Aurelien Amiot

Potential of fecal microbiota for early-stage detection of colorectal cancer

Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC‐associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor‐free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early‐ and late‐stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC‐associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor‐related host–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.

Presentation and Long-Term Follow-up of Refractory Celiac Disease: Comparison of Type I With Type II

BACKGROUND & AIMS Refractory celiac disease (RCD) was recently subdivided into 2 subtypes (RCD I and II) based on a normal or abnormal phenotype of intraepithelial lymphocytes (IELs), respectively. It is not clear, however, if these 2 entities differ in their presentation at diagnosis or long-term outcome. We compared the clinical and biological characteristics of RCD I and RCD II at diagnosis, the risk of developing an overt lymphoma, and the predictive factors of survival. METHODS Medical files of 14 patients with RCD I and 43 with RCD II were analyzed retrospectively. Predictive factors of overt lymphoma and survival were studied in univariate and multivariate analyses. RESULTS At diagnosis, malnutrition, ulcerative jejunitis, and lymphocytic gastritis were more common in patients with RCD II than RCD I (P< .05). Overt lymphomas occurred in 2 patients with RCD I and 16 with RCD II. In the univariate analysis, abnormal IEL phenotype and increased age at diagnosis of RCD were predictive factors for overt lymphoma. Abnormal IEL phenotype (P< .01), clonality (P= .01), and overt lymphoma (P= .001) predicted short survival time. Only abnormal IEL phenotype (P= .03) and overt lymphoma (P= .04) were predictive in the multivariate analysis. The 5-year survival rate was 93% in patients with RCD I and 44% with RCD II. CONCLUSIONS RCD II has a much more severe presentation and prognosis than patients with RCD I; <44% of patients with RCD II survive 5 years after diagnosis. Abnormal IEL phenotype is a predictive factor but not a necessary condition for the development of overt lymphoma.

Current, new and future biological agents on the horizon for the treatment of inflammatory bowel diseases.

Biological agents for inflammatory bowel diseases (IBD) targeting tumor necrosis factor (TNF) have changed the way to treat IBD refractory to standard medications and allowed us to reach new therapeutic goals such as mucosal healing and deep remission. A better understanding of the components of the pathological processes that are a hallmark of IBD has led to the development of a new family of biological agents in Crohn’s disease and ulcerative colitis. Biosimilars, which are copy versions of currently licensed biological agents, will be soon available. The biosimilar of infliximab is as effective and as safe as its originator in rheumatologic conditions, while a new anti-TNF agent, namely golimumab, has been recently approved for refractory ulcerative colitis. Beyond TNF blockers, anti-adhesion molecules appear to be a potent drug class for IBD. Vedolizumab was recently approved for both Crohn’s disease and ulcerative colitis. Numerous other compounds are in the pipeline. Ustekinumab looks very promising for Crohn’s disease. Smad7 antisense oligonucleotide might enrich our armamentarium if preliminary data are confirmed in upcoming clinical trials. Herein, we review the efficacy and safety of new and emerging biological agents that are currently investigated in IBD clinical trials.

Long-Term Outcome of Chronic Intestinal Pseudo-Obstruction Adult Patients Requiring Home Parenteral Nutrition

OBJECTIVES:Chronic intestinal pseudo-obstruction (CIPO) is a rare, disabling disorder responsible for motility-related intestinal failure. Because it induces malnutrition, CIPO is a significant indication for home parenteral nutrition (HPN). The objective of the study was to evaluate long-term outcome of CIPO patients requiring HPN during adulthood.METHODS:In total, 51 adult CIPO patients (18 men/33 women, median age at symptom occurrence 20 (0–74) years, 34/17 primary/secondary CIPO) followed up at our institution for HPN management between 1980 and 2006 were retrospectively studied for survival and HPN dependence rates using univariate and multivariate analysis.RESULTS:Follow-up after diagnosis was 8.3 (0–29) years. Surgery was required in 84% of patients. The number of interventions was 3±3 per patient (mean ± s.d.), leading to short bowel syndrome in 19 (37%) patients. Actuarial survival probability was 94, 78, 75, and 68% at 1, 5, 10, and 15 years, respectively. Multivariate analysis showed that lower mortality was associated with the ability to restore oral feeding at baseline (hazard ratio (HR)=0.2 (0.06–0.65), P=0.008) and symptom occurrence before the age of 20 years (HR=0.18 (0.04–0.88), P=0.03). Higher mortality was associated with systemic sclerosis (HR=10.4 (1.6–67.9), P=0.01). Actuarial HPN dependence was 94, 75, and 72% at 1, 2, and 5 years, respectively.CONCLUSIONS:In this large cohort of CIPO adult patients with severe intestinal failure, i.e., those requiring HPN, we found a higher survival probability than previously reported. These results should be taken into account when considering intestinal transplantation.

Microbial dysbiosis and colon carcinogenesis: could colon cancer be considered a bacteria-related disease?:

Colorectal cancer (CRC) is posing an increasingly important burden on the health care system, with western countries seeing a growing incidence of the disease. Except for germline DNA mutations which have been attributed to less than 5% of patients, little is known about the main causes of CRC. However, environment factors such as food, lifestyle and medication are now suspected to have a major influence on inducing cancers. Today, exhaustive quantitative and qualitative evaluation of all environmental factors is not possible. Various environment-induced diseases have been characterized based on colon microflora, also called microbiota, analyses. Growing data have shown specific changes in microflora (i.e. dysbiosis) in the stools of patients with colon cancer or those adherent to the colonic mucosa. Thus, it appears that microbiota may be considered a platform offering host and environment interactions for studying CRCs. The hypothesis that colon cancer might be a bacteria-related disease is suggested and perspectives are discussed.

