BTK Journal Review in HPB Surgery- Resecting Perihilar Cholangiocarcinoma
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[00:00:00] Greetings, everyone. Welcome to another HPB episode on Behind The Knife. This is your HPB team at the MD Anderson Cancer Center in Houston. I'm Anish, a general surgery resident at Stanford and former T 32 Fellow at MD Anderson. And I'm excited to be joined again by my mentors, Dr. Tim New Hook and John Nikolas vte, the HVB section chief.

Today we'll be discussing Perihilar Cholangiocarcinoma. Specifically we'll review articles regarding the significant morbidity associated with. Surgical resection of this disease. Preoperative management strategies to reduce postoperative morbidity and changes in our surgical approach over time that have also improved outcomes.

Just to give our listeners some context, perihilar Cholangio is a relatively uncommon neoplasm that originates from the malignant transformation of the epithelial and the proximal bile duct, and the tumor typically involves the biliary confluence, but can occasionally extend to the second and third order of biliary branches.

For [00:01:00] patients suffering from Perihilar Cholangio without metastatic disease, the only potentially curative options for treatment are either transplantation of the liver or complete surgical resection. However, surgical resection of Perihilar Cholangio is one of the highest risk elective operations we perform with reported morbidity rates greater than 60% and 90 day mortality rates greater than 10% in large multicenter studies.

So. The first thing I wanna ask you both, and Dr. Newark, we can start with you, is what makes the surgical resection of perihilar cholangiocarcinoma so challenging? Well, it seems like a very directive question, but it's actually a very broad question because there's many different considerations that need to be taken into account.

One considering resection for a patient with this disease. And I should say, when I explain it to patients as well, it's, it's actually quite amazing how many things need to be taken into account. For something in such a small area, this disease is particularly [00:02:00] challenging from a surgical perspective, primarily because of anatomy.

There's a tremendous number of things that are in that area that are important, including the inflow and biliary drainage of the liver, but also the hepatectomy that's required to involve this area. So clearly the first things you have to look at are tumoral involvement of the hepatic arterial system.

The portal venous system, as well as the ability to obtain a margin negative resection with excision of the extra hepatic bile duct distally, but also internally in the intra hepatic portion of the bile duct. As you mentioned, sometimes the disease extends to the left or right second order branches.

The next part of that is liver volume. And that's because unfortunately, we have to sacrifice a tremendous amount of liver volume to allow us to get to a singular target on the intrahepatic portion of the hepatic ducts typically via some form of an extended hepatectomy. And that [00:03:00] also can lead to a lot of postoperative morbidity and major complications based on the amount of liver you leave the patient with afterwards.

So the future liver remnant is something that should, definitely, needs to be taken into consideration. The other reason why it's also important also complicated is because of the patient condition. So we went through a, the anatomy B obviously, biology, which may be beyond the scope of this talk, but c patient condition really matters too.

A lot of times patients can be nutritionally depleted from chronic or more longstanding biliary obstruction, maybe suffering from obstructive jaundice and all of the vitamin deficiencies and weight loss that's associated with this, as well as potentially multiple episodes of cholangitis and systemic sepsis that can be associated with it.

With a lot of the preoperative workout that sometimes occurs before patients even get to a surgeon. So all of these reasons make the care of a patient with Peral cholangiocarcinoma. Incredibly [00:04:00] complex. Thanks Dr. Nuk. I think that's a great summary and one thing I want our listeners to really hold onto is, Dr.

Nuk mentioned about obstructive jaundice, cholangitis and the need for taking portions of the liver, often as a major extent of hepatectomy, which are things we're gonna discuss in detail. Dr. Vte, any other challenges that you see and think about when it comes to resecting this disease or treating this disease?

So I'm gonna just expand a bit on the anatomy and the deconditioning of these patients as they present with obstructive jaundice. First, in terms of anatomy yes, there is a need often for major delivery resection, and in fact, we should always resect the liver when we resect the clat skin tumor because these tumors are centrally located.

