Any patient with cancer needs a functioning gastrointestinal (GI) tract to sustain proper absorption of nutrition and medications. Unfortunately, patients with cholangiocarcinoma often have obstructed bile ducts that limit GI tract functionality and can potentially lead to infections if they have stents or drains in their bile ducts. Cholangiocarcinoma is quite rare. However, intrahepatic bile duct cancer (meaning cancer in the bile ducts inside your liver) is actually increasing in incidence.
Joining the show to discuss Cholangiocarcinoma, and to help you understand this rare disease is Renuka Iyer, MD. She is a Professor of Oncology, Co-Director of the Liver and Pancreas Tumor Center Section and Chief for Gastrointestinal Oncology at Roswell Park Comprehensive Cancer Center.
Selected Podcast
Cholangiocarcinoma: Understanding This Rare Disease
Featured Speaker:
Renuka Iyer, MD
Renuka Iyer, MD, Professor of Oncology, Co-Director, Liver and Pancreas Tumor Center, Section Chief for Gastrointestinal Oncology at Roswell Park Comprehensive Cancer Center. Transcription:
Cholangiocarcinoma: Understanding This Rare Disease
Bill Klaproth (Host): Cholangiocarcinoma is a rare and traditionally difficult-to-treat cancer. So, what is it? Here to talk with us about cholangiocarcinoma is Dr. Renuka Iyer, Co-Director, Liver and Pancreas Tumor Center, Section Chief for Gastrointestinal Oncology at Roswell Park Cancer Institute. Dr. Iyer, thank you for your time today. So, let’s start right at the beginning. What is cholangiocarcinoma?
Renuka Iyer, MD (Guest): Thank you for having me. Cholangiocarcinoma is cancer of the bile duct. These bile ducts actually are little tubes that are within the liver and also outside the liver, and the gallbladder is part of this bile duct tract, and all of these together are called cholangiocarcinoma.
Bill: So, Dr. Iyer, how common is this type of cancer?
Dr. Iyer: It is not very common, and if you look at all of the extrahepatic bile duct cancers, that is the bile duct outside the liver, approximately 11,000 or so cases are diagnosed. Two-thirds of which are gallbladder cancer and about 3,000 or so are extrahepatic bile duct cholangiocarcinomas that are also intrahepatic bile duct cancers, and that is a little hard to estimate the exact number because those are combined with primary liver cancer and the two together are about 40,000 or so.
Bill: And Dr. Iyer, do we know what the risk factors are for cholangiocarcinoma?
Dr. Iyer: That’s a great question. So, there is one inheritable, or rather caused from a risk factor that is an inherent risk factor, which is primary sclerosing cholangitis, an inflammatory disorder of the biliary tree that causes a lot of fibrosis and stricturing, and that unfortunately leads to cholangiocarcinoma in a high percentage of patients. But other than that, the sort of main risk factors for gallbladder cancer, for example, is the presence of gallstones and inflammation in the gall duct, gallbladder itself, and toxic exposures such as some not that common anymore, but a contrast agent called Thorotrast, a long time in the 1960’s, is a carcinogenic thing that was associated, and also viral hepatitis has been related to causing this cancer.
Bill: So, Dr. Iyer, what makes this disease different than other cancers?
Dr. Iyer: Diagnosing this disease is very difficult because patients present with jaundice and the bile duct is strictured or tight and getting a biopsy or a little piece of tissue that confirms that this is cancer is sometimes very difficult, and that’s a challenge for diagnosis, and another difficulty with these patients, unfortunately, is often by the time it’s found, because of its location, surgery is not possible. The diagnosis is made a little late and treating these patients is challenging because keeping that bile duct open while giving them treatment is not very easy. These bile ducts tend to close up. They require stents. They get infected, and that makes it a little harder to treat these patients.
Bill: You mentioned jaundice. Are there any other signs or symptoms?
Dr. Iyer: Some patients will present with weight loss, pain associated with it, but for the most part, jaundice is a very typical presenting symptom.
Bill: And you mentioned that treatment can be difficult. Can you expound on that a bit for us?
Dr. Iyer: As you know, with most patients, when they hear the word cancer, they want it out, and surgery is the best treatment for any cancer, and cholangiocarcinoma is no different. So, if you were to divide these cancers into the liver, the ones that are inside the liver, and the gallbladder, for these patients, surgery is possible, and when it’s done, outcomes can be good—if it’s caught early, for example, if a patient went in with a gallbladder attack and their cancer was diagnosed relatively early. But unfortunately, for the patients who present with jaundice when the bile duct is obstructed and now the cancer is present at the confluence, or the outflow tract, from where the bile comes out of the liver, at that location, what we call hilar cholangiocarcinoma, at the hilum, at the mouth, their surgery is very challenging to do because there’s not enough bile duct to do an operation. And in those patients, it becomes more palliative where we’re giving chemotherapy, trying to prolong survival, and treatments have not been very successful so far. Great advances have been made in the last couple of years, but still, a lot of work remains to be done.
Bill: So, when it comes to those advances, can you tell us about the breakthroughs that have been made?
