Effectiveness of adalimumab for ambulatory ulcerative colitis patients after failure of infliximab treatment: a first "real-life" experience in primary gastroenterology centers in Italy.

BACKGROUND: Adalimumab (ADA) is the key treatment for ulcerative colitis (UC) unresponsive or intolerant to standard treatments. Our aim was to assess the efficacy and safety of ADA in treating ambulatory UC patients in primary gastroenterology centers. METHODS: Fifteen patients (6 male, median age 29.9 years, range 22.8-39.9 years) were enrolled. All were previously treated with infliximab (IFX). Clinical activity and endoscopic severity were scored according to the Crohn's disease activity index (CDAI) score and Mayo subscore for endoscopy, respectively. Patients were clinically assessed at weeks 4, 8, and thereafter at weeks 16, 24, 32, 40, 48, and 54. Colonoscopy was performed before starting treatment, at weeks 24 and 54. The co-primary endpoints were clinical remission at 24 and 54 weeks. The secondary endpoints included: 1) sustained clinical remission; 2) steroid-sparing effect; 3) mucosal healing; 4) need for colectomy. Induction dose of ADA was 160 mg at week 0, and then 80 mg at week 2, while ADA maintenance treatment was 40 mg every two weeks. RESULTS: Clinical remission was obtained in 11 (73.3%) and 15 (100%) patients at weeks 24 and 54 respectively. Ten patients (66.7%) were able to discontinue steroids and were under corticosteroid-free remission at week 54. No patients underwent to colectomy. Eight patients (53.33%) at week 24 and 9 patients (60%) at week 54 achieved complete mucosal healing (Mayo endoscopic score 0). Side effects were reported in 2 of 15 patients (13.3%); none of those patients stopped treatment. CONCLUSION: ADA seems to be effective and safe in UC outpatients affected by UC, and previously treated with IFX.

factors influencing mucosal healing in Crohn's disease during infliximab treatment.

BACKGROUND/AIMS: The effect of infliximab (IFX) on mucosal healing (MH) in clinical setting, as well as what is the effect of scaring of profound ulcers on bowel, is not well known. Aim of our study was to assess how MH occurs in Crohn's disease (CD) in clinical setting during treatment with IFX. METHODOLOGY: Forty patients with CD were followed-up. MH and endoscopic remission (ER) were assessed. Some factors were investigated in predicting development of "uncomplicated" (ulcer healing without alteration of bowel profile) or "complicated" (ulcer healing with alteration of bowel profile) MH. RESULTS: IFX was administered for a mean of 36 months. MH ranged from 67.5% of cases after 6 months to 42.5% of cases after 3 year of treatment. ER ranged from 87.5% of cases after 6 months to 52.5% of cases after 3 year of treatment. Mean CDEIS score decreased from 28 to 8 at the end of follow-up. Uncomplicated MH occurs in 70.37% of patients, complicated MH occurred in 29.63% of patients. Complicated MH was recorded more frequently in patients with severe CDAI (>300 vs. <300, p <0.0362) and higher CDEIS (>35 vs. <35, p >0.0342). CONCLUSIONS: Complicated MH seems to occur frequently in clinical practice when using IFX, especially in patients with higher indexes of activity at entry.

Detection of endoscopic and histological inflammation after an attack of colonic diverticulitis is associated with higher diverticulitis recurrence.

BACKGROUND & AIMS: Colonic diverticulitis shows a high recurrence rate, but the factors associated with such recurrence are still unknown. The aim of our study was to investigate the role of endoscopic and histological inflammation as predictors for the recurrence of diverticulitis. METHODS: One hundred and thirty patients suffering from Acute Uncomplicated Diverticulitis (AUD) (81 males, 49 females, mean age 64.71 years, range 40-85) were prospectively assessed. All patients had AUD confirmed by computerized tomography (CT) and endoscopy. Clinical, endoscopic and histological follow-up was performed after 6, 12 and thereafter 24 months after diagnosis of AUD. RESULTS: Sixteen patients were lost to follow-up. Diverticulitis recurred in 18 patients (13.84%): 15 (13.15%) patients showed recurrence of AUD, whilst 3 (2.63%) showed recurrence of complicated diverticulitis. At the end of the follow-up period, endoscopic inflammation was still detected in 31 (27.67%) patients, and active histological inflammation in 41 patients (36.6 %). Only detection of endoscopic and of histological inflammation during the follow-up was a predictor of diverticulitis recurrence (Log rank test, p = 0.0004). CONCLUSIONS: Detection of endoscopic and histological inflammation after attack of AUD was identified as a predictor of diverticulitis recurrence.

