Welcome to First Incision, the podcast about preparing for the General Surgery Fellowship exam. I'm your host, Amanda Nikolic. Hello, and thanks for joining me today on another episode of First Incision. Let's do our team timeout. Our patient today is the upper gastrointestinal module of the general surgical curriculum. And our patient or the topics we're going to be covering today are gastrointestinal stromal tumors and other gastric tumors. Specifically, I'm going to touch on gastric lymphoma.
neuroendocrine tumours of the stomach. We'll briefly talk about gastronomas and Zolliger-Ellison syndrome and also I'll briefly go through gastric polyps. So let's get started. We'll kick off today with gastrointestinal stromal tumours, or GISTs. Just as a bit of an introduction, these are pretty rare and are mostly discovered incidentally, so the true prevalence of these tumours is not known.
GIST tumours arise from the interstitial cells of Cajal, which are the pacemaker cells in the myenteric plexus, and therefore it's a mesenchymal tumour. Most disturmurs are thought to occur sporadically, but less than 5% are thought to potentially have a hereditary component. And this can be associated with neurofibromatosis 1, or there's also a... syndrome called Cerny's triad, C-E-R-N-E-Y apostrophe S. And this is the presence of a gastric gist.
extraadrenal paraganglioma or phaiochromocytoma, and pulmonary chondrites. So those are the two GIST syndromes to be aware about. GIST is often diagnosed, like I said, instantly, but it can present with symptoms. If it's very large, it can cause nonspecific abdominal symptoms such as bloating, early satiety. pain or even a palpable abdominal mass. Some patients will present with an emergency presentation from a complication of their gist tumour and this can include a bleeding gist, obstruction,
or perforated gist tumor. Approximately 50 to 60% of gists that occur in the gastrointestinal tract are in the stomach. There are juice that occur elsewhere such as in the small bowel, colon and rectum and even esophagus but we won't be talking about those today. They're often diagnosed via endoscopy. This will often find a... rounded, smooth surfaced lesion, often with a central depression.
It's usually found submucosally, so you might find normal mucosa overlying this mass. And the differential diagnoses of this appearance could include an atypical adenocarcinoma, a lymphoma. a leiomyoma or a leiomyosarcoma. So it's important when you're seeing something like that to think about the differentials.
GIST tumors are difficult to biopsy endoscopically because of the usually normal overlying mucosa. It can be difficult to get a representative sample of the tumor through superficial biopsies.
An adjunct that can be used is an endoscopic ultrasound and fine needle biopsy under the guidance of the ultrasound. This may not necessarily... be required if the appearance and imaging suggests an early small lesion that's going to be resected, but especially if there is atypical features, if it's a locally advanced tumour.
potentially involving other organs, or if the patient is going to be considered for neoadjuvant treatment, then a tissue biopsy is required. So you may need to do that via an EUS. Talking about the biopsy, I'll briefly discuss the histopathology findings of a disc tumour. Basically, there are three histopathological subtypes, and this includes spindle cell appearance,
an epithelioid appearance, or it can be a mixed appearance, mixture of those two. The spindle cell appearance is the most common of these with about 70% of GIST having that appearance microscopically. Immunohistochemistry is key in differentiating between GISTs and other types of connective tissue tumors that may have a spindle cell appearance. And the key here is that... More than 90% of GIST will be positive for CKIT. And CKIT codes a tyrosine kinase receptor, which is called KIT.
And this receptor can be stained for on the cells of the tumor. And the stain that's used is the CD117 immunohistochemistry stain. This is really important when talking about treatment, which we'll go into a little bit. but we do have a targeted therapy for CKIT positive GIST tumours. GIST tumors are also mostly positive for the CD34 stain. About 70% of GISTs will be positive for CD34. Less than 5% of tumors will lack that CKIT mutation.
