Of all the digestive tract tumors, small-bowel cancers are the least common. Why should we study these rare tumors, and what, if anything, can we learn from them? Sometimes the absence of an important event can provide the answer to a difficult problem. For example, consider the famous Sherlock Holmes mystery story, "Silver Blaze," in which the master sleuth solved a challenging case, simply because the watchdog didn't bark when he should have, implying that the murderer was well known to the dog.[1]
As Neugut and coworkers point out, small-bowel cancers should be common, because the small bowel is located between the stomach and the colon--two organs with a high risk of cancer. The absence of cancer at this site is even more striking when we take into account the length and large surface area of the small bowel. What is the explanation? Why doesn't the small bowel "bark?"
We might begin by asking whether the low risk of small-bowel cancer is real, or are we overlooking many of these cancers? These tumors are difficult to diagnose preoperatively, and thus, early cases may be overlooked. However, most small-bowel cancers cause life-threatening complications, such as hemorrhage or obstruction. The majority of these cancers will become symptomatic and will eventually be detected. Therefore, ascertainment bias appears to be an unlikely explanation for the scarcity of these cancers.
Why Are Small-Bowel Tumors So Rare?
Assuming that small-bowel cancers are truly uncommon, what is the explanation? Compared to the colon, the small bowel is relatively sterile, suggesting that the relative absence of bacteria may play an important role. This line of reasoning has led to experiments using germ-free animals. In some reports, germ-free animals exposed to a known intestinal carcinogen have a greatly reduced frequency of colon cancer compared to normal animals.[2]
We know that the bacterial flora of the large bowel can be altered by dietary manipulation. In animals as well as humans, these changes can decrease the metabolic activity of certain classes of intestinal microflora, which may alter the risk of large-bowel cancer.[3-5] We can speculate that the increased bacterial burden of the large bowel compared to the small bowel could be one reason that large-bowel cancers are so much more frequent than small bowel tumors.
Are there other reasons that small- bowel cancers are so rare? During embryologic development, the pancreas, biliary tract, and liver develop from the primitive gut wall. Aggressive cancers often arise in these extraintestinal sites, whereas the duodenum itself remains nearly free of cancer. Perhaps, during the growth of the embryo, some protective mechanism is lost, such as a tumor-suppressor gene.
When A Patient Develops Small-Bowel Cancer...
When a patient does contract small- bowel cancer, we should look for an underlying background disease, such as long-standing Crohn's disease or celiac disease. We should also remember that the same genetic alterations that lead to large-bowel cancer can cause small-bowel cancer. For example, the risk of small-bowel cancer is known to be elevated in families with inherited genetic disorders, such as hereditary nonpolyposis colorectal cancer. Indeed, one analysis suggests that the relative risk of small-bowel cancer may be 100 times greater in patients carrying the gene for this hereditary syndrome, as compared with background rates.[6]
Like tumors in the large bowel and stomach, surgery is the main form of therapy for small-bowel cancers. However, because small-bowel tumors are so uncommon, it has been impossible to evaluate the role of adjuvant therapy. Nevertheless, most centers treat patients with small-bowel cancer using regimens that have been developed for large- bowel cancer.
Neugut and coworkers have carefully summarized the available information about the epidemiology and treatment of this rare form of gastro-intestinal cancer. Their report challenges us to discover why these tumors are so rare. If we think creatively, perhaps we can find overlooked clues to this riddle that continues to baffle clinicians. If we do find the answer, we can then use the information to help understand the more common problem of large bowel cancer.
A 70-year-old man with a history of localized prostate cancer treated with whole-pelvis radiation therapy with a boost to the prostate, in conjunction with androgen deprivation therapy 7 years prior, presented with lower back pain. A bone scan revealed an area of activity in the sacrum. What is the most likely diagnosis?
