Gastrointestinal Cancers Lecture Flashcards
LO:
- Organs of the gastrointestinal tract: Summarise the structure of gastrointestinal organs and relate these to their functions
- Gastrooesophageal disorders: Summarise the pathology and pathophysiology of gastrooesophageal disorders
- Gastrooesophageal disorders: Describe the clinical features and treatment options of gastrooesophageal disorders
- Hepatobiliary and pancreatic disorders: Summarise the pathology and pathophysiology of hepatobiliary and pancreatic disorders
- Hepatobiliary and pancreatic disorders: Describe the clinical features and treatment options of hepatobiliary and pancreatic disorders
- Intestinal disorders: Summarise the pathology and pathophysiology of small and large intestine disorders.
- Intestinal disorders: Describe the clinical features and treatment options of small and large intestine disorders
Session Plan:
Terms: -Cancer -Primary -Secondary
Cancer
“A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems”
Primary
•Arising directly from the cells in an organ
Secondary/Metastasis
•Spread from another organ, directly or by other means (blood or lymph)
What is Cancer? The Hallmarks of Cancer
Six biological capabilities acquired by tumours are:
Hanahan and Weinberg published a paper, it was called The Hallmarks of Cancer. And in that, they described six biological capabilities that are required by cancers during the multi-step development of human tumours.
So if we look at this diagram here, we start at the top. These are the six by the first six biological capabilities that are required by humans. They are first sustaining proliferative signalling. Second, evading growth suppressors. They can also activate invasion and metastasis. They can enable replicative immortality in the microenvironment around them. They can induce angiogenesis. And that’s essentially to get the blood supply to support the tumour that’s growing. And they have resistance to cell death. So they were the first Hallmark’s for six described.
Basically take home message of this, is there is too much go, and not enough stop. So everything is driving things to replicate, get bigger and grow.
The following underlie these hallmarks:
They publisehd a second paper, 2011, where they described another two emerging hallmarks of cancer, and they described these as deregulating cellular energetics and avoiding immune destruction by the host body that is trying to destroy the cancers.
They also identified a couple of enabling characteristics, which they described as genome instability and mutation, and tumour promoting inflammation.
So basically what’s happening here is that cancers are gaining a selective advantage that give them an edge over their neighbours. So these can be acquired through genetic change, but also through epigenetic dysregulation. So, for example, chronic inflammation can affect gene expression patterns in the absence of actual sequence changes themselves. So we’re looking at GI cancers. What we’re describing is normal tissue in GI tract that inquires these features in a stepwise manner. So you go from a normal mucosa to primitive lesions, which eventually become an invasive cancer. Happens in a stepwise manner. And you’ll see this throughout the cancers that we discuss.
A Few Instant Truths
- Cancer is a genetic disease
- Cancers contain multiple genetic errors which occur in a stepwise fashion
- Cancers contain more than just malignant cells (They have a structure. You will have stromal cells. You will have neovascular vessels, etc.)
- Killing cancer cells is easy (ie in chemotherapy)
- ONLY killing cancer cells and not affectig other cells around them is very hard
- Developing novel therapies for cancer fraught with problems
Types of Cancer
Last year, we looked at cells of the GI tract. We talked briefly about a squamous cell cancer going on in the oesophagus. And most of our focus was on adenocarcinomas within the GI tract. We’ll be focussing on another adenocarcinoma a bit later. But we’ll also be looking at some specialised cells- neuroendocrine cells, which cause neuroendocrine tumours.
We’ve got connective tissue, smooth muscle causes, Leiomyosarcomas, adipose tissue causes, liposarcomas, etc.
Note: Interstitial cells of Cajal (ICC) are mesenchymal cells located within the muscle layers of the alimentary tract, they act as the pacemaker of the GI Smooth Muscle.
GI Cancers
You can get neuroendocrine tumours throughout the GI tract, from the oesophagus to the stomach to the duodenum them to the pancreas, to the large bowel, small bowel and rectum.
New Cases of Cancer – UK, 2017
In the UK in 2017, the new cases of cancer recorded 367,167. And this is essentially the instance. You see the commonest is breast cancer, followed by prostate cancer, followed by lung cancer.
