Hello my name is Susan Urba, I'm a medical oncologist specializing in the treatment of esophageal cancer. I'm also a palliative care physician, specializing in symptom management and pain control. I've prepared six modules on the treatment of esophageal cancer, from the medical oncologist's point of view. The first module is called Esophageal Cancer, Epidemiology and Risk Factors. The objectives of this lecture are to identify the 2 most common esophageal cancer histologies. To understand the steps in the evolution of esophageal cancer from normal mucosa. And also to list and understand risk factors for esophageal cancer. Let's start with a pre lecture question. And during the course of the lecture, I hope you find the answer if you don't know it already. Which if the following is an important risk factor for adenocarcinoma of the esophagus? A, H pylori. B, heavy alcohol consumption. C, obesity or D, human papilloma virus, or HPV. So take a minute to think about your answer. So let's look now at esophageal cancer's epidemiology. It's actually the 6th most common cause of cancer deaths worldwide. Particularly in developing nations, where it's the 4th most common cause of cancer deaths. In the United States, it's an uncommon malignancy. New cases, 16,980 in 2015 and unfortunately the number of deaths was 15,590. So you can see what a lethal disease this is. Even though it's a very uncommon malignancy, we see a fair number of cases here at the University of Michigan because we are a referral center. The histology of esophageal cancer is typically two fold. Either adenocarcinoma, which is the most common histology, seen in more that 70% of cases. This usually involves the distal esophagus and the gastro esophageal junction. A very rapidly rising group of patients are young while males, in which this disease is increasing in prevalence. Squamous cell carcinoma used to be the most common many years ago, and it was related to smoking and drinking. But currently, the epidemiology has been changing, and now it is less than 30% of esophageal cancers. Most commonly, this is seen in the upper esophagus. And as stated before, it's becoming less and less seen, although a good 25 to 30% of our patients do have this histology. The evolution of cancer starts with normal mucosa, often changes into Barrett's esophagus, which we will talk about in the minute. And then low-grade dysplasia, high-grade dysplasia, and then cancer. I'll talk about the steps of this progression in a minute. Barrett's Esophagus is actually columnar epithelium, which replaces the normal squamous epithelium. You can see in the picture there, that darkish-reddish color, that is taken during an endoscopy. The normal esophageal tissue should look pink, and when that reddish tissue is there, that is Barrett's esophagus. It's intestinal metaplasia, and the hallmark is goblet cells. So when that is biopsied, that's usually what the pathologist will see. Very often it is associated with long standing reflux. Now there's many, many people who have reflex who never get cancer. But in a lot of patients who do get cancer, a fair number have a history of Barrett's esophagus and reflux. As a matter of fact, if a patient has Barrett's esophagus, there is a substantially higher risk of adenocarcinoma, compared to the general population. So for patients having endoscopy for esophagitis, approximately 10-20% of the time, Barrett's esophagus is identified. As a matter of fact, the majority of adenocarcinomas, 60% or more, are found in a bed of Barrett's esophagus. So if someone has Barrett's esophagus, what's the annual risk of progression? Not that great, but about 0.12% per year will progress to cancer. Now if a low-grade dysplasia is seen, that increases the chance of it turning into cancer. And if high-grade dysplasia is present, then it's even higher, and we will discuss that further in a couple minutes. So what kind of surveillance needs to be done if someone does have Barrett's esophagus? The American College of Gastroenterology has put out a statement that if there's no dysplasia, just the presence of these goblet cells, that the patient should have a couple of endoscopies with biopsies within 1 year. If no cancer is diagnosed, then they should go through endoscopy every 3 years. And in my practice, I've had a fair number of patients diagnosed just on that surveillance biopsy alone, without symptoms. If someone has low-grade dysplasia, so the cells actually look worse, they're starting to look abnormal, then endoscopy should be done within 6 months. To make sure that it's only low-grade dysplasia, that it's not high-grade and looking very dsyplastic. So if it is only low-grade dysplasia, but every year then, they should be getting an endoscopy. If they do get high-grade dysplasia, where the cells look quite abnormal, this is a very serious situation. If it's very focal, then they should have a endoscopy every 3 months, routinely. Sometimes if there's an area that looks pretty suspicious, they can undergo endoscopic mucosal resection, where just the mucosa is actually removed via endoscope. kind of like a very complete, extensive biopsy to get rid of that tissue and make sure there's no cancer cells. If there's multifocal areas of