Clancy, J. Clark, MD, assistant professor of Surgical Oncology at Wake Forest School of Medicine, discusses “Surgical Management of Gallbladder and Extrahepatic Cholangiocarcinoma.”
CLANCY J. CLARK: OK, good morning. I'm to take us on a sort of different tangent away from endoscopy techniques and discuss a little bit regarding the surgical management of gallbladder cancer and extrahepatic cholangiocarcinoma. And what we're talking about in the biliary tree are the green portions and the orange portions. We're leaving out of those patients in this discussion who have intrahepatic cholangiocarcinoma. That's a different disease process, frequently managed in a different way. We'll first talk specifically about gallbladder cancer, and how it presents, and how we manage that on a surgical perspective. I think that I would categorize gallbladder cancer patients in three different scenarios. There's a scenario where a patient presents with a mass. And you'll get a report. They may have vague symptoms, nausea. They may actually present with jaundice. And they'll have a mass lesion concerning for a gallbladder cancer. The next one, which I see not infrequently, is where a surgeon is planning on proceeding with a cholecystectomy for what's thought to be symptomatic cholelithiasis. And intraoperatively, there is concern that there's an underlying malignancy. The last one, which does happen and it is a-- most surgeons may encounter this in their career once in a while, but it can happen, which is incidental gallbladder cancer, where they remove the gallbladder. And on that report a week later, they get back a cancer of the gallbladder. So let's focus first on the mass lesion. These, I think, are the most troublesome, because most of them will not be resectable. When a patient presents with symptoms of gallbladder cancer at the same time and it prompts the CT, it's unlikely that it's resectable. That being said, optimal imaging would be either an MRI or CT, three-phase, most beneficial. The liver function tests, CA 19-9, CEA, should be obtained. For those who present with jaundice, most of those patients, 95% of the time will be unresectable. However, using that imaging can help us guide on whether that tumor is, in fact, resectable. Those with intraoperative findings concerning for gallbladder cancer, a frozen section can be helpful. To be honest, when you're in a small hospital or a hospital that does not have an HPB surgeon or a liver-pancreas surgeon and you're concerned about gallbladder cancer, it's preferred that you stop. Biopsies of the gallbladder itself can be challenging. That can result in perforation. If there's liver lesions adjacent to it, those are more amenable to biopsy. Certainly, peritoneal lesions or omental lesions can be biopsied. At that point, you should do your best if you're laparoscopic to assess resectability. Document what you see. If you have the means, capability, and expertise, you could consider, if clearly resectable-- that would be if you had preoperative imaging, that it shows no metastatic disease. If you have good diagnostic laparoscopy, you could consider proceeding with a cholecystectomy. But you have to be in mind that you want to perform a cancer operation, not just remove the gallbladder. Lastly, if you don't have clear resectability, if you don't have adequate preoperative imaging-- you have a right upper quadrant ultrasound as the only test you've obtained-- then stop the operation and proceed with staging after the procedure. I want to highlight one common problem that I encounter frequently, is xanthogranulomatous cholecystitis. And this is-- it looks like gallbladder cancer. It is, on preoperative imaging, appears to be gallbladder cancer. And it's not. Maybe in some situations, you can have preoperative imaging that supports a benign process. It is a struggle when you're in the operating room trying to make a distinction between this type of benign inflammatory process and true gallbladder cancer. And frequently, you have to perform an anatomic cholecystectomy in a gallbladder cancer perspective. And you will come up with benign disease. Frozen sections can facilitate determining what this is and not proceeding with a major operation. That's where you have to trust your pathologist, if you're going to plan to not proceed with the resection. For those with incidental gallbladder cancer, I think there's three key things that you need to know. One is, what is the radial margin? What is the liver margin of that gallbladder? That really is based on what the surgeon documents in their operative note, as well as potentially what the pathologists document. Frequently, that's left out. Cystic duct margin is absolutely essential. Is that cystic margin positive? And then there's theT-stage. And the reason why the T-stage matters is it dictates whether you have to do any other procdures. For those with a T1 lesion, negative margins, you can observe that patient. With those with a T1b or greater, those are patients that you should consider for resection. And I'll just go over really quickly-- a T1 lesion is one that invades the lamina propria. T1b invades the muscular layer. Two, T2 invades