Of those 5%, some of them will instead express a PDGF-alpha receptor. So this is a platelet-derived growth factor receptor alpha. And this is a different tyrosine kinase. receptor, which is structurally very similar to KIT. But it's important to know whether or not that GIST is C-KIT positive or PDGF alpha positive. There is a wild type of GIST tumors, which may be...
positive for BRAF as well. And the mutations matter because of the treatments that we have and will guide which patients get specific treatments and also can help predict which patients may respond to the different treatments that we have. So we've talked about presentation, diagnosis, macroscopic and microscopic appearances. So let's cover...
staging tests, the metastatic and malignant potential of these tumours, and also the management. So once you've diagnosed a gist, you do need to stage that patient. The standard staging test that we do would be a CT scan of the chest, abdomen and pelvis with IV contrast. And this gives you a look at the primary tumor, both the size and location. Usually it will appear as a solid.
mass, which enhances brightly with the IV contrast. However, there may be aspects of necrosis or hemorrhage which do not enhance with contrast. They can grow both submucosally, intraluminally, and they can also have an exophytic appearance where they're growing outside of that organ. So that may not be apparent at endoscopy.
You may also be able to see on the CT scan whether there's any involvement of surrounding organs and also make an assessment about whether there's any distant disease. PET scans are another investigation that can be done for disc tumours. Most of them will be PET-AVID and it can be useful especially in assessing response to treatment, especially if neoadjuvant or adjuvant tyrosine kinase inhibitors are going to be given.
It also is superior to CT alone in assessing whether or not there are liver metastases. Saying that though, it's not funded in Australia according to the most recent... pet funding guidelines. But we had a shoot the other day by a consultant from Peter McCallum Cancer Centre who said that they would routinely do a PET scan for GIST. So I guess it would depend on the clinical situation and probably the MDT discussion.
There is a AJCC TNM staging classification for GIST tumours. This takes into account mostly the size of the tumour when determining the T stage. One tumor is usually less than two centimeters. T2 is greater than two centimeters, but less than five. T3 is five to 10 and T4 is greater than 10. It's pretty rare to have regional lymph nodes, but they do say N1 is if there's regional lymph node metastases. And then distant metastases, they classify as M1.
This classification also takes into account the mitotic rate, which is either low with five or fewer mitoses per 10 high-powered fields or high for more than five mitoses. Stagings of GISTs is important because GISTs do have a malignant potential. Metastatic disease from GISTs usually spread via hematogenous.
and also direct spread through peritoneal metastases. It's pretty rare to have lymph node involvements with GISTs. And at presentation, about half of patients will have distant metastatic disease. The malignant potential of a tumor can be determined based on certain high-risk features. So this includes the tumor size, the mitotic index or mitotic count per 50 high-power fields.
and the primary tumor site, as well as whether the tumor has ruptured and whether there's any presence of vascular invasion or whether the patient is CKIT positive or negative. there is a Fletcher criteria for GIST risk assessment, which is based just on the size and mitotic count. So it's worth having a look at that. And essentially for gastric tumors, the gastric site of GIST is actually... a good prognostic factor. So it has the least metastatic potential of all other sites.
This is reflected if you have a look at the AJCC TNM staging. When you look at the stage grouping, they look at gastric and omental gists separately to gists in other sites when they determine the stage of the disease. So moving on now to a discussion about the management of gastric gists. The first thing is, as with all of our cancer management plans, this should be run through a multidisciplinary team meeting.
And the options really are conservative management, surgical resection, or targeted therapies. Conservative management seems strange when we're talking about a tumor that has a malignant potential. but definitely for incidentally discovered small lesions in the stomach. risk of this disease progressing or becoming metastatic is very low. So for example, if you had a less than two centimeter gastric gist that had a low mitotic rate,
the risk for progressive disease in one study was 0%. So this is a sort of tumour where you could observe it with serial endoscopies and imaging and potentially not need any treatment at all. Surgery is the next management approach and really this is the mainstay of treatment for GIST. Local resection provides the highest chance of a cure. Surgery may be considered first line in low-risk, localised disease. There's no metastatic disease and the tumour looks to be locally resectable.
