Welcome to First Incision, the podcast about preparing for the General Surgery Fellowship exam. I'm your host, Amanda Nikolic. Let's get started with our team timeout. Our patient today is the surgical oncology module from the general surgical curriculum. The topic we'll be covering today is retroperitoneal sarcomas.
And I've added on to the end of this episode the chat I had with Julie Howell about retroperitoneal sarcoma. Julie Howell is a surgical oncologist from Westmead Hospital in Sydney who looks after these tumours. Retroperitoneal sarcomas account for about 15% of all soft tissue sarcomas, but they are still very rare. About half of retroperitoneal sarcomas are liposarcomas, a quarter are leiomyosarcomas, and the other quarter are a mix of those other subtypes.
The most common presentation is that these are found incidentally or accidentally on imaging. Most patients are asymptomatic, but if they do have symptoms, it might be increasing abdominal girth, back pain. or evidence of mass effect of the tumour, so nausea, early satiety, or abdominal discomfort. And the median size at presentation for retroperitoneal sarcomas is 20 centimeters. So they can get really, really big. Most retroperitoneal sarcomas don't have metastatic disease at diagnosis.
In our curriculum, it talks about understanding the regional anatomy of the retroperitoneum. So the retroperitoneum is defined anteriorly by the peritoneal extensions that anchor the transverse colon, small bowel, ascending and descending colon. The posterior aspect of the retroperitoneum is a muscular wall which comprises the psoas major and minor muscles, quadratus lumborum, obturator internus. piriformis, and the tendinous portion of the transversus abdominis muscle.
Superiorly, this space is bordered by the diaphragm and inferiorly by the levator ani muscles and laterally by the ascending and descending colon as well as the peripheral margin of the quadratus lumborum muscles. In terms of the differential diagnoses for our retroperitoneal mass, obviously retroperitoneal soft tissue tumors and sarcomas are on the list. And this also includes desmoid tumors.
Lymphatic tumours are another differential, so primary including lymphoma and secondary, especially... testicular tumors such as germ cell tumor metastases as well as colorectal, ovarian and vesicle metastases to retroperitoneal lymph nodes.
Other differentials include paragangliomas, which are extra adrenal pheochromocytomas, schwannomas that can be benign or malignant, and other tumors that can happen in retroperitoneal organs, such as a adrenocortical, adenocarcinoma, a renal cancer, pancreatic tumor, or tumors extending from the colon or duodenum.
Some benign potential differentials include tuberculosis infections, abscesses, especially extending from diverticular or appendiceal pathology, a psoas abscess or retroperitoneal hematoma. and retroperitoneal fibrosis. So how do we work up retroperitoneal sarcomas or retroperitoneal masses? You're going to start with a history and examination to try to determine whether this is primary versus secondary disease and also to see whether there's any extra abdominal disease.
So asking about secondary disease includes asking about those differential diagnoses we just talked about. So could this be a lymphoma? Have they noticed other masses elsewhere in their lymph node basins? And have they had any type B symptoms such as fevers, night sweats or weight loss? If they're a man, have they noticed any masses or changes in their testes?
Do they have a family history that suggests a familial predilection to any types of tumors, such as FAP and the development of desmoids, leave from any syndrome and sarcomas, or neurofibromatosis? And have they had any exposures that increase their risk of sarcoma, such as radiation exposure? previous surgery that may lead to lymphedema or exposure to different types of carcinogens that we talked about at the start of the episode.
You also want to rule out the possibility of a benign pathology by asking about fevers, chills, sweats, abdominal pain, or an indication that they may have. hematogenous seeding to the psoas muscle such as IVDU or other comorbidities that increase the risk of infections. In terms of blood tests, you want to do your general blood tests such as FBE, UEC and LFTs, but it's also a good idea to add on an LDH to rule out lymphoma or investigate the possibility of lymphoma.
