3-“D” Ultrasound in Oncology: Dilemmas, Drugs and Doppler - HD

Introduction

Hi, my name is Don de Salvo
and I'm the director of ultrasound imaging at the
Dana-Farber Cancer Institute in Boston, Massachusetts.
And today I'll be discussing a 3D ultrasound in oncology
dilemmas, drugs and Doppler.

I have no financial disclosures,
but I will say that I may have a tendency to produce
somewhat misleading and perhaps provocative lecture title.
So if you're looking at this, expecting
to see a lecture on 3D volumetric ultrasound imaging,
this lecture is not for you.
Instead, I'd like to show how we use ultrasound
as a diagnostic sort of problem solving tool relating
to patients undergoing chemotherapy.
And so that's the drugs.
The dilemmas are primarily related to liver
and hepatobiliary disease,
and doppler is frequently a very useful adjunct.

Oncology Imaging Challenges

As a oncology imaging specialist,
we have basically three challenges that we face.
We're looking at the primary tumor and their metastases
and how they're responding to chemotherapy.
And for that we use ct, pet CT and MRI,
but additionally, we have to be sensitive
to intercurrent illness that a patient may have
during the course of chemotherapy,
and also from complications
that could arise from that chemotherapy.
And in particularly, we'll be focusing on
how ultrasound is very useful for this problem, particularly
as it pertains to the liver and the gallbladder.

Standard Cytotoxic Chemotherapy

Just a brief review
of standard cytotoxic chemotherapy.
The agents are here shown on this image,
and these, while they are, have been very useful in treating oncologic problems,
they carry their own side effects.
And some of them can be diagnosed with ultrasound,
including sinusoidal obstruction syndrome,
such as we see here or steatosis.

Molecular Targeted Therapies

But I'd like to turn our attention
to the neuro chemotherapies,
so-called molecular targeted therapies.
And these are things that are targeted
to the cell-surface receptors,
and these include tyrosine kinase such as we see
with epidermal growth factor receptors
and those that target angiogenesis, the vascular endothelial growth factors.
There are other therapies that target intracellular
pathways, others that are primarily antibodies that are
to surface receptors.
And these are typified
by bevacizumab and ipilimumab.
So these are the sort of drugs that I wanna sort
of discuss and show how they can arise lead
to secondary unwanted side effects.

Effects. So this diagram here is taken from an a piece authored by one of our GU oncologists,
and it just shows the multiple levels of sophistication
that we now have available to us in terms
of treating either receptors along the cell surface
with particular agents
or agents that are actually gonna be working on all
of the myriad intracellular pathways that can lead
to unregulated tumor growth.

Why Know About Chemotherapy?

So, briefcase, why should we know about chemotherapy?
So I want to just show you this, an example.
This was a 45-year-old woman
who had chronic myelogenous leukemia undergoing
chemotherapy, and she was referred
for a right upper quadrant ultrasound
for some abdominal discomfort.
So these are images from that study,
and we can see that the gallbladder wall was rather
diffusely thickened here on the sagittal view.
On the transverse view, again, diffuse thickening
and perhaps a little bit of sludge.
We can see here dependently images
through the right upper quadrant sub constantly on the liver
showed a normal appearing liver.
But incidentally, there was some what appeared
to be fluid in the right pleural space.
Images of the left upper quadrant showed a large spleen,
a normal kidney,
but again, some fluid apparently in the left pleural space.
So the official interpretation was gallbladder wall
thickening sludge, possible cholecystitis,
and the bilateral pleural effusions were mentioned,
but they were kind of buried in the body of the text
and not brought out in the impression.

Well, the patient experienced increased shortness
of breath over the next several days leading
to this chest x-ray, which shows lar
sizable bilateral pleural effusions.
And so this was actually directly related
to her chemotherapy of dasatinib.
It was reduced and her symptoms subsequently resolved,
but she was able to be maintained on the
drug, but at a lower level.
So pleural effusions are not incidental findings in a
patient who's on this dasatinib, and that's
because this is one of these newer targeted chemotherapies that particularly acts against the mutant
tyrosine kinase that's switched on all the time leading
to the unregulated cell division.
But a significant side effect of this is pleural effusions.
So it is frequently the limiting sort of side effect
that relates to how much of this dasatinib can be given.
And so it is important to be aware of this
because you can still maintain the patient on this,
this dose, but at a reduced level such
that it doesn't cause pleural effusion.