The principles of resection are firstly to aim for a negative macroscopic margin. Secondly, to keep an intact pseudocapsule and especially to avoid tumor rupture. And thirdly, that an anatomical resection with a extended lymphadenectomy is not required because these tumours spread hematogenously and not through regional lymph nodes.
Like I said, you only need a macroscopic margin. It's not like you need a 5 or 10 centimetre margin as with tumours in other parts of the GIT. So a local resection is sufficient. And the key is to avoid disseminating any tumor cells into the peritoneum or rupturing the tumor capsule. This reduces the median survival of a resection of a local tumour from 46 to 17 months, which is similar to not operating or treating these tumours at all. So it's a pretty significant...
technical factor that can change a patient's outcomes. If there is involvement of adjacent organs, then the involved sections should be removed on block with the GIST resection. The approach to resecting one of these tumours really depends on the tumour's size, the location of the tumour, and whether there's any involvement of adjacent organs.
And there are a number of different options for resection for gastric tumors. This could include a wedge, a sleeve resection, a distal gastrectomy, or a total gastrectomy. And like I said, it depends on the... tumour location, size and involvement of other organs. So for example, a exophytic tumour in the... anterior surface of the stomach or the greater curve may be resected easily with a laparoscopic stapled wedge resection of the stomach.
If there's a large tumour, it may be endophytic, it may be on the posterior wall or lesser curve, it may be... better resected with a formal gastrectomy. So it really depends on looking at the imaging, looking at the endoscopy and making an assessment about how you can safely remove the tumor. Moving on now to targeted therapies. Targeted therapy can be used in the neoadjuvant setting, adjuvant setting, or in the palliative setting. Indications for neoadjuvant targeted treatments include a
Large or locally advanced tumor where you are trying to downstage or downsize that tumor before resection. It can also be given neoadjuvantly if you think that the tumor is high risk pre-operatively. It can be given adjuvantly in patients who have high-risk disease as per that classification I was talking about earlier.
Fletcher criteria which gives you an assessment about the likelihood of local recurrence as well as metastatic recurrence so if you had a high risk tumour you may consider adjuvant targeted treatment and it can also be used as first line in metastatic GIST with metastatic disease. When we're talking about targeted therapies, we're talking about tyrosine kinase inhibitors. The most common one of these is imatinib.
also called Gleevec is the brand name. And basically this blocks the signaling via either that KIT tyrosine kinase receptor or the PDGFRA receptor. It's pretty cool that there is a targeted treatment for this particular tumour. This is what we're hoping to see across the board with our cancer treatments. But the majority of tumours, of GIST tumours, will respond to imatinib. And this confers a significant survival advantage with over 50% five-year survival.
even for metastatic or unresectable disease. There are a couple of other types of tyrosine kinase inhibitors, and this includes sunitinib, which also inhibits VEGF, and that is used as a second line. treatment for patients who are intolerant or refractory to imatinib. And there's also regorafenib, which is good. indicated for locally advanced or inoperable gists that no longer respond to imatinib or synitinib. And there's a couple of others, but those are the main ones to know about.
There's no role for chemotherapy or radiotherapy in primary GIST treatment. There is some evidence that treatment of liver metastases may confer a survival benefit, and that may include... TACE or radiofrequency ablation or even selective resection of liver metastases. But this is probably above the level we need to know for the exam. The last thing I'll touch on in terms of GIST is the follow-up.
So there's no real guidelines about post-surgery surveillance, post-resection of GISTs. Based on some reading and that recent shoot that I listened into from Peter McCallum Cancer Centre, They suggested that if you have a completely resected GIST that's low risk, that these patients undergo a clinical assessment every three to six months for three to five years, and then an annual assessment.
as well as a CT scan every three to six months for the first two years and then annually thereafter. In patients who have a locally advanced or metastatic GIST and patients who are on tyrosine kinase inhibitors,
then these patients should have a clinical assessment and a CT every three to six months. And you want to be looking for indications that the imatinib is working because you may want to consider transferring them across to a different treatment if they become treatment resistant, which some patients...
will. Even with complete resection of localized GISTs, some may recur and it's thought even 30 to 40 percent will recur and about a third of those will be local disease with two-thirds being distal metastases. This is part of the reasons why patients who have high-risk disease may be given an adjuvant tyrosine kinase inhibitor. And the five-year survival after an R0 resection of a local GIST is between 50% and 75%. The next topic for today is gastric lymphoma.
