Efficacy and tolerability of very low-volume bowel preparation in patients with inflammatory bowel diseases.

OBJECTIVES: An adequate bowel preparation is essential for a quality colonoscopy. Patients with inflammatory bowel disease (IBD) show low compliance with bowel preparation due to the large volume of lavage solution to be ingested, especially if active symptoms are present, and the frequency of having a colonoscopy. We evaluated the efficacy and tolerability of a very low-volume (VLV) polyethylene glycol (PEG)-based solution in patients with IBD. METHODS: A cohort of 103 consecutive patients, 56 with Crohn's disease and 47 with ulcerative colitis, received a 1-L PEG-based bowel preparation divided into two 500-mL doses taken the evening before and the morning of the colonoscopy, each dose followed by at least another 500-mL of clear fluids. Colon cleansing was scored according to the Boston Bowel Preparation Scale (BBPS) and evaluated in relation to influencing variables. RESULTS: Bowel cleansing was adequate (BBPS ≥ 6) in 88 patients (85.4%). The time interval between the end of bowel preparation and the beginning of colonoscopy and the disease activity significantly affected colon cleansing. Most patients declared a complete intake of lavage solution (99%), the willingness to repeat the same bowel preparation in a future colonoscopy (86.4%), and a good taste assessment. CONCLUSION: The VLV PEG-based bowel preparation is effective and well accepted by IBD patients. As minimizing the volume of lavage solution required, the VLV-bowel preparation here tested could be of choice in subjects who perform periodically colonoscopy or in those who do not tolerate a larger amount of liquids.

Natural History of Ulcerative Colitis with Coexistent Colonic Diverticulosis.

Ulcerative colitis (UC) and colonic diverticulosis can co-exist in some patients. However, the natural history of UC associated with colonic diverticulosis is not well known. We here compared the disease characteristics and outcome of UC patients with and without concomitant colonic diverticulosis. Medical records of 347 UC patients were included in an observational, retrospective, nested-matched case-control study. Cases were 92 patients with UC and concomitant colonic diverticulosis, while controls were 255 UC patients without concomitant colonic diverticulosis. A propensity score matching (PSM) was used to homogenate cases (n = 92) and controls (n = 153) for age. UC patients with concomitant colonic diverticulosis were less likely to have an extensive disease (25/92, 27.1%) and to experience steroid dependence (8/92, 8.6%) compared to patients without concomitant colonic diverticulosis (70/153, 45.7% and 48/153, 31.3%, respectively; p < 0.001). The use of immunosuppressants (9/92, 9.7% vs. 37/153, 24.1%; p = 0.007) or biologics (3/92, 3.2% vs. 26/153, 16.9%, p < 0.001) was significantly lower in UC patients with concomitant diverticulosis compared to the control group. On multivariate analysis, steroid dependence and extensive colitis were significantly less frequent in UC patients with concomitant colonic diverticulosis compared to UC patients without diverticula. UC patients with coexisting colonic diverticulosis are less likely to have an extensive disease and to be steroid-dependent.

Super selective arterial embolization to treat radiation-induced hemorrhagic gastritis: a case report and review of the literature.

Radiation-induced hemorrhagic gastritis (RIHG) is a rare but potentially fatal event following radiotherapy for locally advanced gastric cancer; the treatment of this condition is not standardized. Only few cases of RIHG have been reported, treated with different therapeutic approaches. Here we report the case of a 79-year-old patient who underwent subtotal gastrectomy for gastric cancer, followed by adjuvant chemo-radiotherapy. Approximately 3 months after the end of the treatment, she developed recurrent diffuse bleeding originating from the entire mucosa of the gastric pouch and from a marginal ulcer. As the bleeding was refractory to several endoscopic treatments and surgery was not indicated, the patient underwent two sessions of transcatheter selective arterial embolization, with resolution of bleeding. Arterial embolization has already been reported for the treatment of hemorrhagic cystitis, developing after irradiation of the pelvis for prostate, bladder, rectum, and cervix cancer. However, to our knowledge, it has never been reported as a treatment for hemorrhagic gastritis. Based on this case, we suggest arterial embolization as an option in the management of RIHG, when standard endoscopic treatment fails.

Effect of Vedolizumab on Anemia of Chronic Disease in Patients with Inflammatory Bowel Diseases.

