Relatives of Crohn's disease patients and breast cancer: An overlooked condition

AbstractRecent data suggest that patients suffering from Crohn’s disease (CD) may be at higher risk of developing extra-intestinal malignancies. This is attributed to inflammation and immunodepression due to medications. However, a genetic predisposition cannot ruled out. In the present study we investigated the prevalence of breast cancer in first-degree female relatives of CD patients compared with relatives of patients without evidence of gastrointestinal diseases. A total of 1302 female first-degree relatives of CD patients and 1294 relatives of controls were included. We found that CD was an independent risk factor for breast cancer development (OR = 2.76, 95% CI = 1.2–6.2; p = 0.017), and this is particularly evident in mothers (3.6% vs 1%, p = 0.009 − OR = 3.7, 95% CI 1.4–10). Among CD group, smoking habit of CD patients was associated with increased risk of cancer compared with relatives of non-smokers (7.7% vs 2.9%, p = 0.01 – OR = 2.8 95% CI 1.2–6.6). Intriguingly, stage at diagnosis was significantly higher in CD relatives (p = 0.04). Our findings suggest that first-degree female relatives of CD patients are at higher risk of developing breast cancer but receive diagnosis at more advanced stages, therefore advocating the need of more active screening protocol in this population

Pathophysiology of non-celiac gluten sensitivity: where are we now?

non-celiac gluten sensitivity (ncGs) is the term used to describe individuals complaining of intestinal and extra-intes- tinal symptoms related to gluten ingestion and rapidly improving after its withdrawal, and in which both celiac disease (cD) and wheat allergy (Wa) were properly ruled out. the prevalence of this condition remains unknown and a lot of questions about the possible pathogenetic mechanisms are still unclarified. It is believed that NCGS represents a het- erogeneous condition with different subgroups potentially characterized by different pathogenesis, clinical history, and clinical course. Moreover, a possible overlap with irritable bowel syndrome (iBs) and other functional diseases could complicate patient selection for clinical studies, slowing down the understanding of this disorder. last but not least, the lack of validated biomarkers remains a significant limitation in research studies on NCGS. Hence, there is a need for strict diagnostic criteria for ncGs

Exploring the concept of deep remission in Crohn’s disease: correlation between transmural healing and biomarkers

Background: While mucosal healing (MH) and transmural healing (TH) predict relevant clinical outcomes in Crohn’s disease (CD), little is known about the real significance and clinical impact of deep remission (DR). Objectives: To better explore the concept of DR, toward a direct correlation between MH, TH, and biomarkers. Design: Real-world observational longitudinal study to evaluate the rate of clinical remission (CR), MH and TH, and the fecal calprotectin (FC)/C-reactive protein (CRP) levels in all consecutive CD patients on biologics. Methods: A receiver operating characteristic (ROC) curve was constructed to define the best FC and CRP cut-offs associated with MH and TH. Finally, patients achieving CR, MH, and TH, in association with the target FC/CRP values, were considered in DR. Results: Among 118 CD patients, CR, MH, and TH were achieved in 62.7, 44.1, and 32.2%, respectively. After 2 years, the mean FC levels decreased from 494 ± 15.4 μg/g to 260 ± 354.9 μg/g ( p  < 0.01). Using the ROC curve analysis, an FC cut-off value of 94 μg/g was associated with both MH [sensitivity: 94.2%, specificity: 84.8%, positive predictive value (PPV): 83.05%, negative predictive value (NPV): 94.92%, area under the curve (AUC): 0.95] and TH (sensitivity: 92.1%, specificity: 70%, PPV: 64.4%, NPV: 94.9%, AUC: 0.88). CRP < 5 mg/L was associated with both MH (sensitivity: 96.1%, specificity: 62.1%, PPV: 66.7%, NPV: 95.35%, AUC: 0.85) and TH (sensitivity: 97.4%, specificity: 52.5%, PPV: 52%, NPV: 95.35%, AUC: 0.78). When considering CD patients with concomitant CR, MH, and TH associated with an FC < 94 μg/g and CRP < 5 mg/L, this association was found identified in 33 patients (27.9%). Conclusion: An FC < 94 μg/g and a normal CRP are associated with CR, MH, and TH and could be included in the definition of DR in association. So by definition, DR could be achieved in approximately 30% of CD patients during maintenance treatment with biologics

Fatigue in inflammatory bowel diseases: Relationship with age and disease activity

A higher rate of patients suffering from inflammatory bowel diseases (IBD) are reported to experience the symptom of fatigue compared with general population. Fatigue can impair quality of life of IBD patients by limiting their daily functioning. However, this problem is poorly understood and addressed. Our aim was to investigate the impact of fatigue in IBD patients compared with controls, and to seek for relation between age and disease activity. IBD patients aged between 16 and 75 years observed at our Unit from June 2011 through June 2012 were evaluated for fatigue. Patients were asked to fill the fatigue impact scale (FIS) questionnaire. A cohort of age- and sex-matched patients observed for other-than-IBD diseases were prospectively enrolled to act as controls. Patients diagnosed with malignancies were excluded from evaluation. Each group included 16 patients, of whom half aged over 65 years. Fatigue was more severe in IBD patients than in controls (p = 0.02), irrespective of age and disease activity. IBD patients with moderate to severe disease activity showed worse fatigue compared with controls at any age (p < 0.0001). Young IBD patients with low disease activity showed a trend toward worse FIS score when compared with old IBD counterparts (p = 0.06). IBD significantly impacted on fatigue in our series. Considering IBD patients in remission, younger patients may experience worse fatigue. Further studies are needed to explore the effects of fatigue on quality of life and the potential of appropriate intervention strategies