Under the segment four of the liver, anteriorly and posteriorly connect with the coate lobe Very early on, these tumors extend posteriorly and [00:05:00] sometimes anteriorly to the bile duct. Left bile duct, right bile duct and third order bowel effects. So you have to resect some liver if you want to resect these patients.

It's very important to resect these patients. Completely with negative margin. That's the only chance to have a curative resection. Regarding the decondition deconditioning of these patients, I think it's very important to realize that most patients will present with very high bilirubin 1520 milligram percent, and major resection of the liver cannot be performed in that situation, and you have to.

Clear the and the the wisdom. Now the recommendation is to have a bin of two milligram percent or less to optimize these patients. But this requires endoscopic drainage and in some cases percutaneous drainage. And it's very [00:06:00] complex. And as these procedures are being performed. There is a risk of cholangitis and sepsis.

So you have to be very careful before you you embark on these drainage procedure to make sure you know the patients are on antibiotics and you don't want, you know, to get them septic in the CT scan while they. Undergoing imaging the day following the drainage. So we preferably do imaging studies before any drainage and hydrate the patient and then do the drainage if the patient presents to us without pary drainage.

Most patients now presents after biliary drainage and it's often incomplete and you have to re grain or optimize the the biliary drainage. And that's, that's a great transition, dr to our first article, all the talk about drainage and the risk of cholangitis. And so the first article we will talk about is titled Preoperative Cholangitis and Future Liver Remnant Volume Determined the Risk of Liver [00:07:00] Failure in Patients Undergoing Resection for Hilar Cholangiocarcinoma.

And this was published in the Journal of the American College of Surgeons in 2016. And essentially this was a multicenter retrospective analysis of 133 patients who underwent curative intent resection for peria between 1996 and 2013. And as Dr. N and Dr. Botta explained, resection consisted of excision of the hepatic bile duct, as well as a N block major extended hepatectomy.

Now, preoperative cholangitis occurred in 42 or 32% of these patients. Preoperative biliary drainage was performed in 98 or 74% of these patients and PVE or portal vein embolization was performed in 32 or 24% of the patients. Overall, 77% of patients suffered a post-op complication, and 73 or 55% suffered a major complication.

And the most common major complication was hepatic insufficiency and postoperative death occurred in 15 patients, 10 of whom died [00:08:00] secondary to liver failure. Now, if we look at the patients. With and without preop preoperative cholangitis and compare them. Compare to patients without preoperative cholangitis, those who suffered preop cholangitis had a higher risk of overall complications, 95 versus 65%.

Major complications, 74 versus 46%, and MA mainly this was due to a higher risk of hepatic insufficiency, 33% versus 16%, and a higher risk of death, 24% versus 5%. Additionally in this study, preoperative cholangitis and having an A future liver remnant volume, less than 30% were the only predictors of death from liver failure, both in the univa and multi-variable analysis, and independently predicted a risk of death from liver failure about sevenfold higher.

And furthermore, when the FLR volume was less than 30%, rates of hepatic insufficiency and death [00:09:00] from liver failure were significantly higher in those patients who also had preoperative cholangitis. So the combination of a low FLR and preop cholangitis had a combined effect in making your survival outcomes much worse.

So, Dr. Nuk, I know you're very familiar with this study. What do, what do you think our listeners should walk away and how should they interpret this study? Well, I'm particularly fond of this study because this gave me, as a trainee and early faculty, some, some very important objective pieces of guidance when helping to take care of these patients.

So to put the court ahead of the horse, it's, it's very. Black and white When you see a patient and you know you need to try to find some way to have an avoidance or eradication of cholangitis. So number one, please don't try to do a major hepo for perihilar cholangiocarcinoma for someone who has active cholangitis or recent [00:10:00] cholangitis in the middle of treatment, something like that.

And then number two, please obtain liver polemetry if possible, particularly when performing a right-sided operation. Right-sided resection to. Ascertain what you believe the future liver remnant will be because it needs to be 30% or higher. If you've obtained those things, then I think that you've at least done due diligence towards trying to afford a patient a safe surgery.

I think we'll get into this, or maybe we have, maybe we won't, but there's a lot of of reports of, of experiences for resection of this disease from around the world that, you know, some experiences have very high. I would say way too high reports of mortality in the 90 day perioperative period.