the high-grade dysplasia, even without a definite diagnosis of cancer, often an esophagectomy will be done. And in our series at University of Michigan, up to 50% of the time cancer is identified in the esophagectomy specimen. So, let's talk for another minute about the endoscopic mucosal resection that I mentioned. Often that can be done for very early abnormalities if there's the high-grade dysplasia I talked about, or if there's actually cancer diagnosed, but the most superficial level in the lamina propria or the muscularis mucosae. If that's done and if it's removed clearly, those patients should undergo endoscopy every 3 months for a year, to make sure there are no cells left behind, and then after that annually. So let's talk now a little more about risk factors for this. Gastro-Esophageal Reflux Disease, or GERD as it's called, is one of the eipidemiologic factors. 30% ,though, of the Western population do have reflux issues. So certainly not all of them are getting cancer. So, who is more at risk? If someone has had severe reflux disease for a long time, usually more than 5 years, they are at higher risk. Often they are being treated with proton pump inhibitors. Sometimes, if there's a lot of reflux that's very annoying, sometimes they'll undergo a surgical procedure called a Nissen fundoplication. The picture on the slide here shows how the cardia of the stomach is wrapped around the lower part of the esophagus. To kind of tighten up that sphincter, so there could be less reflux from the stomach into the esophagus. There's also bacteria called H.pylori. This is actually associated with gastric cancer. Those who have this infection are at a higher risk for gastric cancer. However, not much evidence for association with esophageal cancer. As a matter of fact, we see this less and less in the United States. And there is even some thought that if patients have H.pylori, this might be even protective against having esophageal cancer. So it's a risk factor for gastric cancer, not a risk, maybe protective, for esophageal cancer. How about alcohol and cigarettes? For squamous cell cancer, which is the less common cancer, these are independent risk factors. If you're a smoker, that contributes to your risk. If you're a drinker, that contributes to the risk. And if you do both, it's not just additive, it's multiplicative, and your risk really goes up. For adenocarcinoma, not quite so dramatically. In one study from the National Cancer Institute, smoking was associated with a 2.2-fold increased risk, and even a long time after stopping smoking. So that risk does persist, it must have a early role in carcinogenesis. And even if you stop, the damage is already done. Some studies have actually not shown a risk for alcohol. So it's really more risk factors for squamous cell cancer, not so much for adeno. But obesity, obesity is a risk factor, actually even independent of reflux. Some people say well, gosh, if someone is obese, won't they have a higher risk of reflux? And perhaps so, but when you really look at them separately, just being very high body mass index puts you in an increased risk for adenocarcinoma. Doesn't seem to be the case for squamous cell carcinoma. As a matter of fact, a lot of patients who are maybe heavy drinkers, heavy smokers, often tend to be undernourished. And sometimes they're quite thin, rather than obese. Infectious agents, human papilloma virus, this seems to be associated with squamous cell cancer in China, does not seem to be a risk factor in the United States. it is a risk factor for head and neck cancer, but since we're talking about esophageal cancer, it's really not a risk factor here in the United states. There can be second primary tumors. Patients with upper aerodigestive tract tumors may develop esophageal cancer as a second primary. So a lot of times, if patients are diagnosed with head and neck cancer or lung cancer, endoscopy is done, CT scans are done, often to make sure there's not a second primary. It's not real common, but it does happen enough that it really should be looked for initially. So we've pretty much touched on a lot of the risk factors and aspects of epidemiology. So let's go back to that question we asked before. Which of the following is an important risk factor for adenocarcinoma of the esophagus? H.pylori, heavy alcohol consumption, obesity, or human papilloma virus? Take a minute now to register your answer. The correct answer is obesity. As we saw, H.pylori is protective against esophageal cancer. Heavy alcohol consumption is more associated with squamous cell cancer. Obesity is associated with adenocarcinoma. And human papilloma virus, it may be associated with cases of squamous cell in China, but not adenocarcinoma and in the United States. So I'd like to summarize some of the main take-home points. Esophageal cancer is uncommon, but a deadly cancer in the United States. Risk factors for adenocarcinoma, which is the most common type, include reflux, Barrett's esophagus, particularly if high-grade dysplasia is present, and obesity. Risk factors for squamous cell cancer do include alcohol and cigarettes. I thank you very much for your attention, and please join me in the next module on esophageal cancer very soon.