Tumor Necrosis Factor Alpha Inhibitors Did Not Influence Postoperative Morbidity After Elective Surgical Resections in Crohn's Disease.

BACKGROUND: The real impact of anti-tumor necrosis alpha (TNF) therapy in postoperative complications after intestinal resections in Crohn's disease (CD) still needs to be determined. AIMS: To compare the postoperative complication rates after elective intestinal resections in CD patients, with or without previous exposure to anti-TNF therapy. METHODS: This was a retrospective and observational study, with elective intestinal resections for CD (emergency procedures were excluded). Patients were allocated in two groups according to preoperative anti-TNF status. Surgical and medical complications were analyzed and subsequently compared between the groups. RESULTS: A total of 123 patients were included (71 with and 52 without preoperative anti-TNF). The groups were considered homogeneous, except for perianal CD, previous azathioprine, and stomas. There was no significant difference between the groups regarding overall surgical complications (32.69% in anti-TNF- vs. 39.44% in anti-TNF+ patients, p = 0.457) or overall medical complications (21.15 vs. 21.13%, respectively, p = 1.000). In univariate analysis, previous steroids, perianal CD, and stomas were considered risk factors for surgical complications, and previous steroids and hypoalbuminemia for medical complications. In multivariate analysis, previous steroids were associated with higher rates of surgical and medical complications, while hypoalbuminemia was associated with higher medical complication rates. CONCLUSIONS: There was no influence of the previous use of anti-TNF agents in postoperative surgical and medical complication rates in elective intestinal resections for CD. Previous steroids and hypoalbuminemia were associated with higher complication rates. This was the first case series of the literature describing outcomes in exclusively elective operations.

Disease duration did not influence the rates of loss of efficacy of the anti-TNF therapy in Latin American Crohn's disease patients.

BACKGROUND/AIMS: The efficacy of both Infliximab (IFX) and Adalimumab (ADA) can be reduced over time. The aim of this study was to analyze the incidence of loss of efficacy (LOE) of both IFX and ADA, and outline the influence of disease duration on its occurrence. METHODS: Retrospective, multicenter, observational cohort study, with CD patients treated with anti-TNF therapy. LOE was defined as the need for steroids, occurrence of major abdominal surgery during treatment, dose increase, interval shortening or switching of the anti- TNF agent. Patients were allocated in three subgroups based on disease duration (DD): <24 months, between 24 and 60 months and >60 months. RESULTS: 175 patients were included in the study (117 under IFX and 58 under ADA therapy). LOE occurred in 32% of patients with DD <24 months, in 33.3% with DD between 24 and 60 months and in 31.3% of subjects with DD over 60 months (p = 0.975). CONCLUSIONS: Disease duration (DD) did not influence LOE rates. These results suggest that in real-world observational practice, patients with early CD might have the same rates of LOE than patients with a disease prolonging for a longer duration.

Celiac disease and dermatitis herpetiformis in Brazilian twins: a long-term follow-up and screening of their relatives.

OBJECTIVES: To investigate three pairs of twins with celiac disease (CD) concerning clinical presentation, diagnostic procedures, and long-follow-up, besides screening CD in their first-degree relatives. PATIENTS/METHODS: CD was diagnosed in childhood by endoscopic duodenal biopsy in two monozygotic (MZ) female pairs (A1 and A2, B1 and B2) and one dizygotic (DZ) pair, in which the male (C1) had CD and the female (C2) was negative. The patients had periodic evaluations after a gluten-free diet (GFD) for 16 to 21 years. Nine first-degree relatives were screened by serological tests and when positive, referred for intestinal biopsies. RESULTS: At diagnosis, all CD patients had the classic presentation. A1/A2: scalloped duodenal mucosa with atrophic areas, Marsh III-b, after 16 years of GFD was antiendomysium antibody (EmA) negative, normal mucosa. B1/B2 at diagnosis: mucosal atrophy, Marsh III-b, after 21 years was EmA negative, decreased folds. Patient C1: decreased folds, Marsh III-b, after 16 years was EmA positive, decreased folds, admitted to gluten ingestion. A1, A2, and B1 presented dermatitis herpetiformis. The father of A1/A2 and the mother of C1/C2 were celiac. CONCLUSIONS: The long-term follow-up of the patients allowed some observations such as the concordance for CD in MZ twins, both in relation to the time of onset and the severity of the disease. Also, the findings of serological, endoscopic, and histological analyses were similar. Dermatitis herpetiformis was present in patients with CD, with partial concordance in MZ twins.

Risk factors for complications after ileocolonic resection for Crohn's disease with a major focus on the impact of preoperative immunosuppressive and biologic therapy: A retrospective international multicentre study.