The one cancer we’re going to be talking about in gastroenterology is bowel cancer. That’s the fourth commonest. But then if we go down incident wise. It takes us a while before we get to oesophagus and pancreas, then stomach and liver. So the incidence of those cancers are low.
Cancer Deaths – UK, 2018
Deaths from cancers in the UK in 2018 reached 165, 000 or so. But what’s causing the death? Well, lung cancer, yes, but bowel cancer is up there. And now we’re seeing pancreas which instances low and oesophagus and liver, they’re all at that age. They are nasty cancers and the cause early death.
Death Rates by Cancer Type
And this is just to reiterate those two slides. This is looking at death rates by cancer type. Essentially, we’re looking at the incidence versus death ratio. So when we look at that liver, pancreas, oesophagus, stomach, gall bladder, these are all gastrointestinal tumours, for incidence, is low, but the death rate is high. So there are serious problems that need answers to.
Screening – Catching the Disease Early
How many people survive 5 years from diagnosis? CRUK data
So how does one go about? Managing patients cancer?
Well, I think it’s worth mentioning screening for cancers. This is a slide which shows how many people survive five years from their diagnosis. So, for instance, if you go to colorectal cancer, the overall five year survival rate is pretty high. It’s 60 percent over five years. The percentage of patients that are diagnosed at the stage where they can have their cancer resected is actually high, just less than 50 percent. Is it 45 percent. And that is reflected in the five year survival of those that have resectable diagnoses, so 90 percent are alive at five years. And probably the answer to that is, if you think about the the anatomy is that large bowel is relatively mobile, it has a mesentery and it usually keeps to itself. Other cancers, such as pancreatic, oesophageal and cholangiocarcinoma certainly, involve structures very quickly.
Pancreas overall survival rate is appalling at five percent. But also the percentage of patients that can have their disease resected at the time of diagnosis is only I would say ten to fifteen, but here we have 15 to 20 percent. And that’s reflected in the five year survival for those that have their disease resected, only being around 20 percent. And it’s similar with oesophageal, liver-hepatocellular cancer, gall bladder cancer, and cholangiocarcinomas.
The big problem is finding these cancers early. All these cancers are presenting late before you can do anything about it. So essentially, the earlier you identify cancer, the better the chance you have to dissecting it. And that is subsequently reflected in a better five year survival.
Screening for Cancer
Cancer screening
- Testing of asymptomatic individuals to identify cancer at an early stage.
- What diseases are suitable for screening? Wilson & Jungner criteria.
- Depends on the epidemiology of a disease & features of the test.
So let’s talk about cancer screening. Essentially, that’s testing an asymptomatic individual to try and identify cancer at an early stage before the patient even knows about it.
What diseases are suitable for screening? This brings us to the Wilson and Jungner criteria. Now, this is a paper out from about the 1960s. It was entitled Principles and Practise of Screening for Disease. It’s become a public health classic. And what that’s doing is looking for the criteria of screening for cancers early. So they came up with seven criteria.
First, the condition sort of what you’re looking for should be an important health problem. So lots of people should be dying from it. It needs to be addressed.
Second, if you identify that cancer early, there has to be an accepted treatment for those patients for that recognised disease. So there’s no point finding cancer early. You can’t do anything about it.
You have to have the facilities or the infrastructure for the diagnosis and the treatment. So that should be available.
There should be recognisable latent or early symptomatic stage. I mentioned asymptomatic before, but that was the phraseology they used back in 1968?
You need to have a suitable test or an examination that can identify it easily.
The test should be acceptable to the population, so, for instance, if you’re screening for colorectal cancer, a colonoscopy has to be acceptable to patients. It can’t be a thoroughly unpleasant thing where no one will turn up to have their test done.
And seven, the natural history of the condition, including the development from latent to declared disease, should be adequately understood. So that’s important. Adequately, but not necessarily completely.
So that’s the sort of criteria you need if you’re looking to set up a screening programme. It also depends on the epidemiology of the disease. So you’ll find that rare cancers such as pancreatic cancer. There isn’t any economic sense in screening because you’ll pick up rate is going to be so low that you’re not actually going to be saving that many lives. So you need something that’s the incidence is high and there’s something you can do about it.