Abnormal LFTs and Right Upper Quadrant Pain

So if we now consider the big dilemma, abnormal LFTs
and right upper quadrant pain, and we look at the so-called
general population on the left hand side,
these are the diagnoses that we're all pretty familiar with.
But if we turn instead to the oncology population, which is
what we'll be discussing, these are the kinds
of diagnoses we need to consider.
Drug-induced cholecystitis,
drug-induced hepatitis portal venous air tumor hemorrhage
and venal occlusive disease, or sinusoidal, obstructive.
So these are the things we're now
gonna look at more closely.

Conventional Chemotherapeutic Agents

So once again, just to review,
the conventional chemotherapeutic agents are shown in this
table with the name
and then the type of mechanism, which tumor it's used for,
and some of the adverse side effects.

Molecular Targeted Therapies Table

And then if we turn to the molecular targeted therapies,
which is what we're gonna be spending most of our time with,
again, laid out in a similar fashion.
And I want you to point out, some
of them must be looking at closely add bevacizumab causing
steatosis in bowel perforation
and pneumatosis, erlotinib
or tba that can cause hepatitis, everolimus,
which can lead to a calculus, cholecystitis
and ipilimumab, which can also cause hepatitis.
And I have to say that these two tables are conflation
of the three ultrasound related
or actually just radiology articles
that are at the bottom of the screen.
And these were two of them are actually from coming from our
institution where we have a particular interest in looking
for potential adverse side effects.

Drug-Induced Hepatitis

So first up, drug induced hepatitis.
This is rather rare, a 5% incidence.
The offending agents include tyrosine kinase inhibitors
and also the immune modulators ipilimumab.
And I have to mention that immune modulators are now coming
rapidly to the forefront as being the sort
of major newer attempt at targeted chemotherapy.
Unfortunately, drug-induced hepatitis is a diagnosis
of exclusion after we've sort
of eliminated all the other possibilities that someone
with a diagnosis of cancer can have
for having abnormal LFTs.
And it's really just proved by the fact
that you stop the drug and the LFTs fall.
But it would be helpful if we could actually have a positive
way of making this diagnosis,
because again, the key is we wanna be able
to maintain the patient on chemotherapy,
but perhaps at a lower dose
where it's still effective against the tumor,
but not causing the adverse effect.

So what are the possible imaging findings we can see
with drug induced hepatitis?
Well, for ct, we would look for enlargement of the liver,
some rounding of the contours, especially of the left lobe,
which I'll demonstrate periportal edema, peri hepatic fluid,
gallbladder wall thickening.
In ultrasound, we would again look for similar findings.
And matter of fact, many of these were beautifully elaborated as far back
as the 1980s when we looked at the diagnosis
of viral hepatitis.
And frequently the findings are gonna be overlapping.
So again, we'll look for enlargement of the liver,
hypoechoic parenchyma leading
to the so-called starry sky liver,
gallbladder sludge or wall thickening.
And then a new finding, which I've noted to be edema
of the gallbladder fossa.

Case: Metastatic Melanoma on Ipilimumab

So first case of man with metastatic melanoma undergoing ipilimumab therapy
and his liver function tests are rising.
So this first became apparent
to us when we looked at the cts,
and I have to say this is an example of how CT taught us
to look for some of the ultrasound findings.
But if we look at his baseline compared to his,
when he's coming in symptomatically, it's very easy
to see the liver's gotten larger.
The spleen is larger.
We can see this rounding of the inferior portion
of the left lobe and a change in the angulation
of the fissure for ligament and binum.
A secondary finding is this little bit
of hypo density tracking along the left portal vein,
which is periportal edema.
Looking more inferiorly, again,
the baseline on the left and the acutely symptomatic.
Again, note that the liver is larger,
but we also see multiple small nodes adjacent
to the pancreas.
If we now look at the ultrasound that was done
and where we didn't make the
diagnosis, these are the things we see.
So the gallbladder looks a little thickened
with some sludge, nothing really specific finding there.
However, if we look at the left lobe of the liver,
this is a grossly enlarged left lobe.
And here is that sort of extra rounding of the inferior edge
of the liver that I think can be a very useful sign
for knowing when the liver has enlarged.
Another finding here, if we look at the port of Hetus,
there was a normal common bile duct,
but instead there was a lot
of echogenicity adjacent to the port of hetus.
Again, this is the ultrasound correlate
of the periportal edema that we saw on the CT scan.
So these are the things we need to be sensitive
to when we're trying
to make this diagnosis using ultrasound.