BACKGROUND: Author note: TY, AS, YS, FVT and PGK designed the study. All authors did data collection and gave scientific contribution to the study design and discussion. TY, AS and PGK drafted the article. All authors read and approved the final version of the manuscript.In the era of biologic agents, risk factors for complications following resection for Crohn's disease have not been fully identified. In particular, the association of preoperative use of immunosuppressive and biologic agents with the incidence of complications after resection remains to be elucidated. AIM: This retrospective multicentre study aimed to identify risk factors for complications after ileocolonic resection for Crohn's disease, with a major focus on the impact of preoperative immunosuppressive and biologic therapy. METHODS: A total of 231 consecutive patients who underwent ileocolonic resections for active Crohn's disease in seven inflammatory bowel disease referral centres from three countries (Japan, Brazil and Italy) were included. The following variables were investigated as potential risk factors: age at surgery, gender, behaviour of Crohn's disease (perforating vs. non-perforating disease), smoking, preoperative use (within eight weeks before surgery) of steroids, immunosuppressants and biologic agents, previous resection, blood transfusion, surgical procedure (open vs. laparoscopic approach), and type of anastomosis (side-to-side vs. end-to-end). Postoperative complications occurring within 30 days after surgery were recorded. RESULTS: The rates of overall complications, intra-abdominal sepsis, and anastomotic leak were 24%, 12% and 8%, respectively. Neither immunosuppressive nor biologic therapy prior to surgery was significantly associated with the incidence of overall complications, intra-abdominal sepsis or anastomotic leak. In multivariate analysis, blood transfusion, perforating disease and previous resection were significant risk factors for overall complications (odds ratio [OR] 3.02, 95% confidence interval [CI] 1.21-7.52; P = 0.02), intra-abdominal sepsis (OR 2.67, 95% CI 1.04-6.86; P = 0.04) and anastomotic leak (OR 2.87, 95% CI 1.01-8.18; P = 0.048), respectively. CONCLUSIONS: Blood transfusion, perforating disease and previous resection were significant risk factors for overall complications, intra-abdominal sepsis and anastomotic leak after ileocolonic resection for Crohn's disease, respectively. Preoperative immunosuppressive or biologic therapy did not increase the risk of postoperative complications.

Conventional Versus Biological Therapy for Prevention of Postoperative Endoscopic Recurrence in Patients With Crohn's Disease: an International, Multicenter, and Observational Study.

BACKGROUND/AIMS: Postoperative endoscopic recurrence (PER) occurs in nearly 80% of patients 1 year after ileocecal resection in patients with Crohn's disease (CD). Biological agents were more effective in reducing the rates of PER in comparison with conventional therapy, in prospective trials. The aim of this study was to compare the PER rates of biological versus conventional therapy after ileocecal resections in patients with CD in real-world practice. METHODS: The MULTIPER (Multicenter International Postoperative Endoscopic Recurrence) database is a retrospective analysis of PER rates in CD patients after ileocecal resection, from 7 referral centers in 3 different countries. All consecutive patients who underwent ileocecal resections between 2008 and 2012 and in whom colonoscopies had been performed up to 12 months after surgery, were included. Recurrence was defined as Rutgeerts' score ≥i2. The patients were allocated to either biological or conventional therapy after surgery, and PER rates were compared between the groups. RESULTS: Initially, 231 patients were evaluated, and 63 were excluded. Of the 168 patients in the database, 96 received anti-tumor necrosis factor agents and 72 were treated with conventional therapy after resection. The groups were comparable regarding age, gender, and perianal disease. There was longer disease duration, more previous resections, and more open surgical procedures in patients on biologicals postoperatively. PER was identified in 25/96 (26%) patients on biological therapy and in 24/72 (33.3%) patients on conventional therapy (P=0.310). CONCLUSIONS: In this retrospective observational analysis from an international database, no difference was observed between biological and conventional therapy in preventing PER after ileocecal resections in CD patients.

Direct retrospective comparison of adalimumab and infliximab in preventing early postoperative endoscopic recurrence after ileocaecal resection for crohn's disease: results from the MULTIPER database.