Screening in GI Cancer
(note: Besides these, specific screening programmes exist for individuals with genetic predisposition or strong family histories.)
Colorectal cancer
Offered to healthy individuals:
- Faecal immunochemical test (FIT) - detects haemoglobin in faeces, every 2 years for everyone aged 60-74
- One-off sigmoidoscopy for everyone aged >55 to remove polyps (reducing future risk of cancer).
Screening in GI Cancer
Oesophageal cancer
Regular endoscopy only offered to patients with:
- Barrett’s oesophagus
- or Low- or high-grade dysplasia.
Screening in GI Cancer
Pancreatic & Gastric cancer
- No test exists that meets the W & J criteria.
- Depends on incidence - Japan screens for gastric cancer (as incidence of gastric cancer in Japan is very high, so they offer screening programmes which consist of endoscopies, because the pickup rate there is a lot higher due to ther higher incidence, so it makes economical and clinical sense.)
Screening in GI Cancer
Hepatocellular cancer ie primary cancer of the liver
- Regular ultrasound & AFP for high-risk individuals with cirrhosis
- Viral hepatitis
- Alcoholic hepatitis.
ie patients who have been identified as having cirrhotic livers either secondary to viral hepatitis or alcoholic hepatitis or even now we are looking at patients with NASH (non-alcoholic steatohepatitis). They are offered regular ultrasound scans and AFPs (blood test for alpha fetoprotein)
The Patient’s Cancer Journey:
DST (D.STephen)
Best treatment is to actually take it away so there’s nothing there to cause problems. That’s often not possible, as we saw in an earlier slide. Treatment options would then consist of systemic chemotherapy or local radiotherapy.
The Cancer Multidisciplinary Team (MDT)-what is the path from pickup?
Anyone has anything worrying about a cancer can get referred to what’s called a two week wait cancer pathway. So essentially within two weeks of say a GP saying this patient may have a cancer, that patient has to have had at least diagnostic tests and at least been discussed in an MDT (multi disciplinary team) meeting. And then offer treatment as as required
The Cancer Multidisciplinary Team (MDT)
So what does an MDT consist of?
Surgeon-operating
Oncologist-chemotherapy
etc.
Pathologist:
- Confirms the diagnosis of cancer using biopsy samples
- Provides histologic typing, i.e. what type of cell does the cancer come from?
- Provides Molecular typing, i.e. what Mutations does this cancer have?
- Provides the tumour grade, i.e. how aggressive is the cancer?
Very important to know exactly what cancer you’re dealing with because different cancers can be treated better or worse with surgery or better or worse with chemotherapy. And your chemotherapy choice depends exactly on what that tumour is.
Radiologist
- Reviews scans
- Provides radiological tumour stage, i.e. how far has the cancer spread?
- Provides re-staging after treatment.
- Interventional Radiology
T2 is relatively small. N0 is no lymph nodes involved and M0 again is no evidence of metastastes.
But a patient with the T3 tumour, it would be bigger in size. N1 being it looks like it’s got lymph nodes involved. Remember, it’s never a hundred percent sure till you actually get histological confirmation, you’re just looking at radiological images and N1 has got metastases, so that patient is probably not going to be curable. But again, it depends on on the cancer.
And there are also specialised radiologists who are interventional radiologists. And they will be taking percutaneous biopsies of, let’s say, liver or retroperitoneal pancreas that can’t be reached by endoscopic means and they’ll be putting in radiological stents. So if someone presents with obstructive jaundice secondary to a cholangiocarcinoma in the liver, you can’t get their endoscopicly. It has to be done percutaneously via, remember from last year, PTC per cutaneous tranhepatic cholangiography.
Surgeon & Gastroenterologist (tend to work in tandem)
They can take oesophageal and gastric biopsies to get the diagnosis. They can put in oesophageal endoscopic stents to combat dysphagia.
We have the ERCP to relieve biliary obstruction and endoscopic ultrasound biopsies if required.
