Colo-rectal endoscopic full-thickness resection (EFTR) with the over-the-scope device (FTRD®): A multicenter Italian experience.

BACKGROUND AND AIM: Endoscopic full-thickness resection(EFTR) with FTRD® in colo-rectum may be useful for several indications.The aim was to assess its efficacy and safety. MATERIAL AND METHODS: In this retrospective multicenter study 114 patients were screened; 110 (61M/49F, mean age 68 ±â€¯11 years, range 20-90) underwent EFTR using FTRD®. Indications were:residual/recurrent adenoma (39), incomplete resection at histology (R1 resection) (26), non-lifting lesion (12), adenoma involving the appendix (2) or diverticulum (2), subepithelial lesions(10), suspected T1 carcinoma (16), diagnostic resection (3). Technical success (TS: lesion reached and resected), R0 resection (negative lateral and deep margins),EFTR rate(all layers documented in the specimen) and safety have been evaluated. RESULTS: TS was achieved in 94.4% of cases. EFTR was achieved in 91% with lateral and deep R0 resection in 90% and 92%. Mean size of specimens was 20 mm (range 6-42). In residual/recurrent adenomas, final analysis revealed: low-risk T1 (11), adenoma with low-grade dysplasia (LGD) (24) and high-grade dysplasia (HGD) (3), scar tissue (1). Histology reports of R1 resections were: adenoma with LGD (6), with HGD (1), low-risk (6) and high-risk (1) T1, scar tissue (12). Non-lifting lesions were diagnosed as: adenoma with HGD (3), low-risk (7) and high risk (2) T1. Adverse clinical events occurred in 12 patients (11%),while adverse technical events in11%. Three-months follow-up was available in 100 cases and residual disease was evident in only seven patients. CONCLUSIONS: EFTR using FTRD® seems to be a feasible, effective and safe technique for treating selected colo-rectal lesions. Comparative prospective studies are needed to confirm these promising results.

Paradoxical psoriasis in a large cohort of patients with inflammatory bowel disease receiving treatment with anti-TNF alpha: 5-year follow-up study.

BACKGROUND: Psoriasis is an emerging paradoxical side effect in patients with inflammatory bowel disease (IBD) when treated with anti-TNF alpha. Patients with severe skin lesions unresponsive to topical therapy need to withdraw from treatment. AIM: To estimate the incidence of paradoxical psoriasis in a large cohort of IBD patients treated with anti-TNF alpha and to analyse its clinical correlates. METHODS: A retrospective cohort study on all IBD patients who started anti-TNF alpha at our IBD Centre from January 2008 to December 2013 was performed. Proportional hazards regression models were used to estimate the association between each predictor and time to the development of psoriasis. Time-dependent predictors were updated at each available time point. RESULTS: Four hundred and two patients were included. Participants contributed a total of 839 person-years of follow-up, during which 42 incident cases of psoriasis were recorded, with an incidence rate of five per 100 person-years. Cox-regression survival analysis revealed smoking as independent predictor of psoriasis (HR: 2.37, 95% CI: 1.36-4.48; P = 0.008). Conversely, concomitant immunosuppressive therapy was inversely related to psoriasis (HR: 0.33, 95% CI: 0.12-0.92; P = 0.03). CONCLUSIONS: Paradoxical psoriasis is a relevant side effect of anti-TNF alpha therapy, with an incidence rate of five per 100 person-years. Smoking is confirmed as the main risk factor for developing lesions. The combination therapy with anti-TNF alpha plus immunosuppressants is associated with a reduced risk of paradoxical psoriasis.

Development of psoriasis scalp with alopecia during treatment of Crohn's disease with infliximab and rapid response to both diseases to ustekinumab.

Anti tumor necrosis factor antibodies are used to treat both psoriasis and inflammatory bowel disease. Several paradoxical cases of psoriatic skin lesions induced by tumor necrosis factor antagonist therapy have been described in IBD patients in the recent years. Ustekinumab, a fully human anti-interleukin-12/-23 monoclonal antibody, is the first drug of a new class of biologic therapy approved for the treatment of moderate to severe plaque psoriasis. Data on the efficacy of ustekinumab in patients with moderate-to-severe Crohn's disease, especially in patients previously treated with infliximab, have been recently published. We report about the effectiveness of ustekinumab in the treatment of both severe scalp psoriasis lesions with alopecia and active Crohn's disease.

Achievement of sustained deep remission with adalimumab in a patient with both refractory ulcerative colitis and seronegative erosive rheumatoid arthritis.

