3,000 reported cases of laparoscopic liver resection in total worldwide over the last 17 years.

Southampton has by far the largest experience of laparoscopic liver resection in the UK. In 2006 we performed more than 30% of our liver surgery cases laparoscopically. By 2009 this had risen to over 50%. In the UK there are very few surgeons who routinely perform laparoscopic liver resection and in total there have probably been fewer than six hundred cases performed across the nation in the last ten years, over half of these have been done in Southampton.

In Southampton we performed our first laparoscopic liver resection in 2003 and have performed a further 350 in the 9 years since then with very few serious complications.

At least 60% of patients requiring liver surgery are suitable for laparoscopic resection in our current practice.

The advantages are a much faster recovery time and shorter hospital stay, with fewer respiratory (chest) complications, less risk of infections and less abdominal scarring.

Approaches to liver surgery:

  • Almost all parts of the liver are accessible by laparoscopic surgery, the easiest areas to reach and operate on are at the left hand side of the liver or at the front of the liver near the gallbladder.
  • The far right hand side of the liver is also relatively easy to approach.
  • Superficial tumours on the surface of the liver can usually be managed laparoscopically unless they are very close to the important blood vessels in the liver.
  • Lesions placed centrally in the right or left sides of the liver usually require removal of all or most of that side of the liver (right or left hemi hepatectomy)
  • Lesions in the centre of the liver close to the main blood vessels are very difficult to operate on and may require very large and relatively high risk resections, usually performed as an open operation.

Surgery for Pancreatic Tumours

Cancers in organs close to the pancreas often spread into the pancreas and often require pancreatic surgery so they are considered here with pancreatic cancer:

Pancreatic cancer: this is the sixth commonest cancer in the UK, it is rare under the age of 45 years. The most common symptoms are jaundice, weight loss, diabetes and back pain. In the UK as a whole less than 1:10 patients are treated with surgery, in our experience this can be pushed up to 1:5, by careful case selection.

  • Ampullary cancer: this is usually the easiest of the pancreatic cancers to treat because even very small tumours cause jaundice which means that the cancer is often picked up at an early stage which makes the surgery easier and likely to be more successful.
  • Bile duct cancer: lower bile duct tumours are treated the same as pancreatic cancers because they are hard to tell apart and behave in the same way. This tumour also usually causes jaundice at an early stage.
  • Duodenal cancer: this rare tumour usually causes a blockage to the exit of the stomach so it is common to get bloating and vomiting as the initial symptoms. Some patients also get anaemia because of blood loss into the gut.
  • Sarcomas: these are very rare cancerous tumours that arise from cells in the fat, muscles, nerves or blood vessels in or around the pancreas. The one we see most often is the GIST (Gastro-Intestinal Stromal Tumour) which develops from muscle cells in the wall of the gut. They often grow very slowly pushing other structures out of the way. Due to their slow progression they often do not cause many symptoms, thus by the time patients are aware of them they may be very large and attached to several different organs. However, because of their less aggressive nature it means that surgery to remove even massive tumours is worthwhile because a cure may still be possible. This extensive surgery may involve removal of parts of other adjacent organs (such as liver, kidney, stomach or colon) as well as part of the pancreas.
  • IPMT: this stands for intra ductal papillary mucinous tumour. These are very slow growing cancers that arise in the cells lining the ducts of the pancreas. They often cause chronic pancreatitis (see above) and they are often diffuse or multifocal (arising simultaneously in more than one part of the organ). They are usually surgically resectable, but sometimes require removal of the whole of the pancreas.

If you have one of these difficult tumours you must be assessed by a surgeon with a specialist interest in this disease. Your investigations should then be reviewed by your surgeon with the specialist pancreatic multidisciplinary team including radiologists, oncologists, physicians and surgeons.

This section will briefly describe just a few of the commonest operations that we do for pancreatic disorders, it would take a thousand page text book to cover all the many types of pancreatic surgery in detail.

Whipple’s pancreatico duodenectomy

This is the operation most commonly performed for tumours of the pancreatic head. It involves removal of part of the stomach, the whole of the duodenum, part of the small bowel, the head of the pancreas, the bile duct and the gallbladder, leaving behind the major blood vessels. There are many modifications of this procedure, which vary slightly in the extent of the resection in one direction or another, however, there is no proven advantage of one variation over another.