An alpha-feta protein and beta-HCG if you're worried about germ cell tumors. And also if it's not clear whether this might be an adrenal tumour to make sure you're doing the functional testing for adrenal cancers or other adrenal tumours. So the next step for retroperitoneal sarcomas, which is different from soft tissue extremity sarcomas or trunk sarcomas, is that usually a CT chest, abdomen, and pelvis with oral and IV contrast is used.
to further characterize these lesions and not an MRI. With these tumors being very large, it can sometimes be difficult to tell whether they truly are retroperitoneal or intraperitoneal. And some potential clues on the CT is that you may see displacement of the pelvic ureter, effacement or encasement of the iliac vessels. effacement of the pelvic sidewall musculature and displacement of the rectum. And the other thing that's quite pathognomonic is like an anterior.
displacement of the kidney. I definitely suggest having a look at some CT scans of retroperitoneal sarcomas because they can be quite subtle, especially if they're mostly lipomatous lesions and you may not be able to gain a good appreciation of the full extent of the tumor because it just looks like fat. But having a look at different pictures can help increase the likelihood you're going to see this in the exam if you're given a picture of one.
On the imaging as well, you want to be looking generally to make sure there's no evidence of any metastatic disease. With retroperitoneal sarcomas as well, at least from the Peter Mac tutes I've been to, it seems like they would consider a PET scan more frequently than they would for peripheral tumors.
Mostly, I think this is because the most common tumors are liposarcomas and these will often have a de-differentiated segment. So they're mostly fat, but then there may be a solid component. And determining the most... pet avid part of the tumor helps to guide the biopsy. MRI is sometimes used for retroperitoneal sarcomas, but definitely not routinely.
You can use it if you're worried about the anatomic relationship of the tumor to adjacent organs and also to look for liver metastases. The other thing to consider is if... Your operative plan might include a nephrectomy. You need to do some functional renal imaging, such as with a MAG3 or a DMSA scan, in order to determine that the other kidney is functioning.
At this point, again, you should be referring the patient to a sarcoma center because, as we've already talked about, these patients should be managed at a specialty center. The question is... from here, whether a biopsy is required. And to be honest, I've heard different opinions about whether or not you definitely need a biopsy if you're planning on doing a resection anyway.
In general, I would say that a CT-guided core biopsy would be important for preoperative diagnosis of the tumor, what type it is and its grade, because that may influence your treatment. Another indication for a biopsy would obviously be if the tumour was not resectable in order to guide adjuvant treatment. A biopsy should be done at a specialty center and it should be a CT-guided core biopsy and not an excisional biopsy.
And the sarcoma service will guide where the biopsy should be performed. That both takes into account the risk of tumor tract seeding and also... trying to target the area of the lesion that's most likely to give you the correct pathological answer, which will be guided by the radiology and the PET scan. The other important reason to do a biopsy is that...
Some of the differential diagnoses we've talked about don't need surgery, such as lymphoma. So obviously you want to tailor your surgery to the type of the tumour and you can't always tell that from the imaging. And the other interesting thing we've already talked about is... that for a lipomatous lesion, we can do that special testing, the MDM2 fish testing, which will be able to differentiate a simple lipoma from a well-differentiated liposarcoma.
The TNM staging system for retroperitoneal sarcoma is basically the same as for soft tissue sarcomas elsewhere. So the T stage is based on the size of the tumor going up in five centimeter increments. The N stage has to do with nodal metastases, present or not, and M with distant metastases. And they also have the same grading consideration as for...
extremity sarcomas. So grade one, grade two, and grade three, which is based on the differentiation mitotic count and necrosis score. Interestingly though, most
Retroperitoneal sarcomas are very big, so the T-stage doesn't really play into it, and most of them don't have any nodal or distant metastases. So the real... determinant of the likely prognosis for the patient more has to do with the grade of the tumor, with low-grade tumors having a much better prognosis and high-grade tumors having a much poorer prognosis. So let's talk about the management of retroperitoneal sarcomas.
In general, chemotherapy isn't used for retroperitoneal sarcomas. So the two most commonly used treatment modalities are radiotherapy and surgery. In general, the best chance of curative intent resection is at the time of the primary presentation. And these patients should be managed by a multidisciplinary team in a sarcoma service. And you may need to involve other teams such as urology.
or vascular or colorectal. Patients who have inoperable and metastatic disease have a really poor prognosis and they should be referred to a clinical trial. In terms of radiotherapy, it can be given preoperatively or postoperatively. In contrast with extremity sarcomas, where the most common site of recurrence is a distant recurrence, With retroperitoneal sarcomas, the most likely site of recurrence is locally. And so there is a argument for adding radiotherapy.
in order to improve the local control. But there isn't great evidence for improving overall survival in these tumours. The argument to giving preoperative radiotherapy is that The tumor itself can displace the small bowel away from the radiation treatment area. And obviously irradiating the small bowel has lots of complications and problems in the longer term. The gross tumor volume and size.
can be precisely defined for the radiation treatment area. You can give higher doses of radiotherapy to the tumour field. The risk of intraperitoneal tumour dissemination at the time of surgery is reduced with preoperative radiotherapy. And it's thought that you could potentially downstage an unresectable tumor to a resectable one as well.