I chose to cover this topic because this comes up a lot as a differential diagnosis when we're talking about findings of abnormal ulceration or tumors in the stomach. And I have seen one diffuse large B-cell lymphoma that presents... like a large intestinal type gastric cancer, but on biopsy was a B-cell lymphoma. And they're obviously treated very differently. So it's good to have a bit of an idea about these tumors and their management.
So in general, any type of lymphoma can occur in the gastrointestinal tract, and the gastrointestinal tract is the most common extranodal site for lymphoma. 50 to 70% of lymphomas that occur in the gastrointestinal tract occur in the stomach. The two most common types that we see in the stomach are malt lymphoma and diffuse large B-cell lymphoma. The risk factors for development of gastric lymphoma include Helicobacter pylori, HIV, Campylobacter, EBV, Hepatitis B,
and immunosuppressive treatment. And these patients will present similarly to gastric cancer. So they can present with local symptoms of early satiety, abdominal pain, bloating. vomiting, or they can present with complications such as bleeding or obstruction or even perforation. In addition, they can get non-specific symptoms that may be related to the lymphoma itself. which are those B symptoms such as night sweats and fatigue. The diagnosis of gastric lymphoma is often made on endoscopy.
The findings can be quite varied and can include just an ill-defined thickening of the mucosa, contact bleeding, erosions or ulcerations. multifocal disease, or can even be a mass or large ulcer like you might expect in a gastric adenocarcinoma. It's important when taking biopsies to take good bites as gastric malt lymphoma may only infiltrate the submucosa and not the mucosa. So like I said, make sure you're getting good bites with the biopsy forceps.
Microscopically, you may see a dense lymphoid infiltration, and this is termed a lymphoid epithelial lesion, and this destroys the gastric glands, which is sort of the pathognomonic microscopic finding for lymphoma. The immunophenotype of staining with immunohistochemistry includes CD20 positivity, positivity for CD5 and negativity for CD10, CD23 and cyclin D1.
Once gastric lymphoma has been diagnosed on biopsy, it's important to complete the staging investigations for these patients. So firstly, this includes a full examination, including an examination of the lymph nodes, liver and spleen. Blood tests should be taken, which include an FBE, UEC, liver function tests, a lactate dehydrogenase, HIV and hepatitis B, C testing, as well as a beta-2 microglobulin.
Patients should also have a staging CT neck, chest, abdo, and pelvis with IV contrast. And in addition to this, they should have a unilateral bone marrow biopsy and aspirate. In order for a lymphoma to be essentially confirmed to be a gastric lymphoma and not a disseminated lymphoma, there's a few diagnostic criteria that need to be met. And this includes an absence of palpable lymphadenopathy.
A normal peripheral blood and bone marrow aspirin to refine result. The absence of mediastinal lymphadenopathy on the chest x-ray. the disease confined only to the affected gastrointestinal segment with regional lymphadenopathy only and the absence of hepatic or splenic involvement.
And there is a staging classification that's used, which is the Lugano classification, or also there's the modified Blackledge classification. They're quite similar. Basically, this classifies stage one to stage four disease. Stage 1 disease is tumour that's confined just to the gastrointestinal tract with no serosal involvement or perforation. Stage 2 involves lymph nodes local to the primary tumour.