And this matter of fact, now it's just a summary slide.
This patient actually went on to have a biopsy,
and the biopsy images are shown on the bottom.
And this was confirmed as drug-induced hepatitis.
The dose of ipilimumab was reduced,
the patient's liver function tests abnormalities resolved
and he was able to continue on the chemotherapy.
And this actually was written up again by my colleagues at the Dana-Farber.

Another Case: 60-Year-Old Man with Metastatic Melanoma

Another case, again,
a 60-year-old man metastatic melanoma, again on ipilimumab
and with a similar constellation of symptoms, nausea,
vomiting, rising LFTs.
But his ultrasound findings are actually slightly different.
The only thing we saw when we looked at his gallbladder is
what, right next to sort of the mid portion
of the gallbladder, there appeared to be some,
maybe some focal wall thickening,
but there was no tenderness.
However, when we look at this clip, we can actually see
that the thickening is not involving the whole wall,
but instead right next to it, in so-called the,
what I collect to call edema of the gallbladder fossa,
which is again, just another manifestation
of the diffuse hepatitis.
And this was really his only manifestation.

Case: Woman with Recurrent Breast Cancer

Another example showing the so-called starry sky liver,
a woman with a recurrent breast cancer on undergoing
chemotherapy, and again, with abdominal pain
and elevated LFTs.
And here again, it was the CT
that first tipped us off to it.
And we can see again on these coronal images,
the gross enlargement of both the right
and left lobes, as well as the sleeves
of hypo density indicating the periportal edema.
And there was some patchy enhancement in
segments five and six.
But then when we look at the ultrasound,
and here's a clip kind of passing through,
starting up at the sort of junction of right
and left lobe was Porto hepititis.
And then going down into segments five
and six, we really made no observations here.
But in retrospect, if you look at the periportal triads,
particularly down here in segments five
and six, you can see that there are very genic.
So this is again,
that periportal so-called edema, starry sky liver.

Cholecystitis in Chemotherapy Patients

All right. Now I'd like to turn our attention
to cholecystitis
and the unique manifestations that
patients undergoing chemotherapy can manifest.
And this is we think is an a calculus cholecystitis.
So generally they don't have stones.
They, again, here, these are some of the offending agents,
tyrosine kinase inhibitors, sorafenib, sunitinib,
everolimus and mTOR inhibitor.
And in all of these, we think
that the mechanism is probably stasis
or an atonic gallbladder.
And this may lead to mu ischemia.
And generally the symptoms resolve
and the gallbladder function returns when the
agent is discontinued.

Case: 62-Year-Old Woman with Metastatic Breast Cancer

So this was the first case, a 62-year-old man,
woman rather with metastatic breast cancer to lung
and bone on a VEGF inhibitor with right upper quadrant pain.
And we look in the right upper quadrant with ultrasound,
we see a gallbladder that's rather distended, has a lot
of echogenic,
apparently crystal like sludge within the gallbladder.
But if we look at the wall, it's very thin,
it's less than three millimeters.
And the patient didn't have a Murphy sign just a little bit
of right upper quadrant discomfort.
Well, it was felt to be related to her chemotherapy
because her gallbladder had previously been normal,
so it was discontinued.
She came back one week later feeling better,
her gallbladder starts to look better.
Maybe there's a little bit of wall thickening,
but all of that thick looking sludge
that was in the gallbladder is gone.
Just maybe a few little crystals.
But because it had been the drug had been
so effective against her metastatic disease,
the oncologists weren't anxious to restart.
And they did. And three weeks later she came back
and we have a very similar looking picture.
Again, a rather distended gallbladder.
But again, note that the wall is not thickened,
but it is completely filled
with this apparently immobile sludge.
So we suspected that there was something interfering
with emptying of the gallbladder.
So we gave her a fatty meal challenge.
And when we look here at the volumes before and
after, we can see they're absolutely unchanged.
So this again, prove that this was just biliary restasis.
And somehow the drug was interfering
with gallbladder emptying.
So basically stopped the drug
and then just restart it on a lower dose
and the patient was able to continue on
with their chemotherapy without any further symptoms.

