Faculty Bibliography

OBJECTIVE:To create a map of iodine densities within affected segments of small-bowel Crohn disease (CD) derived from contrast-enhanced dual-energy computed tomography enterography (DECTE) studies. METHODS:Twenty CD patients imaged with intravenous contrast-enhanced DECTE between June 2016 and December 2017 were retrospectively identified. Ten patients without clinical evidence of CD and 8 normal-appearing jejunal segments in CD patients were controls. Using prototype software, 8 manual contours were drawn along the mucosa of affected segments. Relatively normal-appearing bowel was included at the edges. These contours served as a basis for iodine density calculation and 3-dimensional iodine density map rendering. Color-coded iodine densities allowed detection and quantification of the most and least dense portion of each segment and also permitted relative comparison between segments. RESULTS:The average iodine density per CD involved segment ranged 1.0 to 3.3 mg/mL, which differed significantly from normal ileum (P < 0.0001) and normal-appearing jejunum in patients with CD (P = 0.0009). Standard deviations ranged from 0.8 to 1.7 mg/mL, which differed significantly from normal ileum (P = 0.0039) and normal-appearing jejunum in patients with CD (P = 0.0056). The amplitude of the power spectrum ranged from 0.66 to 3.3 demonstrating patches of iodine rather than uniform distribution. This differed significantly from normal ileum (P = 0.0005) and normal-appearing jejunum in patients with CD (P = 0.0004). CONCLUSIONS:Heterogeneous CD activity and distribution can be displayed as iodine density maps created from DECTE.

Dual-energy CT (DECT) has been available for clinical use in the United States for close to 15 years. Although multiple applications in all areas of the body have been described that are only possible with DECT, the adoption into clinical practice has been slow. This paper will attempt to address many of the impediments the author has encountered from his discussions with radiologists across the country. A hopeful outcome would result in more practices adopting more DECT into their CT practices.

OBJECTIVE:The objective of this study was to assess if bowel wall iodine density obtained from dual-source, dual-energy computed tomography enterography (DECTE) could be a biomarker of Crohn's disease activity. METHODS:Twenty-two patients with Crohn's disease imaged with DECTE from February 2016 to May 2018 were retrospectively identified by departmental report search. Iodine maps were created with commercial software (Syngovia). Iodine content was normalized to the aorta, and then manual dual-energy region-of-interest cursors were placed over the visibly assessed maximal and minimal iodine density within segments of involved as well as unaffected small bowel. The mixed Hounsfield unit value, maximum iodine density (Imax), and minimum iodine density (Imin) were recorded. The length of affected bowel demonstrating maximum disease activity as a percentage of overall involvement was subjectively assessed. A weighted iodine density (Iweighted) was calculated. The clinical assessment of disease activity using erythrocyte sedimentation rate, C-reactive protein, fecal calprotectin, colonoscopy/endoscopy, and surgery, if available, served as the reference standard. The Crohn's disease activity index was also used as a separate additional reference standard. RESULTS:Significant heterogeneity within the affected segments was present. The average Imax and Imin of affected bowel was 4.27 ± 1.11 (2.4-7.4) mg/mL and 2.71 ± 0.51 (2.2-3.9) mg/mL, respectively. Iodine density of normal-appearing small bowel was 1.40 ± 0.26 (0.9-1.9) mg/mL. The Imax and Imin of affected bowel differed significantly from normal bowel (P < 0.0001). Mixed Hounsfield unit (101.82 ± 27.5) also statistically differed (46.33 ± 19.62) (P < 0.0001). Using overall clinical assessment as the reference standard, all patients with Imin of greater than 2.6 mg/mL, Iweighted of greater than 3.3 mg/mL, or Imax of greater than 4.7 mg/mL had clinically active disease. Sixteen of 17 patients with Imin of greater than 2.2 mg/mL and 14/15 with Iweighted of greater than 3 mg/mL had clinically active disease. Using Crohn's disease activity index as the reference standard, all patients with Imin of greater than 2.7 mg/mL, Iweighted of greater than 3.6 mg/mL, or Imax of greater than 5.4 mg/mL had clinically active disease. The median effective dose was 4.64 ± 1.68 mSv (range, 2.03-8.12 mSv). CONCLUSIONS:Iodine density obtained from DECTE highlights regions of maximal activity within affected bowel segments. An iodine density of 2 mg/mL appears to be a threshold between normal bowel segments and those with active Crohn's disease. Iodine density measurement thresholds Imin of greater than 2.6 mg/mL, Iweighted of greater than 3.3 mg/mL, and Imax of greater than 4.7 mg/mL correlate with established clinical markers of disease activity, with Imin seemingly most useful in daily clinical practice.