After the head of the pancreas and the tumour have been removed it is necessary to reconstruct the anatomy in a functional form. Again there are seemingly endless variations for the reconstruction all of which have their exponents and their pro’s and con’s, two of the commonest reconstructions which we use are shown below.

  • hepatico-jejunostomy
  • gastro-enterostomy
  • pancreatico-gastrostomy
  • entero-enterostomy

Reconstructions after pancreatico-duodenectomy

This is very major surgery; there is no other routinely performed abdominal operation which can be considered greater in extent or impact on normal function.  Risks include:

Risks of anaesthesia these have been minimised by improvements in pre operative evaluation and peri-operative care, however major surgery such as this places a huge strain on the bodies resources; the risks for any individual patient are different and are assessed person by person. If we think the risks are too great then we will advise against surgery.

Anastomotic leakage this is the risk of one of the joins in the reconstruction leaking after the operation. The join which is most likely to leak is that between the pancreas and stomach (number 3 above), this join is most likely to leak because of the caustic nature of the substances passing through it. Pancreatic juice contains very potent digestive enzymes which can break down proteins trying to heal the join and thus disrupt the reconstruction.

Diabetes: around 60% of patients having this operation will be diabetic afterwards, this varies in severity from just having to change your diet all the way up to requiring Insulin.

Malabsorption of food: almost all patients after a Whipple’s operation require extra supplements of concentrated pancreatic enzymes to digest their food. These are supplied as capsules to take with meals.

Infection: this is a broad term that encompasses everything from a mild chest infection to abscesses inside the abdominal cavity.

Haemorrhage: most patients lose between 500-1500ml of blood during the operation. Patients who lose more than this or who are anaemic to start with usually require blood transfusion. Rarely patients develop a late postoperative haemorrhage and need to go back to theatre to control the problem again.

Despite all of these risks and potential complications, approximately 2/3 of patients will have returned home within 3 weeks of the surgery without significant complication. Fit patients should expect to stay in hospital for 10-15 days after the surgery.

Distal pancreatectomy

This involves dividing the left side of the pancreas to remove areas of disease in the tail and body of the pancreas. The tail of the pancreas lies directly in front of the blood vessels to the spleen, if these vessels cannot be preserved then we usually have to remove the spleen as well as it cannot survive without a blood supply. This occurs in around 60% of the cases we operate on, usually because there is tumour invading around the vessels. The spleen is an important part of the immune system, if we think there is a risk of having to remove the spleen then we routinely vaccinate you before the operation against a number of serious infections that you may be more prone to without a spleen.

Some patients are diabetic after this surgery because the body and tail of the pancreas contain most of the insulin secreting cells. Diasbetes is more likely to occur if the remaining pancreas is already damaged, for example by chronic pancreatitis. Diabetes is unusual after distal pancreatectomy for tumours.

Average hospital stay is 7-10 days after the surgery.

Pancreatic bypass

This operation is occasionally performed for patients with blockage of the bile duct or duodenum caused by pancreatic tumours that cannot be removed. In most cases we try and treat the blockages without surgery by placing plastic or metal drainage tubes internally by passing a telescope via the mouth into the stomach and duodenum. If this does not work then we can perform bypass surgery, however this is major surgery for such seriously ill patients to undergo and not something we under take lightly.

Thoracoscopic splanchnicectomy

This operation is a keyhole procedure that involves dividing nerves (splanchnic nerves) within the chest that supply sensation of pain to and from the pancreas. It is a very effective procedure for controlling pain from chronic pancreatitis or untreatable tumours. Unfortunately in some patients the response starts to wear off after a year or two. Most patients go home within 48 hours of the operation.

Pancreatic bypass

This operation is occasionally performed for patients with blockage of the bile duct or duodenum caused by pancreatic tumours that cannot be removed. In most cases we try and treat the blockages without surgery by placing plastic or metal drainage tubes internally by passing a telescope via the mouth into the stomach and duodenum. If this does not work then we can perform bypass surgery, however this is major surgery for such seriously ill patients to undergo and not something we under take lightly.

The above is a guide and may be useful to refer back to after an appointment where a lot of information was given.   However, every patient is different and your surgeon would always discuss your options with you as well as explain the risks associated with any procedure.

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