During this 20-25 minute pre-recorded lecture, Dr. Charissa Chang discusses the topic of liver tumors. This in-depth review will provide an update on this topic for your clinical practice as well as supplement your learning for the ABIM Gastroenterology and Hepatology boards. CME pre-requiste of live Q & A webinar, 8th Annual Mount Sinai Intensive Board Review in Gastroenterology & Hepatology on Oct 13.
I'm going to spend the next 20 minutes discussing liver tumors. This shows you a list of benign liver mass lesions and it's a laundry list of all the various different benign space occupying lesions that can be seen on imaging for the purposes of this board review. Um We will cover focal nodule or hyperplasia hepatic adenoma. But in the interest of time I will not be reviewing these other ones that are on the list. However, know that this is a list of the differential diagnosis. And this slide shows you a list of malignant liver mass lesions, the most common being metastatic tumors and of the primary tumors that we can see in the liver. The most common are a patio cellular carcinoma, Colangelo carcinoma and know that you can also get mixed apatow cellular Colangelo carcinomas. Question one a 65 year old man has referred to you by his primary care physician for hepatitis C infection diagnosed through routine screening. He reports a history of drug use 20 years prior and has never been treated for hepatitis C. On exam he is well appearing abdomen is soft with a palpable spleen tip and no distention. Further labs reveal platelets that are slightly low at 95,000 normal total billy Rubin albumin I. N. R. And A. Hepatitis C. RNA A. Level that is one million. He's genotype. One fiber scan shows the stiffness of 14 which is in the early psoriatic range. All the following are appropriate management steps at this time, accept a check. Hepatitis B serology, be check hep A antibodies for immunity C check HIV status D order abdominal imaging whether ultrasound or ct scan e refer for liver transplant evaluation. So the correct answer is that you would do all of these. Um but he's a little early for a liver transplant evaluation and therefore you would not choose e at this point. And the main point here is that this is a patient who has cirrhosis in the setting of hepatitis C. And you do want to order imaging for liver cancer screening. So um the last time that we have updated guidelines from the A. S. L. D. Is uh 2000 and 18. So it's somewhat recent and um This is what the guidelines say in terms of which patients weren't HCC screening. So among patients with hepatitis b. Um regardless of cirrhosis status um Asian males over 40. Asian females over 50 any Hepatitis B patient who has a family history of HCC and hepatitis B patients of african or north american black um um descent all weren't HCC screening. And then um pretty much anybody with cirrhosis whether it's from hep B. Hep C. PVC metabolic conditions all warrant um HCC uh screening with surveillance imaging every six months. Um These are the categories of patients for which surveillance benefit is uncertain and lumped into. There is um hepatitis C. With stage three fibrosis. Although um many of us would would still do HCC screening um when you consider that sometimes are uh fibrosis um estimates um good err on the side of underestimation. And although we are seeing HCC and nash patients who do not have cirrhosis the um incidents and prevalence of this at this point based on current literature is not high enough to warrant a routine screening in our nash patients who do not have cirrhosis. Question two. So the patient in question one is treated successfully with D. A. S. For the hepatitis C. And um you do get an ultrasound for HCC screening. You see a nodule or liver confirming uh cirrhosis um um there's no other important imaging findings. Um The patient has some small viruses on a screening E. G. D. What is the following which of the following is appropriate for this patient at this point a reassure the patient that he has been cured of hepatitis C. And no further testing or follow up is warranted. Be performed abdominal imaging yearly for HCC screening. See perform imaging every six months for HCC screening. D refer for liver transplant evaluation or e repeat E. G. D. In one year for various eel surveillance. So the correct answer here is see perform abdominal imaging every six months for HCC screening. So again this is a patient who has hepatitis C. Cirrhosis. Um You want to do imaging for HCC screening and the interval should be every six months. Um The point of this question is that although his hepatitis C. Has now been cured with D. A. S. He still is at risk for HCC um based on his underlying cirrhosis and um this is based on uh studies that show that although you do um lower your risk for HCC with successful treatment of hepatitis C their risk for HCC is not eliminated. And so this is one of a somewhat older study from Vandermeer showing the cumulative risk of HCC in patients who have hepatitis C. And um of course those patients who have S. V. R. Have a much lower cumulative risk of HCC compared to those patients who do not achieve SVR. But even with SVR um the accumulative risk of HCC