Endoscopic stenting for colorectal cancer obstruction as a bridge-to-surgery strategy.

BACKGROUND: Acute obstructive colorectal cancer requires prompt decompression commonly by emergency surgery (ES). However, self-expanding metal stents (SEMS) have been increasingly used as a bridge-to-surgery (BTS) strategy. MATERIALS AND METHODS: In an 8-year period, consecutive patients with acute left-sided colonic obstruction, due to locally advanced colorectal cancer, underwent ES or SEMS implantation. We evaluated technical/clinical success of SEMS, adverse events, and overall (OS) and disease-free survival (DFS) of the two therapeutic options. RESULTS: Forty-five patients underwent ES (n = 23) or SEMS (n = 22). The two groups were comparable for sex, age, ASA score and cancer site/stage. Technical and clinical successes of SEMS were 100% and 72.7%, respectively. Clinical success correlated with neutrophil-lymphocyte ratio (NLR) at baseline (OR = 0.65, 95% CI 0.43-0.98, P = .04). SEMS allowed primary anastomosis in the 45.5% of cases (0% in ES). SEMS implantation allowed a higher rate of surgery carried out by a laparoscopic approach: 36.4% vs 13.0% in ES. Performance of a definitive stoma and complications were similar. Median OS (34 in SEMS; 45 in ES, P = .33) and DFS (36 in SEMS; 35 in ES, P = .35) did not differ between the two groups. At univariate analysis, DFS was positively associated with primary anastomosis (HR = 2.44, 95% CI 1.4-16.6, P = .04) and laparoscopic surgery (HR = 8.33, 95% CI 1.08-50, P = .04), and inversely associated with a NLR > 3.6 (HR = 0.59, 95% CI 0.16-0.92, P = .03). At multivariate analysis, no feature retained an independent predictive power. CONCLUSION: SEMS is an effective and safe procedure, equivalent to emergency surgery in terms of complications, OS and DFS, providing the chance of a primary anastomosis in the majority of patients.

The sharp decline of beta estrogen receptors expression in long-lasting ulcerative-associated carcinoma.

OBJECTIVE: Colorectal carcinoma is an important cause of death in inflammatory bowel diseases, thus requiring surveillance for dysplasia in long-standing ulcerative colitis (UC). Females show a lower incidence probably related to hormonal factors; therefore, a role of estrogen receptors (ERs) has been supposed in carcinoma-associated colitis (CAC) development. Our aim was to identify ER beta/alpha expression in long-lasting pancolitis through each grade of dysplasia to carcinoma and, furthermore, to investigate the simultaneous epithelial apoptosis/proliferation. MATERIALS AND METHODS: Forty-eight patients affected by long-lasting pancolitis were retrospectively investigated. Samples were divided into four groups: UC, low-grade dysplasia/high-grade dysplasia (UC-HGD), and CAC. Normal colon samples were used as controls. ER-beta, ER-alpha, Ki-67, and TUNEL expression (labeling/H index) were evaluated by immunohistochemistry. RESULTS: ER-beta expression revealed an impressive reduction in CAC (10.4 ± 5.1; p < 0.001) compared to controls and UC (34.3 ± 3.1 and 26.8 ± 7.8, respectively), meanwhile ER-beta level in LGD (29.4 ± 3.7) was comparable to UC. As far ER-beta/ER-alpha mean value ratio revealed a progressive reduction. Ki67 demonstrated a progressive significant increase from UC until CAC (37.9 ± 6.4 < 45.7 ± 6.2 < 60.6 ± 5.2 < 71.1 ± 5.1; p < 0.001). Apoptotic index (TUNEL) revealed a strong fall in UC-HGD and CAC. CONCLUSIONS: ER-beta fall could be considered as a biomarker of UC-dysplasia progression. It occurs in HGD and overt neoplasia, while in LGD shows a normal expression. At the moment, we are unable to use this tool in the clinical practice to predict tumor progression, but it would be appropriate to encourage ER expression investigations in large samples for the interesting perspectives of application.