BACKGROUND: Small bowel cancer (SBC) is a rare entity that can be associated with Crohn's Disease. The incidence of SBC in patients with CD is increased by 18.75-fold compared to normal population. The pathogenesis of SBC in the setting of CD is not fully understood, but the disease has a poor prognosis due to diagnostic challenges associated with the primary disease. The aim of this study is to present 2 cases treated within a year in a high volume IBD center and to conduct a systematic literature review of small bowel adenocarcinoma (SBA) associated with small bowel CD.
METHOD(S): Systematic literature review was done by using MEDLINE and EMBASE databases and data regarding demographics, presentation, diagnosis, treatment and survival were extracted. Articles that did not clearly state the location of the Crohn's disease and type of the cancer were excluded.
RESULT(S): We identified 216 patients diagnosed with small bowel adenocarcinoma in the setting of small bowel Crohn's disease from 117 studies. In this review obstruction was the most common initial symptom (n = 82, 59%; data are missing in 77 patients). Other common symptoms were abdominal pain (n = 12), anemia-bleeding (n = 11), diarrhea (n = 10), and fistulas (n = 5). there were 206 patients with one adenocarcinoma and 10 patients with 2 different adenocarcinomas. Among the patients with only one tumor, 154 patients (74.7%) were found to have ileal SBA. The median time to diagnosis of SBA from the diagnosis of CD was 18 months (1-300 months, data on 10 patients were missing). Out of 129, 64 patients (49.6%) were diagnosed with cancer after the surgical procedure whereas 46 patients (35.6%) were diagnosed intraoperatively and 15 (11.6%) were diagnosed preoperatively. Four patients (3.2%) were diagnosed at the autopsy without any surgical interventions and data were missing in 87 patients. 36.7% (18/49 patients) of the patients operated for obstruction were alive at one year, and 15.2% (7/46 patients) at 2-year. Although these percentages are lower than other studies reported in the literature, data was missing in 34 patients, so this might have affected the outcomes. CONCLUSION(S): Small bowel adenocarcinoma should be in the differential diagnosis in patients with longstanding ileal Crohn's disease presenting with small bowel obstruction, anemia, and perforation. Diagnosis and management of the small bowel adenocarcinoma in the setting of Crohn's disease is challenging and awareness and early diagnosis may avoid mortality

The lack of prospective outcomes studies for many types of incidental findings limits our understanding of both their natural history and the potential efficacy of treatment. To support decision making for the management of incidental findings, major sources of uncertainty in management pathways can be mapped and analyzed using mathematical models. This process yields important insights into how uncertainty influences the best treatment decision. Here, we consider a classification scheme, grounded in decision science, which exposes various levels and types of uncertainty in the management of incidental findings and addresses (1) disease-related risks, which are considered in context of a patient's competing causes of mortality; (2) potential degrees of intervention; (3) strength of evidence; and (4) patients' treatment-related preferences. Herein we describe how categorizing uncertainty by the sources, issues, and locus can build a framework from which to improve the management of incidental findings. Accurate and comprehensive handling of uncertainty will improve the quality of related decision making and will help guide future research priorities.