And I bet you if we were able to dissect a lot of those patients, you may find that unfortunately some of these objective things that I mentioned were, were not met with polemetry or cholangitis. So going back to the data, [00:11:00] how do we get those numbers is important to know. And it's not necessarily that having.

30% or more volume means you will not have problems. It just means that having over 30% in our experience, abrogates the detrimental impact of these patients likely having at least low grade cholangitis. So these patients have their bile ducts instrumented most times. They are no longer having a sterile biliary tree.

There's some level of cholangitis in almost all of these patients. You can detect it in their blood work. So having over 30% FLR decreased the risk of death due to liver failure to zero. So that doesn't mean that they don't have insufficiency, doesn't mean that they can have a difficult time, but it abrogated the clear detrimental impact of cholangitis.

On death from liver failures. So take it another way. [00:12:00] Volume under 30% more people died and it's probably because of cholangitis having volume over 30% abrogated the detrimental impact of cholangitis, which is why we tried to eliminate those two, because when looking at a multi-variable analysis, those two were the independent, the factors that were independently associated with death due to liver failure after resection of this disease.

So to me those are red lines. Those are, those are things that I, that we need to try to obtain preoperatively before discussing reception. Thanks for that Dr. Nhu. Now, Dr. Aya, I have two questions for you and I think your answer will probably, that you'll give, may be able to answer both of them. One is, you know, what your kind of big take home message paper from this is.

And then the other is, how did the findings of these paper change your practice and your institution's practice in terms of. Prevention and treatment of cholangitis and obstructive jaundice. This paper, you know, is almost 10 years old now, and it really looks [00:13:00] at an era when we were tackling Highline drug carcinoma with major, major delivery sections.

In most cases, trying to expand, get the negative margin, get the card flow. And, and the tendency was really to do extended right hept, me taking advantage of the so-called long left hepatic duct, which in reality is not so long, and we were trying to optimize also the anastomosis. Between the the B duct and the, the small bowel, the run wide loop.

And it was an easy reconstruction because it was only one duct on the left. And that's not the case. If you, if you do left or extended, left ectomy, you have more b ducts to anastomosis. So this, this was an era where we were kind of a [00:14:00] maximus. In terms of our oncologic goals, not necessarily getting better margins, in fact, as we'll discuss later, but this has to be taken into context.

I think you have to also understand that when these patients have had cholangitis after poorly performed endoscopic drainage or incomplete drainage, this damages the hepatic pain, comma. So you do a liver resection and in your liver has been damaged, so it's an abnormal liver. So you have to apply the rule of.

More liver, more, bigger liver. And then because the, there is damage. So it's, it's similar to chronic liver disease in a sense. So you have to appreciate that and I think you have to focus. And now we focusing on better drainage, better endoscopy. And as much as you can, you need to discuss this patient.

With gastroenterologist and know which side needs to be [00:15:00] drained and not do multiple drainage if needed. The first shot is the best shot and if it can be done endoscopically, nice. Now these patients are very different. You have different SMUs type business classification of loc cholangiocarcinoma, and the type one and type two are certainly drained.

Easier endoscopically than the more complex type, such as the type three or three B, where the tumor extend either on from the hy, either to the right B duct beyond the right hepatic duct, or on the left beyond the left hepatic duct into third order ducts. So these are. These patients have a more complex situation when they present and they are harder to drain and they have a worse prognosis, and they have high risk of, of cholangitis from incomplete drainage.

These are the patients in which sometimes you have to use [00:16:00] percutaneous trans hepa drainage of the bowel in addition, or instead of the endoscopic drainage. Thank you both for that. I think that was a great. Breakdown of the, the keys behind this paper, especially like Dr. N, you talk about draw some red lines or lines in the sand in terms of standards we need to look at in terms of resection.

Just to add to that real quick, real quick to add that Dr. Vte brought up, just something for that I think is very critical mm-hmm. Is how important it is to have a surgeon involved in the initial management of these patients, if at all possible is how we look at imaging. How we look at the path to potential resection because it really matters how we drain these patients, but also where and what side we drain these patients with eyes towards future resection.