Another Case: Woman with Triple Negative Breast Cancer

Another example of a cholecystitis.
Another woman younger
with triple negative breast cancer metastatic.
She had progressed on prior standard chemotherapy.
She was now on a VEGF inhibitor.
She came in with abdominal pain, nausea, and vomiting.
So if you look at her gallbladder,
it actually does have a similar look appearing to be, have,
be filled with sludge.
But in addition, we see this sleeve of hypo echogenicity,
again, very reminiscent of what we saw with the hepatitis picture earlier.
And this is again, this edema that's
around the gallbladder in the gallbladder fossa reflecting,
some hepatic irritation.
And it's very easy to see when we do this sweep here
that the gallbladder wall is actually not emus,
but instead it's all this edema
of the fossa of the gallbladder.
So this was this person's manifestation of hepatic
and gallbladder dysfunction.
This was the ct, and again, pre contrast,
very dense appearing material corresponding to the sludge.
And this again, is that diffuse edema surrounding the gallbladder.
An additional unexpected finding was a small amount
of free air up around the edge of the liver.
And this was felt to probably represent an unsuspected bowel
perf, which is a, again, a not uncommon finding with many
of these tyrosine kinase inhibitors.
So the drug was stopped and her symptoms in free
air resolved in two days.

Case: Elderly Man with Renal Cell Carcinoma

Another example, elderly man,
renal cell carcinoma on sunitinib therapy begun three months
previously with new right upper quadrant pain.
And again, we see what appears
to be a sludge field gallbladder,
but this time the wall looks thickened.
The patient has a positive Murphy sign.
So this now elevates our concern
that there's more going on than just gallbladder stasis.
And in fact, when he had the ct, this was confirmed.
We see diffuse stranding all around the gallbladder,
some free fluid around the liver.
And so based on these findings,
the patient was treated with a chole cystostomy tube.
He could not undergo a,
a gallbladder resection at this time and antibiotics.
And then ultimately two months later,
he underwent an open cholecystectomy,
and this was a necrotic gallbladder.
So again, this shows that the, this parent stasis
of the gallbladder can pro can extend
to finally include ischemia
and frank diffuse inflammation of the gallbladder.

Case: 72-Year-Old Man with Esophageal Cancer

And finally this last case was probably the most extreme
72-year-old man esophageal cancer on many chemotherapies,
including bevacizumab, the new VEGF inhibitor.
And he comes in with new fever, white count of 15,000,
and a very rapid clinical deterioration.
And this was his baseline gallbladder from six months prior.
And it looked like there were some stones,
maybe a little bit of he patient had some ascites, but not
otherwise, not a particularly remarkable gallbladder.
Well, at the time of his symptoms, when we tried
to find the gallbladder, it appeared
to be completely collapsed.
And here we've sort of drawn it out for you.
Maybe there were still a few stones there,
but when we looked just adjacent to it,
we saw this unusual area
of hypo echogenicity right next to the gallbladder.
And then it's a little bit easier
to see when we look at this clip.
We could see this hypo focus
and then the gallbladder
that's completely collapsed right next to it.
And so this led us to be concerned based on his rapid
clinical deterioration that this gallbladder
had in fact perforated.
And this was an abscess.
And this was confirmed on the subsequent CT scan.
Here we see the gallbladder with the frank perforation
and the peri ctic collection in the liver.
And so this patient was treated with percutaneous drainage and fortunately survived.