Oncologist
Coordinate the whole thing.
So some some cancers, let’s say get gastric, will have preoperative chemotherapy because there’s a lot of evidence to show that patients who have the preoperative chemotherapy do better than those to go straight to surgery.
So remember, there’s a big difference between neo adjuvant and adjuvants. Neoadjuvant is before surgery sometimes to try and get the tumour to become smaller, to make it operable.
Adjuvant is essentially the tumour has been taken away. In theory, there’s nothing left there. But there is hard evidence that patients that have no chemotherapy after their cancer surgery operation compared with cancer patients that have adjuvant therapy, the adjuvant therapy patients will do better if they are offered that.
Overall, is this patient suitable for radical ie potentially curative cancer? We say potentially because you never know what’s going to happen in the future.
Or should they have palliative therapy. So that’s chemotherapy, knowing that you’re not going to cure the patient. But the aim there is to extend that person’s life.
Or palliative care, which is no treatment at all. And they allow the disease to progress. They’re not fit enough for any other treatment.
If the patient has decided, they’re not fit enough for any form of treatment, and that she was going to make them worse. They will be then seen by another member of the MDT team called Palliative Care Physicians, and they’re supported by CNS’s and CNS. You saw in the previous slide is cancer nurse specialist.
Gastric Cancer - Pathogenesis
Essentially, the major driver of gastric adenocarcinoma is anything causing a chronic gastritis.
- So the commonest cause, which is treated very effectively, is Helicobacter pylori infection. And essentially, that’s causing inflammation of the gastric mucosa, causing a gastritis, especially in the antrum of the stomach and infection of the antrum of the stomach can actually lead to duodenal ulcers, and that can lead to increased acid, pensinogen liberation etc. Epithelium is exposed to increased chemical attacks that would cause metaplasia of the epithelium and then that’ll progress through to cancer.
- Another thing we mentioned before was pernicious anaemia. That’s essentially autoantibodies, the body producing antibodies against themselves, against parts and products of the parietal cells. That’s a known predisposition to gastric adenocarcinoma.
- Patients that have partial gastrectomy before. So before PPIs ie proton pump inhibitors, surgery was the commonest way of treating an ulcer. With that, you have to join a piece of small bowel to the stomach, so bile go straight into the stomach. And that bile reflux into the stomach is known to predispose to gastric cancers again, it causes chronic gastritis.
- Epstein bar virus infection is associated.
- Family history is very important. There is some heritable cancers, eg diffuse-type gastric cancers due to E-cadherin mutations.
- High salt, diet and smoking are associated, but not necessarily that strong an association.
Pathogenesis
This slide is just merely to point out we got chronic gastritis. This is surface cells, stem cells, parietal cells. You get inflammation. You get atrophy. It responds with hyperplasia. You get mucinous metaplasia, and you get intestinalization, otherwise known as intestinal metaplasia, that then progresses to dysplasia and then that would become a cancer.
So as I said before, normal GI tissue can acquire changes in a stepwise manner, going from Premalignant lesions eventually onto a cancer. And you’ll see that pretty much all cancers you see in colorectal cancer, we’ve seen that with Barrett’s oesophagus and so forth. You’ve also seen it with pancreatic cancer. etc.
Presentation
So if you’ve got gastric cancer, how do you present?
Usually symptoms are not that strong. The most common presentation is dyspepsia, and that’s upper abdominal discomfort after eating or drinking. And they don’t have any hard symptoms, so you can have a cancer and not know anything about it. But there are certain red flags. ALARMS55
So think of the patient presenting with anaemia, always have in the back of your minds, they might need an endoscopy.
If they have weight loss or appetite, again, non-specific symptom, but always have it in the back of your minds.
If they have an abdominal mass. Well, that’s an examination. That’s obviously you have to react to that.
If they’ve had sudden progressive symptoms, so background of six months, a year of a certain particular problem, then it suddenly accelerates.
They described Melaena or haematemesis definitely red flags
If they have any swallowing difficulty. That’s a hard sign.