It does seem like it is a little bit controversial though, and obviously giving pre-op radiotherapy has higher wound complications. At a Peter Mac shoot I went to recently, they talked about... giving pre-op radiotherapy for retroperitoneal sarcomas for patients with low-grade disease because they're much more likely to have issues with recurrent local disease, but patients with high-grade disease are more likely to have issues with distant metastases.
For patients who don't have preoperative radiotherapy, postoperative radiotherapy has also been shown to improve local recurrence-free survival significantly. Just briefly to talk about the two main subtypes of retroperitoneal sarcoma, liposarcoma. Definitely has higher risks of local recurrence, as I've just talked about. But leiomyosarcomas make up about 10% to 20% of retroperitoneal sarcomas. And these often come from the large vessels, such as the inferior vena case.
either the renal vein, gonadal vein or iliac vein. actually have higher rates of distant recurrence as their primary recurrence site. And so they may be an exception to that rule where you wouldn't necessarily organize preoperative radiotherapy for that group.
The next treatment modality for retroperitoneal sarcoma is surgery. And the principles are that you need to achieve a macroscopically complete... resection with a single specimen that's going to involve the tumor and all involved contiguous organs without rupturing the tumor. This may involve resection of bowel, urinary structures, and vascular structures requiring reconstruction, so it can be quite significant surgery. But an R0 resection is the most important.
factor that contributes to the survival and local recurrence of the tumour. These operations are often extensive and require significant preoperative planning and review of the preoperative imaging in order to anticipate what the extent of the tumor might be and what organs might be involved. And the relevant subspecialties such as urology, vascular and colorectal should be involved from the start.
As I mentioned in the extremity sarcoma section, sarcomas form a pseudocapsule, which basically is compressed normal tissue around the tumor because of the fast growth of sarcomas. And this pseudocapsule isn't the... true capsule. So you can get little tongue-like projections of tumor that infiltrate through this into adjacent. tissues. So you also need a margin of tissue around the tumor in the same way that you do in extremity sarcomas.
The margin should be at least one to two centimeter gross margins around the pseudocapsule, but it obviously depends what is at the margin and what you can take. And that's also where radiotherapy comes in to play a role. In terms of the specific subtypes of retroperitoneal sarcoma, if you have a liposarcoma, all of the retroperitoneal fat on that side is considered malignant and needs to be removed.
And in terms of a leiomyosarcoma, the local resection of the mass with the appropriate margin is required. The other thing to consider when looking at a retroperitoneal sarcoma is what factors might make it irrespectable. So in general, extensive major vessel involvement such as the aorta, vena cava or the iliacs, circumferential involvement of the SMA or SMV, so the root of the mesentree.
Peritoneal implants or sarcomatosis. So these are distant metastases that aren't potentially resectable for a cure. Multifocal disease, although this is quite an uncommon primary presentation. if there's extensive liver hilar involvement or bilateral involvement of the renal vessels, or extensive spinal or spinal cord involvement.
And the other thing to consider is the staging of the patient themselves. So if the patient isn't fit enough due to age or comorbidities to undergo an extensive retroperitoneal dissection, then that may mean that the tumor is unresected. The last thing that's mentioned in our curriculum is talking about the role of molecular targeted therapies in retroperitoneal sarcoma.
I'll definitely ask our special guests when we get them on the program about this because I didn't see when I was looking many targeted treatments for sarcoma. I came across the use of tyrosine kinase inhibitors such as imatinib or sinitinib if the sarcoma has a CKIP mutation and the use of platelet-derived growth factor alpha. so PDGFR, alpha receptor monoclonal antibodies for sarcomas.