So involvement of a surgeon is critical. Now as you can imagine, some with widespread metastatic disease, things [00:17:00] like that, you can imagine why that patient may not be seeing a surgeon. But still input can be very helpful. And then number two. Another red line. And it's not, it's not something sometimes if you have it under your control, but it is so absolutely critical to try to find some way to either obtain the images or get imaging done for patients before biliary drainage to to be able to have a roadmap towards potential surgery.

'cause once patients have any element of cholangitis or multiple attempts at drainage performed, knowing where the. Where the best chance is for a margin negative resection can be quite difficult to judge. So one of the very first things you need to be finding as a surgeon seeing these patients for the first time is what their very first cross-sectional imaging was to look at the anatomy 'cause all the ducks are dial in and I think it's important to realize this imaging is [00:18:00] key because it is.

You look at the an actual CT or MRI in an ingrain patient without a stent, you could have really good imaging of the B duct. So it's just as good as the cholangiography. In fact, it's better than the cholangiography because if you, if you take a ct, you'd have the relationship of the tremor with the vessel, with the portal vein, with the hepatic artery.

And these relationships define whether the the patient will be resectable or not. These patients are resectable locally, but if it's locally advanced, you may have to do a resection. Extremely rarely. Very rarely we perform arterial resection, but most patients resectable are patients who do not have involvement of the of the vessels.

And I think this is, needs to be looked at. Also on the initial imaging, you can look at the [00:19:00] nature of the Langio carcinoma, if there are three subtypes. Anatomically there is the infiltrating type, the nodular type, and the papillary type. And I think based on the first image, you can have a hint at which type you're dealing with, and they have a different prognosis and.

And different resectability rates. So a careful imaging. We do ary protocol CT in these patients with with four phases and thin cuts. One millimeter, it's obliged coronal axial cuts, and and in, in the direction of the bowel duct. I think it gives you a very good imaging of the tumor and relationship with surrounding structures.

Yeah, that's another excellent point. I'm now thinking back to, I think the first time I sat and Dr. Vte gave this presentation on Perry Highly Cholangio in the Fellows Education Conference. I remember one of the first slides said, make sure you get high quality [00:20:00] imaging prior to drainage. 'cause that's always key to have that baseline.

All right, so I think now we'll move on to our, our next paper, which is kind of a continuation of this previous paper, and it's titled, improved Outcomes Following Resection of Per Cholangio. 27 year experience, and it was published in an, in the Annals of Search Oncology this year in 2025. And so this was a single center retrospective review of 100 patients who underwent curative intent resection.

Hyler cholangio patients were divided into two cohorts based on the date of resection, the past cohort from 1996 to 2013, and a recent cohort of 2014 to 2023, and that cutoff year of 2014 was chosen because this is when the institution MD Anderson at the time. Implemented the changes that we discussed previously regarding ensuring proper, timely drainage of the bio duct tree without increasing the risk of cholangitis, as well as ensuring patients had an adequate SFLR greater than 30% ahead of resection.

And it's all this happened right [00:21:00] after that initial, the data was gathered for that initial paper we previously discussed. So that's how we have those two cohorts of those two eras, the past 1996 to 2013 and the recent 2014 to 2023. And so the idea behind this paper was to compare how the changes in management may have affected changes in outcomes.

And so there's 55 patients in the past cohort and 45 in the recent cohort. There's no differences between the cohorts in terms of age, sex, or bismuth colorectal classification. However, preoperative cholangitis was less common in the recent cohort. It was 31% compared to 53% in the past. Additionally. 78% of patients in the recent cohort were able to undergo successful pre-op biliary drainage via endoscopic procedures alone compared to 50% in the past.

And along the same lines, far fewer patients in the recent cohort required a combination of both endoscopic and those percutaneous trans hepatic biliary drainage [00:22:00] procedures to achieve successful preoperative biliary drainage. So the percentage needing the combination in the new, the recent era was only 2% versus 35% in the old era or the past era.