BACKGROUND: Anemia of Chronic Disease (ACD) can negatively influence the clinical course of Inflammatory Bowel Disease (IBD) patients. The aim of this study was to evaluate the effect of Vedolizumab on ACD in IBD. METHODS: Clinical data of 75 IBD patients (25 Crohn's disease (CD) and 50 Ulcerative Colitis (UC)) receiving Vedolizumab in a tertiary referral IBD center were retrospectively evaluated and the effect of the drug on ACD was ascertained at weeks 14 and 24. RESULTS: ACD was diagnosed in 35 (11 CD and 24 UC) out of 75 (47%) IBD patients. At both week 14 and week 24, improvements and resolutions of ACD were achieved by 13/35 (37%) and 11/35 (31%) patients, respectively. Baseline demographic/clinical characteristics did not differ between patients with ACD improvements/resolutions and those with persistent ACD. Clinical response occurred more frequently in patients who achieved ACD resolution (10/11, 91%) than in those without ACD improvement (5/11, 45%, p = 0.022). When analysis was restricted to anemic patients, ACD resolution was documented in 10/22 patients (45%) achieving clinical response and 1/13 of non-responders (8%; p = 0.02). CONCLUSIONS: ACD occurs in half of the IBD patients and, in nearly two thirds of them, Vedolizumab treatment associates with ACD resolution/improvement.

No effect of a liquid diet in the management of patients with stricturing Crohn's disease.

PURPOSE: Patients with stricturing Crohn's disease (CD) may experience episodes of intestinal sub-occlusions, which in many cases lead to surgery. The aim of this study was to examine whether adding a liquid diet to medical therapy could improve the management of patients with stricturing CD. METHODS: Medical records of CD outpatients with a small bowel stricture, either receiving (group 1) or not (group 2) a 24-h liquid diet every 10-14 days, were retrospectively analyzed. Number of sub-occlusive episodes, frequency, and timing of intestinal resections for strictures were analyzed. RESULTS: During the 12-month follow-up, there was no significant difference in the occurrence of new sub-occlusive episodes between the 2 groups (10/37 patients (27%) in group 1 vs 9/45 patients (20%) in group 2). Similarly, the number of patients undergoing bowel resections for sub-occlusive episodes non-responsive to medical therapy did not statistically differ between the two groups (9 patients (24.3%) in group 1 vs 7 patients (15.5%) in group 2). In group 1, surgeries were equally distributed along the 12-months of follow-up, while 85.7% of patients in group 2 underwent intestinal resection within the first 3 months of follow-up. CONCLUSION: Adding a liquid diet to medical therapy does not help management of patients with stricturing CD.

Extent of Mucosal Inflammation in Ulcerative Colitis Influences the Clinical Remission Induced by Vedolizumab.

Randomized controlled clinical trials and real-life observations indicate that less than 50% of patients with Crohn's disease (CD) or ulcerative colitis (UC) respond to vedolizumab, a humanized monoclonal antibody that blocks the α4ß7 integrin. Since α4ß7-expressing lymphocytes mainly infiltrate the left colon, we assessed whether localization of CD and UC influences vedolizumab-induced remission. One hundred and eighty-one patients (74 CD and 107 UC) receiving vedolizumab in 3 referral centers were retrospectively evaluated for clinical remission at week 14. Demographic and clinical characteristics were compared between remitters and non-responders, and multivariable multinomial analysis was performed to identify predictors of remission. Remission was achieved in 17 CD (23%) and 34 UC (32%) patients, respectively. In CD, localization of the lesions did not influence clinical remission. In UC, the remitters had more frequently a distal/left-sided colitis (21/34, 62%) as compared to the non-responders (9/47, 19%), and extensive colitis was more frequent in the non-responders (38/47, 81%) than in the remitters (13/34, 38%). The multivariable multinomial analysis showed that distal/left-sided colitis was associated with a higher probability of clinical remission while extensive colitis was inversely associated with induction of remission. Data indicate that UC patients with distal or left-sided colitis are more likely to achieve remission than patients with extensive colitis following vedolizumab treatment.

Role of Interleukin-34 in Cancer.

