Gianluca M. Sampietro

Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells.

Objective: In mice, a subpopulation of gut dendritic cells (DCs) expressing CD103 drives the development of regulatory T (Treg) cells. Further, it was recently described that the cross-talk between human intestinal epithelial cells (IECs) and DCs helps in maintaining gut immune homeostasis via the induction of non-inflammatory DCs. In this study, an analysis was carried out to determine whether IECs could promote the differentiation of CD103+ tolerogenic DCs, and the function of primary CD103+ DCs isolated from human mesenteric lymph nodes (MLNs) was evaluated. Methods: Monocyte-derived DCs (MoDCs) and circulating CD1c+ DCs were conditioned or not with supernatants from Caco-2 cells or IECs isolated from healthy donors or donors with Crohn’s disease and analysed for their ability to induce Treg cell differentiation. In some cases, transforming growth factor β (TGFβ), retinoic acid (RA) or thymic stromal lymphopoietin (TSLP) were neutralised before conditioning. CD103+ and CD103− DCs were sorted by fluorescence-activated cell sorting (FACS) from MLNs and used in Treg cell differentiation experiments. Results: It was found that human IECs promoted the differentiation of tolerogenic DCs able to drive the development of adaptive Foxp3+ Treg cells. This control was lost in patients with Crohn’s disease and paralleled a reduced expression of tolerogenic factors by primary IECs. MoDCs differentiated with RA or IEC supernatant upregulated the expression of CD103. Consistently, human primary CD103+ DCs isolated from MLNs were endowed with the ability to drive Treg cell differentiation. This subset of DCs expressed CCR7 and probably represents a lamina propria-derived migratory population. Conclusions: A population of tolerogenic CD103+ DCs was identified in the human gut that probably differentiate in response to IEC-derived factors and drive Treg cell development.

Contrast radiology, computed tomography and ultrasonography in detecting internal fistulas and intra-abdominal abscesses in Crohn’s disease: a prospective comparative study

OBJECTIVES:Accurate assessment of intestinal complications of Crohns disease (CD) is extremely important, both in clinical practice and in trials. The accuracy of radiographic and ultrasonographic diagnosis of internal fistulae and abscesses complicating CD is still debated and requires further investigation. We compared ultrasonography (US) and contrast radiography in detecting intestinal fistulae and abscesses complicating CD.METHODS:A prospective study was carried out on 625 consecutive CD patients who underwent complete evaluation of the intestinal tract by means of colonoscopy and double contrast barium enema, small bowel enteroclysis, and abdominal ultrasound (US). Computed tomography (CT) was also carried out in cases of severe CD with clinical suspicion of septic complications. The accuracy of US, barium radiology, and CT in detecting internal fistulae and abscesses was assessed by comparing results with intraoperative findings in 128 consecutive patients who underwent operation immediately after diagnostic workup.RESULTS:Internal fistulae and intra-abdominal abscesses were identified intraoperatively in 56 (43.7%) and 26 (20.3%) patients, respectively. Diagnostic accuracy of US and x-ray studies in detecting internal fistulae was comparable (85.2% vs 84.8%), with sensitivity of 71.4% for US and 69.6% for x-ray studies, and specificity of 95.8% for both. Combination of radiographic techniques and US significantly improved diagnostic accuracy in detection of internal fistulae. In severe cases of CD with clinical suspicion of septic complications such as abdominal mass or fever, the accuracy of US, barium studies, and CT was 88.5%, 80.3%, and 77%, respectively (p = ns). The presence of abscesses was correctly detected in 90.9% of cases by means of US and in 86.4% by CT (p = ns), although accuracy was higher for CT (91.8%) than for US (86.9%) because of false positive results in US studies.CONCLUSION:Despite the fact that barium radiology is widely considered the method of choice in detection of internal fistulae, accuracy is not entirely satisfactory. Comparable accuracy was found for US and CT. The combination of barium and US studies, or the sole use of US in more CD patients with more severe disease, can reliably detect most internal fistulae and abscesses.

