Most of the current research in gastrointestinal oncology is focused on biology of cancer itself, but there is growing interest in the patient's immune system response and its relation with cancer cells.

To review the impact of the antitumoural immune response on epidemiology, prognosis and treatment of colorectal cancer.

Search of the literature published in English using the PubMed database.

The role of the immune system in the antitumoural immunosurveillance is clearly supported by the increased incidence of colorectal cancer and adenomatous polyps in immunosuppressed patients. Moreover, the degree of infiltration of the tumours by the immune cells has been shown to be a strong prognostic factor of both disease recurrence and survival. The immune system plays an important role in the chemotherapy-induced cell death. New therapeutic strategies targeting the antitumoural immunity are being currently investigated with promising results.

Better knowledge of antitumoural immune system can have a major impact on patients' management in daily clinical practice. Colorectal cancer screening is an important issue in immunosuppressed patients, and recommendations should be refined for selected high-risk patients. The use of an immune score to guide the therapeutic strategies in the adjuvant setting should be supported. Further and larger clinical trials are necessary to accelerate the development of innovative immune therapies.

Inflammatory bowel disease (IBD) affects a substantial number of female patients in their reproductive years. Therefore, many physicians face the dilemma whether thiopurines, prescribed to maintain remission, can be taken safely during pregnancy. Data on long-term development outcome of children exposed to maternal thiopurine therapy are very limited.

To assess the long-term effects of in utero exposure to thiopurines during pregnancy on infant health status.

A prospective multicentre follow-up study was performed in children exposed intrauterine to maternal thiopurine therapy. Physical, cognitive and social aspects of infant health status were assessed with the 43-item TNO-AZL Preschool Children Quality of Life Questionnaire (TAPQOL). Furthermore, information on visits to general practitioner and medical specialists, and physician's advice regarding lactation was evaluated. Data were compared with normative data from a control group consisting of 340 children.

Thirty children were included in this study [median 3.8 years (IQR 2.9–4.7)]. No differences on global medical and psychosocial health status were found between children exposed to intrauterine thiopurines and the reference group. Exposure to intrauterine thiopurines was not associated with increased susceptibility to infection or immunodeficiency in childhood. Twenty-one of 30 children were exclusively formula-fed based on a negative advice of medical specialists directed at thiopurine use during lactation.

Thiopurine use during pregnancy did not affect long-term development or immune function of children up to 6 years of age. Our results underscore the present notion that mothers, even those using thiopurines, should be encouraged to breastfeed their infants.

Symptoms compatible with irritable bowel syndrome (IBS) are frequently present in patients with inflammatory bowel disease (IBD); however, the cause of this phenomenon is unclear.

To determine the different contributions of ‘true IBS’ and sub-clinical inflammation in producing IBS-type symptoms in IBD patients, and to ascertain the impact these symptoms have on the clinical assessment of IBD activity.

In this cross-sectional study, 169 IBD patients completed questionnaires to assess disease activity, presence of IBS-type symptoms, and levels of anxiety and depression. Stool samples were collected for analysis of faecal calprotectin (FC).

IBS-type symptoms were significantly more common in female patients (OR = 4.64, 1.55–13.88) and were associated with higher levels of anxiety (OR = 1.11, 1.01–1.21). There was no statistical difference between the FC levels of patients in clinical remission with IBS-type symptoms compared with those without (median values = 111 μg/g vs. 45.5 μg/g respectively, P = 0.171). The prevalence of IBS-type symptoms in patients with a normal FC level was 31%.

A substantial number of IBD patients with normal faecal calprotectin level experience IBS-type symptoms. These patients exhibit similar features to people diagnosed with IBS in the general community, suggesting that the conditions are not mutually exclusive and may coexist in a considerable number of IBD patients. A systematic diagnostic approach is required to assess IBD patients with IBS-type symptoms as sub-clinical inflammation may play a role in a proportion of cases.