Cross-talk between cancer cells and the immune cells occurring in the tumor microenvironment is crucial in promoting signals that foster tumor growth and metastasis. Both cancer cells and immune cells secrete various interleukins (IL), which, either directly or indirectly, stimulate cancer-cell proliferation, survival, and diffusion, as well as contribute to sculpt the immune microenvironment, thereby amplifying tumorigenic stimuli. IL-34, a cytokine produced by a wide range of cells, has been initially involved in the control of differentiation, proliferation, and survival of myeloid cells. More recent studies documented the overexpression of IL-34 in several cancers, such as hepatocarcinoma, osteosarcoma, multiple myeloma, colon cancer, and lung cancer, and showed that tumor cells can produce and functionally respond to this cytokine. In this review, we summarize the multiple roles of IL-34 in various cancers, with the aim to better understand the relationship between the expression of this cytokine and cancer behavior and to provide new insights for exploring a new potential therapeutic target.

The TLR9 Agonist Cobitolimod Induces IL10-Producing Wound Healing Macrophages and Regulatory T Cells in Ulcerative Colitis.

BACKGROUND AND AIMS: The topically applied Toll-like receptor 9 [TLR9] agonist cobitolimod is a first-in-class DNA-based oligonucleotide with demonstrated therapeutic efficacy in clinical trials with ulcerative colitis [UC] patients. We here characterized its anti-inflammatory mechanism in UC. METHODS: Luminal cobitolimod administration was evaluated in an experimental dextran sodium sulfate [DSS]-induced colitis model. Cultured blood and mucosal cells from UC patients were treated with cobitolimod and analysed via microarray, quantitative real-time PCR, ELISA and flow cytometry. Intestinal slides of cobitolimod-treated UC patients were analysed by immunohistochemistry. RESULTS: Cobitolimod administration markedly suppressed experimental colitis activity, and microarray analyses demonstrated mucosal IL10 upregulation and suppression of IL17 signalling pathways. Cobitolimod treatment was associated with significant induction of mucosal IL10+Tr1 and Treg cells and suppression of Th17 cells. TLR9 knockout mice indicated that cobitolimod requires TLR9 signalling for IL10 induction. In UC patients, mucosal TLR9 levels correlated with severity of inflammation. Cobitolimod inhibited IL17A and IL17F, but increased IL10 and FoxP3 expression in cultured intestinal UC T cells. Cobitolimod-mediated suppression of intestinal IL17+T cells was abrogated by IL10 blockade. Furthermore, cobitolimod led to heightened IL10 production by wound healing macrophages. Immunohistochemistry in intestinal biopsies of cobitolimod-treated UC patients indicated increased presence of IL10+mononuclear and regulatory T cells, as well as reduction of IL17+cells. CONCLUSION: Activation of TLR9 via cobitolimod might represent a novel therapeutic approach in UC, as it suppresses Th17 cells and induces anti-inflammatory IL10+macrophages and regulatory T cells, thereby modifying the dysregulated intestinal cytokine balance. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Oligonucleotides-A Novel Promising Therapeutic Option for IBD.

Inflammatory Bowel Diseases (IBD), whose denomination comprehends Crohn's Disease (CD) and Ulcerative Colitis (UC), are intestinal chronic diseases that often require lifelong medical therapy. In the last two decades monoclonal antibodies against the cytokine TNF have become integral parts in the treatment of IBD patients, however there are unwanted side-effects and one third of patients show primary non-response while another subgroup loses response over time. Finding novel drugs which could act as therapies against precise pro-inflammatory molecular targets to avoid unwanted systemic side effects and additionally the process of immunization, represents an important aim for subsequent therapeutic approaches. Oligonucleotide based therapies represent a promising novel concept for the treatment of IBD. The molecular action of oligonucleotides ranges from inhibition of the translational process of mRNA transcripts of pro-inflammatory molecules, to mimicking bacterial DNA which can activate cellular targets for immunomodulation. Alicaforsen, selectively targets ICAM-1 mRNA. ICAM-1 is an adhesion molecule which is upregulated on endothelial cells during IBD, thereby mediating the adhesion and migration of leucocytes from blood to sites of active inflammation. In CD parenteral application of alicaforsen did not show therapeutic efficacy in phase II trials, but it demonstrated an improved efficacy as a topical enema in distal UC. Topical application of alicaforsen might represent a therapeutic perspective for refractory pouchitis as well. SMAD7 is a protein that inhibits the signaling of TGFß, which is the mainstay of a regulatory counterpart in cellular immune responses. An antisense oligonucleotide against SMAD7 mRNA (mongersen) demonstrated pre-clinical and phase II efficacy in CD, but a phase III clinical trial was stopped due to lack of efficacy. Cobitolimod is a single strand oligonucleotide, which mimics bacterial DNA as its CpG dinucleotide sequences can be recognized by the Toll-like receptor 9 on different immune cells thereby causing induction of different cytokines, for example IL10 and IFNα. Topical application of cobitolimod was studied in UC patients. We will also discuss two other novel oligonucleotides which act on the GATA3 transcription factor (SB012) and on carbohydrate sulfotransferase 15 (STNM01), which could both represent novel promising therapeutic options for the treatment of UC.