Stage three involves perforation or penetration of the serosa with involvement of adjacent structures or organs. And stage four is disseminated extranodal disease. And this can include localization to the bone marrow.
liver, or sub-diaphragmatic nodal involvement. And it's important to stage the patient's disease adequately because this basically guides your treatment. I should say here though that the surgeon's role does... mostly end here in that we are usually involved in diagnosis and can potentially be involved in managing symptoms.
usually a referral at this point will be made to the medical oncologist who will guide treatment from here. I'll briefly take a bit of a segue now to talk about malt lymphoma in the stomach because I think this is quite interesting. Basically, the pathogenesis of malt lymphoma in the stomach is thought to be related to Helicobacter pylori and actually eradicating Helicobacter pylori in patients who have malt lymphoma and are positive.
helicobacter infection, can cause remission in up to 77% of patients within 12 months, which is pretty interesting. So usually the stomach is actually devoid of lymphoid tissue and a multoma forms. because of an aggregation of activated B cells, usually in response to an inflammatory trigger, which in this case we think is due to acute inflammation due to Helicobacter pylori infection. Those B cells can then...
Due to chronic activation, undergo malignant transformation into a malt lymphoma. Typically, gastric malt lymphoma is a low-grade disease. There's only a small proportion of patients that may develop high-grade progression. And that's thought to be due to further genetic abnormalities. But for stage one disease, so disease that's localized only to the stomach and not going through the serosa, the treatment is actually... treatment of the Helicobacter pylori with a gastroscopy.
three to six months after completion of eradication treatment and repeat sampling for both malt lymphoma and helicobacter pylori. And it's important to repeat the endoscopy to confirm both endoscopic and histological remission of the tumor. These patients can also have local radiotherapy if that fails at that point, and they do have a pretty good prognosis. For patients who...
however, have persistent disease despite helicobacter pylori treatment and also a couple of subtypes of the disease which basically have been shown to have a lower response rate to treatment. So this includes... patients with a translocation of 11 and 18, or patients with a BCL locus, so who have strong nuclear staining for anti-BCL10, these patients usually would...
have helicobacter pylori treatment, but also undergo chemotherapy. Usually this is chlorambucil and rituximab with or without radiation therapy for local disease. And their five-year survival even if they have these poor prognostic factors, is still between 90 and 100%.
For patients who have stage 2 disease or higher, they are not a candidate for just having helicobacter pylori eradication. They will usually have radiation with eradication and usually... progress to chemotherapy if they don't have a good response. Just to remind ourselves as well, rituximab is an immunotherapy, which is an anti-CD20 monoclonal antibody that, remember, when we talked about the immunohistochemistry, these tumors are often positive for CD20.
that's a good targeted therapy in this disease. There's not much of a role for surgical resection anymore in gastric lymphoma. It's definitely not considered a first-line curative. And even patients who fail their helicobacter pylori eradication therapy, these patients usually progress to chemotherapy or radiotherapy rather than having resection. There may be a role.
for surgery in patients who are in an emergency situation, such as those that present with bleeding, obstruction, or perforation, but that would have to be something that was considered on a case-by-case basis. So a pretty interesting tumour. to know about. Briefly diffused large B-cell lymphoma is a little different. This often shows on microscopy B-cells with a huge sort of nuclear size.
equivalent to a macrophage nucleus or twice the size of a normal lymphocyte. And these again destroy that gland architecture of the stomach. And some of these cancers will also have a foci of malt lymphoma associated with them, which may regress after helicobacter pylori treatment, but it's definitely not the same pathogenic pathway.
And these tumors often present as a mass rather than that sort of infiltrative appearance on endoscopy. So these are more likely to be confused for an advanced gastric cancer. But once again, these are treated by the oncologists. with chemotherapy and radiotherapy. And sometimes we are asked to help out with surgery in the case of complicated local disease.