Barium meal enteroclysis (BM) is the recommended imaging technique for small bowel inaccessible by ileo-colonoscopy when diagnosing paediatric-onset inflammatory bowel disease, but it has poor sensitivity and involves ionising radiation. MRI enterography (MRE) is an alternative methodology.

To critically appraise the published evidence on MRE in the assessment of Paediatric inflammatory bowel disease by systematic review.

Review of all English language data reporting MRE for the investigation of patients <18 years with known or suspected IBD. Primary searches of Medline (Jan 1950–April 2012), Cinahl (1966–April 2012) and Pubmed (Jan 1950–April 2012) were performed using keyword and MeSH terms; IBD; Magnetic resonance imaging; small bowel imaging; EMBASE was then searched. Two authors independently assessed the quality of studies using the quality assessment of diagnostic accuracy studies tool.

Searches yielded 930 035 hits, combination word searches limited to 1983 titles. Fifty-two studies were fully reviewed, 41 were excluded due to lack of paediatric data. Eleven studies of 496 children were included. All studies used endoscopy as the reference test. 10/496 patients required jejunal intubation for bowel preparation. Meta-analysis of six comparable studies gave a pooled sensitivity and specificity for MRE detection of active terminal ileal Crohn's disease of 84% and 97% respectively. Studies displayed heterogeneity in bowel preparation, scanning technique, reporting methodology and timing of ileo-colonoscopy in relation to MRE. In three studies comparing BM, MRE had greater sensitivity and specificity.

MRE is a sensitive and specific tool for diagnosis in paediatric inflammatory bowel disease. Technical considerations require refinement and standardisation; however, MRE has no radiation. Current data suggest that MRE should supersede BM as the SB imaging technique in centres with appropriate expertise.

Most drugs have not been well studied in cirrhosis; recommendations on safe use are based largely on experience and/or expert opinion, with dosing recommendations often based on pharmacokinetic (PK) changes.

To provide a practical approach to prescribing medications for cirrhotic patients.

An indexed MEDLINE search was conducted using keywords cirrhosis, drug-induced liver injury, pharmacodynamics (PDs), PKs, drug disposition and adverse drug reactions. Unpublished information from the Food and Drug Administration and industry was also reviewed.

Most medications have not been adequately studied in cirrhosis, and specific prescribing information is often lacking. Lower doses are generally recommended based on PK changes, but data are limited in terms of correlating PD effects with the degree of liver impairment. Very few drugs have been documented to have their hepatotoxicity potential enhanced by cirrhosis; most of these involve antituberculosis or antiretroviral agents used for HIV or viral hepatitis. Paracetamol can be used safely when prescribed in relatively small doses (2–3 g or less/day) for short durations, and is recommended as first-line treatment of pain. In contrast, NSAIDs should be used cautiously (or not at all) in advanced cirrhosis. Proton pump inhibitors have been linked to an increased risk of spontaneous bacterial peritonitis (SBP) in cirrhosis and should be used with care.

Most drugs can be used safely in cirrhosis, including those that are potentially hepatotoxic, but lower doses or reduced dosing frequency is often recommended, due to altered PKs. Drugs that can precipitate renal failure, gastrointestinal bleeding, SBP and encephalopathy should be identified and avoided.

Recent advances in eosinophilic oesophagitis (EoE) have confirmed the existence of a new disease phenotype, proton pump inhibitor (PPI)-responsive oesophageal eosinophilia (PPI-REE).

To summarise evidence supporting the use of PPI therapy in patients with suspected EoE (oesophageal dysfunction plus >15 eos/HPF in oesophageal biopsies).

A literature search was conducted through MEDLINE, using the MeSH search terms ‘eosinophilic oesophagitis’, ‘proton pump inhibitors’ and ‘oesophageal eosinophilia’. Relevant articles and their reference lists were identified through manual review.