OBJECTIVE:The objective of our study was to test for the possibility that published malignancy risks for side-branch intraductal papillary mucinous neoplasms (IPMNs) are overestimates, likely due to verification bias. MATERIALS AND METHODS/METHODS:We tested for possible verification bias using simulation modeling techniques. First, in age-defined hypothetical cohorts of 10 million persons, we projected the frequency of pancreatic ductal adenocarcinoma (PDAC) arising from side-branch IPMNs over 5 years using published estimates of their prevalence (4.4%) and rate of malignant transformation (1.9%). Second, we projected the total number of PDAC cases in corresponding cohorts over the same time horizon using national cancer registry data. For each cohort, we determined whether the percentage of all PDAC cases that arose from side-branch IPMNs (i.e., side-branch IPMN-associated PDAC cases) was clinically plausible using an upper limit of 10% to define plausibility, as estimated from the literature. Model assumptions and parameter uncertainty were evaluated in sensitivity analysis. RESULTS:Across all cohorts, percentages of side-branch IPMN-associated PDACs greatly exceeded 10%. In the base case (mean age = 55.7 years), 80% of PDAC cases arose from side-branch IPMNs (7877/9786). In the oldest cohort evaluated (mean age = 75 years), this estimate was 76% (14,227/18,714). In a secondary analysis, we found that if an upper limit threshold of 10% for side-branch IPMN-associated PDAC was imposed, the model-predicted rate of malignancy for side-branch IPMNs would be less than 0.24% over a 5-year time horizon, substantially lower than most literature-based estimates. CONCLUSION/CONCLUSIONS:Our results suggest that reported malignancy risks associated with side-branch IPMNs are likely to be overestimates and imply the presence of verification bias.

See also the article by Tirkes et al in this issue.

OBJECTIVE:The objective of this study is to evaluate whether the water siphon maneuver improves detection of gastroesophageal (GE) reflux during barium esophagography compared with observation for spontaneous reflux only. Histopathologic analysis is the reference standard. MATERIALS AND METHODS/METHODS:This retrospective study assessed 87 outpatients who underwent both barium esophagography and upper endoscopy-guided biopsy within a 30-day interval. The water siphon maneuver was routinely performed when spontaneous GE reflux was not observed during the fluoroscopic study. Radiology reports were reviewed for mentions of the presence of reflux and the circumstances in which it was observed (as a spontaneous occurrence or as a result of the water siphon maneuver). Pathology reports from subsequent endoscopic biopsies were reviewed to identify histologic changes of reflux disease. The sensitivity, specificity, and accuracy of esophagography, observation for spontaneous reflux, and the water siphon maneuver were calculated and then compared using a McNemar test. RESULTS:Of the 87 patients, 57 (65.5%) had GE reflux diagnosed on the basis of histologic changes noted on endoscopy, and 30 (34.5%) did not. A total of 57 patients (65.5%) showed reflux during esophagography, 41 (71.9%) of whom had reflux diagnosed by the water siphon maneuver, and 16 (28.1%) had reflux diagnosed on the basis of observation of spontaneous reflux. Forty-four patients had reflux diagnosed on the basis of both a barium study and histologic findings; 13 patients had reflux noted on esophagography but had negative histologic findings. The overall sensitivity, specificity, and accuracy of esophagography for reflux were 77.2%, 56.7%, and 70.1%, respectively. Spontaneous reflux alone had a sensitivity, specificity, and accuracy of 21.1%, 86.7%, and 43.7%, respectively. The water siphon maneuver showed a sensitivity of 71.1%, a specificity of 65.4%, and accuracy of 69.0%. The differences in the sensitivity, specificity, and accuracy of the water siphon maneuver versus observation of spontaneous reflux were statistically significant (p ≤ 0.004). CONCLUSION/CONCLUSIONS:A properly performed and interpreted water siphon maneuver significantly increases the sensitivity and accuracy for GE reflux during esophagography, compared with observation for spontaneous reflux alone. The water siphon maneuver is a simple addition to barium esophagography that improves sensitivity and accuracy for the diagnosis of GE reflux compared with observation alone.