Fletcher, Joel G.

Abstract Background Crohn’s rectovaginal fistulizing disease remains notoriously difficult to treat. A phase I clinical trial to evaluate the safety and feasibility of a novel protocol using a mesenchymal stem cell (MSC)–coated Gore Bio-A fistula plug for the treatment of medically and surgically refractory Crohn’s rectovaginal fistulas was conducted. Methods Five patients underwent an autologous subcutaneous adipose tissue harvest via a 2-cm abdominal wall incision at time of exam under anesthesia (EUA) with seton placement. MSCs were isolated, expanded, and impregnated on the plug. After 6 weeks, patients returned to the operating room for placement of the MSC-coated plug. The primary end points were safety and feasibility; the secondary end point was clinical and radiographic healing at 6 months. Results Five female patients (median age [range], 49 [38–53] years) with a median disease duration (range) of 23 (7–34) years who were on biologic (n = 5) or combination therapy (n = 3) had successful harvest and expansion of MSCs and delivery of the Gore Bio-A plug. There were no serious adverse events or adverse events related to the MSCs or plug during the 6-month follow-up. At 6 months, 3 patients had complete cessation of drainage, and 2 had >50% reduction in drainage; all had a persistent fistula tract identified on magnetic resonance imaging and EUA at 6 months. Conclusions Surgical placement of an autologous adipose-derived MSC-coated fistula plug in diverted patients with Crohn’s rectovaginal fistulas was safe and feasible. All patients had a reduction in the size of their fistula tract, and 3 of 5 had cessation of drainage, but none achieved complete healing. This was a phase I clinical trial of autologous mesenchymal stem cells on a plug for rectovaginal Crohn’s fistulas.

Abstract Background We aim to assess the impact of a multidisciplinary inflammatory bowel disease (IBD) conference on the management of patients with complex IBD. Methods Data were collected during each conference from February 2017 through October 2018 with chart review performed at 6 months to determine if conference recommendations were successfully implemented. Results Eighty-five patients were discussed. The presenting diagnosis was changed by 11.8%. Recommendations for further testing, medical therapy, and surgery were successfully implemented in 77.1%, 98.1%, and 88.4%, respectively. Conclusions This study supports the role of IBD multidisciplinary conferences in the management of patients with complex IBD.

Objective The aim of this study was to determine if computed tomography (CT) angiography using an individualized transition delay (CTA-ID) would facilitate reductions in injection rate and iodine dose. Methods The CTA-ID was performed in 20 patients with routine injection rate and iodine dose; 20 patients with injection rate lowered by 1 mL/s; and 40 patients with injection rate lowered by 1 mL/s with 29% less iodine. Routine CTAs in the same or size-matched patients served as controls. Diagnostic image quality and intra-arterial CT numbers were assessed. Results The median transition delay between aortic threshold and CTA-ID image acquisition was significantly longer than with conventional bolus tracking (mean increase, 13.3 seconds; P < 0.0001), with image quality being the same or better. Intra-arterial CT numbers were 200 Hounsfield units or greater for 80 of 80 CTA-ID, but not for 6 of 49 (12%) internal control or for 11 of 80 (14%) size-matched control patients. Conclusion The CTA-ID bolus-tracking software alters transition delays to permit diagnostic CTA examinations despite slower injection rate and less iodine.