Portal Venous Air

Okay, now I'd like to turn our topic a little bit
to portal venous air.
We recognize portal venous air, as you know,
and two basic clinical settings,
those in which we're worried about bowel
ischemia or infarction.
And these use patients are usually
clinically very, very ill.
And it usually prompts an urgent surgical con consultation.
However, we're recognizing that some drugs,
in particular bevacizumab,
can cause a benign pneumatosis where actually
air is seeping through the wall of the mucosa
of the bowel into the wall of the bowel,
and then ultimately leaving to portal venous air.
And there have even been cases of frank perforation
and pneumoperitoneum in a small number of cases.
And it's thought to be due to the, this anti-VEGF drug
that's decreasing capillary density of the mucosa leading
to a micro perforation.
And generally these patients are treated
with just simply discontinuing the agent.
And usually these do not require any surgical intervention.
This type of complication has also been found
with tyrosine kinase inhibitors, mTOR inhibitors, including,
some of the older agents, Cytoxan and steroids.

Case: Relapsed Refractory Multiple Myeloma

And I'd like to show you an example of that.
So this next patient had relapsed
refractory multiple myeloma.
He was undergoing chemotherapy, and
because a secondary effect of the chemotherapy was
to lower his absolute neutrophil count, he was dexamethasone
or a very powerful steroid was added on two weeks prior to our seeing him.
And he came in with new elevated transaminase
and minimal symptoms, a little bit
of right upper quadrant discomfort.
When we look at his liver,
there was nothing particularly remarkable.
Maybe it looked a little bit echogenic, it was kind of hard
to see because it had a lot of per hepatic fat.
But actually, if we look at this clip, we can see
that there's actually little moving echoes
within the portal vein.
And this is actually portal venous gas.
And again, an abundant amount of fat
around the liver made the imaging a little suboptimal,
and this was using a four megahertz.
If we switch to a higher frequency trans transducer,
we can see these bubbles really just jump right out at us.
And that's a known now that we're considering using contrast enhanced ultrasound.
It's known that if you image microbubbles
with a higher frequency transducer,
it'll make them much more conspicuous.
And when we actually looked at the venous outflow,
namely here, the hepatic veins, we see these same little
high density foci moving through, indicating that these gas bubbles had moved completely
through his hepatic circulation
and were now completely circulating back
to the hepatic vein.
Because the patient was minimally symptomatic,
patient was allowed to go home
after consultation with the physician.
Came back two days later just to confirm our suspicion,
which was what, that this patient had pneumatosis.
And we were just happened to catch the air as it was passing
through the portal venous system.
And in fact, this Topo Graham confirms
that diffuse pneumatosis.
And here on these coronal recons with a bone window,
it really brings out this extensive air within the wall of his colon.
So at this point, there was no portal venous
gas seen on the ct.
We even actually re-looked at him again at this point with ultrasound, and it was completely gone.
So again,
because of minimal symptoms, patient's,
dexamethasone was stopped.
And when he was re-image three weeks later,
everything had gone back to normal.
So again, a really dramatic representation of how
what we used to consider to be a really dire predictor,
pneumatosis and portal venous air
with actually a benign outcome.
But we think it's due, again, purely to the chemotherapy,
causing a change in the mucosal integrity of the colon.

Intratumoral Hemorrhage

I'd next like to turn now to examples
of intratumoral hemorrhage
and how they can lead to acute symptoms.
And this was a 62-year-old woman.
She had ovarian cancer with known peritoneal metastases
around the liver, and she experienced sudden abdominal pain
and she had been on gemcitabine for the past six months.
We looked at her, we saw a large complex fluid collection
indenting the surface of the liver at a site of a known per hepatic metastasis.
And this corresponded exactly to where it hurt.
And if we look at this sort of clip, we can see this large fluid collection complex with strands very,
very typical for hemorrhage.
And so this was a,
an acute hemorrhage into a metastatic lesion.
Her chemotherapy was stopped
and the hemorrhagic component was drained percutaneously,
and then she was allowed
to continue on with her chemotherapy.