And if they’re over 55 years of age
Diagnosis & Staging
Diagnosis is very similar to oesophageal cancer, you can usually get your answer with an endoscopy and a biopsy. Once proven by the pathologist that this patient has gastric cancer. You then have to stage that tumour, to see extensive it is. Start off with a C.T. scan of the chest, abdomen, pelvis. Abdomen is obviously looking for local disease around the stomach, looking for local nodes. Chest is to look for lung metastases. And obviously you also need to look at the pelvis, as sometimes there will be dropped metastases within the pelvis, so that’ll give you information on distant lesions.
People with gastric cancer that they are considering to operate on, they will also do a PET scan, positron emission tomography C.T. And that is there to pick up lesions you just can’t see on C.T. scans, and you’re looking for metastases. There’s no point doing a local resection if they have distant metastases. If the patient has clear C.T. scan, just abdomen, pelvis and clear PET scan, Upper GI surgeons will also do a diagnostic Laparoscopy, so essentially putting a camera inside quickly to look at the liver, the peritoneum or the lining of the abdomen to check they haven’t got any micro metastases that won’t be picked up on conventional imaging and are too small to be picked up on PET scans. If there’s any query about getting that local invasion. You always have an endoscopic ultrasound scan as backup to see if any local vessels are involved and so forth.
Treatment Options?
So I’ve mentioned that some pay a lot of patients with gastric cancer will have neoadjuvant chemotherapy. So they’ll have chemotherapy, which is used to reduce the size of the tumour before surgery.
If they have a tumour in the oesophago-gastric junction, there is no no choice but to do an oesophago-gastrectomy. You have to take away part of the oesophagus and part of the stomach and then use the stomach to join what’s left of the oesophagus. If it is less than five centimetres to the oesophago-gastric junction, you then need to total gastrectomy because you can’t save the Sphincter mechanism.
Anything further than five centimetres has a subtotal gastrectomy, usually a Distal gastrectomy. You need as much stomach as possible and you divide the first part of the duodenum.
If someone has had successful gastric surgery, then you also have the discussion about adjuvant chemotherapy, which may be needed in advanced cancers. So on top of the neoadjuvant, they may think of neoadjuvant if the histology is unfavourable, so lots of lymph node metastases, etc.
Sometimes it is not possible to resect something and you have to think of doing gastro-jejunal anastomosis.
Neuroendocrine Tumours (NETs)
They’re an unusual and diverse group of tumours. But they’re common within what is described as the gastroenteropancreatic tract, so stomach, bowel, pancreas.
They’re regarded as a common entity, whether they’ve come from, let’s say, the oesophagus, or they’ve come from all over the place with the GI tract. They’re all lumped together because they come from the same cells.
The other place that they occur is in the bronchopulmonary system. They used to be known as carcinoid tumours but now they are called neuroendocrine tumours.
NETs - Presentation
So, as I said, they can be from anywhere, the oesophagus stomach, et cetera. Most of the neuroendocrine tumours are actually asymptomatic. People can have very extensive disease and know nothing about it. They tends to be an incidental finding. A lot of these tumours, up to 40 percent, will secrete hormones or their metabolites. So, for example, tumours may secrete serotonin, which is 5-hydroxytryptamine. They may secrete tachykinins such as substance P and other vasoactive peptides.
But even though 40 percent of them may produce some form of hormonal metabolite, only a small percentage actually get symptoms from those metabolites. So they’re what we call secreting neuroendocrine tumours, so less than 10 percent.
If they do secrete, let’s say, Serotonin, it can result in a very distinctive syndrome called carcinoid syndrome. So the thing to remember is that if you have say, a small bowel neuroendocrine tumour and it’s secreting serotonin, it goes straight into the portal circulation, but the liver is very good in metabolising serotonin. So even though it’s secreting a lot and you see it in the blood, the liver metabolises it. So in the absence of metastatic liver deposits, you don’t see any symptoms.
Very differently, Bronchopulmonary carcinoids, because there they’re releasing their serotonin directly into the systemic circulation. So they are the ones that present with carcinoid syndrome in the absence of the hepatic metastases. If you’ve got lots of hepatic metastases and they can’t metabolise the serotonin, then patients with gastrointestinal neuroendocrine tumours will get carcinoid syndrome.