I did mention I would talk about neuroendocrine tumors of the stomach. I'm only briefly going to touch on this topic because this is not a common site for neuroendocrine tumors and it's a huge topic. So I think we'll probably be covering this a lot more in depth in our... our next module, which will be colorectal and small bowel. Essentially, neuroendocrine tumors arise from the enterochromaffin-like cells of the...
lining of the gastrointestinal tract and only 6% of gastrointestinal tract neuroendocrine tumors are located in the stomach. There's considered to be three distinct types of neuroendocrine tumors in the stomach based on their pathogenesis. The first is type 1, and this is the large majority of gastric neuroendocrine tumors. 70 to 85% of the tumors are type 1, and these present as often small
polypoid multicentric tumors, and they are diagnosed at a mean age of 63 years and more common in females than males. And these are most associated with chronic atrophic gastritis and pernicious anemia. These tumours can metastasise. Approximately 7% to 12% of cases will have local lymph node metastases on presentation.
But these are considered neuroendocrine tumors, which means they have a low KI-67 index, usually less than 2%. And the treatment is local resection, or if there's evidence of metastases, then treatment with octreotide or somatostatin. Analogues. Type 2 is associated with multiple endocrine neoplasia type 1 or MEN1. This is a hereditary condition which is associated with tumours of the endocrine glands.
and specifically is associated with loss of the tumor suppressor gene MEN1, which is on chromosome 11p13. is associated with multicentric neuroendocrine tumors of the stomach and also duodenum and pancreatic head. And these are often... gastron secreting tumors, which can cause Zollinger-Ellison syndrome, which I will be talking about next. These can be locally invasive and can also be metastatic to lymph nodes or further.
And the type 3 are the sporadic neuroendocrine tumors. These are usually actually neuroendocrine carcinomas, which we'll probably talk about this another time, but based on the WHO classification, these are more aggressive type tumors that... usually have a high KI-67 index and mitotic rate. These are usually solitary lesions, more common in middle-aged men and very aggressive with metastases to the lymph nodes and liver.
So that brief introduction to neuroendocrine tumors of the stomach leads me into talking about gastronomas and Zollinger-Ellison syndrome. So gastronoma is, I guess, the common colloquial name for a gastrin-secreting neuroendocrine tumor. These tumors are... most commonly located in the pancreas, but can also be located in the duodenum or in the stomach. The typical description of where these tumours are found is the gastronoma triangle.
It's worth Googling a picture of the gastronoma triangle while I describe how to draw it. But basically, the top angle of the triangle is the confluence of the cystic and common bile duct. inferior angle of the triangle is the junction of the second and third parts of the duodenum and the medial angle of the triangle is the junction of the neck and the body of the pancreas and 90% of
gastronomas are located in that triangle. The size of these tumours can be pretty variable. Duodenal ones can be very small, less than one centimetre, and pancreatic ones are typically larger, up to three or four centimetres or even. even bigger. These tumors present usually due to the physiological action of the gastrin that they are secreting. Gastrin results in increased gastric acid secretion.
through stimulation of the enterochromaffin-like cells, which release histamine, and also through stimulation of the parietal cells, which release hydrochloric acid into the stomach cavity. This in turn leads to the clinical manifestations of reflux disease and peptic ulcer disease. And often you'll find that there are multiple ulcerations. intractable ulcers that aren't responding to treatment and often in unusual locations, including distal to the first part of the duodenum.
It can also cause diarrhea due to the large volume of hydrochloric acid, as well as the effect of gastrin on the small bowel. Patients who you may consider investigating for Zollinger-Ellison syndrome are patients who have refractory or recurrent peptic ulcer disease in the absence of... non-steroidal anti-inflammatory drug use or recurrent helicobacter pylori. In patients with ulceration in unusual locations, such as I just mentioned, distal to the first part of the duodenum.
Patients who have other manifestations of MEN1 syndrome who have ulceration, especially resistant ulceration. Patients with... reflux disease, refractory to PPI or with distal esophageal strictures, in chronic secretory diarrhea, and also in known gastric carcinoid tumors. And the test that you send in order to diagnose Zollinger-Ellison syndrome is a fasting gastrin level.