Safety and efficacy of switching from infliximab biosimilar CT-P13 to infliximab biosimilar SB2 in patients with inflammatory bowel disease.

INTRODUCTION: For patients with inflammatory bowel diseases, switching from infliximab originator to biosimilars is effective and safe. Few data on single switch have been published, and data on multiple switches of different infliximab are unavailable. METHODS: A retrospective analysis of patients who switched from CT-P13 to SB2, and of those with multiple switches among different infliximab compounds was conducted. Clinical activity, C reactive protein (CRP), adverse events (AE) and loss of response (LOR) were recorded. RESULTS: Thirty-six patients (26 males, 14 Crohn's disease and 22 ulcerative colitis) were enrolled and followed up for >6 months. All patients switched from CT-P13 to SB2; 12 of them (33.3%) had already switched from reference Infliximab to CT-P13, and for the remaining patients CT-P13 was the first infliximab. The clinical remission rate six months before and three months after SB2-switch was the same (58.3%) and the rate of mild activity varied from 27.8 to 33.3% (P = 0.68); the percentage of patients with normal CRP values passed from 94.4 to 91.7% (P = 1). Two patients (5.5%) had AE and 11 (30.5%) a LOR. At univariate analysis, patients with a single switch had a non-significant risk of LOR during SB2 [odds ratio (OR) = 7.86; 95% confidence interval (CI) 0.87-71, P = 0.06]. SB2-LOR was associated with previous AE under CT-P13 (OR = 9.1, 95% CI 0.82-100, P = 0.07). None of such factors was significant at multivariate analysis. CONCLUSION: Switching from CT-P13 to SB2 seems to be safe and effective either in patients with a single than in those with multiple switches.

A Case of Severe Transaminase Elevation Following a Single Ustekinumab Dose with Remission After Drug Withdrawal.

BACKGROUND: Ustekinumab is a fully human monoclonal antibody which binds Interleukin (IL)-12/23. It is indicated for the treatment of moderate-severe psoriasis and active psoriatic arthritis. Few data are available about the possibility of an interaction between ustekinumab and the liver. CASE DESCRIPTION: We reported a case of a 61-year old woman admitted to our Unit for severe transaminase elevation (aspartate transaminase 756 IU/l, alanine transaminase 1212 IU/l) occurred after a single Ustekinumab infusion for psoriasis. All other possible causes of liver damage, including drugs, hepatitis viruses, auto-antibodies and metabolic disorders were excluded. Liver biopsy showed lymphocytic infiltration, biliary duct damage and piecemeal necrosis. On the bases of the nonspecific histological picture and Rucam score, we accomplished the diagnosis of "liver injury of iatrogenic origin". After drug withdrawal, a spontaneous normalization of liver enzymes occurred within six months.

Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Disease: Prevalence and Risk Factors.

Background: Nonalcoholic fatty liver disease (NAFLD) is common in inflammatory bowel diseases (IBD). Herein, NAFLD prevalence and risk factors in a large IBD cohort were evaluated and compared to that of a non-IBD sample. Methods: Crohn's disease/ulcerative colitis outpatients referred to IBD service of our Gastroenterology Unit were enrolled. Subjects affected by functional and motor gastrointestinal disorders, in whom IBD was ruled out, referred to general outpatient service in the same area, were considered as nonIBD group. Exclusion criteria were based on previous diagnosis of nonNAFLD chronic liver diseases and secondary causes of fat liver overload. Characteristics of IBD and liver status were collected. Risk factors for metabolic syndrome were analyzed. Ultrasonographic presence and degree of steatosis were assessed. Data were examined by univariate and multivariate analyses. Results: For this study 465 IBD and 189 non-IBD subjects were consecutively enrolled. NAFLD was found in 28.0% and 20.1% in IBD and non-IBD subjects, respectively (P = 0.04). IBD patients with NAFLD were younger than non-IBD ones. There was no significant difference in steatosis grade and association between NAFLD and IBD behavior, extension, activity, and drugs. In the IBD group, multivariate analysis demonstrated that NAFLD was independently associated to metabolic syndrome (OR=2.24, 95%CI 1.77-28.81), diabetes (OR=1.71, 95%CI 1.43-12.25), fasting blood glucose (OR=1.36, 95%CI 1.13-1.68), and abdominal circumference (OR=1.68, 95%CI 1.15-14.52). Conclusions: NAFLD is more common and occurs at a younger age in IBD than in nonIBD subjects. However, further investigation is required to ascertain possible NAFLD pathogenic IBD-related factors other than conventional/metabolic ones. 10.1093/ibd/izy051_video1izy051.video15774874877001.

