Small Bowel Adenocarcinoma in Crohn’s Disease
carcinogenic in the colon upon degradation by bacteria, are not degraded to a significant degree in the small bowel, which contains orders of magnitude fewer bacteria than the colon.22
Finally, the large immune network of the small bowel may in fact inhibit the growth of malignant cells, as witnessed in an early study by Calman in which T cell-deficient mice were compared with immune-reconstituted mice.24
turnover of small bowel epitheilial cells may prevent the growth of cancerous cells.23
Immunosuppression in
adding further support to the notion that the immune system may serve as a check on the growth of malignancy.
humans may also be associated with a higher risk of small bowel cancers,25
Diagnosis
As mentioned above, SBA in CD is frequently not diagnosed pre-operatively.3
The insidious non-specific presentation of the disease makes it very difficult for the clinician to diagnose these tumors early. Presenting symptoms may mimic those of underlying CD, and include abdominal pain, obstruction, weight loss, anorexia, and gastrointestinal bleeding.26
Treatment Fourth, the rapid
The treatment of SBA is the same regardless of whether the cancer is associated with CD or occurs de novo. As SBA in CD is located most commonly in the ileum and jejunum, wide resection of the involved intestinal segment with the surrounding mesentery is required, and because lymph node metastases are often present at diagnosis, regional lymph node dissection is usually performed at the time of surgery.32
Many physicians will use
For locally advanced disease, the role of adjuvant chemotherapy and/or radiotherapy is unclear as no randomized controlled trials have been conducted.33
chemotherapeutic regimens based on randomized controlled data from studies in colorectal cancer patients, most notably 5-fluorouracil (5-FU) and leucovorin combined with a platinum agent such as oxaliplatin (FOLFOX). Since combination chemotherapy with capecitabine and oxaliplatin (CAPOX) has shown promise in patients with metastatic disease,34
some physicians will use this regimen In addition, since a number of tumors
may present as a stricture, differentiating SBA from a CD stricture may not be possible in many cases. Another diagnostic problem is that many of these tumors lie beyond the reach of conventional endoscopic examination. For all of these reasons, it comes as no surprise that the diagnosis of SBA is commonly delayed for up to six to eight months.27,28
Diagnostic modalities currently available to aid clinicians include radiographic tests (barium studies, computed tomography (CT) enterography, and magnetic resonance enterography), capsule endoscopy, and double-balloon enteroscopy.
A recent detailed review of the barium radiographic literature revealed that SBA in CD most often assumed the appearance of a benign smooth CD stricture, thus rendering differentiation from a malignant stricture extremely difficult.29
CT enterography and magnetic
resonance enterography are relatively new options to investigate the small bowel in a non-invasive fashion and only limited data exist regarding their utility compared with other diagnostic modalities for CD as a whole. Capsule endoscopy is also relatively new and allows visualization of the small bowel mucosa. Although capsule endoscopy is useful and safe for detecting new CD lesions in patients without stricturing disease and small bowel tumors in patients without CD, capsule retention proximal to a stricture may occur in up to 13% of patients with known CD.30
Given the high incidence of SBA in CD
strictures, this test may be potentially unsafe in such patients. Double-balloon enteroscopy, the newest member of the diagnostic arsenal for CD, is attractive in that the endoscopist is able to visualize the small bowel mucosa directly and perform targeted biopsies of suspicious areas as needed. In fact, a case of SBA identified by a combination of positron emission tomography(PET)/CT and double- balloon in a CD patient was reported in 2010.31
However, this
procedure has a number of drawbacks, including the large amount of time, labor, and sedation required as well as the need for a second endoscopist in order to complete the examination. Thus, taken collectively, the available diagnostic tools for SBA in CD patients are disappointing at best.
US GASTROENTEROLOGY & HEPATOLOGY REVIEW
first-line as adjuvant therapy for locally advanced disease. Data regarding neoadjuvant chemoradiotherapy (with 5-FU as the chemotherapeutic agent) in this setting are even more scarce. For patients with unresectable or metastatic disease, no randomized controlled trials have been conducted to examine various chemotherapeutic regimens, and treatment is again based upon the colorectal cancer data in which 5-FU combined with a platinum agent offers reasonable results.
The prognosis of SBA in CD is somewhat difficult to assess given its rarity. However, much more is known is about the welfare of patients with de novo SBA. A review of the National Cancer Data Base from 1985 to 1995 by Howe et al. examined 4,995 cases of SBA and reported an overall five-year disease-specific survival of 31% with a median survival of 20 months.35
These rates are somewhat lower than those for similarly staged colorectal cancers. Although the majority of tumors were located in the duodenum (55%, compared with 18% in the jejunum and 13% in the ileum), survival was significantly lower in patients with duodenal tumors than those with either jejunal or ileal tumors (28% versus 38%, p<0.0001) and in those with higher levels of nodal disease. Although some earlier reports in small numbers of patients intimated that SBA in CD patients was associated with a worse prognosis compared with patients with de novo SBA, perhaps due to the high proportion of tumors with poorly differentiated histology at presentation,36
the population-based study by Palascak-Juif et al. suggested that survival may actually be better in patients with CD (median survival 28 months versus 12 months), although this difference did not attain statistical significance.3
Conclusion
SBA in CD is a challenging disease from both diagnostic and therapeutic standpoints, for it has an insidious, non-specific presentation, is difficult to diagnose even when suspected, and treatment outcomes are often disappointing. The question then remains: should we screen for SBA in CD patients? The answer at the present time (and likely in the future as well) is ‘no’. First, while the relative risk of SBA in CD patients is high, the absolute risk is very low and thus many patients would have to be screened unnecessarily to pick up the few cancers that eventually develop. Second, we do not have effective screening tests for SBA, and with a disease this rare,
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