Abstract Background The decision to either escalate medical therapy or proceed to ileocecal resection (ICR) in patients with terminal ileal Crohn disease (CD) remains largely subjective. We sought to develop a risk score for predicting ICR at 1 year from computed tomography or magnetic resonance enterography (CTE/MRE). Methods We conducted a retrospective cohort study including all consecutive adult (> 18 years) patients with imaging findings of terminal ileal CD (Montreal classification: B1, inflammatory predominant; B2, stricturing; or B3, penetrating) on CTE/MRE between January 1, 2016, and December 31, 2016. The risk for ICR at 6 months and at 1 year of CTE/MRE and risk factors associated with ICR, including demographics, CD-specific immunosuppressive therapeutics, and disease presentation at the time of imaging, were determined. Results Of 559 patients, 121 (21.6%) underwent ICR during follow-up (1.4 years [IQR 0.21–1.64 years]); the risk for ICR at 6 months and at 1 year was 18.2% (95% CI 14.7%–21.6%) and 20.5% (95% CI 16.8%–24.1%), respectively. Multivariable analysis revealed Montreal classification (B2, hazard ratio [HR] 2.73, and B3, HR 6.80, both P < 0.0001), upstream bowel dilation (HR 3.06, P < 0.0001), and younger age (19–29 years reference, 30–44 years, HR 0.83 [P = 0.40]; 45–59 years, HR 0.58 [P = 0.04], and 60+ years, HR 0.45 [P = 0.01]) to significantly increase the likelihood of ICR. A predictive nomogram for interval ICR was developed based on these significant variables. Conclusions The presence of CD strictures, penetrating complications, and upstream bowel dilation on CTE/MRE, combined with young age, significantly predict ICR. The suggested risk model may facilitate objective therapeutic decision-making.

AbstractBackgroundDuring proctography, rectal emptying is visually estimated by the reduction in rectal area. The correlation between changes in rectal area, which is a surrogate measure of volume, is unclear. Our aims were to compare the change in rectal area and volume during magnetic resonance (MR) proctography and to compare these parameters with rectal balloon expulsion time (BET).MethodsIn 49 healthy and 46 constipated participants, we measured BET and rectal area and volume with a software program before and after participants expelled rectal gel during proctography.Key ResultsAll participants completed both tests; six healthy and 17 constipated patients had a prolonged (>60 seconds) BET. During evacuation, the reduction in rectal area and volume was lower in participants with an abnormal than a normal BET (P < 0.01). The reduction in rectal area and volume were strongly correlated (r = 0.93, P < 0.001) and equivalent for identifying participants with abnormal BET. Among participants with less evacuation, the reduction in rectal area underestimated the reduction in rectal volume. A rectocele larger than 2 cm was observed in eight of 18 (44%) participants in whom the difference between change in volume and area was ˃10% but only 14 of 77 (18%) participants in whom the difference was ≤10% (P = 0.03).ConclusionsMeasured with MR proctography, the rectal area is reasonably accurate for quantifying rectal emptying and equivalent to rectal volume for distinguishing between normal and abnormal BET. When evacuation is reduced, the change in rectal area may underestimate the change in rectal volume.

Patients with Crohn’s disease commonly develop ileal and less commonly colonic strictures, containing various degrees of inflammation and fibrosis. While predominantly inflammatory strictures may benefit from a medical anti-inflammatory treatment, predominantly fibrotic strictures currently require endoscopic balloon dilation or surgery. Therefore, differentiation of the main components of a stricturing lesion is key for defining the therapeutic management. The role of endoscopy to diagnose the nature of strictures is limited by the superficial inspection of the intestinal mucosa, the lack of depth of mucosal biopsies and by the risk of sampling error due to a heterogeneous distribution of inflammation and fibrosis within a stricturing lesion. These limitations may be in part overcome by cross-sectional imaging techniques such as ultrasound, CT and MRI, allowing for a full thickness evaluation of the bowel wall and associated abnormalities. This systematic literature review provides a comprehensive summary of currently used radiologic definitions of strictures. It discusses, by assessing only manuscripts with histopathology as a gold standard, the accuracy for diagnosis of the respective modalities as well as their capability to characterise strictures in terms of inflammation and fibrosis. Definitions for strictures on cross-sectional imaging are heterogeneous; however, accuracy for stricture diagnosis is very high. Although conventional cross-sectional imaging techniques have been reported to distinguish inflammation from fibrosis and grade their severity, they are not sufficiently accurate for use in routine clinical practice. Finally, we present recent consensus recommendations and highlight experimental techniques that may overcome the limitations of current technologies.