Does infliximab short infusion have a beneficial impact on the quality of life in patients with inflammatory bowel diseases? A single centre prospective evaluation.

BACKGROUND & AIMS: Infliximab (IFX) is an anti-tumor necrosis factor alpha agent used in inflammatory bowel diseases (IBD) therapy. Usually, it is administered over a 2-hour intravenous infusion. However, shortening the infusion duration to 1 hour has proved to be feasible and safe. In the present study we evaluated whether shortening the IFX infusion could affect the patients' quality of life (QoL) compared to the standard protocol. METHODS: Subjects affected by IBD receiving IFX were prospectively recruited. The main criterion to shorten the infusion was the absence of IFX-related adverse reactions during the previous three 2-h infusions. For each patient, demographic, clinical and anthropometric data were collected. A questionnaire investigating their overall/job/social/sexual QoL was administered. Ordinal regression was performed with odds ratios (OR) for significant independent variables. RESULTS: Eighty-one patients were included (46 with ulcerative colitis - UC, 35 with Crohn's disease - CD). Sixteen received the 2-h infusion due to previous adverse reactions, and the remaining 65 underwent the 1-h schedule. Shortening the infusion to 1 hour determined a better QoL (OR=0.626). However, the QoL was negatively influenced by age (OR=1.023), female sex (OR=2.04) and severe disease activity (OR=7.242). One-hour IFX infusion induced a better outcome on work (OR=0.588) and social (OR=0.643) QoL. Long-standing disease was correlated with a slightly better sexual QoL (OR=0.93). Conversely, older age (OR=1.046), severe clinical score (OR=15.579), use of other immunomodulators (OR=3.693) and perianal CD (OR=3.265) were related to an unsatisfactory sexual life. The total number of infusions (OR=0.891), proctitis (OR=0.062) or pancolitis (OR=0.1) minimized the perception of infusion-related side effects. CONCLUSION: The 1-h short infusion improves overall, social and job QoL, so that, when indicated, it should be recommended.

Intestinal microbiota: The explosive mixture at the origin of inflammatory bowel disease?

Inflammatory bowel diseases (IBDs), namely Crohn's disease and ulcerative colitis, are lifelong chronic disorders arising from interactions among genetic, immunological and environmental factors. Although the origin of IBDs is closely linked to immune response alterations, which governs most medical decision-making, recent findings suggest that gut microbiota may be involved in IBD pathogenesis. Epidemiologic evidence and several studies have shown that a dysregulation of gut microbiota (i.e., dysbiosis) may trigger the onset of intestinal disorders such as IBDs. Animal and human investigations focusing on the microbiota-IBD relationship have suggested an altered balance of the intestinal microbial population in the active phase of IBD. Rigorous microbiota typing could, therefore, soon become part of a complete phenotypic analysis of IBD patients. Moreover, individual susceptibility and environmental triggers such as nutrition, medications, age or smoking could modify bacterial strains in the bowel habitat. Pharmacological manipulation of bowel microbiota is somewhat controversial. The employment of antibiotics, probiotics, prebiotics and synbiotics has been widely addressed in the literature worldwide, with the aim of obtaining positive results in a number of IBD patient settings, and determining the appropriate timing and modality of this intervention. Recently, novel treatments for IBDs, such as fecal microbiota transplantation, when accepted by patients, have shown promising results. Controlled studies are being designed. In the near future, new therapeutic strategies can be expected, with non-pathogenic or modified food organisms that can be genetically modified to exert anti-inflammatory properties.