And then another interesting finding was that in the recent cohort. When you looked at the laterality of hepatectomy amongst all patients in the past and recent cohort, the proportions who underwent or right, or extended right hepatectomy were similar, but if you looked at patients who had bismuth cot types one, two, and four, where you can technically resect either side, the left side, a left hepatectomy was more frequently performed in the recent cohorts in these patients, 61% versus only 13%.

In the, in the past cohort and Reassuringly, there was no increase in the R one resection rate or po. The positivity of margins amongst patients with BIM Correl one, two, or four disease, despite increased utilization of the left sided [00:23:00] hepatectomy over time. Now, in terms of outcomes. There were trends towards lower rates of major complications.

In the recent cohort, it was 38% versus 55%, and while it didn't reach statistical significance, it was an encouraging trend. But what was very, very good to see was that there was no postoperative hepatic insufficiency in the recent cohort. Zero cases that compared to 20% or one in five cases in the past cohort.

Additionally, there was significantly less perioperative mortality in the new cohort, only 2% versus 15% in the past. And that only death came in 2014, the very first year of that new or present cohort. And this resulted, understandably, in a significantly improved median overall survival. I mean, the present cohort, which is not yet reached, actually compared to only 33 months in the past cohort.

So, Dr. Nuk, you're, you're the senior author on this paper, so I want to get your. Your take and your interpretation of these results and what our listeners should walk away with. Yes. [00:24:00] Thank you for that. And WA was the senior author on this, but this is a longstanding experience from, you know, a a lot of which I was not a part of.

So a lot of, most of the credit for this entire thing goes to Dr. Botte for really pushing for these quality improvement pieces. And it's very clear that the proof is in the footing, so to speak, of. Of how much this has impacted our practice in terms of safe surgery and quality of resection. I have to say as an aside that this is very critical.

I mean, it's very easy to listen to this podcast episode and say, well, maybe we are not operating on people like we used to, who would otherwise potentially derive benefit from surgery. So what is an acceptable level of 90 day mortality when you're trying to give people an opportunity? And I would push back on that to say that, you know, there's been improvements in other areas of oncology care for these patients where the, the alternative [00:25:00] is not as bad as it used to be either, right?

So again, the, the point is you have more options when you're safe. And this data really has shown us that we are offering more safe options. So as you noted, this was an evaluation of our experience since figuring out from our prior experience. That we need to have a certain amount of volume and we need to replicate cholangitis and all the other improvements that came along with that, that that very immeasurable.

I think the important thing to see here is that there has not been, you know, fortunately, a death due to liver failure or death overall within 90 days in 10 years. Knock on wood. And I think that that's a real testament is really the biggest part of this whole paper, is that we need to find these things.

I think a humongous part of this paper. That we could talk about forever is that if you have the opportunity to restore a right side of resection versus a left side of resection, the preference should be [00:26:00] for a left hepatectomy with cot extended left hepatectomy if you have to with CO eight. Whereas the older teaching, I would say, and I use the term holder on purpose, is because when I was a surgery trainee in textbooks, and even still, people now believe that there is oncologic benefit to a right sided resection.

I mean, we could argue that, but the truth is there's no oncologic benefit if you're at high risk for death due to liver failure. So the left sided resections are preferable when able, we've shown that with this data very clearly. I think we have to give credit as well to other groups who have shown this.

There's a nice paper in anal surgical oncology as well. From Memorial Sloan Kettering in the Netherlands published around the same time as our paper that has showed the same thing. I think the data is very clear that when possible we should perform left sided resections, and that's likely all due to volume.

You have more volume on the left side of the liver. Abrogates, as we said, the detrimental, [00:27:00] inter detrimental impact of cholangitis. I think also it's un, it's not able to be measured statistically. And clearly tremendous amount of bias when looking retrospectively at this. But I have a serious hunch that a lot of this is due to decrease in cholangitis is also due to the improvements in our discussions about biliary drainage.

As you mentioned, clearly endoscopy has improved there has gotten better and better and better. As times go on on the talent of people that we've been able to include on our team has has become immeasurable. And everyone thinks like a surgeon. Now our colleagues know what we want. They know as a team, this is what we're trying to get to.