Ten articles, including 258 patients with suspected EoE (152 children, 106 adults) undergoing clinico-histological re-evaluation after PPI therapy, were identified. In children, clinical response ranged from 78% to 86% and histological remission from 23% to 40%. In adults, symptom response ranged from 25% to 80% and histological remission from 33% to 61%. Among PPI-REE patients with oesophageal pH-monitoring, 35 showed pathological and 10 normal studies. PPI-REE was significantly commoner with documented gastro-oesophageal reflux disease (GERD) when compared to patients with negative pH monitoring (70% vs. 29%, P < 0.001). Symptom improvement/resolution occurred in 50–85% of patients without histological remission on PPI therapy. Six PPI-REE patients demonstrated clinico-histological relapse on PPI therapy.

At least one third of patients with suspected EoE achieve clinico-histological remission on PPI therapy. Response is more limited in children compared with that in adults. pH monitoring does not accurately predict response to PPI therapy, albeit histological remission is significantly higher, up to 70%, upon documented GERD. Symptom improvement is common with PPI therapy despite persistent eosinophilic infiltration.

Success in H. pylori eradication with conventional therapies has decreased to unacceptable levels (≤80%). New schemes of combined treatment are currently needed.

To test a miscellaneous therapy for H. pylori eradication.

Open-label, pilot, single-centre and prospective study. Patients received a 15-day treatment scheme that consisted of 5 initial days of lansoprazole 30 mg b.d., amoxicillin 1 g b.d., and metronidazole 500 mg t.d.s.; days 6 to 10: lansoprazole 30 mg q.d.s. and metronidazole 500 mg t.d.s.; days 11 to 15: lansoprazole 30 mg b.d., clarithromycin 500 mg b.d. and metronidazole 500 mg t.d.s. Each patient underwent an upper endoscopy before treatment and a second follow-up endoscopy at least 4 weeks after therapy. Success was defined on the basis of an eradication rate following a per-protocol analysis ≥95%. Biopsies before and after therapy were obtained for histological evaluation and rapid urease test.

One hundred and twenty-two patients were enrolled and 118 patients completed the study. The eradication rate for H. pylori with miscellaneous therapy was 94% (confidence Interval (CI) 95%, 90–98.3%) in the per-protocol analysis (PP) and 91% (95% CI, 86–96%) in the intention-to-treat (ITT) analysis. Adherence to treatment was 96% (113 patients). Among patients who completed treatment, 55% presented adverse events, mainly nausea and abdominal pain.

A miscellaneous therapy, based on the combination of multiple medications in high doses for 2 weeks, and with gastric pH elevation, is a highly effective treatment as a first-line therapy for the eradication of H. pylori.

Infliximab (IFX) is a chimeric murine/human anti-TNF antibody (Ab) used for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Loss of response is common and associated with development of anti-IFX Abs during ongoing therapy. However, human anti-murine immunoglobulin Abs are common and may cross-react with the murine part of IFX.

To investigate if Abs binding to IFX's Fab region (IFX-Fab) are present in IBD patients before exposure to IFX, and whether they predict efficacy and safety of IFX therapy.

Observational, retrospective cohort study of patients with CD (n = 29) and UC (n = 22).

Pre-treatment levels of IFX-Fab reactive IgG Abs were significantly lower in CD patients in remission after 1 year of maintenance IFX (median 91 mU/L, n = 8) than in the rest of the patients (639 mU/L, n = 21; P < 0.01), and lower than in patients with secondary loss of response in particular (692 mU/L, n = 7; P < 0.01). A cut-off concentration of <439 mU IFX-Fab reactive IgG Ab per litre comprised all patients who later obtained long-term sustained remission on IFX (sensitivity 100%, specificity 67%). Similar trends were observed in UC. The pre-treatment levels of IFX-Fab reactive IgG Abs were markedly higher in patients developing infusion reactions to IFX (1037 mU/L, n = 7) than in the remaining patients (349 mU/L, n = 44; P = 0.036).

