Pouchitis: Clinical Features, Diagnosis, and Treatment.

Procto-colectomy with an ileal pouch anal anastomosis is the procedure of choice for ulcerative colitis patients that require colectomy. Pouchitis is a non-specific inflammation of the ileal reservoir, and the most common, inflammatory and long-term, complication after pouch surgery for ulcerative colitis. The aetiology is still unknown, but many risk factors have been individuated. Pouchitis can be classified based on aetiology, duration, clinical course, and response to antibiotic therapy. Accurate diagnosis and classification is the key factor for an adequate management, and exclusion of secondary causes of pouchitis is pivotal. Most of the patients consistently respond to antibiotic therapy, but management of the subgroup of patients with chronic-antibiotic-resistant-pouchitis is still challenging, being this entity one of the major causes of pouch failure.

COVID-19 in IBD: The experience of a single tertiary IBD center.

BACKGROUND: Italy has been one of the most affected countries in the world by COVID-19. There has been increasing concern regarding the impact of COVID-19 on patients with inflammatory bowel disease (IBD), particularly in patients treated with immunosuppressants or biologics. The aim of our study is to understand the incidence of COVID-19 in a large cohort of patients with IBD. Furthermore, we analyzed possible risk factors for infection and severity of COVID-19. METHODS: This was an observational study evaluating the impact of COVID-19 on IBD patients in a single tertiary center. A 23 multiple-choice-question anonymous survey was administered to 1200 patients with IBD between March 10th and June 10th 2020. RESULTS: 1158 questionnaires were analyzed. The majority of patients had Crohn's disease (CD) (60%) and most of them were in clinical remission. Among the 26 patients (2.2%) who tested positive for COVID-19, only 5 (3CD) were on biological treatment and none required hospitalization. Two patients died and were on treatment with mesalazine only. Of the 1158 patients, 521 were on biological therapy, which was discontinued in 85 (16.3%) and delayed in 195 patients (37.4%). A worsening of IBD symptoms was observed in 200 patients on biological therapy (38.4%). Most of these patients, 189 (94.5%), had stopped or delayed biological treatment, while 11 (5.5%) had continued their therapy regularly (p<0.001). CONCLUSIONS: Our data are in line with the current literature and confirm a higher incidence compared to the general population. Biological therapy for IBD seems to not be a risk factor for infection and should not be discontinued in order to avoid IBD relapse.

Long term remission after ileorectal anastomosis in Crohn's colitis.

BACKGROUND: Crohn's disease represents a heterogeneous entity, but its location tends to be relatively stable overtime. For extensive refractory Crohn's colitis, ileorectal anastomosis after colectomy is an engaging option, since the necessity of a permanent ileostomy is avoided. AIMS: In our study, the long-term outcome of two groups of patients with Crohn's colitis who underwent colectomy and ileorectal anastomosis was compared. The first group had isolated colonic Crohn's disease without rectal involvement and perianal disease, while the second group included patients who had rectal and/or ileal involvement, with or without perianal disease. METHODS: Between 1996 and 2016, in a single IBD tertiary center, 80 patients with a history of colectomy and ileorectal anastomosis for refractory Crohn's colitis were retrospectively identified. RESULTS: Recurrence of disease was diagnosed in 57/64 of patients with Crohn's colitis with rectal and/or ileal and/or perianal involvement compared with 1/16 of patients with isolated Crohn's colitis without rectal and perianal disease in a median time of recurrence of 2 years (IQR 1-6 years, minimum to maximum, 1-18 years, p < 0.001). Only 6 patients (7,5%) underwent definitive end ileostomy without proctectomy (1 in the noIRP group and 5 in the IRP group). CONCLUSION: Our data suggest that colectomy with ileorectal anastomosis may represent a curative option in patients with refractory isolated colitis without rectal and perianal involvement.

Refractory Complex Crohn's Perianal Fistulas: A Role for Autologous Microfragmented Adipose Tissue Injection.

BACKGROUND: Complex perianal fistulas represent one of the most challenging manifestations of Crohn's disease. Combined surgical and medical therapy with biologic drugs today represent the first-line treatment option, but its efficacy does not exceed 60%. Recently, new therapeutic approaches, such as the use of mesenchymal stromal cells, have shown promising results. The adipose tissue is an abundant and easy to access source. The effectiveness, safety, and feasibility of local injections of microfragmented adipose tissue in patients with refractory complex fistulizing perianal Crohn's disease (PCD) were evaluated. METHODS: Fifteen patients with persistent complex fistulizing PCD after biosurgical approach and subsequent surgical "rescue" repair were treated in S. Orsola-Malpighi Hospital with a single-local administration of microfragmented adipose tissue prepared using a minimal manipulation technique (Lipogems) in a closed system. Clinical outcomes were determined at 24-week follow-ups assessing success rate, defined as combined clinical and radiological remission. RESULTS: Upon clinical examination at 24 weeks, 10 patients had combined remission (clinical and radiographic), 4 patients showed improvements, and 1 patient failed. The results were confirmed in all patients by pelvic MRI. No relevant postoperative complications nor adverse events were reported. CONCLUSION: These results suggest that the local injection of autologous microfragmented adipose tissue is a safe and promising "rescue therapy" for patients with multiresistant complex fistulizing PCD. This approach might be proposed as routine because it is affordable, is minimally invasive, has no risk of sphincteric damage, and can be carried out in a day-surgery setting.