So the first shot is, your best shot is the truth. And our first shot is often adequate. So I think it's important to evaluate our data. It's important for groups to report their data, and that's really what our goal was with this paper, was to really show what we've [00:28:00] been able to do. When evaluating our newer experience compared to our prior report.

Thanks, Dr. I think that's a great breakdown and that that point about this being like a, having a multidisciplinary approach, especially in when it comes to the biliary drainage is really, really key. And like you said, a lot of this paper is built upon work that Dr. Botte star. So Dr. Patay, what do you feel is the big take home message for our listeners?

I think the message here is that best treatment of complication is prevention. And how have we pre prevented the, the complications is by this dedicated approach preoperatively at the best management of these patients as as indicated before. And this includes the imaging review, detailed imaging.

We review pre be deport drainage to define which surgery needs to be done, which type of of resection the, the patient needs. This goes with the management of jaundice, the [00:29:00] clearance of the jaundice, how this is gonna be done and best approached. I think this goes with the prevention throughout this for cholangitis in getting these patients to surgery fairly soon before we were using, quite a number of portal vein embolization because that was needed. We were performing right hepatectomy or extended hepatectomy, removing more than 50% of the liver volume. And and we have changed that by avoiding this delay. Also, we avoid the occurrence of CHO preoperatively because if you do a portal vein embolization, you inevitably delay the surgery.

4, 5, 6 weeks depending on the, on the scheduling. So I think this is very very important to note in this paper is, is a combined effort of a multidisciplinary team imaging with better imaging radiology [00:30:00] interventional radiology when needed. Endoscopy. So I think it's a multidisciplinary team.

And clearly if you look at the different SME types, type one through four. The only types where the anatomy really dictates a right or left hepatectomy are the types three A and three B, three A, because it's extending beyond the right hepatic duct towards the right deeply. Or three B on the other side towards segment four and segment segment two.

But as you mentioned the other types, type 1, 2, 4, you could really decide whether you go with a right hepatectomy or with a left hepatectomy because it's just extending evenly on both sides. And and we have made the choice to do. Left hept me in these cases with much better results. The right lobe [00:31:00] accounts for 60 66% of the total liver volume on average.

So you want to have a al sparing approach, al saving approach just as we we doing now with colorectal liver metastasis. It's it's the era of parenchymal sparing. Surgery not only for colorectal metastasis, but also for kin that has made this possible. Well, once again, this was an extremely engaging and educational conversation.

I wanna thank you both again for sitting down with me and, and doing this and it's a ton of great information this episode. So we're gonna just leave our listeners with some key takeaway points. The first is that perihilar clanger are rare, but aggressive malignancy. And transplantation or complete surgical resection are the only curative treatment options for patients without metastatic disease.

The second is that complete curative intent. Surgical resection entails a bile duct incision and major hepatectomy, both for [00:32:00] oncologic and for anatomical reasons as Dr. New Hook and Dr have outlined. But this does come with high risk of post-op morbidity and mortality. But as Dr. Vte mentioned, the best way to treat this is to prevent them.

And so some ways you can prevent them is ensuring an adequate post-op liver remnant. The number we like to use is A-S-F-L-R greater than 30%. 'Cause this will really help you avoid postoperative hepatic insufficiency and liver related death. In addition to using portal venous embolization, increased adoption of left-sided hepatectomy when feasible and based on the bismuth cot classification as Dr.

VTE outlined, can help ensure adequate SFLR by. Sparing or saving that right side of the liver, that accounts for about 60% or more of your liver volume. And then the last thing is you want to avoid pre-op cholangitis. And this is paramount to reducing post-op morbidity and mortality, especially liver failure related [00:33:00] deaths.

And as we've outlined here, this can be achieved via. Ensuring adequate biliary drainage pre-op, via multidisciplinary approach that includes our IR radiology and advanced GI colleagues. And the one caveat I will say there is make sure you get high quality imaging before you drain, or you can obtain that high quality imaging 'cause that's gonna be your baseline.

And so those are the key points that we'll leave everyone with. And as always, thanks to everyone for tuning in and as always, dominate the day.