BACKGROUND AND AIMS: Both adalimumab [ADA] and infliximab [IFX] seem to be effective in the prevention of early postoperative endoscopic recurrence [EPER] after ileocaecal resection in Crohn's disease [CD] patients. There is lack of data with direct comparison between the two agents in the postoperative scenario. The aim of this study was to compare the rates of EPER in patients treated with ADA and IFX after ileocaecal resection for CD. METHODS: This was a multicentre retrospective analysis of EPER rates in CD patients after ileocaecal resections, from seven referral centres in three countries. Endoscopic recurrence was defined as Rutgeerts' score ≥ i2. The patients were allocated according to treatment to two groups: ADA or IFX. The EPER rates were compared between the two treatment groups. RESULTS: Among the 168 patients included in the database, 96 received anti-tumour necrosis factor [TNF] agents after resection [37 in the ADA and 59 in the IFX groups] and were included in this comparative study. The groups were comparable in all baseline characteristics, mainly age, gender, previous resections, perianal CD, and mono or combination therapy. EPER was identified in 9/37 [24.32%] in the ADA group vs 16/59 [27.12%] in the IFX group [p = 0.815]. CONCLUSIONS: In this retrospective direct comparison between ADA and IFX therapy after ileocaecal resection, there was no significant difference between the two anti-TNF agents in terms of EPER rates. However, prospective randomised studies are needed to confirm these data and better define the role of each agent in the prevention of EPER.

Mannan-binding lectin levels related to spontaneous abortion in Brazilian patients with celiac disease.

Low concentration of mannan-binding lectin (MBL) has been related to unexplained spontaneous abortion (SA), which has also been observed in an increased frequency in patients with celiac disease (CD). In this study, plasma levels of MBL were determined in patients with CD and irritable bowel syndrome (IBS) in order to investigate whether there is an association of MBL levels and the occurrence of SA in these patients. MBL concentration was determined in 46 patients with CD (28 without and 18 with report of SA) and 38 patients with IBS (25 without and 13 with report of SA). A higher frequency of SA was observed in women with CD when compared to IBS patients (23.2 vs. 13.9%; P = 0.046). No significant difference was observed in MBL concentrations between patients with CD, IBS, and healthy controls, nor between patients with or without occurrence of SA. These results suggest that the serum levels of MBL and the occurrence of SA in women with CD and IBS are not causally related.

Serum mannan-binding lectin levels in patients with celiac disease: an analysis of clinical and autoimmune features.

Mannan-binding lectin (MBL) is the central protein in the activation of complement through the lectin pathway. MBL plasma concentration is genetically determined and varies significantly among individuals. Recent findings suggest that MBL is associated with the pathogenesis of celiac disease (CD). In this study, MBL and C-reactive protein (CRP) levels were determined in 101 celiac patients and 120 controls, with the aim to associate with the presence of gluten in the diet, disease severity, and the presence of concomitant autoimmune diseases. MBL concentration was determined by ELISA and CRP by nephelometry, using a high-sensitivity method. EmA-IgA and other autoantibodies were tested by indirect immunofluorescence. Although a significant increase in MBL levels was observed in male patients compared to female (P = 0.024), the absence of any other association suggests that circulating MBL and CRP concentrations are not associated with clinical and autoimmune CD features in Brazilian patients.

Thyroid disorders in Brazilian patients with celiac disease.

INTRODUCTION/AIM: Patients with celiac disease (CD) can develop a gluten related autoimmune disorder that affects not only the small intestine but other tissues as well. An increased prevalence of autoimmune diseases has been reported, particularly autoimmune thyroiditis. The aim of this study was to characterize thyroid disorders in patients with CD. PATIENTS/METHODS: Fifty-two patients with CD (43 female, 9 male; mean age, 41.1 years) were studied. Nine were on a gluten-free diet (GFD). They were divided into four groups: Group 1, without thyroid involvement (n=30); Groups 2A-C, with thyroid involvement (n=22); Group 2A, subclinical hypothyroidism (n=11); Group 2B, clinical hypothyroidism (n=10); and Group 2C, other thyroid disorders (n=1). CD was confirmed by serologic and histologic criteria. Thyroid involvement was detected by measurement of thyroid stimulating hormone (TSH) and anti-thyroperoxidase antibodies (anti-TPO). RESULTS: Increased levels of TSH and/or anti-TPO levels were detected in Groups 2A (21.1%) and 2B (19.2%). The patients of Group 2B presented clinical symptoms of hypothyroidism before the diagnosis of CD, and 5 of these patients were receiving levothyroxine. One woman (Group 2C; 1.92%) had a medullary carcinoma. There was statistical significance between the age when thyroid disease was diagnosed (current age) and the age of CD diagnosis between Groups 1 and 2B. Patients with thyroid involvement presented associated diseases such as diabetes mellitus (2), Down's syndrome (2), ulcerative colitis (1), and dermatitis herpetiformis (2). CONCLUSIONS: Our findings demonstrated an increased prevalence of thyroid disorders (hypothyroidism, 19.2%; and subclinical hypothyroidism, 21.2%), and other associated diseases in celiac patients, even on a GFD, increasing with the age of the patients. Screening for associated diseases is recommended for patients with CD, independent of age at diagnosis or treatment duration.