Tumour necrosis factor-alpha expression in segmental colitis associated with diverticulosis down-regulates after treatment.

BACKGROUND AND AIMS: Tumour necrosis factor-α (TNF-α) expression may be increased in segmental colitis associated with diverticulosis (SCAD). Our aim was to assess TNF-α expression in SCAD in relationship to the treatment. METHODS: 10 patients affected by severe (type B and D) SCAD were studied (6 males, 4 females, mean age 60.54 years, range 43-85 years). All patients were treated with beclomethasone dipropionate 10 mg/day plus a probiotic preparation VSL#3 for 8 weeks. At that time, clinical, endoscopic and histological reassessment was performed. Controls were 5 patients with active ulcerative colitis (UC). RESULTS: After treatment, all SCAD B and no SCAD D patients were in remission. The TNF-α expression dropped from 42.7% (+/-7.58) to 15.7% (+/-2.6) in SCAD B patients (p=0.001), and from 40% (+/-5.9) to 28.6% (+/-5.3) in SCAD D patients (p=0.005). In UC patients, the TNF-α expression dropped from 45.5% (+/-5.09) to 22.5% (+/-2.5) (p=0.001). Neither SCAD B nor SCAD D patients showed a significant difference in TNF-α expression compared to UC after treatment. Finally, TNF-α was significantly overexpressed in SCAD D than in SCAD B at the end of treatment (p=0.048). CONCLUSIONS: TNF-α expression in SCAD down regulates after treatment, and seems to be related to the clinical response to therapy. This behaviour, similar to that of Inflammatory Bowel Diseases (IBD), confirms that this disease should be considered as a subtype of IBD.

Tumour necrosis factor-alpha expression in segmental colitis associated with diverticulosis is related to the severity of the endoscopic damage.

BACKGROUND: Tumour necrosis factor-α expression may be increased in segmental colitis associated with diverticulosis. AIMS: To assess tumour necrosis factor-α expression in segmental colitis associated with diverticulosis in relation with the severity of the endoscopic damage. METHODS: 21 patients affected by segmental colitis associated with diverticulosis were studied (15 M, 6 F, mean age 58.87 years, range 43-85 years). Segmental colitis associated with diverticulosis was graduated as mild-moderate (patterns A and C) and severe (patterns B and D). Ten patients with moderate-to-severe ulcerative colitis, 10 patients with moderate-to-severe Crohn's disease, and 10 patients with irritable bowel syndrome served as control groups. RESULTS: Tumour necrosis factor-α expression was significantly higher in segmental colitis associated with diverticulosis B (42.7%) and segmental colitis associated with diverticulosis D (40%) than in segmental colitis associated with diverticulosis A (19.1%) and segmental colitis associated with diverticulosis C (21.1%).Tumour necrosis factor-α expression was lower in segmental colitis associated with diverticulosis A and C than in ulcerative colitis and Crohn's disease, whilst no different tumour necrosis factor-α expression was found between segmental colitis associated with diverticulosis B and D and both ulcerative colitis and Crohn's disease.Finally, tumour necrosis factor-α expression was significantly lower in irritable bowel syndrome (8%±4) than in every type of segmental colitis associated with diverticulosis. CONCLUSIONS: Tumour necrosis factor-α expression in segmental colitis associated with diverticulosis seems to be related to the severity of the endoscopic damage. This behaviour, similar to that of the inflammatory bowel diseases (IBD), confirms that this disease should be considered as a subtype of IBD.

Predictive value of serologic markers of degree of histologic damage in acute uncomplicated colonic diverticulitis.