over 10 years was up to 9%. Um And again though these are patients who had baseline advanced fibrosis or cirrhosis at the time of their HCC treatment. And the more recent data that comes from the V. A. Shows a very large cohort of patients with hepatitis C cirrhosis and you can see um that um patients who had SVR in the setting of cirrhosis had a cumulative risk of HCC. That approached 10%. Um at at 10 years compared to those who did not have cirrhosis um who achieved SVR with hepatitis C treatment. So um so if you're going to treat a patient who has hepatitis C it's important to know their underlying fibrosis um status at baseline if they don't have cirrhosis you don't you probably don't have to worry about HCC screening after you get SVR. But if you have a Sirat IQ HEP C patients you cannot discharge them from care after they've achieved successful SVR. These are patients you have to keep um engaged in care and engaged in a surveillance um uh schedule every six months Question three a 42 year old man with chronic Hepatitis B is found to have a 1.5 centimeter mass on screening ultrasound of the abdomen labs show elevated amino transfer races platelets in the low hundreds range. Normal creatinine billy Rubin. I. N. R. Is alpha feta protein is a little elevated at 23 which of the following is appropriate. A C. T. Scan of the abdomen without ivy contrast cT scan with multi phase contrast, repeat an ultrasound in three months. The biopsy the mass E. MRI abdomen without contrast. So the correct answer is B you want to do a ct scan with multi phase contrast. And um the point of this question is we have here a patient with hepatitis B. And suspected HCC. This certainly looks suspicious. He's got a 1.5 centimeter mass. His alpha feto protein is a little elevated. Um And you know the question is what is the best kind of imaging modality to diagnose a suspected HCC. Um The point here is that you need to use I. V. Contrast and so that's why A. And E. Are inappropriate. Um you wouldn't simply repeat an ultrasound in three months. You're concerned enough that you need to do better imaging than an ultrasound. Um And um we don't need to biopsy at this point. Um And I'll show you in the next slide by. So what's unique about HCC among all types of cancers is that it has um a dual blood supply. And so in the liver we have arterial supply coming from the hepatic artery and then we have a venus supply coming from the portal vein. Liver cancers are very arterial ized. And so they'll get a lot of their um blood flow from the hepatic artery. And so if you do a scan with multi phase contrast, what you're doing is you're getting images at different phases um As the contrast moves to the arterial system and then through the venus system. And so what you expect to see with the cancer is that it should light up during the arterial phase. And then in the venus phase you get relative hypo perfusion of the cancer with respect to the background liver. And what you should see is that the background liver should look a little brighter than the cancer itself. And so we call that um arterial enhancement with venus washout. And this is examples of what you might see on imaging. So this is an M. R. I. With gadolinium contrast. And here you can see on the arterial phase. You know this because the earth as well at uh that the tumors light up and then on the venus phase the US look relatively less bright compared to the background liver. And so the imaging characteristics are diagnostic enough to allow us to make the diagnosis with imaging alone and without requiring a liver biopsy confirmation. This is another example of arterial enhancement with delayed venus washout in a uh HCC. So um when the radiologists interpret these images um they use what's called a liar AD system and a definitive HCC will be reported on your radiology report as a liar adds five um liar. It's for is probable HCC. Where the imaging characteristics are not quite diagnostic. And that's a situation where if you're getting a cT scan you could get an MRI as an alternate mortality which could show better more diagnostic findings. Or you might consider doing a biopsy for pathologic confirmation. A liar as three lesion um is suspicious but not quite diagnostic. And that's a situation where you could either get uh an alternate modality. So if you've done a ct scan, get an M. R. I. And said or you may want to repeat imaging at a shorter interval. Say like three months question for a 52 year old man with hepatitis B. Presents to the emergency room with abdominal pain C. T. Scan shows a four centimeter right lobe mass with arterial enhancement in venus washout on exam. He is well appearing with no stigma of cirrhosis labs reveal a platelet count of 120,000 billy Rubin I. NR albumin, normal alpha feta protein, normal hepatitis B. DNA levels 2700. What is the next step in management a perform a biopsy of the mass. Be referred for liver transplantation? See referred for surgical resection of suspected HCC. D. Treat with trans arterial chemo embolization. He referred to oncology to initiate systemic therapy with sarafina. Correct answer. Here is c. So um we have diagnostic findings um the arterial enhancement