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 Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's 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].

Human cord blood-derived platelet lysate enhances the therapeutic activity of adipose-derived mesenchymal stromal cells isolated from Crohn's disease patients in a mouse model of colitis.

INTRODUCTION: Due to their immunomodulatory properties, mesenchymal stromal cells (MSCs) have been used for auto-immune disease treatment. Crohn disease (CD) and ulcerative colitis are two major inflammatory bowel diseases (IBDs), resulting from pathological immune responses to environmental or microbial antigens. Preclinical and clinical studies have suggested that MSC-based cellular therapy hold promising potential for IBD treatment. However, open issues include the selection of the proper cell dose, the source and the optimal route of administration of MSCs for more effective results. Platelet lysate has gained clinical interest due to its efficacy in accelerating wound healing. Thus, we propose to combine the administration of MSCs with a human umbilical cord blood-derived platelet lysate (hCBPL) as a novel strategy to improve MSC-based therapy for IBD resolution. METHODS: Colitis was induced in 8-week-old C57BL/6J mice by daily oral administration of dextran sulphate sodium (DSS) (1.5 % w/v in tap water) for 9 days. MSCs were isolated from adipose tissue of CD patients (adCD-MSCs), expanded in proliferation medium, resuspended in hCBPL or PBS and administrated via enema for three times (1 × 10(6) cells/mouse/time) every other day starting on day +7 from DSS induction. The colitis evolution was evaluated by daily monitoring of body weight, stool consistency and bleeding. Histopathological analysis was performed. Inflammatory cytokine plasma levels were determined. adCD-MSCs stained with lipophilic membrane dye Nile Red, were injected in DSS mice as described above. Colon section of mice sacrificed 24 hours after last cell administration, were analyzed by confocal microscopy. RESULTS: We found that adCD-MSCs could be easily isolated and expanded from CD patients. Upon injection, adCD-MSCs exerted a therapeutic effect on DSS-induced colitis. Moreover, hCBPL increased adCD-MSCs efficacy by significantly reducing colitis scores, extension of the colon inflamed area and plasma levels of inflammatory mediators. Finally, Nile Red staining of MSCs is very efficient, stable and does not impair their vitality and function. Nile Red-labelling was clearly detected in the colitic area of adCD-MSCs injected mice and it was significantly brighter in the colon sections of mice that had received adCD-MSCs/hCBPL. CONCLUSIONS: In summary, with this study we propose a novel and promising adCD-MSC/hCBPL-based therapy for refractory IBDs.

Oral beclomethasone dipropionate in chronic refractory pouchitis.

BACKGROUND: Pouchitis is the major long-term complication after ileal-pouch anal-anastomosis for ulcerative colitis. Ten to 15% of patients develop chronic pouchitis, either treatment responsive or treatment refractory. AIM: To evaluate the efficacy of oral beclomethasone dipropionate in inducing remission and improving quality of life in patients with chronic refractory pouchitis. METHODS: Ten consecutive patients with active pouchitis, not responding to 1-month antibiotic treatment, were treated with beclomethasone dipropionate 10 mg/day for 8 weeks. Clinical, endoscopic and histological evaluations were undertaken before and after treatment, according to the Pouchitis Disease Activity Index (PDAI). Remission was defined as a combination of PDAI clinical score of ≤2, endoscopic score of ≤1 and a total PDAI score of ≤4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: Eight of 10 patients (80%) achieved remission. The median total PDAI scores before and after therapy were, respectively, 12 (range 8-14) and 3 (range 2-9) (P<0.001). The median IBDQ score also significantly improved from 120 (range 77-175) to 175 (range 85-220) (p<0.001). CONCLUSION: Eight-week treatment with oral beclomethasone dipropionate appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment.

Obscure gastrointestinal bleeding: single centre experience of capsule endoscopy.