BACKGROUND: Acute uncomplicated diverticulitis (AUD) may show histologic and serologic signs of inflammation. GOALS: To assess whether serologic markers of inflammation may be predictive of abnormal histology in AUD. STUDY: Twenty-one consecutive patients affected by AUD were studied (15 Males, 6 Females, mean age 66.19 y, range 43 to 85 y). Diagnosis of AUD was based on specific endoscopic and CT scan patterns. Several serologic markers were assessed [White blood cells (WBC), Erytro-sedimentation Rate, C-reactive protein (CRP), fibrinogen, α1-acid glycoprotein]. Neutrophilic and lymphocytic inflammatory infiltrate was also scored. RESULTS: WBC was increased in 4/21 pts (19.4%), Erytro-sedimentation Rate in 12/21 pts (57.14%), CRP in 13/21 pts (61.9%), fibrinogen in 5/21 pts (23.8%), and α1-acid glycoprotein in 6/21 pts (28.57%). All serologic markers were related with the degree of histologic damage. In patients scoring 3 in neutrophilic infiltrate (severe active inflammation), all markers showed a statistical significant relation (ranging from P=0.004 for WBC to P=0.00001 for fibrinogen). CRP was the most sensitive marker of mild-moderate histologic damage, as it was increased in 4/10 (40%) patients scoring 0 or 1 in neutrophilic infiltrate (absence of mild active inflammation) (P=0.005). CONCLUSIONS: Serologic markers showed a strict relation with the degree of histologic damage in AUD. Moreover, CRP is the most sensitive marker of mild-moderate histologic damage.

Complications in celiac disease under gluten-free diet.

We assessed the onset of malignant and nonmalignant complications in a cohort of celiac disease (CD) patients under gluten-free diet (GFD). Five hundred and forty-nine CD patients were retrospectively assessed. Two hundred and fifty-one (45.7%) showed classical, 262 (47.7%) subclinical, and 36 (6.6%) silent form of CD at the time of the diagnosis. The mean time under GFD was 7.13 years (range 1-15 years). Out of 549 patients, 381 (69.4%) were fully compliant, 112/549 (20.4%) reported less than one dietary transgression/month, and 56/549 (10.2%) reported at least one dietary transgression/month. Out of 549 patients, 18 (3.3%) patients developed complications under GFD (seven malignant and 11 nonmalignant complications). Fourteen patients were previously affected by classical CD (5.6% of the overall patients with classical CD), and four were affected by subclinical CD (1.5% of the overall patients with subclinical CD). None of the patients affected by silent CD developed complications. There was no statistical difference between the mean age of the two groups developing complications (P = n.s.). Complications appeared after a mean time under GFD of 6.5 years in classical CD, and after a mean time of 3.5 years in subclinical CD (P = n.s.). Finally, 6/14 (42.8%) patients with classical CD were not fully compliant to GFD, while 2/4 (50%) of subclinical CD patients were not fully compliant to GFD (P = n.s.). Less than 5% of CD patients may develop complications under GFD. Complications seem to affect more classical CD than subclinical CD, and seem to be irrespective of optimal GFD adherence.

Faecal calprotectin in colonic diverticular disease: a case-control study.

BACKGROUND AND AIMS: Information about faecal calprotectin (FC) in colonic diverticular disease (DD) are lacking. We assessed FC in colonic DD, comparing it with irritable bowel syndrome (IBS) patients and healthy controls. Moreover, we compared FC levels in different degrees of DD and assessed FC in symptomatic DD before and after treatment. MATERIALS AND METHODS: Forty-eight consecutive patients with a new endoscopic diagnosis of DD (16 with asymptomatic diverticulosis, 16 with symptomatic uncomplicated DD, 16 with acute uncomplicated diverticulitis), 16 healthy controls, and 16 IBS patients were studied. FC was assessed by semi-quantitative method and compared with histological inflammation. Moreover, FC was reassessed in symptomatic DD after 8 weeks of treatment. RESULTS/FINDINGS: FC was not increased in healthy controls and IBS patients. No difference was found between asymptomatic diverticulosis, healthy controls, and IBS patients (p = n.s.). We found higher FC values in acute uncomplicated diverticulitis (p < 0.0005) and in symptomatic uncomplicated DD (p < 0.005) than in healthy controls and in IBS patients. FC values correlated with inflammatory infiltrate (p < 0.0005). FC decreased after treatment to normal values both in acute uncomplicated diverticulitis (p < 0.0005) and in symptomatic uncomplicated DD (p < 0.005) after treatment. INTERPRETATIONS/CONCLUSIONS: FC may be useful to detect colonic inflammation in DD and in distinguishing symptomatic DD from IBS, as well as in assessing response to therapy in DD.

