G. Maconi

Mucosal Healing Predicts Late Outcomes After the First Course of Corticosteroids for Newly Diagnosed Ulcerative Colitis

BACKGROUND & AIMS It is uncertain whether mucosal healing after the first course of corticosteroids therapy predicts outcome in patients with ulcerative colitis (UC). We evaluated whether early clinical and endoscopic responses to this therapy are associated with late outcomes in UC. METHODS Patients with newly diagnosed UC who were prescribed corticosteroid therapy (n = 157) were followed up for 5 years. They were evaluated using clinical (Powel-Tuck [PT]) and endoscopic (Baron) indexes after 3 and 6 months, then every 6 months. Outcomes at month 3 (early response) were used to identify patients with complete (group A: PT, 0-1; Baron, 0), partial (group B: PT, 0-1; Baron, 1-3), or no response (group C: persistence of clinical and endoscopic activity). The association between early and late outcomes was assessed. RESULTS After 5 years, there were significant differences between complete and partial responders in the rates of hospitalization (25% in group A vs 48.7% in group B; P = .0152; odds ratio [OR], 2.85; 95% confidence interval [CI], 1.21-6.72), immunosuppression therapy (5% in group A vs 25.6% in group B; P = .0030; OR, 6.55; 95% CI, 1.67-25.67), colectomy (3.3% in group A vs 18.0% in group B; P = .0265; OR, 6.34; 95% CI, 1.24-32.37), and their combination (26.7% in group A vs 48.7% in group B; P = .0249; OR, 2.61; 95% CI, 1.12-6.11). After multivariate analysis, lack of mucosal healing was the only factor associated with negative outcomes at 5 years (immunosuppressors: hazard risk [HR], 10.581; 95% CI, 2.193-51.039; P = .0033; hospitalization: HR, 3.634; 95% CI, 1.556-8.485; P = .0029; colectomy: HR, 8.397; 95% CI, 1.278-55.186; P = .0268). CONCLUSIONS No mucosal healing after corticosteroid therapy is associated with a more aggressive disease course.

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.

Ultrasonographic detection of intestinal complications in Crohn's disease

The aim of this study was to evaluate the sensitivity and specificity of ultrasound (US) in assessing the main abdominal complications of Crohns disease (CD), such as strictures, fistulas and abscesses. A series of 98 consecutive inpatients with complicated and uncomplicated Crohns disease, having undergone a complete endoscopic and radiographic evaluation of the intestinal tract, entered the study. In particular, in these patients the presence of strictures, fistulas, and abscesses, detected by means of colonoscopy, small bowel x-ray, double-contrast barium enema, and computed tomography, was also assessed by means of transabdominal US. US sensitivity and specificity in the assessment of stenosis of Crohns disease were 74.4% and 93.1%, respectively. When ileal and colonic stenosis were considered separately, transabdominal US correctly assessed 84.6% of ileal stenosis and 58.8% of colonic stenosis. Eight of 12 fistulas were detected, but only 50% of enteroenteric fistulas were diagnosed. The presence of abscesses was correctly detected in 83.3% of cases by means of US. Our data suggest that US is a suitable complementary method for the detection of abdominal complications of Crohns disease, such as strictures and abscesses; however, its usefulness in assessing enteroenteric fistulas seems to be fairly limited.

Autologous haematopoietic stem cell transplantation without CD34 + cell selection in refractory Crohn’s disease

Objectives: Autologous haematopoietic stem cell transplantation (HSCT) with CD34+ cell selection has recently been used in the treatment of refractory Crohn’s disease, showing good safety and promising efficacy. We investigated the safety and efficacy of HSCT with unselected peripheral blood stem cells (PBSCs) in moderate–severe refractory Crohn’s disease. Patients: Four patients (three male, one female; age range 26–45 years) with active moderate–severe Crohn’s disease (median Crohn’s Disease Activity Index (CDAI) 319, range 272–345), refractory or intolerant to multiple drugs including infliximab, were enrolled. Interventions: Unselected PBSCs were collected after mobilisation with cyclophosphamide (CTX) 1.5 g/m2 and granulocyte-colony stimulating factor (G-CSF) 10 μg/kg. The conditioning regimen included CTX 50 mg/kg on days −5 to −2 and rabbit anti-thymocyte globulin (ATG) 2.5 mg/kg on days −4 to −2. Main outcome measures: Primary endpoints were toxicity and clinical remission (CDAI<150) at 3 months. Secondary endpoints were clinical and endoscopic response at 3 months and toxicity, clinical and endoscopic remission at 12 months. Results: No improvement or slight deterioration was observed following mobilisation (median CDAI 339, range 258–404). At the third month, the primary endpoint of clinical remission was achieved in all patients, with a median CDAI of 91 (range 56–102), and complete endoscopic remission was achieved in 2/3 patients. After a median follow-up of 16.5 months, 3/4 patients maintained both clinical and endoscopic remission, despite withdrawal of all drugs, and complete fistula closure was observed in all affected patients. No deaths or life-threatening infection occurred. Unexpected adverse events included a perianal abscess after mobilisation in one patient, pleural and pericardial effusions in another and BK virus-related macrohaematuria in another, all rapidly resolved with conservative treatment. Conclusion: Autologous HSCT with unselected PBSC appears to be safe and can induce and maintain remission in previously refractory Crohn’s disease patients.

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.