We can also get hemorrhage into preexisting cysts,
not only preexisting cancer,
and this was shown in this case a 55-year-old man
with colorectal cancer on standard five Fluor uracil
and oxaliplatin adjuvant therapy.
And he had sudden right flank pain.
We look at this right kidney, we can see that yeah,
there's some echogenic foci
and a little bit of dilatation
of the collecting system suggesting
that he's formed some stones and he has some stones.
But the real cause of his pain is this phytic cyst that
has now developed a hemorrhage.
When we turn transversely on it, we see this kind
of amorphous low density, nonvascular dependent clot.
And here as we sweep through it on this clip,
it's got the very typical geographic shape of a
of hemorrhage.
So this, again, is, is a known complication of of this drug.

Hepatic Veno-Occlusive Disease or Sinusoidal Obstruction Syndrome

I'd like next to turn to a consideration of hepatic immuno occlusive disease
or sinusoidal obstruction syndrome, which again, we see with increasing frequency in our oncology population.
Most importantly, gonna remember is
that this is not Bud Chiari syndrome,
but rather hepatic venal occlusive disease.
And what this is due to is
to microscopic obstruction at the hepatic sinusoid
and venial level leading to portal hypertension.
And that's why a better name actually is sinusoidal
obstruction syndrome or SOS, which is
what actually now the preferred nomenclature
for this syndrome is.

So the clinical definition of patients present
with a painful hepatomegaly, jaundice and ascites.

So why is it important? Why should we consider it?
Well, it occurs in two groups of patients, those
that are under undergoing
or going to undergo stem cell transplantation
for leukemia or lymphoma.
And as part of the pre
stem cell transplantation regimen, they undergo this regimen
with busulfan, Cytoxan and gemcitabine,
and they have total body irradiation.
And this somehow sets them up
for this sinusoidal obstruction syndrome,
but it usually doesn't manifest until 35 days
after the stem cell transplant.
So that's why it's important to know this person's history
when you're examining them.
The other group of patients,
of which we're now seeing it increasingly are those
with oligometastatic liver disease from colorectal cancer.
These are surgical candidates
because of the low tumor burden in the liver,
and they undergo neoadjuvant chemotherapy prior
to the plan surgery to help shrink the size
of hepatic metastases.
And one of the usual drugs used here is oxaliplatin.
And this is the drug that is known
to cause this sinusoidal obstruction.
So it's important to know because if you're treating them
and you don't recognize it, pad tumors appear
to be shrinking.
The patient then plans to go to surgery,
he will then go into hepatic failure.
So that's why it is important to know
before it gets to this stage.

So the ultrasound diagnosis
of sinusoidal obstruction syndrome is challenging.
There were multiple earlier studies that suggested doppler
or gray scale ultrasound wasn't sensitive
or specific for the diagnosis of sinusoidal obstruction.
But the problem was these were small population studies.
So I'd like to share with you our experience
with a large multicenter study of 140 patients
who are undergoing defibrotide therapy for this very
syndrome of sinusoidal obstruction.
And here is the reference from our local group that performed the multicenter study.

So just to review briefly the structure
of the hepatic aous.
We see the portal veins, hepatic artery, bile duct out
of the periphery, and then the hepatic
sinusoids and the central vein.
And if we look at the blood supply, again,
the portal vein is most supplies
and the hepatic artery supplies the rest of it.
And these are the hepatic sinusoids.
The blood flows down
and ultimately gets to the central vein.
And there are three separate zones of the liver that are defined pathologically.
And it appears that the third zone
or the part that's furthest away from the richly oxygenated
portal, blood is the most prone to any kind
of endothelial damage.
And that's presumably
where this sinusoidal obstruction is happening due
to the toxic effects of the preconditioning regimen,
which interferes with the endothelium at this site leading to obstruction.

So there are two groups that define it clinically,
a Baltimore group and a Seattle group.
And they all basically have similar findings
of hepatomegaly weight gain and ascites.

So our particular protocol for trying
to detect this at the Dana-Farber includes looking at the
liver size and we measure the left lobe in
the midsagittal plane.
And again, looking at that similar finding of rounding
of the inferior contour of the left lobe like we saw
with the hepatitis cases,
we also measure the right lobe in relationship
to the lower pole, the right kidney.
We make sure there's no biliary dilatation.
We look at the gallbladder
because frequently they will have edema
of the wall of the gallbladder.
And then portal venous flow is very key
because what we're looking for are signs
of portal hypertension, which is slow or even bidirectional
or frankly reversed flow,
especially in the left portal vein.
It seems that the left portal vein is a little
bit more sensitive to this.
The hepatic venous tracings are not particularly useful in this.
And then of course we look for ascites in Morrison's
pouch and in the pelvis.