Small bowel adenocarcinoma in a patient with Coeliac disease: A case report.

Coeliac disease is a chronic inflammatory disease of the gut with increased risk of gastrointestinal malignancy. Although enteropathy T-lymphoma is the most common neoplasm in patient affected by coeliac disease, an increased frequency of small bowel carcinoma has been described. We present a case of jejunal carcinoma in a patient suffering for coeliac disease in which gastrointestinal and extraintestinal symptoms of disease developed although he was treated with a gluten-free diet.

Assessment and grading of mucosal inflammation in colonic diverticular disease.

GOAL: The aim of this study was to assess and grade the mucosal inflammatory infiltrate in different degrees of diverticular disease (DD) and to compare them with healthy matched controls. BACKGROUND: Mucosal inflammation in colonic DD has never been investigated. In particular, it is unknown whether inflammation may be found in every degree of DD. MATERIALS AND METHODS: Thirty consecutive patients with a new endoscopic diagnosis of DD (10 with asymptomatic diverticulosis, 10 with symptomatic uncomplicated DD, and 10 with acute uncomplicated diverticulitis) and 10 healthy controls were studied. RESULTS: A neutrophilic inflammatory infiltrate was found only in acute uncomplicated diverticulitis (overall score, 26). The mean lymphocytic cell density was significantly higher in symptomatic DD (median lymphocytic density, 7) and acute uncomplicated diverticulitis (median lymphocytic density, 11). Subdividing the patients according to different degrees of DD, we found higher lymphocytic cell density even in asymptomatic diverticulosis (median lymphocytic density, 6.5) than healthy controls (median lymphocytic density, 4; P<0.02). CONCLUSIONS: We found an increased inflammatory infiltrate in DD according to the degree of the disease and higher than healthy controls. Moreover, also asymptomatic diverticulosis shows higher inflammatory cell density than controls.

Effect of lactoferrin supplementation on the effectiveness and tolerability of a 7-day quadruple therapy after failure of a first attempt to cure Helicobacter pylori infection.

BACKGROUND: Up to 35% of H. pylori-positive patients remain infected after a first eradication attempt. Lactoferrin, a natural anti-bacterial glycoprotein, seems a promising tool in treating H. pylori infection, but it has never been used in second-line treatment. MATERIAL/METHODS: A prospective, randomized study was conducted on 70 consecutive patients with persistent H. pylori infection after failure of the first standard treatment schedule. All patients were randomly treated with ranitidine bismuth citrate (RBC, 400 mg b.d.), esomeprazole (40 mg/day), amoxycillin (1 g t.d), and tinidazole (500 mg b.d.) without (group A) or with (group B) supplementation of bovine lactoferrin (200 mg b.d). One month after conclusion of therapy, endoscopy was performed in those patients for whom the examination was clinically relevant. The remaining patients were checked by 13C-urea breath test. RESULTS: Sixty-seven patients were fully compliant and completed the study (33, i.e. 94.28%, in group A and 34, 97.14%, in group B). One group A patient (2.85%) was excluded for protocol violation and one group B patient (2.85%) was lost to follow-up. H. pylori eradication was obtained in 31/33 (on intention-to-treat: 88.57%, 95%CI: 87-99%) group A patients and in 33/34 (on intention-to-treat: 94.28%, 95%CI: 86-100%) group B patients (p=ns). 16/68 patients (23.53%) experienced side effects (29.41% in group A and 17.64% in group B, p= 0.05). CONCLUSIONS: Lactoferrin supplementation was found effective in reducing side-effect incidence. Moreover, it seems capable of achieving a slight (and not statistically significant) improvement in eradicating H. pylori when used in second-line treatment.