It's important to stop a PPI or histamine receptor antagonist prior to the test because that can cause false positives. And basically a level above 100. PG per mil is diagnostic of Zollinger-Ellison syndrome. Another way to measure it is a secretion stimulation test or a provocative secretion test. This is done after an overnight fast and basically involves measuring serum gastrin levels after an injection of secretin. IV and a positive is a greater than 200 pg per mil above the basal level.
You can also measure the gastric pH, which if it's less than two, can be consistent with Zolling-Gate-Ellison syndrome, but is not diagnostic. And all patients who are diagnosed with Zollinger-Ellison syndrome should be screened for an MEN1 syndrome as well. And this includes a serum parathyroid level. ionized calcium levels and prolactin levels. And we'll talk a little bit about monitoring or follow-up of patients with MEN1 in another episode.
Other tests that should be done if you are suspicious for Zollinger-Ellison syndrome include FBE, UEC, LFTs. CA19-9 and CEA, as well as a chromogranin A. Chromogranin A being a marker we look for in neuroendocrine tumors. So once you've diagnosed a patient with high gastrin levels and are suspicious for this Zollinger-Ellison syndrome, the next step is actually diagnosing where the tumor is that's secreting the gastrin.
That is easier said than done, though. It can be quite difficult to localise the gastronoma. There are a number of different tests we can do. The first is a CT scan. And these tumors are often hypervascular. So we would usually do a CT with an arterial phase, which may help localize the tumor. There's about a 50% detection rate for the primary tumour depending on its size and location with a high incidence of being able to localise it with a CT if the tumour is more than one centimetre in size.
We can also do an Octrea scan, which is basically a somatostatin receptor scintigraphy, so a nuclear medicine scan. These neuroendocrine tumors will have abundant somatostatin receptors. That's why somatostatin analogues are useful in treatment of neuroendocrine tumors. And specifically for gastronomas, about 80% of gastronomas can be detected with an Octrea scan, which is better than the other modalities. Another option includes a dotatate PET.
which is usually more sensitive for high-grade neuroendocrine carcinomas than it is for neuroendocrine tumors. Patients may undergo an endoscopic ultrasound with a biopsy. This can be very useful if you're looking for an intrapancreatic neuroendocrine tumor or intrapancreatic, especially in the head gastronoma, but may not be that helpful with duodenal wall or gastric wall tumors.
MRI scans with gadolinium can be done to look for liver metastases, but usually aren't helpful in localizing the primary tumor. And all patients should have a staging CT chest, abdo pelvis. to determine the extent of disease and guide treatment. About 50% of these tumours will be metastatic at diagnosis. The treatment of gastronomas or neuroendocrine tumors secreting gastrin or Zollinger-Ellison syndrome, whatever you want to call it, is multimodal. This includes medical treatment, surgery.
radiotherapy and systemic chemotherapy. Medical therapy is the most important first step. And this is to control the patient's symptoms and reduce the ulceration associated with the high gastrin levels. And this is a high-dose PPI. Patients can also have somatostatin analogs, such as octreotide, which can be quite successful at inhibiting that gastrin secretion. And this can be given as first line and may result in symptom control for many years.
Surgery is indicated to remove the primary tumour and also will result in decreasing the likelihood of developing metastatic disease in the future and can also reduce the amount of medical therapy that patients require. However, easy to say surgery, but depending on whether you've been able to localize the tumor beforehand and also given, especially with the MEN1 syndrome, that these tumors can be multiple, the actual...
surgery for these tumors is quite complex. It usually requires an extensive exploration, looking at the duodenum with a duodenotomy, looking... At the whole gastronoma triangle, you can use endoscopic transillumination to find duodenal disease and also often involves mobilization of the hepatic flexure. examination of the lesser sac, cocorizing the duodenum, and lifting up the head of the pancreas to allow inspection, palpation, and even intraoperative ultrasound.
