Gastrointestinal Cancers Lecture Flashcards

Question

Gastric Cancer - Pathogenesis

Answer 1

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.

Answer 2

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.

Answer 3

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

Answer 4

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.

Answer 5

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.

Answer 6

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.

Answer 7

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.

Answer 8

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. 1. You have to have symptoms that can be caused by hypoglycaemia, so query epilepsy, blurred vision, etc. 2. They have to be proven to have a low plasma glucose measured at the time of their symptoms. 3. 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.

Answer 9

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.

Answer 10

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.

Answer 11

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.

Answer 12

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.

Answer 13

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.

Answer 14

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.

Answer 15

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.