Definitely haven't seen this used routinely in an adjuvant or neoadjuvant setting. So maybe there's something I'm missing and we'll ask our special guest about this. Patients who present with metastatic psychomas have an overall poor outcome. Treatment is usually palliative and typically consists of single-agent chemotherapy. In terms of liposarcoma, the first-line therapy is anthracycline-based chemotherapy. And for leiomyosarcomas, doxorubicin or ifosphamide have...
been demonstrated to be the chemotherapy agents of choice. Saying this though, the response rate to systemic chemotherapy for sarcomas is somewhere between 10 and 25%. After resection of a sarcoma, patients have a high risk of recurrence both locally and distantly. They require lifelong surveillance and this should be every three to six months in the first few years and then can slowly be spread out to six monthly.
There is a role for metastatectomy for isolated lung metastases, but I think this is outside of the scope of our exam. So I'm going to roll straight into the discussion I had with Julie Howell about management of retroperitoneal sarcoma. I hope you enjoy learning from Julie as much as I did. In terms of retroperitoneal sarcoma, my first question is, when would you suggest that we biopsy a retroperitoneal mass? I've heard...
both schools of thought. So I've been told that if you're going to cut it out anyway, that you don't need a biopsy. But then on the flip side of that, it could be a lymphoma or something. completely different. And also I think the grade of the tumor may change what you do so that you should always do a biopsy. What's your recommendation for a retroperitoneal mass? So I'm a probiopsy person.
So in our MDT, that's what we do with all our sarcoma patients, basically. And the reasons are you've alluded to them already. So not all retroperitial masses are. sarcoma and there are some that aren't treated with by surgery such as lymphoma there are some benign things that you know you could argue whether you need to operate on at all and
Particularly if you're going to do a sarcoma operation, you're going to be more radical in removing the tumour plus contiguous organs, et cetera. So you're not going to do that. if you don't know what it is and you don't want to go in and remove something and then find that it is a sarcoma and you haven't done the right operation because I think with sarcomas It doesn't matter where they are. I think the surgery needs to be planned quite carefully.
Because the outcome of what they call a whoops procedure, where you've just removed a lump of, oh, it's a sarcoma. The outcomes for patients who undergo a whoops procedure, even then when they go and have the proper treatment. worse than if the patient had presented and been worked up properly and had the correct operation. They talk about in peripheral or soft tissue sarcomas making your biopsy in the line of your incision. I can anticipate that might be a bit tricky with a retroperitoneal.
sarcoma from the pictures i've seen most of those removed with a big operation through a laparotomy but accessing it with a biopsy would usually be via the flank or the back. Is that a consideration? Yeah, the reason that you try to opt for a posterior approach to the core biopsy is so you don't see the peritoneal cavity. With core biopsy needles, it's...
the risk of seeding is pretty low if you're going the posterior approach. But if you've got a tumour and you cross the peritoneal cavity, you... perforate the tumour to get the thing out, then potentially the tumour will contaminate the peritoneal cavity. And you don't have to excise the tract at the time of surgery? No.
So our curriculum talks about understanding the natural history of benign, borderline and malignant primary tumours of the retroperitoneum. Could you run us through what the natural history is of these tumours? Well, it depends on what type it is. So if a tumour is benign, it's going to be benign. It's not going to transform into a malignancy. Lipomas don't turn into liposarcomas.
Rarely you can have a retroperitoneal lipoma and they can be quite challenging to distinguish because a well-differentiated liposarcoma can look. very much like a lipoma radiologically. So one reason that we biopsy these things is that the core biopsy is done and the tissue is sent for fish for MDM2. And if that's present, it's a liposarcoma. So if it's not present, it's a lipoma. So again, it makes a big difference to whether you would operate.
if you did operate the type of operation that you would do. Because for liposarcoma, the recommendation is to remove the tumour plus any organ that's next to, plus all the fat in that side of the retroperitoneum. So having a biopsy is quite important to that. In terms of the natural history, I'm not sure what they're getting at exactly, but... In the world of liposarcoma, there are four different subtypes and you can have a well differentiated.
liposarcoma, which is a very slow growing thing, is less likely to develop distant metastases compared to a myxoid liposarcoma or a de-differentiated liposarcoma or a pleomorphic liposarcoma, which are the other type. But with a well differentiated liposarcoma, it can develop into a de-differentiated liposarcoma, which has more metastatic potential and grows more quickly.