Beclomethasone dipropionate for the treatment of mild-to-moderate Crohn's disease: an open-label, budesonide-controlled, randomized study.

BACKGROUND: Budesonide is a steroid with low systemic effect and high effectiveness in the treatment of Crohn's Disease (CD). Beclomethasone dipropionate (BDP) is also a steroid with the same systemic effects, but it has been never investigated in CD. MATERIAL/METHODS: To evaluate the effectiveness and tolerability of BDP versus budesonide in treating CD, we enrolled 30 consecutive patients affected by mild-to-moderate non-fistulizing, non-obstructive Crohn's disease (CDAI < or = 250) (13 M and 17 F, mean age: 33.4 years, range: 16-71 years) in whom this diagnosis was made for the first time. The patients were randomly treated for 8 weeks with budesonide 9 mg/day (group A, 15 patients) or with BDP 10 mg/day (group B, 15 patients). RESULTS: Of group A patients, 13/14 (on intention to treat (i-t-t): 86.67%) showed response to budesonide and 10/14 (on i-t-t.: 66.66%) were in remission after 8 weeks of treatment. In group B patients, 10/14 (on i-t-t: 66.66%) showed response to BDP and 8/14 (on i-t-t: 53.33%) were in remission after 8 weeks of treatment (p<0.001). Budesonide was also faster in the time to obtain symptomatic remission (p=n.s.) and was better in improving IBDQL (p<0.05). Regarding side effects, two group A patients (6.66%) and three group B patients (10%) experienced mild-to-moderate side effects which were transitory and did not require any specific treatment or stopping the treatment. CONCLUSIONS: BDP seems to be less effective than budesonide in treating CD, probably due to better the pharmacokinetic properties of budesonide.

High prevalence of celiac disease among patients affected by Crohn's disease.

BACKGROUND: Recent literature has shown a correlation between Crohn's disease (CD) and celiac disease, but a prospective study has not been performed. Our aim was to evaluate the prevalence of celiac disease in a consecutive series of patients affected by CD, in whom the disease was diagnosed for the first time. METHODS: From January to December 2004, we diagnosed 27 patients affected by CD (13 men and 14 women; mean age, 32.3 yrs; range, 16-69 yrs). In all patients, we performed antigliadin, antiendomysium, and antitransglutaminase antibody tests, and the sorbitol H2 breath test evaluation. In case of antibodies and/or sorbitol positivity, esophagogastroduodenoscopy was performed for a small bowel biopsy. RESULTS: Antigliadin, antiendomysium, and antitransglutaminase antibody tests were positive in 8/27 (29.63%), 4/27 (14.81%), and 5/27 (18.52%) patients, respectively, whereas the sorbitol H2 breath test was positive in 11/27 (40.74%) patients: all of them underwent esophagogastroduodenoscopy. Nine of 11 patients showed signs of duodenal endoscopic damage, and 5/9 (55.55%) showed histologic features of celiac disease (18.52% of overall CD population studied): 2 showed Marsh IIIc lesions (1 patient affected by ileal CD and 1 affected by ileo-colonic CD), 2 showed Marsh IIIb lesions (all of them affected by ileo-colonic CD), 1 showed a Marsh IIIa lesion (1 patient affected by colonic CD). CONCLUSIONS: Prevalence of celiac disease seems to be high among patients affected by CD, and this finding should be kept in mind at the time of the first diagnosis of CD; a gluten-free diet should be promptly started.

Lack of usefulness of anti-transglutaminase antibodies in assessing histologic recovery after gluten-free diet in celiac disease.