IFX-Fab reactive IgG antibodies present in serum from IBD patients before infliximab therapy associate with lack of long-term efficacy and safety. Assessments of such antibodies may help clinicians to choose between treatment with infliximab and more humanised agents.

Gut-directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown.

To determine the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients.

Forty-four women with moderate-to-severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high- (45 mmHg) and low-intensity (15 mmHg) rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). Thirty-one patients completed treatments and posttreatment fMRI.

Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high-intensity distension in the dorsal and ventral anterior insula (cluster size 142, P = 0.006, and cluster size 101, P = 0.005 respectively). Moreover HYP responders demonstrated a pre–post treatment BOLD attenuation in posterior insula (cluster sizes 59, P = 0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, P = 0.05). Pre–post differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalising effect on the central processing abnormality of visceral signals in IBS.

The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalised by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. Clinical trial number: NCT01815164.

Gastro-oesophageal reflux disease (GERD) and gastric acid hypersecretion respond well to suppression of gastric acid secretion. However, clinical management and research in diseases of acid secretion have been hindered by the lack of a non-invasive, accurate and reproducible tool to measure gastric acid output (GAO). Thus, symptoms or, in refractory cases, invasive testing may guide acid suppression therapy.

To present and validate a novel, non-invasive method of GAO analysis in healthy subjects using a wireless pH sensor, SmartPill (SP) (SmartPill Corporation, Buffalo, NY, USA).

Twenty healthy subjects underwent conventional GAO studies with a nasogastric tube. Variables impacting liquid meal-stimulated GAO analysis were assessed by modelling and in vitro verification. Buffering capacity of Ensure Plus was empirically determined. SP GAO was calculated using the rate of acidification of the Ensure Plus meal. Gastric emptying scintigraphy and GAO studies with radiolabelled Ensure Plus and SP assessed emptying time, acidification rate and mixing. Twelve subjects had a second SP GAO study to assess reproducibility.

Meal-stimulated SP GAO analysis was dependent on acid secretion rate and meal-buffering capacity, but not on gastric emptying time. On repeated studies, SP GAO strongly correlated with conventional basal acid output (BAO) (r = 0.51, P = 0.02), maximal acid output (MAO) (r = 0.72, P = 0.0004) and peak acid output (PAO) (r = 0.60, P = 0.006). The SP sampled the stomach well during meal acidification.

SP GAO analysis is a non-invasive, accurate and reproducible method for the quantitative measurement of GAO in healthy subjects. SP GAO analysis could facilitate research and clinical management of GERD and other disorders of gastric acid secretion.

Relapse after treatment for idiopathic achalasia is common and long-term outcome data are limited.

To determine the cumulative relapse rate and long-term outcome after pneumatic dilatation (PD) for achalasia in a tertiary referral centre.

A retrospective study of 301 patients with achalasia treated with PD as first-line therapy. Short-term outcome was measured at 12 months. Long-term outcome was assessed in those who were in remission at 12 months by cumulative relapse rate and cross-sectional analysis of long-term remission rate regardless of any interval therapy, using a validated achalasia-specific questionnaire.

Eighty-two percent of patients were in remission 12 months following initial PD. Relapse rates thereafter were 18% by 2 years; 41% by 5 years and 60% by 10 years. Whilst 43% patients underwent additional treatments [PD (29%), myotomy (11%) or botulinum toxin (3%)] beyond 12 months, 32% of those who had not received interval therapy had relapsed at cross-sectional analysis. After a mean follow-up of 9.3 years, regardless of nature, timing or frequency of any interval therapy, 71% (79/111) patients were in remission. The perforation rate from PD was 2%. Chest pain had a poor predictive value (24%) for perforation.

Long-term relapse is common following pneumatic dilatation. While on-demand pneumatic dilatation for relapse yields a good response, one-third of relapsers neither seek medical attention nor receive interval therapy. Close follow-up with timely repeat dilatation is necessary for a good long-term outcome. Given the poor predictive value of chest pain for perforation, routine gastrografin swallow is recommended postdilatation.