Dr. Iyer: Absolutely. So, I think two big, big breakthroughs that have been made is molecular classification of bile duct cancers have allowed us to identify that intrahepatic cholangiocarcinomas have a higher frequency of some mutations that are actionable, ID each one Fibroblast Growth Factor Receptor. These are just a couple of examples of mutations for which there are drugs that actually work and finding this mutation in about 22, 25% of patients. It’s often intrahepatic cholangiocarcinoma has made this option available to patients through clinical trials, and this has been a big breakthrough for those patients.
Similarly, for gallbladder cancer patients, finding HER2 expression, this is another receptor for which there are multiple targeted drugs, has been another breakthrough for those patients, and so this is just one example, and the second has been that there has been a greater interest in focusing on this patient population on this community and several Phase III studies have been done to define standards. What should be the first therapy that we give? What should be the second therapy that we give? Adjuvant therapy after surgery. Phase III studies had not been done up until just a few years ago, and some of those studies have been completed in just the last five years, and many more studies are ongoing and will be completed in the next five years. So, there is a lot of hope for these patients because of this.
Bill: Right now, what is the long-term prognosis or outcome for someone with cholangiocarcinoma?
Dr. Iyer: For a patient who is able to have surgery, if it’s intrahepatic cholangiocarcinoma or gallbladder or even extrahepatic cholangiocarcinoma, not affecting the lymph nodes, the outlook is good. The likelihood of surviving this and beating this is more than 50%. It’s even for gallbladder cancer, it crosses over 80-90%, but when we look at patients who have, unfortunately, Stage 4 disease when it is not curable, survival is still, unfortunately, on an average about a year, and much work remains to be done.
Bill: Well, there is good news about those breakthroughs, and we’ll keep hoping that those outcomes do improve with subsequent advances, and Dr. Iyer, how can patients with this type of cancer become self-advocates?
Dr. Iyer: Oh, I think that just the knowledge that a lot is being done and staying hopeful, I think. Attitude is big, and as you know, in fighting anything, for starters. The Cholangiocarcinoma Foundation has been a great source for resources, education, support and on there is a card. It’s a biliary emergency card, and I would encourage patients to, if they have stents and tubes, PTC tubes, to fill one out, and they can be their own advocate if they get an infection and end up in an emergency room to help the doctors there who may not be as familiar with how to manage emergencies to help guide them and get the right care and facilitate communication between doctors. And this card is designed to help make that happen, and doctors at Roswell Park helped make that happen, and so I think, that’s another reason, I feel, strongly that I should mention it. It has helped a lot of our patients. Another thing that patients should consider is participating in clinical trials, and that’s how advances are made. It has helped them. It has helped others, and I think just these three things—staying hopeful, positive and doing the best they can. Even they get infection emergencies—being their own advocates, having this card facilitating interactions between their doctors and the doctors in the emergency room and participating in trials.
Bill: Dr. Iyer, thank you for your time today and sharing that information with us. If you want to learn more, please visit roswellpark.org. That's roswellpark.org. You're listening to Cancer Talk with Roswell Park Cancer Institute. I'm Bill Klaproth. Thanks for listening.
Cholangiocarcinoma: Understanding This Rare Disease
Bill Klaproth (Host): Cholangiocarcinoma is a rare and traditionally difficult-to-treat cancer. So, what is it? Here to talk with us about cholangiocarcinoma is Dr. Renuka Iyer, Co-Director, Liver and Pancreas Tumor Center, Section Chief for Gastrointestinal Oncology at Roswell Park Cancer Institute. Dr. Iyer, thank you for your time today. So, let’s start right at the beginning. What is cholangiocarcinoma?
Renuka Iyer, MD (Guest): Thank you for having me. Cholangiocarcinoma is cancer of the bile duct. These bile ducts actually are little tubes that are within the liver and also outside the liver, and the gallbladder is part of this bile duct tract, and all of these together are called cholangiocarcinoma.
Bill: So, Dr. Iyer, how common is this type of cancer?
Dr. Iyer: It is not very common, and if you look at all of the extrahepatic bile duct cancers, that is the bile duct outside the liver, approximately 11,000 or so cases are diagnosed. Two-thirds of which are gallbladder cancer and about 3,000 or so are extrahepatic bile duct cholangiocarcinomas that are also intrahepatic bile duct cancers, and that is a little hard to estimate the exact number because those are combined with primary liver cancer and the two together are about 40,000 or so.
Bill: And Dr. Iyer, do we know what the risk factors are for cholangiocarcinoma?
Dr. Iyer: That’s a great question. So, there is one inheritable, or rather caused from a risk factor that is an inherent risk factor, which is primary sclerosing cholangitis, an inflammatory disorder of the biliary tree that causes a lot of fibrosis and stricturing, and that unfortunately leads to cholangiocarcinoma in a high percentage of patients. But other than that, the sort of main risk factors for gallbladder cancer, for example, is the presence of gallstones and inflammation in the gall duct, gallbladder itself, and toxic exposures such as some not that common anymore, but a contrast agent called Thorotrast, a long time in the 1960’s, is a carcinogenic thing that was associated, and also viral hepatitis has been related to causing this cancer.