Perianal Fistulae Following Infliximab Treatment Clinical and Endosonographic Outcome

BackgroundManagement of perianal and rectovaginal fistulae complicating Crohn’s disease (CD) is unsatisfactory. Infliximab is effective in the treatment of fistulating CD. However, reopening of fistulae is frequent, suggesting the persistence of deep fistula tracts despite superficial healing. In this study, the clinical and endosonographic behavior of perianal fistulae were evaluated following infliximab infusions, as well as the role of anal endosonography (AE) in predicting their outcome. MethodsThirty CD patients presenting with perianal and/or rectovaginal fistulae received an infusion of infliximab at a dose of 5 mg/kg at weeks 0 (entry into the study), 2, and 6. Laboratory and clinical assessments were repeated at same intervals and at week 10. AE was performed at entry and at week 10. Thereafter, the perianal region was re-examined every 6 months, and patients were investigated regarding draining of the fistula in the previous months. ResultsFifteen patients (53.6%) showed closure of the fistulae at week 10, but only 5 patients had the fistula tracts disappeared at AE. Clinical and AE closure of rectovaginal fistulae was less prevalent than that of perianal fistulae [14.3% versus 63.6% at week 6 (p = 0.035); 28.6% versus 59.1% at week 10 (p = 0.21); 14.3% versus 22.7% at AE (p = 1.00)]. The behavior of fistulae was not affected by their number and AE classification, presence of rectal disease, or setons. Twenty patients with perianal fistulae were followed for a median of 15.5 months. Patients with closed perianal fistulae at week 10 and disappearance of fistulae tract at AE showed a lower relapse rate than those with endosonographic persistence of fistula tract. ConclusionsInfliximab can heal perianal and rectovaginal fistulae in approximately 60% and 30% of patients, respectively. Despite closure, most fistula tracts are still detectable at AE. Persistence of the internal tract is a condition at higher risk of fistula recurrence.

Focal gastric inflammatory infiltrates in inflammatory bowel diseases : Prevalence, immunohistochemical characteristics, and diagnostic role

OBJECTIVES:To date, few studies have evaluated gastric histology in patients with inflammatory bowel disease (IBD). The aim of this prospective controlled study was to establish the frequency of focal gastritis in Crohns disease (CD) and ulcerative colitis (UC) patients, as well as to evaluate its immunohistochemical characteristics and clinicoanatomical determinants.METHODS:We evaluated 141 consecutive patients with known CD of the large and/or small bowel, 79 patients with UC, and 141 CD- and UC-free controls; all underwent upper gastrointestinal (GI) endoscopy and 13C urea-breath test. Biopsy specimens taken from the antrum, angulus, and gastric body were evaluated by histology and immunohistochemistry. A series of variables, including CD activity index, duration, extent and location of disease, intestinal resection, number of recurrences, and previous and current medical therapy, as well as the presence of dyspeptic symptoms and mucosal lesions at endoscopy, were determined in all CD patients and correlated with the presence or absence of focal gastritis.RESULTS:Helicobacter pylori-associated gastritis was found in 47 patients with CD (33%), in 37 patients with UC (47%), and in 60% of CD-/UC-free controls (p < 0.01). In H. pylori-negative CD patients focal gastritis was found in 43% of cases (40/94), compared with 12% (5/42) of UC patients and 19% (11/57) of controls (p < 0.05). Specificity and positive predictive value of focal gastritis in CD were 84% and 71%, respectively. It was characterized by a focal perifoveolar or periglandular lymphomonocytic infiltrate, with CD8+/CD4+ cells predominant both in CD and UC patients. There were no significant correlations between the occurrence of focal gastritis and any clinicoanatomical CD features.CONCLUSIONS:Focal gastritis is relatively common in CD patients although it is not exclusive to this condition. Its recognition could be useful in the diagnostic workup of any patient with suspected or indeterminate inflammatory bowel disease, as it makes a diagnosis of CD more likely.

Sonographic prevalence of liver steatosis and biliary tract stones in patients with inflammatory bowel disease: study of 511 subjects at a single center.

Goals: Inflammatory bowel diseases (IBDs) are associated with pathologic findings in the liver and biliary tract. Ultrasonography (US) represents a noninvasive means to study hepatobiliary abnormalities. This study evaluated the prevalence of US hepatobiliary changes and their relationship to clinical variables in a large IBD patient population followed in a single center. Study: Five hundred eighty‐three consecutive IBD patients were studied with US. After excluding patients with preexisting acute or chronic hepatitis, metabolic disorders, or obesity, 511 patients were investigated for age, duration, site, and severity of the disease, history of surgery, and present medical treatment. At US, liver size, echogenicity (graded as mild‐to‐moderate or severe indicating a corresponding degree of hepatic steatosis), focal lesions of the liver and gallbladder, and biliary tract abnormalities were recorded. Results: Three hundred eleven patients with Crohn disease (CD) and 200 patients with ulcerative colitis (UC) were recruited for the study. Hepatobiliary abnormalities were found at US in 54.2% and 55.9% of CD and UC patients, respectively. Liver enlargement and mild‐to‐moderate to severe liver steatosis were found in 25.7% and 39.5% of CD patients and in 25.5% and 35.5% of UC patients, respectively, a higher prevalence than among healthy controls (P < 0.001). The prevalence of gallstones among CD patients was 11%, higher than that among UC patients (7.5%) and controls (5.5%) (P = 0.016). The higher risk of gallbladder stones in CD was related to age, female sex, and previous surgery. Conclusion: The prevalence of liver enlargement and liver steatosis was higher among IBD patients. The prevalence of gallstones was increased in CD patients only. This risk was related to age, female sex, and previous surgery.

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.