- At a celiac disease tertiary referral center, small bowel adenocarcinoma (SBA) was as rare as previous estimates suggest—it was detected in five of 770 patients (0.65%)
- Some differences from other subtypes of SBA were that all five patients were female, three had a non-classical celiac disease symptom profile and four had tumors located in jejunum
- The five-year survival rate was 80%, suggesting that SBA related to celiac disease is less aggressive than sporadic SBA
- The researchers offer advice for recognizing and managing celiac disease–associated SBA in patients
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Small bowel adenocarcinoma (SBA), an extremely rare cancer, can occur in association with celiac disease (CD), as well as with Crohn's disease and certain hereditary conditions. Patients with CD have a 14 times greater risk of SBA; delay in diagnosis of CD or low compliance with a gluten-free diet increases that risk even more.
Because SBA is so rare, not much is known about how it manifests in patients with CD. Giacomo Caio, MD, PhD, gastroenterology researcher at MassGeneral Hospital for Children, Robert De Giorgio, PhD, and colleagues recently conducted a retrospective study that uncovered new information about the main clinical features. Their findings and suggestions for diagnosis and management are published in BMC Gastroenterology.
An Unexpectedly High Incidence
The researchers reviewed records on 770 patients who were diagnosed with CD at an Italian celiac disease referral center between January 1995 and December 2014. The median age at diagnosis was 36 years (range, 18–80 years) and 78% of the patients were female.
There were five cases of SBA among patients (0.65%). By comparison, the estimated worldwide incidence is 5.7 cases per million people. Conducting the study in a tertiary referral center may have influenced the incidence.
Differences from Non-CD SBA
In this series, all cases of SBA were diagnosed in women. In studies of sporadic SBA and SBA associated with other predisposing conditions, there has been a slight male predominance.
The mean age at onset of SBA was 53 years, lower than that reported in the literature for other SBA subtypes (63 years). In three of the five cases, the SBA diagnosis was established at the same time as the CD diagnosis, at a mean age of 41 years.
Prior research has indicated that nearly all patients with CD-related SBA have a long history of CD characterized by classical symptoms (diarrhea and malabsorption) before SBA is diagnosed. However, three of the five patients showed a non-classical CD symptom profile characterized variously by iron deficiency anemia, constipation and abdominal pain.
Current literature reports that most SBAs (of any subtype) are located in the duodenum, but four of these five tumors were located in the jejunum.
The study also provided further insight into the genetic pattern of CD-related SBA. Positivity for HLA-DQ2 and/or DQ8 is crucial for the development of CD, and several studies have demonstrated that HLA-DQ2 homozygosity is closely related to CD complications such as refractory CD and small intestinal lymphoma. All patients in this series were HLA-DQ2 positive, but only one displayed homozygosis, and none had a previous diagnosis of refractory CD.
All five patients underwent surgery, and the three patients with advanced cancer also received 5-fluorouracil, leucovorin and oxaliplatin, plus bevacizumab in one case. The five-year survival rate was 80%, as one patient died 13 months after SBA diagnosis. Another patient died 63 months after diagnosis. Both of these patients had high-stage, high-grade poorly differentiated SBA.
Based on their findings, the researchers have developed a set of recommendations for the diagnosis and management of CD-related SBA. These include:
- Early diagnosis: CD-related SBA appears to be less aggressive than sporadic SBA, so early diagnosis is mandatory for optimal management
- Thorough diagnostic workup: Because three patients were diagnosed with SBA at the same time as CD, at a relatively young age, the researchers advise a thorough diagnostic workup for CD patients who present with alarming symptoms and signs. These include abdominal pain, nausea, vomiting, weight loss and detection of fecal occult blood
- Suspect SBA in all CD patients: SBA should be considered in any patient with CD, even those who have non-classical and less severe extraintestinal manifestations. This is especially important for patients who are diagnosed late with CD (after 45 years of age) or comply poorly with a gluten-free diet
- Endoscopists, pathologists and physicians should rule out CD in patients with SBA or small-intestine adenoma: This will avoid significant delays in diagnosis
- Test resected material of all patients undergoing surgery for SBA to rule out CD: Testing should include histopathological evaluation particularly looking for mucosal atrophy in tumor-free margins, possibly preceded by intraoperative duodenal biopsies and serological tests
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