And I've seen some pictures of a fatty mass with some solid components and the solid components lighting up on the pet and that being where you target your biopsy thinking maybe that's a de-differentiated component. The other thing with doing the biopsy is... It does also dictate your treatment because there are some centres that do neoadjuvant treatment, particularly radiotherapy, and that includes our centre. So if we know it's a sarcoma, it does.
change our management because if the tumor needs radiotherapy it's given in the neoadjuvant setting rather than the adjuvant setting and that's because the total dose will be lower because if you've operated on someone there's a lot of scar tissue so they have to increase the dose to penetrate through the scar tissue When the tumour is still in situ, there's a defined target for the radiation oncologist. So often the radiotherapy field is smaller.
So there are a few advantages. The disadvantages of neoadjuvant radiotherapy are you have to operate in someone who's been irradiated, which can be problematic. Tumour is involving other organs, such as the IVC, for example, with a low myosarcoma. How do you decide what you're going to cut out? How do you plan your surgery? It just boggles my mind to think.
about the extent of surgery that you do for these retroperitoneal tumours. How do you actually decide what you're going to do for these patients? So I guess the first thing with this sort of thing is you discuss the patient in an MDT. And the second thing is with the giant retroperitoneal tumours, I think it's a good idea to involve people from other specialties.
If you have a tumour that's Lyomyosarcoma developing from the IVC, you do need to resect the IVC. So that's not something I would do by myself. So I enlist the help of either a vascular surgeon or a surgeon who's used to doing that sort of resection. And the same goes for things that are deep in the pelvis that we might need to take the rectum out and that sort of thing, operate with a colorectal surgeon.
So I think one of the principles we apply is they're big operations, they're complex surgeries. So having the appropriate level of expertise. there and making sure that they've been planned out. Now, as for what you take out, it does depend a little bit also on the tumor type.
So as I was saying with the liposarcomas, you do tend to do... take out more tissue because with the fat, for example, it's very difficult to, well, pretty much impossible to see where the tumour begins and ends in terms of the well differentiated component. It's quite easy to see where the DIF part is because it's a firm part, looks like a tumour, and it's in this sea of fat. So where does it stop, start and finish? Because the problem with liposarcomas is local recurrence.
And they can recur where you've removed them from and they can recur at other points in the abdomen as well. And sometimes it's appropriate to resect blood vessels along with the tumour. So particularly if it's arising from a blood vessel, so if it's a loma sarcoma, you do that. More with the liposarcomas, they tend to, unless it's actually invading.
the vessel we tend to just peel them off the vessels but often we need to remove a kidney so you're as part of the workup you need to make sure that the other kidney is functioning adequately So say you've got a left-sided retroperitoneal liposarcoma, often I will take out the spleen, the tail of pancreas, the kidney, sometimes the left colon as well. So they'd be quite, you know, removing a lot of things. And does the radiotherapy reduce the risk of the local recurrence?
Yeah, that's the rationale for doing the radiotherapy. There was a recent trial called the STRESS trial, which looked at... the use of neoadjuvant radiotherapy and retroperitoneal sarcomas. And there are a lot of problems at the trial because there was quite a mixture of different tumours. And the results are a little bit difficult to interpret, but most people would agree.
that it did show some benefit for the well-differentiated liposarcomas, whereas for tumours such as leiomyosarcomas, they have a higher distant metastatic. So the argument for radiotherapy is not as strong, although it depends. They're sort of discussed on a case-by-case basis. In the sarcoma part of our curriculum... There's a comment about understanding the molecular biology of the tumors and the targeted therapies.
I did a little bit of a deep dive into this and I came across tyrosine kinase inhibitors for their CKIP mutations, but I couldn't really find much else in terms of targeted. therapies for sarcomas am i missing something is there a whole field of treatment that i just haven't come across there's probably not a lot more than what you've already read um the problem For sarcoma patients, the majority there's no effective, well, really effective systemic treatments. And chemo is...
given, but the survival's not great. In terms of targeted treatments, approaching patients as to whether they should have systemic therapy or not, it does depend on the tumour type. to some extent so if you have a well differentiated liposarcoma chemo won't be useful for them. Whereas a high-grade leiomyosarcoma, the benefit would be greater. So that would be the sort of time where you would consider someone for that.
Thanks for listening to today's episode of First Incision. I found sarcoma really difficult to talk about because it's not something as trainees I think we see commonly unless we're rotated to a sarcoma center. Hopefully I did the topic justice. Please let me know if there's something that I missed or something you think that I should know about sarcoma.
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