the perimuscular connective tissue. T3 are those that invade the serosa, invade the liver, adjacent structures. And T4 are those that have vascular involvement. So next question is, if you're refer a patient who has concerning imaging for gallbladder cancer or has undergone a cholecystectomy and has gallbladder cancer, and you're thinking about, should you do a diagnostic laparoscopy before resection? Generally, imaging quality is so good now with MRI and high-quality CT scan that diagnostic laparoscopy has limited benefit. However, there are particular categories of patients that I will do a diagnostic laparoscopy on-- those with positive margins, those with poorly-differentiated adenocarcinomas of the gallbladder, and those with T3 or T4 lesions. Given with T4 lesions with potential vascular involvement, performing a laparotomy in those patients can increase morbidity, when you're really questioning if you can even remove that tumor. So back to surgical intervention and what operation you should do, and I think there's four parts to that operation. One is removing the gallbladder en bloc with the adjacent liver. The extent of that liver resection is debated. There are people who favor a small, two centimeter margin, a sort of large wedge resection gallbladder fossa to anatomic resection. And I would favor somewhere in between. You have to know the anatomy of the region, and the middle hepatic vein, and the blood supply to that aspect of the liver. And you can perform a nice anatomic resection, IVb and V, to get a good adequate margin for gallbladder cancer. I will say that if there is evidence of invasion of the right hepatic artery, portal vein on the right side, that it may require an extended hepatectomy. Next is you want to achieve a negative margin at the bile duct. And so if your cystic duct margin is in question, you should re-resect that cystic duct margin, identify, and obtain a frozen section to determine if there's any evidence of malignancy at that margin. And in fact, if there is a positive margin there, you may consider re-resecting the extent of the cystic duct. And if you're limited, you may require resecting the extrahepatic biliary tree. A hilar lymphadenectomy is an extremely important aspect, both for prognosis and potentially therapy for patients with gallbladder cancer. And the last thing that has been debated over the last 10 years is whether you should take out port sites. I don't routinely do that. I think that there's no real solid evidence that it provides improved survival in a patient. To really get an adequate resection of those port sites requires a large section of the abdominal wall. And that could cause some hernias, increase the length of the operation with unknown benefit. Typically, patients who had port site recurrence, that's just an indicator of systemic disease, and likely peritoneal disease. I just wanted to highlight here a schematic of the lymphatic drainage of the gallbladder. And it's unique in that when you have a gallbladder cancer, the tumor cells are going to cascade down the biliary tree, rather than retrograde up into the liver. And what we think is that the lymphatic spread of those tumor cells passes through lymphatic channels along the cystic duct, along the common bile duct, and then descend down posterior to the pancreas, and then ultimately along the SMA, aorta, and cava. That really guides us in what kind of lymphadenectomy we perform. Here's a schematic of the liver. The en bloc resection of the gallbladder is marked out here in red. That is segments IVb and V of the liver. The lymphadenectomy that we're referring to is here in-- you see, here is the portal vein, the hepatic artery in black, the small lymph nodes marked out here, both along the portal vein, posterior, posterior to the pancreas, and along the common hepatic artery. All of those nodes are denuded. And the blue area marks those regions where our hilar lymphadenectomy are performed. Pretty much by the time you finish this operation, the hepatic artery, and portal vein, and common bile duct are skeletonized. Just to highlight, in gallbladder cancer, some key factors in survival-- I just highlight here that T-stage, those with lower T-stage live longer than those with more advanced extension of tumor. Those with lymph node-positive disease do significantly worse than those with lymph node-negative disease. And similarly, those with poorly-differentiated disease do significantly worse than those with well-differentiated disease. What I want to highlight from the Memorial data is that we learned that if you can technically do the operation, you should do the operation. However, when you look at the extent of operation, if you're doing a major hepatectomy versus minor hepatectomy, or en bloc resection, there's no real difference in survival in those patients. If you have to do a bile duct resection versus no resection, no real difference in survival. If you have to do a vascular resection, no difference. And similarity, if you have to resect adjacent organs, no difference in survival. I think the take-home message there is if you can achieve an R0 resection, you should attempt to achieve R0 section. But