and venus wash out and I just showed you that we can make the diagnosis from imaging and therefore we don't do not need to biopsy the mass. Um This is a single four centimeter tumor. Um You could question whether this patient might be better off with transplantation or resection. Um And in this situation um this patient is otherwise compensated with Platelet count over 100,000. Which is what um many surgeons will use as a surrogate for portal hypertension. And so this is a patient who will likely be able to tolerate curative resection. And so you would go for resection in this patient before liver transplantation. You could argue that the next step would actually be to treat the hepatitis B. Um But that's not listed as an option. Um I only mention that because you don't wanna overlook the importance of controlling the virus mania. And this patient if you bring the hepatitis B. DNA level down to non detectible. It will definitely lower this patient's risk for recurrent HCC wants to treat the tumor. And so um we have this B. C. L. C. Staging system that is endorsed by A. S. L. D. And easel. That gives us a framework for how we approach liver cancer and all the different stages and links the diagnostic stage to the treatment modality. And so this is a patient who has a single tumor. Um no portal hypertension and therefore can be respected. If they have increased portal hypertension. Then this is these are patients who will decompensate with resection and so you're either gonna refer them for liver transplantation or if they're not a good transplant candidate or if it's a single small tumor accessible to uh ablation that's a patient who are going to treat with ablation. Um So the next stages um are the ones that are not amenable to curative modalities. So the curative modalities are resection, liver transplantation or ablation. And then once you start to have multi nodule er tumors. Um This is where we're getting into systemic therapies. If you have no total invasion or metastatic disease. These are patients who you cannot transplant and you would treat with um systemic chemotherapy. And then if they have um advanced cirrhosis, poor performance status. Those are patients who are not going to tolerate therapies and are going to be managed with best supportive care. Question five. A 64 year old man with nash cirrhosis is found to have two lesions on ultrasound ct shows a 1.2 centimeter leaders in the left lobe and a 2.4 centimeter lesion in the right lobe. They each enhance on arterial phase. They have washed out during venus phase diagnostic of HCC. He has some viruses. Uh He's on that'll offer that. His exam is unremarkable. He has low platelet count, elevated billy Rubin, elevated I. Nr. His alpha feta protein is normal. What is the next step in the management of this patient and referred for transplant? Be starts sarava nib see refer for reception. D treat with chemo embolization E. Palliative care. And the answer to this question is um on that previous slide with the B. C. L. C. Staging. And so this patient has portal hypertension, there's um lesions in the left and right lobes. So certainly you wouldn't offer reception. Um He's already got a little bit of decompensation with his billy Rubin and various is and so he otherwise might benefit from liver transplantation. And um he meets milan criteria. So um what are milan criteria? Um These are the patients who have T. Two stage tumors. So one HCC up to five centimeters or you can have up to three each less than three centimeters. And um this is the uh criteria that was published in the landmark uh publication from moses farrow out of milan back in 1996. And this has been well validate. And so if you have patients who undergo liver transplantation with HCC satisfying those criteria. These are patients who have a satisfactory uh 70% recurrence free survival after liver transplantation. Um Now HCC comprises um a increasing uh proportion of the liver transplant waiting lists. And so you can see over the years that um as we become successful at curing hepatitis C, hep C is no longer the leading cause of liver transplantation and HCC is right as an indication. Um However, among the HCC registrants, hepatitis C continues to comprise us. Uh The largest majority of the underlying reasons for developing HC. And then over the years, uh the way that we prioritized HCC patients for liver transplantation has um evolved. Uh This current system patients must meet Milan criteria at the time of listing, there's a six month holding period and then the patients will get Uh points that are equivalent to your medium build a transplant for your region -3. And so in this region here are medium build a transplant happens to be 31. And so are HCC patients currently get 28 points and they stay at 28 points um every three months until they get transplanted. Um They do need to get imaging reassessment every three months. And um the HTC needs to remain within Milan in order for the points to get renewed. So if they grow outside of Milan. Um they then drop off the list in are no longer eligible for points. Um And again, uh these are the imaging criteria. Um I talked to you about the lie rod system that you'll see on