Psoriasis Phenotype in Inflammatory Bowel Disease: A Case-Control Prospective Study.

BACKGROUND AND AIMS: Whether inflammatory bowel disease [IBD] is associated with specific psoriasis phenotypes is undefined. In a case-control prospective study, we aimed to assess the severity and phenotype of psoriasis in IBD vs matched non-IBD controls with psoriasis [non-IBD]. METHODS: From 2011 to 2013, dermatological assessment was performed in all IBD patients showing lesions requiring characterisation. In patients with psoriasis, assessment included: presence, characteristics, and severity. Each IBD patient with psoriasis was matched [gender, ethnicity, age ± 5 years] with one non-IBD patient with psoriasis. STATISTICAL ANALYSIS: data were expressed as median [range], chi-square, Student's t test. RESULTS: Dermatological assessment was performed in 251 IBD patients [115 females, age 47 [16-85]; IBD duration 9 years [1-46]]: 158 Crohn's disease [CD] [63%], 93 ulcerative colitis [UC] [37%]. Psoriasis was detected in 62 [25%] IBD patients: 36 [58%] CD, 26 UC [42%; p = 0.44]. Clinical characteristics were comparable between IBD patients with or without psoriasis: age 50 [23-72] vs 47 [16-85]; IBD duration 9.5 [1-46] vs 9 [1-41]; p = non-significant]. The non-IBD group included 62 patients with psoriasis: 35 male; age 47 [18-75]. Mild psoriasis was more frequent in IBD vs non-IBD [87% vs 53%; p < 0.0001], whereas moderate and severe psoriasis were more frequent in non-IBD vs IBD [37% vs 13%, p = 0.004; 10% vs 0%; p = 0.036]. Plaque-type psoriasis was the most common phenotype in both IBD and non-IBD [p < 0.0001 vs others phenotypes].The frequency of plaque-type, nail psoriasis and psoriatic arthritis was lower in IBD vs non-IBD [p = 0.008; p < 0.0001; p = 0.006]. Psoriasis occurred after anti-tumour necrosis factor [TNF]α treatment in six CD patients [7%]. CONCLUSIONS: Severity and phenotypes of psoriasis may differ between patients with IBD and their matched non-IBD controls.

A sonographic lesion index for Crohn's disease helps monitor changes in transmural bowel damage during therapy.

BACKGROUND & AIMS: Therapeutic antibodies against tumor necrosis factor α (anti-TNF) are effective in patients with Crohn's disease (CD). Mucosal healing is a surrogate marker of efficacy, but little is known about the effects of anti-TNF agents on structural damage in the intestine. Small-intestine contrast ultrasonography (SICUS) is a valuable tool for assessing CD lesions. A new sonographic quantitative index (the sonographic lesion index for CD [SLIC]) was developed to quantify changes in CD lesions detected by SICUS. We explored whether the SLIC can be used to monitor transmural bowel damage in CD patients during anti-TNF therapy. METHODS: We performed a prospective study of 29 patients with ileal or ileocolonic CD treated with anti-TNF agents; patients underwent SICUS before and after scheduled induction and maintenance therapy. To determine whether changes that can be detected by SICUS occur independently of anti-TNF therapy, 7 patients with ileal CD treated with mesalamine were enrolled as controls. A clinical response was defined as steroid-free remission, with CD activity index scores less than 150. RESULTS: We observed significant improvements in SLIC scores and subscores after induction and maintenance therapy with anti-TNFs, compared with before therapy. SLIC scores and subscores and index classes were improved significantly in patients with vs without clinical responses. Controls had no improvements in terms of CD activity index or SLIC scores, or index classes. CONCLUSIONS: Sonographic assessment using the quantitative index SLIC can be used to monitor changes in transmural bowel damage during anti-TNF therapy for CD.