the caveat to that is you have to do it with low morbidity, given the significant high risk of local recurrence and likelihood of disease progression, despite the best operation you can provide. Here, we'll highlight here the differences between achieving an R0 resection versus an R1-2 resection. As you can see, if these are patients who had known gallbladder cancer who undergo an exploration, if you did not find disease, they had significantly improved survival, whereas those who had an R0 resection had worse survival. And even more dismal, those who an R1 or two resection did very poorly. We'll jump of over to extrahepatic cholangiocarcinoma. This encompasses the perihilar and distal cholangiocarcinomas. What we're talking about is limited to those with perihilar-- outside of the liver-- and distal common bile duct tumors. We've seen this this morning. There's a Bismuth classification scheme. The reason why this scheme is vitally important from a surgical decision making standpoint is it determines what operation you are going to perform. And those with type I, type II, potentially do not require a major hepatectomy. Those with type III a and b typically will require a extended hepatectomy. Type IV lesions, which involve bilateral secondary radicals, potentially could be candidates for a liver transplant and typically are not candidates for surgical resection. We went over this a little bit before. The challenge, And I'll just-- I'll move quickly through this-- is getting a diagnosis. And multiple strategies, including imaging, EUS, FNA, brushings, biopsies, spyglass, are all used to help facilitate establishing that diagnosis. Unfortunately, many patients, we will not be able to establish a diagnosis. And if imaging suggest that they're resectable, we should proceed with a resection. Again, just like gallbladder cancer, the goal is to achieve an R0 resection. That means resecting the hilum of the liver, if that's required, resecting a large portion of the liver, if that's required. The second part of that is, can you get them back together? Yes, if we can get a negative margin, can you sew to the secondary biliary radicals and get reestablishment of the biliary-enteric continuity? And that often is a barrier. If your tumor extends high up into the liver and you cannot reconstruct the biliary tree, then that would preclude resection. The type of resection is also dependant on where in the biliary tree it is. If it's distal, that will be a Whipple. Proximal, that's going to be a major hepatectomy with bile duct reconstruction. And there's a rare, uncommon occurrence where a person has a limited short segment stricture but common bile duct cancer, where a segmental resection can be performed with the hilar lymphadenectomy. There is a subgroup of very selected patients that will find to be candidates for a liver transplant. However, that's extremely uncommon. Some of the considerations for hilar cholangiocarcinoma is that you should be wary of longitudinal spread. It may be that a patient has a well-defined lesion at the hilum of the liver, but intraoperatively may encounter positive margins. And you'll be marching up or marching down, trying to identify where that negative margin is. What's extremely important is using a high-quality MRI to help facilitate that preoperative planning. You will need to determine your future remnant liver volume, given that if you're requiring an extended right hepatectomy, you might have a small left lateral sector. And that might not be adequate for your resection. And a portal vein embolization may be required. There's also discussion about resecting the caudate lobe. Given hilar lesions frequently have extension into the caudate lobe posterior, then a caudate lobe resection should be considered. Here, I just want to highlight several outcomes. Basically, it's clear that if you explore a patient and you're able to do a resection for cure, those patients who undergo a resection will live longer. Those patients who achieve an R0 resection will live longer. And those patients who have node-negative disease will also live longer. In summary, preoperative for resectability is exceedingly important. We are trying to achieve an R0 resection. An R1, R2 resection provides limited benefit to this subgroup of cancer patients. Summarily, we need to know that lymph node status. And there are some indications based on large registry data that we do not do a good job. And I'll just have a commentary that most of the studies show that surgeons are only able to isolate one to two nodes on these hilar lymphadenectomies. And that's registry-based data. And I think this is a strong discussion with your pathologist in performing your lymphadenectomy to help them identify where those nodes are. We should aim for a goal of six lymph nodes. Often, when you have a reoperative field, all of the hilum is sclerotic. And what is true node versus perihepatic, periarterial tissue, versus actual true lymph node is difficult and challenging. But we should strive as surgeons to remove as much of that tissue to provide an adequate lymph node dissection as we can.
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