The burden of anaemia in patients with inflammatory bowel diseases

tBackground: Anaemia (AN) is frequently associated with inflammatory bowel diseases (IBD) and cannegatively influence the quality of life of patients.Aim: To evaluate the prevalence and causes of AN in IBD.Methods: We prospectively performed a one-year multicentre observational study including all IBD casesattending six Units. We also investigated patients’ main serological parameters.Results: The study population included 965 IBD patients (582 CD; 383 UC), of whom 142 were in-patientsand 823 out-patients. AN was diagnosed in 134 out of 965 IBD patients (14%). No significant difference inAN prevalence was observed between CD and UC. The prevalence of AN was higher in the hospitalized IBD(26% in- vs. 11.7% out-patients; p &lt; 0.01; OR 2.2) and in active disease (CD: 34% active vs. 16% inactive;p &lt; 0.01; OR 2.1 – UC: 26% active vs. 19% inactive; p = 0.03; OR 1.3). Iron deficiency was present in 72patients (53.7%), AN of chronic diseases in 12 (8.2%), mixed type AN in 11 (8.2%), thalassemia in 9 (6.7%),and macrocytic AN in 8 (5.9%).Conclusions: In Southern Italy, AN is common in IBD and is more frequent in active disease and hospitalizedpatients. Iron deficiency still remains the major cause of AN in IBD

Incident Colorectal Cancer in Inflammatory Bowel Disease

Colorectal cancer (CRC) risk is increased in Inflammatory Bowel Disease (IBD) and surveillance needs to be tailored according to individual risk. The open issues include the role of the characteristics of IBD and CRC in determining the long-term outcome. These issues were assessed in our multicenter study, including a cohort of 56 IBD patients with incident CRC. The clinical and histopathological features of IBD patients and of CRC were recorded. Incident CRC in IBD occurred at a young age (&le;40 years) in 25% of patients (median age 55.5 (22&ndash;76)). Mucinous signet-ring carcinoma was detected in 6 out of the 56 (10.7%) patients, including 4 with Ulcerative Colitis (UC) and 2 with Crohn&rsquo;s disease (CD). CRC was more frequently diagnosed by colonoscopy in UC (85.4% vs. 50%; p = 0.01) and by imaging in Crohn&rsquo;s Disease CD (5.8% vs. 31.8%; p = 0.02). At onset, CRC-related symptoms occurred in 29 (51.9%) IBD patients. The time interval from the diagnosis of IBD to CRC was shorter in UC and CD patients with &gt;40 years (p = 0.002; p = 0.01). CRC-related death occurred in 10 (29.4%) UC and in 6 (27.2%) CD patients (p = 0.89), with a short time interval from CRC to death (UC vs. CD: 6.5 (1&ndash;68) vs. 14.5 (8&ndash;40); p = 0.85; IBD: 12 months (1&ndash;68)). CRC occurring at a young age, a short time interval from the diagnosis of IBD to CRC-related death in the elderly, CRC-symptoms often mimicking IBD relapse and the observed high mortality rate may support the need of closer surveillance intervals in subgroups of patients

Real-Life Effectiveness and Safety of Golimumab and Its Predictors of Response in Patients with Ulcerative Colitis

Background Golimumab is a new anti-TNF-alpha monoclonal antibody for patients with ulcerative colitis. Aims To assess the short- and long-term effectiveness and safety of golimumab in daily clinical practice and to identify predictors of response. Methods Consecutive patients treated with golimumab in 22 Italian centers were enrolled. Clinical, laboratory, and endoscopic data were prospectively collected before and during treatment. A subgroup of patients completed a questionnaire to assess personal satisfaction with a golimumab autoinjector system. Results A total of 196 patients were included. After 3 months, 130 patients were responders (66.3%) and showed significant reductions in mean partial, total, and endoscopic Mayo scores and in mean ESR, C-reactive protein, and fecal calprotectin levels (p &lt; 0.001). Multivariate analysis revealed that a higher total Mayo score (p &lt; 0.001, OR 1.5, 95% CI 1.2-1.8) and naive status to anti-TNF-alpha (p = 0.015, OR 3.0, 95% CI 1.2-7.5) were predictive of a favorable response. Seventy-seven (39.3%) of the 130 responders maintained a response at month 12 of therapy. There were 17 adverse events, 28 patients needed hospitalization, and 15 patients underwent surgery. Self-administration of the drug was appreciated by most patients. Conclusions The efficacy and safety of golimumab in daily clinical practice were confirmed for the short- and long-term treatment of patients with active ulcerative colitis. Patients naive to the anti-TNF-alpha monoclonal antibody and those with a higher total Mayo score were more likely to respond to golimumab