Bowel ultrasound in assessment of Crohn's disease and detection of related small bowel strictures: a prospective comparative study versus x ray and intraoperative findings

Background and aim: Despite the fact that bowel ultrasound (US) has recently been proved to be useful in the assessment of bowel diseases, uncertainty persists as to its diagnostic role in patients with complicated Crohns disease (CD). Therefore, we have prospectively investigated the accuracy of US compared with x ray procedures and intraoperative findings in detecting small bowel strictures complicating CD as well as its reliability in assessing disease extent and location within the bowel. Methods: A series of 296 consecutive patients with proven CD admitted to L Sacco University Hospital between 1997 and 1999, having undergone complete radiographic evaluation (including small bowel x ray, colonoscopy, or double contrast barium enema), were enrolled in the study. Bowel US was performed in each patient by two experienced operators unaware of the results of other diagnostic procedures. The accuracy of US in detecting strictures compared with x ray studies was determined separately in two different groups of patients: 211 patients treated conservatively (non-operative CD) and 85 patients who were candidates for surgery for CD complications or unresponsiveness to medical therapy (operative CD). Results: Overall sensitivity and specificity of US in assessing the anatomical distribution of CD were 93% and 97%, respectively. The extent of ileal disease measured at US correlated well with that determined by x ray (r=0.52, p<0.001) in medically treated patients as well as with that measured intraoperatively in surgical patients (r=0.64, p<0.001). One or more stenoses were detected in 75 patients (35.5%) at small bowel enteroclysis in the non-operative CD group compared with 70 (82%) in the operative CD series. Sensitivity, specificity, and positive predictive values of bowel US in the detection of strictures were 79%, 98%, and 95% in non-operative CD patients and 90%, 100%, and 100% in operative CD cases, respectively. Conclusions: In experienced hands, bowel US is an accurate technique for assessing CD extent and location and is very helpful in detecting small bowel strictures, especially in very severe cases that are candidates for surgery. The use of bowel US is therefore justified as a primary investigation in CD patients in whom complications are suspected.

Oral contrast enhanced bowel ultrasonography in the assessment of small intestine Crohn’s disease. A prospective comparison with conventional ultrasound, x ray studies, and ileocolonoscopy

Background/Aim: Although ultrasound (US) has proved to be useful in intestinal diseases, barium enteroclysis (BE) remains the gold standard technique for assessing patients with small bowel Crohn’s disease (CD). The ingestion of anechoic non-absorbable solutions has been recently proposed in order to distend intestinal loops and improve small bowel visualisation. The authors’ aim was to evaluate the accuracy of oral contrast US in finding CD lesions, assessing their extent within the bowel, and detecting luminal complications, compared with BE and ileocolonoscopy. Methods: 102 consecutive patients with proven CD, having undergone complete x ray and endoscopic evaluation, were enrolled in the study. Each US examination, before and after the ingestion of a polyethylene glycol (PEG) solution (500–800 ml), was performed independently by two sonographers unaware of the results of other diagnostic procedures. The accuracy of conventional and contrast enhanced US in detecting CD lesions and luminal complications, as well as the extent of bowel involvement, were determined. Interobserver agreement between sonographers with both US techniques was also estimated. Results: After oral contrast, satisfactory distension of the intestinal lumen was obtained in all patients, with a mean time to reach the terminal ileum of 31.4 (SD 10.9) minutes. Overall sensitivity of conventional and oral contrast US in detecting CD lesions were 91.4% and 96.1%, respectively. The correlation coefficient between US and x ray extent of ileal disease was r1 = 0.83 (p<0.001) before and r2 = 0.94 (p<0.001) after PEG ingestion; r1 versus r2 p<0.01. Sensitivity in detecting strictures was 74% for conventional US and 89% for contrast US. Overall interobserver agreement for bowel wall thickness and disease location within the small bowel was already good before but significantly improved after PEG ingestion. Conclusions: Oral contrast bowel US is comparable with BE in defining anatomic location and extension of CD and superior to conventional US in detecting luminal complications, as well as reducing interobserver variability between sonographers. It may be therefore regarded as the first imaging procedure in the diagnostic work up and follow up of small intestine CD.

Role of early ultrasound in detecting inflammatory intestinal disorders and identifying their anatomical location within the bowel

Background : Although bowel ultrasound is a widely accepted diagnostic tool in bowel diseases, its value as the primary imaging procedure in patients with symptoms/signs suggestive of inflammatory bowel disorders is still unclear.

3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 2: Surgical Management and Special Situations

This paper is the second in a series of two publications relating to the European Crohns and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohns disease [CD] and concerns the surgical management of CD as well as special situations including management of perianal CD and extraintestinal manifestations. Diagnostic approaches and medical management of CD of this ECCO Consensus are covered in the first paper [Gomollon et al JCC 2016].

Small bowel stenosis in Crohn's disease: clinical, biochemical and ultrasonographic evaluation of histological features

Aim : To establish whether intestinal ultrasound, clinical or biochemical indices of activity can assess histological features of ileal stenosis in Crohns disease.

