Calcium supplementation for the prevention of colorectal adenomas: a systematic review and meta-analysis of randomized controlled trials

AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.METHODS: We conducted a systematic review and meta-analysis of published studies. We searched Pub Med, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the Clinical Trials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes(recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's riskof-bias. Between-study heterogeneity was assessed, and pooled risk ratio(RR) estimates with their 95% confidence intervals(95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat(NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE.RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas(fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; randomeffects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20(95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance(fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.

Narrow-band imaging endoscopy to assess mucosal angiogenesis in inflammatory bowel disease: A pilot study

AIM: To investigate whether narrow band imaging (NBI) is a useful tool for the in vivo detection of angiogenesis in inflammatory bowel disease (IBD) patients. METHODS: Conventional and NBI colonoscopy was performed in 14 patients with colonic inflammation (8 ulcerative colitis and 6 Crohn’s disease). Biopsy samples were taken and CD31 expression was assayed immuno- histochemically; microvascular density was assessed by vessel count. RESULTS: In areas that were endoscopically normal but positive on NBI, there was a significant (P < 0.05) increase in angiogenesis (12 ± 1 vessels/field vs 18 ± 2 vessels/field) compared with areas negative on NBI. In addition, in areas that were inflamed on white light endoscopy and positive on NBI, there was a significant (P < 0.01) increase in vessel density (24 ± 7 vessels/f ield) compared with NBI-negative areas.CONCLUSION: NBI may allow in vivo imaging of intestinal angiogenesis in IBD patients.

Prognostic value of innate and adaptive immunity in colorectal cancer

Colorectal cancer(CRC) remains one of the major public health problems throughout the world.Originally depicted as a multi-step dynamical disease,CRC develops slowly over several years and progresses through cytologically distinct benign and malignant states,from single crypt lesions through adenoma,to malignant carcinoma with the potential for invasion and metastasis.Moving from histological observations since a long time,it has been recognized that inflammation and immunity actively participate in the pathogenesis,surveillance and progression of CRC.The advent of immunohistochemical techniques and of animal models has improved our understanding of the immune dynamical system in CRC.It is well known that immune cells have variable behavior controlled by complex interactions in the tumor microenvironment.Advances in immunology and molecular biology have shown that CRC is immunogenic and that host immune responses influence survival.Several lines of evidence support the concept that tumor stromal cells,are not merely a scaffold,but rather they influence growth,survival,and invasiveness of cancer cells,dynamically contributing to the tumor microenvironment,together with immune cells.Different types of immune cells infiltrate CRC,comprising cells of both the innate and adaptive immune system.A relevant issue is to unravel the discrepancy between the inhibitory effects on cancer growth exerted by the local immune response and the promoting effects on cancer proliferation,invasion,and dissemination induced by some types of inflammatory cells.Here,we sought to discuss the role played by innate and adaptive immune system in the local progression and metastasis of CRC,and the prognostic information that we can currently understand and exploit.

Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis

AIM:To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy.METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk).Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn(R), Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life(IBDQ), and laboratory tests.RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI＜4, EI＜4). Quality of life (IBDQ) increased significantly (24 points, P＜0.01)at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia.CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

Balanced propofol sedation administered by nonanesthesiologists:The first Italian experience

AIM:To assess the efficacy and safety of a balanced approach using midazolam in combination with propofol,administered by nonanesthesiologists,in a large series of diagnostic colonoscopies.METHODS:Consecutive patients undergoing diagnostic colonoscopy were sedated with a single dose of midazolam(0.05 mg/kg)and lowdose propofol(starter bolus of 0.5 mg/kg and repeated boluses of 10 to 20 mg).Induction time and deepest level of sedation,adverse and serious adverse events,as well as recovery times,were prospectively assessed.Cecal intubation and adenoma detection rates were also collected.RESULTS:Overall,1593 eligible patients were included.The median dose of propofol administered was 70 mg(range:40120 mg),and the median dose of midazolam was 2.3 mg(range:24 mg).Median induction time of sedation was 3 min(range:14 min),and median recovery time was 23 min(range:1040 min).A moderate level of sedation was achieved in 1561(98%) patients,whilst a deep sedation occurred in 32(2%) cases.Transient oxygen desaturation requiring further oxygen supplementation occurred in 8(0.46%;95% CI:0.2%0.8%)patients.No serious adverse event was observed.Cecal intubation and adenoma detection rates were 93.5%and 23.4%(27.8%for male and 18.5%for female,subjects),respectively.CONCLUSION:A balanced sedation protocol provided a minimalization of the dose of propofol needed to target a moderate sedation for colonoscopy,resulting in a high safety profile for nonanesthesiologist propofol sedation.