Bill: So, Dr. Iyer, what makes this disease different than other cancers?
Dr. Iyer: Diagnosing this disease is very difficult because patients present with jaundice and the bile duct is strictured or tight and getting a biopsy or a little piece of tissue that confirms that this is cancer is sometimes very difficult, and that’s a challenge for diagnosis, and another difficulty with these patients, unfortunately, is often by the time it’s found, because of its location, surgery is not possible. The diagnosis is made a little late and treating these patients is challenging because keeping that bile duct open while giving them treatment is not very easy. These bile ducts tend to close up. They require stents. They get infected, and that makes it a little harder to treat these patients.
Bill: You mentioned jaundice. Are there any other signs or symptoms?
Dr. Iyer: Some patients will present with weight loss, pain associated with it, but for the most part, jaundice is a very typical presenting symptom.
Bill: And you mentioned that treatment can be difficult. Can you expound on that a bit for us?
Dr. Iyer: As you know, with most patients, when they hear the word cancer, they want it out, and surgery is the best treatment for any cancer, and cholangiocarcinoma is no different. So, if you were to divide these cancers into the liver, the ones that are inside the liver, and the gallbladder, for these patients, surgery is possible, and when it’s done, outcomes can be good—if it’s caught early, for example, if a patient went in with a gallbladder attack and their cancer was diagnosed relatively early. But unfortunately, for the patients who present with jaundice when the bile duct is obstructed and now the cancer is present at the confluence, or the outflow tract, from where the bile comes out of the liver, at that location, what we call hilar cholangiocarcinoma, at the hilum, at the mouth, their surgery is very challenging to do because there’s not enough bile duct to do an operation. And in those patients, it becomes more palliative where we’re giving chemotherapy, trying to prolong survival, and treatments have not been very successful so far. Great advances have been made in the last couple of years, but still, a lot of work remains to be done.
Bill: So, when it comes to those advances, can you tell us about the breakthroughs that have been made?
Dr. Iyer: Absolutely. So, I think two big, big breakthroughs that have been made is molecular classification of bile duct cancers have allowed us to identify that intrahepatic cholangiocarcinomas have a higher frequency of some mutations that are actionable, ID each one Fibroblast Growth Factor Receptor. These are just a couple of examples of mutations for which there are drugs that actually work and finding this mutation in about 22, 25% of patients. It’s often intrahepatic cholangiocarcinoma has made this option available to patients through clinical trials, and this has been a big breakthrough for those patients.
Similarly, for gallbladder cancer patients, finding HER2 expression, this is another receptor for which there are multiple targeted drugs, has been another breakthrough for those patients, and so this is just one example, and the second has been that there has been a greater interest in focusing on this patient population on this community and several Phase III studies have been done to define standards. What should be the first therapy that we give? What should be the second therapy that we give? Adjuvant therapy after surgery. Phase III studies had not been done up until just a few years ago, and some of those studies have been completed in just the last five years, and many more studies are ongoing and will be completed in the next five years. So, there is a lot of hope for these patients because of this.
Bill: Right now, what is the long-term prognosis or outcome for someone with cholangiocarcinoma?
Dr. Iyer: For a patient who is able to have surgery, if it’s intrahepatic cholangiocarcinoma or gallbladder or even extrahepatic cholangiocarcinoma, not affecting the lymph nodes, the outlook is good. The likelihood of surviving this and beating this is more than 50%. It’s even for gallbladder cancer, it crosses over 80-90%, but when we look at patients who have, unfortunately, Stage 4 disease when it is not curable, survival is still, unfortunately, on an average about a year, and much work remains to be done.
Bill: Well, there is good news about those breakthroughs, and we’ll keep hoping that those outcomes do improve with subsequent advances, and Dr. Iyer, how can patients with this type of cancer become self-advocates?
Dr. Iyer: Oh, I think that just the knowledge that a lot is being done and staying hopeful, I think. Attitude is big, and as you know, in fighting anything, for starters. The Cholangiocarcinoma Foundation has been a great source for resources, education, support and on there is a card. It’s a biliary emergency card, and I would encourage patients to, if they have stents and tubes, PTC tubes, to fill one out, and they can be their own advocate if they get an infection and end up in an emergency room to help the doctors there who may not be as familiar with how to manage emergencies to help guide them and get the right care and facilitate communication between doctors. And this card is designed to help make that happen, and doctors at Roswell Park helped make that happen, and so I think, that’s another reason, I feel, strongly that I should mention it. It has helped a lot of our patients. Another thing that patients should consider is participating in clinical trials, and that’s how advances are made. It has helped them. It has helped others, and I think just these three things—staying hopeful, positive and doing the best they can. Even they get infection emergencies—being their own advocates, having this card facilitating interactions between their doctors and the doctors in the emergency room and participating in trials.
Bill: Dr. Iyer, thank you for your time today and sharing that information with us. If you want to learn more, please visit roswellpark.org. That's roswellpark.org. You're listening to Cancer Talk with Roswell Park Cancer Institute. I'm Bill Klaproth. Thanks for listening.