On the right here, this is the typical flushing the patients get to their face, which is to do with the vasodilatation caused by the serotonin. They get bronchoconstriction, they get diarrhoea, increased intestinal motility. They can also get problems with their hearts, so particularly right sided, serotonin causes endocardial fibrosis, which can then lead to predominately right sided valve lesions, such as Pulmonary and tricuspid incompetence. So this is pulmonary regurgitation, and tricuspid regurgitation, and that’s known as carcinoid heart disease. Again, relatively unusual.
NETs – Clinical features
So, as I say, only 10 percent produce hormones that produce a symptom. The commonest we come across are patients with insulinomas. And what they’re doing is they’re producing too much insulin, so they’re forever becoming hypoglycaemic. And they work out that if they can eat food, then they don’t have their odd episodes. When I say odd episodes, a lot of people are diagnosed as having epilepsy because their blood sugar goes too low, they then collapse and have seizures. They are then thought to be an epileptic, they have their driving licence taken away from them, and they eventually, many years later, are found to have an insulinoma, which is persistently lowering their blood sugars. Other patients have partners, husbands, wives etc. who think that their partner has been drinking, but actually they’ve become hypoglycaemic and are acting as though they’re drunk.
The Whipple’s triad is used to help diagnose an insulinoma.
- You have to have symptoms that can be caused by hypoglycaemia, so query epilepsy, blurred vision, etc.
- They have to be proven to have a low plasma glucose measured at the time of their symptoms.
- And number three of the triad is that the symptoms must be relieved when you give them glucose to make their blood sugar rise.
So these patients are often undiagnosed for many years and they’re absolutely enormous because they’re constantly having to eat. Some people set alarms in the middle of the night to be able to eat food.
Glucagonomas are exactly the opposite, you get diabetes mellitus, you also get a very distinctive necrolytic migratory erythema. It’s very distinctive, it’s a red blistering rash that spreads across the skin, usually around the mouth, distal extremities but you can get it on the lower abdomen, buttocks. It is strongly associated with glucagonoma, but sometimes with liver disease or intestinal malabsorption (think due to lack of aminoacids?).
Further on here, gastrinomas can cause Zollinger Ellison syndrome, and essentially what that’s doing is, your gastrinoma is producing too much gastrin, that increase in gastrin is causing peptic ulcers, lots of abdominal pain and diarrhoea. So that happens within the pancreas and duodenum.
Within the entire gastrointestinal tract, you can get what we call VIPomas. These are vasoactive intestinal peptides. Too much of that can cause something called Verner-Morrison Syndrome, which presents with watery diarrhoea. (think VIP causes VMS)
Somatostatinomas are associated with gallstones, diabetes, steatorrhea.
In the midgut, most of these are non-functioning. In fact, most neuroendocrine tumours we see we describe as non-functioning- we find them, but they’re not causing symptoms.
Hindgut are usually non-functioning as well.
NETs - Diagnosis
So when suspected, you need to do investigations to localise that tumour or prove it’s there. You need to confirm the diagnosis, also with histology. Biochemical assessment, will be to look for gut hormones, we’ve mentioned insulin, gastrin, glucagon, somatostatin and VIP already. And also PYY-peptide tyrosine tyrosine-which is associated with appetite. So all of these must be measured in the fasting state.
Should always do other screening, as mentioned for MEN1, looking for pituitary adenoma, parathyroid hyperplasia, pancreatic tumours, etc. Multiple endocrine neoplasia type 1 (MEN1) is a hereditary condition associated with tumors of the endocrine (hormone producing) glands. The most common tumors seen in MEN1 involve the parathyroid gland, islet cells of the pancreas, and pituitary gland.
You also do a 24 hour urinary 5-HIAA (5-Hydroxyindoleacetic acid), which is the main metabolite of serotonin.
Then imaging to see exactly where it is and to see if there have been any metastases, cross-sectional C.T. scan, bowel imaging which would be either endoscopy, rarely do barium follow throughs now, but certainly do capsule endoscopies, that is essentially a little capsule which has got a camera in it and you swallow it, and it goes all the way through the GI tract, and you use it especially to look at the small bowel. You can access the oesophagus stomach and duodenum with endoscopy. You can access the whole of the large bowel, but the bit in between the small bowel is difficult. So using capsule endoscopy for that.