The advent of capsule endoscopy (CE) has resulted in a paradigm shift in the approach to the diagnosis and management of patients with obscure gastrointestinal bleeding (OGIB). With increasing global availability of this diagnostic tool, it has now become an integral part of the diagnostic algorithm for OGIB in most parts of the world. However, there is scant data on optimum timing of CE for maximizing diagnostic yield. OGIB continues to be a challenge because of delay in diagnosis and consequent morbidity and mortality. We evaluated the diagnostic yield of CE in identifying the source of bleeding in patients with OGIB. We identified patients who underwent CE at our institution from May 2006 to May 2011. The patients' medical records were reviewed to determine the type of OGIB (occult, overt), CE results and complications, and timing of CE with respect to onset of bleeding. Out of 346 patients investigated for OGIB, 246 (71.1%) had some lesion detected by CE. In 206 patients (59.5%), definite lesions were detected that could unequivocally explain the OGIB. Small bowel angiodysplasia, ulcer/erosions secondary to Crohn's disease, non-steroidal anti-inflammatory agent use, and neoplasms were the commonest lesions detected. Visualization of the entire small bowel was achieved in 311 (89.9%) of cases. Capsule retention was noted in five patients (1.4%). In this study, CE was proven to be a safe, comfortable, and effective, with a high rate of accuracy for diagnosing OGIB.

The role of antibiotics and probiotics in pouchitis.

Pouchitis is a non-specific inflammation of the ileal reservoir and the most common complication of proctocolectomy with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis. Its frequency is related to the duration of the follow up, occurring in up to 50% of patients 10 years after IPAA in large series from major referral centers. Treatment of pouchitis is largely empirical and only small placebo-controlled trials have been conducted. The rationale for using probiotics and antibiotics in pouchitis is based on convincing evidence that implicates intestinal bacteria in the pathogenesis of this disease. Probiotics are living organisms, which, upon ingestion in certain numbers, exert health benefits beyond inherent basic nutrition. VSL#3, a highly concentrated cocktail of probiotics has been shown to be effective in the prevention of pouchitis onset and relapses. Antibiotics are the mainstay of treatment of pouchitis, and metronidazole and ciprofloxacin are the most common initial approaches, often with a rapid response. The use of antibiotics in pouchitis is largely justified although proper controlled trials have not been conducted.

Surgery in presence of dysplasia in IBD.

UNLABELLED: Patients with longstanding ulcerative colitis (UC) and Crohn's disease have an increased risk of developing colorectal cancer. Dysplasia can be defined as neoplastic intraepithelial change, paralleling the location ofneoplasia, arising from chronic inflammation, divided in different grades from low to high grade. Different types of dysplasia have been described in UC such as "flat dysplasia", DALM or ALM. The management of dysplasia and cancer associated with UC has been strongly influenced by the considerable progress in the surgical treatment of the disease that has taken place in the last decades. The presence of dysplasia modifies the surgical attitude in sphincter-saving procedures such as ileorectal and ileoanal anastomosis where colonic mucosa is left in situ. With the stapled-anastomosis few centimeters of colonic mucosa (1-2 cm) are left in site below ileo-anal anastomosis with a risk of malignant degeneration. The hand-sewn IPAA with mucosectomy reduces the risk of retained colonic mucosa below the anastomosis, but does not allow complete removal of columnar epithelium with its potential evolution to a malignant state. CONCLUSIONS: in case of preoperative diagnosis of dysplasia we strongly recommend an oncologic resection of the specimen with TME, ligation at the origin of all the vascular pedicles and a extended lymphadenectomy.

Infliximab in the treatment of Crohn's disease.

The recent introduction of infliximab, a chimeric monoclonal antibody against tumor necrosis factor-alpha, has greatly modified the treatment of Crohn's disease (CD). Data from the literature show encouraging results after intravenous infusion both for closure of intestinal or perianal fistulas and for induction and maintenance of remission in patients with moderate to severe intestinal disease unresponsive to other treatments. However, some contraindications such as fibrostenosing CD and sepsis have been identified. In addition, the data on long-term outcomes and safety is still limited. Our initial experience showed that in selected cases local injection of infliximab is effective in the treatment of complex perianal disease offering the possibility of using such treatment even in small bowel obstructing disease with minimal systemic effects. This paper analyzes the state of the use of both intravenous and local injection of infliximab in patients with CD.

Management of pouch dysfunction or pouchitis with an ileoanal pouch.

Pouchitis, a non-specific inflammation of the ileal reservoir, is the most frequent long-term complication after pouch surgery for ulcerative colitis. Incidence rates vary widely. The etiology is still unknown, but genetic susceptibility and fecal stasis with bacterial overgrowth seem to be important factors. A clinical diagnosis should be always confirmed by endoscopy and histology, and Pouchitis Disease Activity Index (PDAI), based on clinical symptoms, endoscopic appearance and histologic findings, represents an objective and reproducible scoring system for pouchitis. The treatment of pouchitis is largely empiric given the few controlled studies available. Antibiotics, especially metronidazole and ciprofloxacin, are the therapy of choice. Chronic pouchitis occurs in about 10-15% of patients; in these cases, further diagnostic tests should be performed to exclude alternative diagnoses. Highly concentrated probiotics (VSL#3) have been shown to be effective in preventing the onset and relapse of pouchitis.