Inflammatory bowel disease (IBD) is commonly associated with peripheral inflammatory arthritis, and it has been estimated that as many as 12% of IBD patients report these manifestations. However, rheumatoid arthritis (RA) is rarely associated with ulcerative colitis (UC). Among all the biological agents available, nine have been currently approved for the treatment of RA. Conversely, only Infliximab and recently Adalimumab have been approved for UC. In particular, the efficacy of Adalimumab in UC has been demonstrated by both recent randomized controlled trials and real-life studies. Moreover, Adalimumab is a well-established treatment for RA. Herein, we describe a patient with RA and UC treated successfully with ADA.

A case of pyoderma gangrenosum with ulcerative colitis treated with combined approach: infliximab and surgery.

Pyoderma gangrenosum (PG) is an ulcerating noninfectious disease of the skin seen in 1-2% of patients with inflammatory bowel disease (IBD). The pathogenesis of PG has yet to be determined, but may be related to abnormal T cell responses and the production of TNF-α, a pathway also involved in IBD pathogenesis. Infliximab, a chimeric monoclonal antibody to TNF-α, is used to treat moderate to severe IBD and several case reports and studies suggest the efficacy of infliximab in the treatment of PG. The surgical approach to PG is reserved to a few selected cases. We report here the case of a patient with ulcerative colitis (UC) and PG localized on the left breast, treated with a simultaneous combined medical and surgical approach.

Immune response to influenza A/H1N1 vaccine in inflammatory bowel disease patients treated with anti TNF-α agents: effects of combined therapy with immunosuppressants.

BACKGROUND AND AIMS: Our first objective was to evaluate the immune response to the adjuvanted 2009 A/H1N1 pandemic (pH1N1) vaccine in inflammatory bowel disease (IBD) patients treated with anti-TNF-α alone or combined with immunosuppressants (IS). Second and third aims were the safety of pH1N1 vaccine and the effects on IBD clinical activity. METHODS: 36 patients with Crohn's disease (CD) and 26 with ulcerative colitis (UC) and thirty-one healthy control (HC) subjects were enrolled. 47 patients were on anti TNF-α maintenance monotherapy and 15 on anti TNF-α combined with IS. Sera were collected at baseline (T0) and 4 weeks after the vaccination (T1) for antibody determination by hemagglutination inhibition (HAI). Disease activity was monitored at T0 and T1. RESULTS: Seroprotective titers (≥1:40) in patients were comparable to HC. Seroconvertion rate (≥4 fold increase in HAI titer) was lower than HC in IBD patients (p=0.009), either on anti TNF-α monotherapy (p=0.034) or combined with IS (p=0.011). Geometric mean titer (GMT) of antibodies at T1 was significantly lower in patients on combined therapy versus those on monotherapy (p=0.0017) and versus HC (p=0.011). The factor increase of GMT at T1 versus T0 was significantly lower in IBD patients versus HC (p=0.042), and in those on combined immunosuppression, both versus monotherapy (p=0.0048) and HC (p=0.0015). None of the patients experienced a disease flare. CONCLUSION: Our study has shown a suboptimal response to pH1N1 vaccine in IBD patients on therapy with anti TNF-α and IS compared to those on anti-TNF-α monotherapy and HC.

Anti-TNF alpha therapy in the management of extraintestinal manifestation of inflammatory bowel disease.

Inflammatory bowel disease, Crohn's disease and ulcerative colitis, are immune-mediated disorders of unknown etiology that primarily affect the gastrointestinal tract. In addition, other organ systems can be involved such as joint/bones, skin, eyes, hepatobiliary tract, lungs and kidney. Overall, they represent extraintestinal manifestations of inflammatory bowel disease and may present before, in conjunction or after the onset of bowel disease. Extraintestinal manifestations are observed in 20-40% of patients and frequently have a negative impact on quality of patients' life. Some extraintestinal manifestations such as arthritis, erytema nodosum, pyoderma gangrenosum, iritis, uveitis have a pathogenic tumor necrosis factor alpha-dependent mechanism common with Crohn's disease and ulcerative colitis. Early recognition and treatment of extraintestinal manifestations can minimize potential severe complications. In this review we provide an overview on the prevalence and clinical aspects of the more commonly reported extraintestinal manifestations of Crohn's disease and ulcerative colitis and the role of tumor necrosis factor alpha inhibitors in their treatment.

New therapeutic approach in inflammatory bowel disease.

In the last decade, biologic agents, in particular infliximab and adalimum-ab, have deeply changed the therapeutic armamentarium of inflammatory bowel disease (IBD). However, these drugs have a number of contraindications and side-effects that physicians should know so to avoid and eventually manage them. Another important issue is the early introduction of immunomodulators and biologics in the therapeutic algorithm of IBD, the so called "top-down" approach compared to the traditional "step-up" approach. In this review, the indications to the use of anti-TNF-alpha molecules in IBD are briefly reported and the potential benefits and disadvantages of a more aggressive approach are discussed.