Endoscopic ultrasound Scan is invaluable in trying to find pancreatic neuroendocrine tumours. And there’s something called somatostatin receptor scintigraphy. Basically neuroendocrine tumours express somatostatin, so you give radio labels intravenously and then you take x rays and nuclear medicine.
NET - Insulinoma
left pic:
This is a C.T. scan of the abdomen and it’s an arterial phase. This is the pancreas. And I’m hoping you can see just here, the really white bit is the splenic artery, but just above that is a very distinct round lesion, and that’s an insulinoma.
right pic:
This is the gallium dotatate whole body PET/CT scan. So you’re identifying somatostatin receptors, spleen lights up, kidneys light up, liver lights up, that’s normal. But this is the pancreas. And then you see that this (white circle bit) is what we call have it gallium avid. It’s bigger than the actual lesion itself because it’s so active, so that’s how you help diagnose it.
NET- Midgut
Just an example of a midgut tumour. This is all small bowel. Often you don’t actually see the primary tumour, but what is very distinctive is they metastasise to the local lymph nodes very quickly, and that is a metastatic lymph node deposit. (see where marker is)
Top right
This is in real life, that small bowel. Obviously, all that small bowel has to be removed because that’s the blood supply coming in there, that is the mesenteric metastases.
Bottom right
Often tiny lesions can only be found at operation itself, it is usually very small.
Grading of GEP-NETs
Very briefly, tumour grading of gastrointestinal mets is very important. Gives valuable prognostic information and influences the management.
Grade one is essentially described as being lazy. You look at something called Ki-67 index.
If you go to grade three, you’ve got mitosis greater than 20 and a Ki-67 index greater than 20. That is equivalent to a neuroendocrine carcinoma. So I find neuroendocrine tumours very difficult to describe. They are described as cancers, especially when they’re high grade at G3, but even lower grades act like cancers, they metastasise. Patients often do a lot better than patients with cancer per say adenocarcinomas or squamous cell cancers. But they’re important within the gastrointestinal tract.
Survival according to Grade of pNET
Why is the grading so important? Well, you go to years here. Green is patients with grade three, most of them are dying. Grade two, not many. Grade one. Lots of people living. This is months 240, you’ll have patients living for many years with very widespread disease.
Primary GEP-NET Sites & Frequency of Liver Metastases
They can all metastasise. The small intestine makes up a total of 28 percent of the neuroendocrine tumours within the gastrointestinal tract.
But they’re the ones that metastasise the most to the liver, etc.
With the pancreas being second highest.
Treatment Modalities for NETs
Treatment is if possible resect it, so it’s gone and there’s nothing left.
Gets a bit more complicated when people have syndromes MEN1, because then they often have multiple tumours, and you have to do very big surgeries to take them away so that there are options to watch and wait.
Unlike Adenocarcinomas, you can actually do operations where you take away say 90 percent of the tumour and leave 10 percent. Those patients do a lot better than not doing anything at all. That doesn’t happen with adenocarcinomas, but you can do that with those. These patients do have liver transplants. So, Steve Jobs, you remember he had a liver transplant as he had a neuroendocrinetumour in his pancreas, which he treated with herbal remedies, et cetera, to start with, then had his operation, then got liver mets, then had a liver transplant.
There are many different ways of treating neuroendocrine tumours.
Embolisation-(ie cutting off blood supply to mass) TAE stands for trans arterial embolisation, so that’s what we call bland embolisation. RFA stands for Radio Frequency Embolisation. The alternative nowadays is microwave ablation.
Chemoembolisation TACE is trans arterial Chemoembolisation. You can use radioactive microspheres that’s called SERT, otherwise known as selective internal radiotherapy.
I’ve told you before, gallium scans work because neuroendocrine tumours express somatostatin receptors so you can radio label somatostatin eg with Lutetium and use that as a therapy.
At the bottom are the experimental ones.
Session review
