We typically spend the bulk of our interest and research activity focused on the cancers that are most common—breast, prostate, colorectal, lung, etc. This is as it should be, as these cancers are most responsible for the morbidity and mortality for which cancer is primarily responsible. However, there are many other less common cancers that are of significant interest for a variety of reasons. For one thing, lessons learned from an uncommon cancer can often be utilized in the management of the more common cancers. Much of the early treatment of many cancers, for example, was learned from Hodgkin lymphoma, a very uncommon malignancy. Another reason to study uncommon cancers is that they can be interesting in their own right and can give more general lessons as to the nature of the overall problem of cancer.
It is estimated that rare cancers as a group make up about 25% of all cancers. The definition used by the National Cancer Institute is an incidence rate of less than 15/100,000 per year. In contrast, breast cancer and prostate cancer occur at rates of about 120-130/100,000/year. The NCI has just launched a new program to address rare cancers in the U.S., so perhaps we will focus an occasional article on a rare cancer.
To begin, let us consider the alimentary tract—the length of the digestive tract that runs from the mouth to the anus. Within it, at either end, are two of the most common cancers in the world—colorectal cancer and gastric cancer, the former predominating in the U.S. and the West while the latter is highly prevalent in Asia, Africa and Latin America. But between the stomach and the large bowel lies the small bowel or small intestine, which actually is the largest organ of the alimentary tract, comprising about 75% of its length, with significantly more surface mucosa, about 90% of the total, than either of the other two organs. So logically, by all rights, since adenocarcinomas arise in the surface epithelium, we should be seeing more adenocarcinomas of the small intestine than of either the stomach or large intestine.
Instead, adenocarcinoma of the small bowel is an extremely uncommon malignancy, about one per 100,000 per year in the U.S. So how did this length of bowel escape the carcinogenesis phenomenon while sitting between two high-frequency zones? In 1977, Al Lowenfels, a surgeon from New York Medical College in Westchester, published a list of 10 possible reasons for the rarity of this tumor. I will just mention a few of the more interesting ones. He noted that the turnover rate of the mucosal cells in the small bowel is very rapid, i.e., they are shed very rapidly, so the cells do not have a chance to progress through the changes we associate with the multistage process of carcinogenesis. Another possibility is that, in contrast to the stomach and large bowel, the small bowel is largely sterile and without bacteria—an interesting observation in an era that predated our current obsession with the microbiome. A third possibility is that peristalsis and transit time is very rapid through the small bowel so that whatever carcinogens may be ingested or may be present in intestinal contents, they do not maintain contact very long with the small bowel mucosa. In addition, the contents of the small bowel are relatively alkaline—perhaps that is important.
While the incidence rate of small bowel tumors is consistently 1/100,000 in most populations and countries around the globe, the New Zealand Maori stand out with a rate of about 5/100,000. Why? I haven’t got a clue. But then again, I know nothing about the New Zealand Maori.
Two other facts deserve mention. While the majority of SB tumors occur in the first part of the small bowel, the duodenum (the small bowel has 3 parts—duodenum, jejunum, ileum), its incidence is much increased in the ileum in those with Crohn’s disease or celiac disease. However, since the baseline risk is so small, even a very high increased risk does not really lead to many cases.
Finally, it is important to recognize that SB adenocarcinoma very much resembles adenocarcinoma of the large intestine. Both types of cancer arise from adenomatous polyps. Both progress in similar fashions. Both are at increased risk in the same genetic disorders—Lynch syndrome and familial adenomatous polyposis. Thus, for those individuals who do get this rare tumor, the approach to management tends to mimic that of cancer of the large bowel: Surgery and the same chemotherapy regimens are utilized.
One problem in the past has been that the small bowel has been inaccessible to the same endoscopic procedures as the stomach and large bowel, and thus visualization of tumors in the small bowel with fiberoptic colonoscopy or esophagogastroduodenoscopy has not been possible. A major advance for this problem has been a technology called capsule endoscopy, invented by an Israeli, Gavriel Iddan, that has now made evaluation of the small bowel much simpler.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