PurposeThis work aims to develop a new framework of image quality assessment using deep learning‐based model observer (DL‐MO) and to validate it in a low‐contrast lesion detection task that involves CT images with patient anatomical background.MethodsThe DL‐MO was developed using the transfer learning strategy to incorporate a pretrained deep convolutional neural network (CNN), a partial least square regression discriminant analysis (PLS‐DA) model and an internal noise component. The CNN was previously trained to achieve the state‐of‐the‐art classification accuracy over a natural image database. The earlier layers of the CNN were used as a deep feature extractor, with the assumption that similarity exists between the CNN and the human visual system. The PLSR model was used to further engineer the deep feature for the lesion detection task in CT images. The internal noise component was incorporated to model the inefficiency and variability of human observer (HO) performance, and to generate the ultimate DL‐MO test statistics. Seven abdominal CT exams were retrospectively collected from the same type of CT scanners. To compare DL‐MO with HO, 12 experimental conditions with varying lesion size, lesion contrast, radiation dose, and reconstruction types were generated, each condition with 154 trials. CT images of a real liver metastatic lesion were numerically modified to generate lesion models with four lesion sizes (5, 7, 9, and 11 mm) and three contrast levels (15, 20, and 25 HU). The lesions were inserted into patient liver images using a projection‐based method. A validated noise insertion tool was used to synthesize CT exams with 50% and 25% of routine radiation dose level. CT images were reconstructed using the weighted filtered back projection algorithm and an iterative reconstruction algorithm. Four medical physicists performed a two‐alternative forced choice (2AFC) detection task (with multislice scrolling viewing mode) on patient images across the 12 experimental conditions. DL‐MO was operated on the same datasets. Statistical analyses were performed to evaluate the correlation and agreement between DL‐MO and HO.ResultsA statistically significant positive correlation was observed between DL‐MO and HO for the 2AFC low‐contrast detection task that involves patient liver background. The corresponding Pearson product moment correlation coefficient was 0.986 [95% confidence interval (0.950, 0.996)]. Bland–Altman agreement analysis did not indicate statistically significant differences.ConclusionsThe proposed DL‐MO is highly correlated with HO in a low‐contrast detection task that involves realistic patient liver background. This study demonstrated the potential of the proposed DL‐MO to assess image quality directly based on patient images in realistic, clinically relevant CT tasks.

BACKGROUND: Management of transsphincteric cryptoglandular fistulas remains a challenging problem and the optimal surgical approach remains elusive. Mesenchymal stem cells, increasingly being utilized for perianal Crohn’s disease, offer a novel therapy to treat cryptoglandular fistulas. OBJECTIVES: This study aimed to determine safety and feasibility of using an autologous mesenchymal stem cell-coated fistula plug in patients with transsphincteric cryptoglandular fistulas. DESIGN: This study is a phase I clinical trial. SETTING: This study was conducted at a tertiary academic medical center. PATIENTS: Adult (>18 years) male and female patients with transsphincteric cryptoglandular fistulas were selected. MAIN OUTCOMES MEASURES: The primary outcomes measured were the safety, feasibility, and efficacy of a mesenchymal stem cell-coated fistula plug in patients with transsphincteric fistulas. RESULTS: Fifteen patients (8 women, mean age 39.8 years) with a single-tract transsphincteric fistula received a mesenchymal stem cell-loaded fistula plug and were followed for 6 months. Duration of disease at the time of study enrollment was a median of 3.0 years (range, 1–13 years) with a median of 3.5 (range, 1–20) prior surgical interventions. Adverse events included 1 plug extrusion, 1 abdominal wall seroma, 3 perianal abscesses requiring drainage, and 1 patient with perianal cellulitis. There were no serious adverse events. At 6 months, 3 patients had complete clinical healing, 8 had partial healing, and 4 patients showed no clinical improvement. Radiographic improvement was seen in 11 of 15 patients. LIMITATIONS: This study was limited by the small cohort and short follow-up. CONCLUSIONS: Autologous mesenchymal stem cell-coated fistula plug treatment of transsphincteric cryptoglandular fistulas was safe and feasible and resulted in complete or partial healing in a majority of patients. See Video Abstract at http://links.lww.com/DCR/A897.