Incidence and risk factors for gallstones in patients with inflammatory bowel disease: A large case‐control study

The risk for gallstones (GD) in inflammatory bowel diseases and the factors responsible for this complication have not been well established. We studied the incidence of GD in a cohort of Crohns disease (CD) and ulcerative colitis (UC) patients and investigated the related risk factors. A case‐controlled study was carried out. The study population included 634 inflammatory bowel disease (IBD) patients (429 CD, 205 UC) and 634 age‐matched, sex‐matched, and body mass index (BMI)‐matched controls free of GD at enrollment, who were followed for a mean of 7.2 years (range, 5‐11 years).The incidence of GD was calculated by dividing the number of events per person‐years of follow‐up. Multivariate analysis was used to discriminate among the impact of different variables on the risk of developing GD. The incidence rates of GD were 14.35/1,000 persons/year in CD as compared with 7.75 in matched controls (P = 0.012) and 7.48/1000 persons/year in UC patients as compared with 6.06 in matched‐controls (P = 0.38). Ileo‐colonic CD location (OR, 2.14), disease duration >15years (OR, 4.26), >3 clinical recurrences (OR, 8.07), ileal resection >30 cm (OR, 7.03), >3 hospitalizations (OR, 20.7), multiple TPN treatments (OR, 8.07), and long hospital stay (OR, 24.8) were significantly related to GD in CD patients. Conclusion: Only CD patients have a significantly higher risk of developing GD than well‐matched hospital controls. Site of disease at diagnosis, lifetime surgery, extent of ileal resections, number of clinical recurrences, TPN, and the frequency and duration of hospitalizations are independently associated with GD. (HEPATOLOGY 2007;45:1267–1274.)

Are Colonoscopy and Bowel Ultrasound Useful for Assessing Response to Short-Term Therapy and Predicting Disease Outcome of Moderate-to-Severe Forms of Ulcerative Colitis?: A Prospective Study

OBJECTIVES:Mucosal healing has been proposed as an important sign of the efficacy of medical treatment of inflammatory bowel disease; however, direct evidence in ulcerative colitis (UC) is scarce. We evaluated the usefulness of colonoscopy and bowel ultrasound (US) as indexes of response to short-term therapy and as predictors of subsequent outcome in UC.METHODS:A total of 83 patients with moderate-to-severe UC were recruited; endoscopic and US severity was graded 0–3 at entry according to validated scores. Of the recruited patients, 74, who were clinically responsive to steroids, were followed up with repeated colonoscopy and bowel US at 3, 9, and 15 months from recruitment. Concordance between clinical, endoscopic, and US scores at various visits was determined by kappa statistics. Multiple unconditional logistic regression models were used to assess the predictivity of clinical, endoscopic, and US scores measured at 3 and 9 months on the development of endoscopic UC relapse within 15 months.RESULTS:A variable concordance was found over time between endoscopic and clinical score (weighted κ between 0.38 and 0.95), with high and consistent concordance between endoscopic and US scores (weighted κ between 0.76 and 0.90). On logistic regression analysis, moderate-to-severe endoscopic and US scores at 3 months were associated with a high risk of endoscopic activity at 15 months (odds ratio (OR): 5.2; 95% confidence interval (CI): 1.6–17.6 and OR: 9.1; 95% CI: 2.5–33.5, respectively).CONCLUSIONS:Bowel US may be used as a surrogate of colonoscopy in assessing the short-term response of severe forms of UC to therapy. Both US score and endoscopic score after 3 months of steroid therapy predict outcome of disease at 15 months.

Long-term results and multivariate analysis of prognostic factors in 138 consecutive patients operated on for Crohn’s disease using “bowel-sparing” techniques

BACKGROUND Conservative surgery has become accepted as a useful option for the surgical treatment of complicated Crohns disease (CD). METHODS One hundred thirty-eight consecutive patients treated with strictureplasty or miniresections for complicated CD have been observed prospectively. The possible influence of a number of variables on the risk of recurrence was investigated using the Cox proportional hazard model, and a time-to-event analysis was made using the Kaplan-Meier function. RESULTS There was no perioperative mortality; the morbidity rate was 5.7%. A close correlation was found between the risk of recurrence and the time between diagnosis and first surgery. The overall 5-year recurrence rate was 24%, being 36% in the patients requiring surgery within 1 year of diagnosis and 14% in those operated on more than 1 year after diagnosis. CONCLUSIONS Risk factor analysis highlighted a group of patients at high risk of surgical recurrence. Given that our results are similar to those reported in other series, we consider strictureplasty and miniresections safe and effective procedures for the treatment of complicated CD.