Gluten-free diet (GFD) plays a key role in the treatment of celiac disease (CD), but it is difficult to evaluate the effect of GFD on the improvement of villous architecture using sensitive, non-invasive tests. Aim of this study is to evaluate anti-transglutaminase (tTG) antibodies in the follow-up of CD to detect histologic recovery. We studied 42 consecutive patients with CD. In all the patients anti-tTG antibodies (evaluated by the enzyme linked immunosorbent assay method) and EGDscopy with multiple bioptic samples before GFD and then 6, 12, and 18 months after GFD were evaluated. For comparison, a sorbitol H2-breath test (H2-BT) and anti-endomysium (EMA) antibodies test were carried out concomitantly. Anti-tTG results were positive in 36 of 42 patients before GFD (80.95%), while they were positive in 11 of 34 (32.35%), 1 of 17 (5.88%), and 0 of 6 (0%) of patients with a persistence in histologic lesions 6, 12, and 18 months of GFD respectively, without any correlation with persistence of histologic lesions (P = NS). Also EMA failed to show correlation with improvement of histologic lesions. They were positive in 31 of 42 patients before GFD (73.80%), while they were positive in 18 of 34 (52.94%), 3 of 17 (17.64%), and 0 of 6 (0%) cases 6, 12, and 18 months of GFD respectively (P = NS). Regarding sorbitol H2-BT, it was positive in 40 of 42 (95.24%) patients before GFD, while it was positive in 31 of 34 (91.17%), 13 of 17 (76.47%), and 4 of 6 (50%) of patients with a persistence in histologic lesions 6, 12, and then 18 months after GFD starting (see Fig. 2, infra). So, anti-tTG and EMA were ineffective in assessing the histologic recovery at each follow-up visit (P = NS), while sorbitol H2-BT seems more effective than anti-tTG and EMA in this field (P < 0.0001 sorbitol H2-BT versus anti-tTG and versus EMA at 18 months after gluten withdrawal). Thirty-eight of 42 (90.47%) patients adhered to a strict GFD. Four patients were found to have occasional dietary transgression, and in all we noted a progressive decreasing of anti-tTG after 6 months of GFD and negative anti-tTG after 12 months of GFD, but sorbitol H2-BT persisted being positive during the entire follow-up. Intestinal damage persisted during the follow-up, despite anti-tTG and EMA negativity, and worsened in the presence of dietary lapses. Anti-tTG does not seem effective to assess histologic recovery in the follow-up of celiac patients after they have started GFD due to its poor correlation with histologic damage.

Prevalence of antitissue transglutaminase antibodies in different degrees of intestinal damage in celiac disease.

GOALS: Although anti-tissue transglutaminase antibodies (anti-tTG) are effective for celiac disease (CD) routine laboratory screening, there are no studies evaluating correlation between degree of intestinal damage and positivity to anti-tTG. Since recent studies showed that anti-gliadin (AGA) and anti-endomysium (EMA) antibodies are ineffective in diagnosing mild gluten-sensitive enteropathy, the aim of this study was to evaluate the prevalence of anti-tTG in different degrees of intestinal damage of celiac patients and whether there is a correlation between serum value of anti-tTG and the degree of histologic damage. STUDY: We studied 119 consecutive adult patients affected by CD (47 men and 72 women; mean age, 28 years; range, 22-51 years). All patients were stratified for histologic damage according to Marsh classification, and in all of them an anti-tTG evaluation was performed. RESULTS: Marsh I lesions were present in 13 patients (10.92%), Marsh II in 24 anti-tTG (20.16%), Marsh IIIa in 27 anti-tTG (22.68%), Marsh IIIb in 31 anti-tTG (26.05%) and Marsh IIIc in 24 anti-tTG (20.16%). Anti-tTG positivity was ranging from 1 of 13 anti-tTG (7.69%) in Marsh I lesions to 23 of 24 anti-tTG (95.83%) in Marsh IIIc lesions respectively ( P< 0.005), while mean serum value of anti-tTG ranged from 3.61 (range, 0.7-9.2) UA/mL in Marsh I lesions to 7.3 (range, 1-25.1), 18.5 (range, 1.8-56.2), 36 (range, 3.7-83.5) and 74.95 (range, 6.5-257) UA/mL in Marsh II, IIIb and IIIc lesions respectively (P < 0.005). CONCLUSIONS: Our study showed that anti-tTG prevalence and their mean serum value was higher in celiacs with severe enteropathy (Marsh IIIb-c lesions) than in those showing slight enteropathy (Marsh I-IIIa). So, serologic tests without histologic evaluation may underestimate the real prevalence of CD and there is the risk of delaying the diagnosis of CD in patients who run an increased risk of deficiencies, non-malignant conditions and malignancy.