Usually the tumours are able to be enucleated, especially if they are sporadic and not associated with MEN1. Lymph endectomy is usually not indicated unless the tumour is very large or locally aggressive. Because this is a neuroendocrine tumor, and I'm sure we'll go into this bit more when we talk about them in detail, but there is some evidence of improved survival with metastatectomies from the liver for these tumors. So there may be a role.
for liver surgery, either resection, radiofrequency ablation or cryoablation or even liver transplant with metastatic disease. Patients who are very symptomatic but not surgical candidates I may benefit from radiotherapy. However, these tumors are not particularly radiosensitive, but that's always an option. And there's also sometimes systemic chemotherapy used, especially in the setting of metastatic disease.
In terms of prognosis, 90% of these neuroendocrine tumors or gastronomas are malignant. The sporadic ones have a cure rate of about 60% with resection. and have 40% disease-free survival at five years. The patients who have MEN1 syndrome-associated gastronomas have a worse prognosis and... Few patients with gastronomas or Zollinger-Ellison syndrome are cured in the context of MEN1.
Gosh, it's been a bit of a mixed bag of topics today. Sorry to be jumping all over the place. I wanted just briefly to go through gastric polyps. I guess I've been studying a bit of colorectal recently, so I've got polyps on the brain. Just in summary, there are a few different types of polyps found in the stomach. The most common ones of these are fundic gland polyps, hyperplastic polyps, and adenomatous polyps.
Funded gland polyps are the most common type. These can be associated with familial conditions such as FAP or can be sporadic in about 10% of people and also is associated with PPI use. Typically, there's a few polyps and they're small, sort of half centimeter in size. And their risk of dysplasia is very, very low. And their malignant risk is also very, very low. So usually we would, if we saw these, biopsy a sample of them to prove that they are benign fundic gland polyps.
sometimes I've seen them not be biopsied at all. Hyperplastic polyps are polyps that are composed of both epithelial and stromal components. And these are frequently found in the antrum of patients, especially if they have an underlying inflammatory condition, such as Helicobacter pylori infection. Most of these will resolve once the inflammatory cause is removed. So treating the helicobacter pylori and putting them on a PPI will usually result in these polyps going away.
And the pathogenesis of these polyps is basically a hyper-proliferative response to the inflammation and injury to the mucosal lining. Some of these polyps will have dysplasia or focus of dysplasia. And this is more likely the larger that they get. So polyps that are more than two centimeters in size have a small risk of being dysplastic. These aren't thought to be part of the...
polyp 2 carcinoma sequence. These are more a surrogate masker of cancer risk. So patients who have this plastic, hyperplastic polyps are more likely to have asynchronous gastric cancer. And these usually look... quite smooth or can be sort of more polypoid and look like they have a villus-type surface and can be eroded on the surface as well. Usually these are resected to rule out dysplasia or malignancy.
The last type I'll talk about is the adenomatous polyp. And the classical intestinal type adenoma is pretty rare to be found in the stomach. If it is found, it's usually found along the lesser curve. It's usually solitary. They're usually quite well circumscribed and can either be pedunculated or cessar like adenomatous polyps elsewhere. But these are potentially a precursor to gastric adenocarcinoma with an increasing risk of malignancy as the size of the polyp increases.
So as in colorectal carcinoma, for example, a polyp that's more than two centimeters in size can have up to a 50% chance of harboring an adenocarcinoma. So that's good to know about. There are other polyps that... can be found in the stomach, including like hematomatous polyps, such as in juvenile polyposis, Cowden disease, or Piotrziaga disease. And also, I forgot to mention that adenomatous polyps are also commonly found.
in FAP mutations. So that's something to be aware of. And those patients do require endoscopic monitoring for the development of these polyps. I think that mostly covers the gastric component of the curriculum for the upper gastrointestinal module. I have a couple more topics to cover for esophageal pathology, but I think that that's enough for stomach for now.
Let me know if there is a topic I haven't covered yet that you would like to hear. Also remember to rate, review and subscribe so that other people can find the podcast. It's time to close up. Thanks for listening to First Incision. If you have any comments or feedback, send us a message at firstincisionpodcast at gmail.com or follow us on Instagram at firstincision. Happy studying!