reports. You'll also see radiologist report out um HCC's that fall under these criteria. And um this is just for background reference if you see radiology reports come from us um where there's a list of transplant patient and this is just part of you knows reporting criteria. Question six A 68 year old man with hepatitis C cirrhosis is found to have HCC on a C. T. Scan which shows a nine centimeter right lobe mass. With arterial enhancement and venus washout. There's tumor thrombosis in the portal vein C. T. Scan shows a 1.2 centimeter nodule consistent with metastatic disease in his lungs. He's otherwise well compensated without societies or various is or encephalopathy. He has elevated alpha feta protein. What is the next step in the management of this patient transplant resection systemic therapy, palliative care, radio frequency ablation. So the answer here is the stomach treatment. Um So um over the years we have um increasingly been successful at identifying new agents for um systemic therapy. And so currently we have two agents for primary treatment. First lines sarafina blend that nip and then there are increasing number of uh agents for second line systemic p the targeted therapies are small molecule inhibitors that across the cell membrane and um target various different steps in the pathway of HCC. We also have immunotherapy that is actively under investigation. And these are the in uh this just shows you the laundry list of recent studies um that have been a breakthrough and showing um survival advances in these systemic agents C. C. And these are the trials for sarin, ib one Vietnamese line record at paragraph in it for second line uh Cabazon to neb line rumors, serum ob second line. And then there are increasing number of immunotherapy trials for HCC. Uh in the interest of this uh talk. I'm not going to go into these in detail but this is just um a list that shows you all the exciting advances in this field. Uh most recent one has been this combination of a test Golimumab and this is a map showing survival benefit so much more to come. And this is an exciting time for systemic thing for HCC. Um So switching gears, this is the um I have two more questions questions. Seven a 35 year old woman presents to the emergency room for sudden onset abdominal pain. Her past history is unremarkable. She's been taking oral contraceptive pills for many years on exams. She's in mild distress, abdomen is soft. Un remarkable labs show a slightly low hemoglobin, normal platelets and negative viral markers and on imaging she has an eight centimeter mass in the right lobe of the liver with some hemorrhage. So um which of the following is the next step. MRI abdomen surgical resection liver biopsy, discontinue oral contraceptive pills, radio frequency embolization. And uh the answer here is um referral for surgical resection. So um this is a young woman who's been on oral contraceptive pills who has a eight centimeter hemorrhagic mass. And uh this is a panacea adenoma. So these are benign tumors um and they're classically associated with oral contraceptive use. If this were smaller, uh you could Take the route of discontinuing oral contraceptives and following her expectantly. However, this is pretty large. Um and when they get to over five cm they're at risk for hemorrhage as well as malignant transformation. And so if you do have a tumor, one of these that has blood, that is an indication for surgical resection. Um There is there are different subtypes that have been identified through molecular classification. And um briefly uh the subtype that has this beta cuttin in mutation um is the subtype that is at risk for developing HCC. You see here is sort of the Stella feature and this is a um F. N. H. And the classic imaging finding is a central fibrous scar. Um These tend to be more of a vascular phenomenon and in fact, but chiari uh esperandieu are risk factors and they can also be associated with hemangioma as um So these, unlike adenomas are at low risk for malignant transformation and hemorrhage. And therefore it can be managed conservatively. Um And so comparing and contrasting adenoma versus f NH adenomas are a bit more common. F NHS have this classic central scar on imaging um more vascular risk factors, whereas the autonomous have more hormonal risk factors and then the adenomas are the ones that can develop complications. Whereas F NHS tend to stay benign and can therefore be managed conservatively. So to conclude these are the take home points patients with cirrhosis and those with hepatitis B. Warrant screening for HCC, patients with hepatitis C cirrhosis who achieved SVR still need HCC screening transplantation. Resection and ablation are curative treatments for HCC and for those who don't um uh qualify for curative treatments but can tolerate systemic therapies. There's a encouraging expanding list of effective 1st and 2nd line systemic agents that are becoming available and then this is a classic. Uh These are classic board questions um studying and no differences between the Peninsular norman focal modular hyperplasia. That's a high yield topic that you probably will see a question on. Um Thanks for your attention and um good luck