Case: Young Man with Acute Leukemia

So I'd like to show you two cases illustrating the key
ultrasound findings of this syndrome.
This first one was a young man who had acute leukemia
and had gone through the preconditioning,
had his stem cell transplantation,
and then post transplantation began having weight gain
and abnormal liver function tests.
So here are images of the left lobe and right lobe.
And right off the bat we see
that the left lobe is markedly en large.
It spans almost 15 centimeters
and the lower margin of it is rounded similar to
what we saw in the hepatitis cases, the right lobe
of the liver, not particularly enlarged,
but there is some ascites,
which is a key finding in this syndrome.
Here's the gallbladder completely filled with sludge,
with wall thickening, not surprising.
And then when we do the doppler,
we look at apparently a discordant finding.
We look at the main portal vein, normally antegrade flow,
but when we look at the left portal vein,
it appears like it's reversed.
We can see the two hepatic arteries tremendously aliasing reflecting
that the hepatic arteries are doing everything they can,
but it appears to be that the portal vein is reversed.
Well, how can this be?
Really the answer is shown when you do the pulse doppler.
And when we look there is normal pulsatile flow in the main
portal vein, but the left portal vein is actually biphasic
and there is transient reversal and antegrade flow.
So this again is that early manifestation
of portal hypertension seeming
to manifest itself first in the left portal vein.
So we made the diagnosis of sinusoidal obstruction syndrome
and this was confirmed with a subsequent he wedged hepatic venous pressure tracings.

Case: Older Man with Chronic Biologic Leukemia

And then the second case, an older man, again,
his chronic biologic leukemia had undergone stem cell
transplantation again, having increased girth.
LFTs were rising. Starting out in the left lobe again,
we see a very similar picture markedly enlarged,
spanning 13 centimeters.
The left lobe in the mid midline of the lined up
with the aorta shouldn't be more than 10 centimeters.
We again, see that rounding
of the posterior part of the left lobe.
His right lobe looked slightly enlarged.
It was hanging down below the lower pole of the kidney
and there was a moderate amount of ascites.
And we looked at his gallbladder again,
diffuse wall thickening.
We turn on the color doppler.
It looked like he had portal vein thrombosis.
Here in the main portal vein,
there's absolutely no signal in the portal vein.
And we have nice signals coming from the hepatic arteries.
But the important thing is to recognize is that patients
with this syndrome have,
they don't just suddenly reverse flow
or develop thrombosis, the flow slows down.
And so we need to be very, very sensitive to make sure
that we're optimizing our Doppler color scale
and particularly the velocity range.
And here we're at what should be okay
for a normal liver 18 centimeters per second.
But in fact, when we drop to five centimeters per second,
we see yes, actually there is
antegrade flow in this portal vein.
It is not thrombo, it's just very, very slow.
And then again, we can confirm this, we always do
with a pulse doppler
and we can see again a very slow
undulating portal venous flow.
We also have some aliasing coming from the adjacent hepatic artery.
And this again reflective of the very slow flow.
So this person is not actually, frankly reversed,
but is again experiencing the increased pressure in the
sinusoids from the sinusoidal obstruction syndrome.
So he, again, this was confirmed with wedge pressure
and this is where defibrotide, which is this newer agent
that's being specifically developed
to treat this complication, was successful
and the patient recovered.

Summary

So in summary, it's important
to consider special diagnoses when you're looking at an
oncologic patient who comes
with abnormal liver function tests
or right upper quadrant pain.
And they should include thinking about drug related
complications of hepatitis cholecystitis,
portal venous air intratumoral hemorrhage,
or sinusoidal obstruction syndrome.
And it is very important to know the patient's chemotherapy
in order to make a timely and accurate diagnosis.
I'd like to thank you for your attention. I.