Effects of a Multimodal Management Strategy for Acute Mesenteric Ischemia on Survival and Intestinal Failure

BACKGROUND & AIMS Acute mesenteric ischemia (AMI) is an emergency with a high mortality rate; survivors have high rates of intestinal failure. We performed a prospective study to assess a multidisciplinary and multimodal management approach, focused on intestinal viability. METHODS In an Intestinal Stroke Center, we developed a multimodal management strategy involving gastroenterologists, vascular and abdominal surgeons, radiologists, and intensive care specialists; it was tested in a pilot study on 18 consecutive patients with occlusive AMI, admitted to a tertiary center from July 2009 to November 2011. Patients with left ischemic colitis, nonocclusive AMI, chronic mesenteric ischemia, and other emergencies were excluded. Patients received specific medical management: revascularization of viable small bowel and/or resection of nonviable small bowel; 12 patients received arterial revascularization. We evaluated the percentages of patients who survived for 30 days or 2 years, the number with permanent intestinal failure, and morbidity. Lengths and rates of intestinal resection were compared with or without revascularization, and in patients with early or late-stage disease. RESULTS Patients were followed up for a mean of 497 days (range, 7-2085 d); 95% survived for 30 days, 89% survived for 2 years, and 28% had morbidities within 30 days. Intestinal resection was necessary for 7 cases (39%), with mean lengths of intestinal resection of 30 cm and 207 cm, with or without revascularization, respectively (P = .03). Among patients with early or late-stage AMI, rates of resection were 18% and 71%, respectively (P = .049). Patients with early stage disease had shorter lengths of intestinal resection than those with late-stage disease (7 vs 94 cm; P = .02), and spent less time in intensive care (2.5 vs 49.8; P = .02). CONCLUSIONS A multidisciplinary and multimodal management approach might increase survival of patients with AMI and prevent intestinal failure.

Chronic intestinal pseudo-obstruction.

Chronic intestinal pseudo-obstruction (CIPO) is a disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. Pseudo-obstruction is an uncommon condition and can result from primary (40%) or secondary (60%) causes. The most common symptoms are nausea, vomiting, abdominal distension, abdominal pain and constipation or diarrhea. These symptoms are usually present many years before CIPO diagnosis. They can lead to severe electrolyte disorders and malnutrition. Principles for management of patients with CIPO are: to establish a correct clinical diagnosis in excluding mechanical obstruction; to perform a symptomatic and physiologic assessment of the gastrointestinal tract involved; to look for extra-intestinal manifestations, especially for myopathy and neuropathy; to discuss in some cases a surgery for full-thickness intestinal biopsies, and/or a neuromuscular biopsy in case of mitochondrial cytopathy suspicion. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. Treatment of CIPO includes prokinetic agents which may help to reduce gastrointestinal symptoms Courses of antibiotics may be needed in patients with symptoms suggestive of bacterial overgrowth. When necessary, enteral nutrition is preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Intestinal transplantation can be discussed in selected patients.

Increased intestinal absorption by segmental reversal of the small bowel in adult patients with short-bowel syndrome: a case-control study

BACKGROUND Segmental reversal of the small bowel (SRSB) is proposed in patients with short-bowel syndrome (SBS) as a rehabilitative therapy, but its effects on absorption have not been studied. OBJECTIVE We aimed to determine intestinal macronutrient absorption and home parenteral nutrition (HPN) dependence in SBS patients with intestinal failure. DESIGN We included in a retrospective study all consecutive patients who had an SRSB between 1985 and 2010 and underwent a study of macronutrient absorption. Patients were matched to SBS controls with the same digestive characteristics. Energy and macronutrient absorption were measured. The dependence on HPN was expressed by the number of infusions per week and by the calories infused daily divided by the basal energy expenditure multiplied by 1.5. RESULTS Seventeen patients who had an SRSB were matched to 17 control patients. Intestinal absorption was higher in the SRSB group for total calories (69.5% compared with 58.0%), fat (48.4% compared with 33.2%), and protein (62.7% compared with 53.4%) (P < 0.05). Median oral autonomy was 100% ± 38.4% in the SRSB group, whereas it was 79% ± 39.6% in the control group (P < 0.05). The number of calories infused was lower in the SRSB group (500 ± 283 compared with 684 ± 541; P < 0.05), as was HPN dependence (33% ± 20% compared with 48% ± 38%; P < 0.05) at the time of the study. CONCLUSION SRSB allows a gain in macronutrient absorption, which is associated with a lower HPN dependence. To our view, SRSB should be integrated in intestinal rehabilitative adult programs.

Factors associated with pregnancy outcome in anti-TNF treated women with inflammatory bowel disease

The safety of anti‐tumour necrosis factor (TNF) agents during pregnancy is a major concern for child‐bearing women and physicians.

Faecal microbiota transplantation in recurrent Clostridium difficile infection: Recommendations from the French Group of Faecal microbiota Transplantation

Faecal microbiota transplantation is effective for treating recurrent forms of Clostridium difficile infection and its use in this indication is recommended in the most recent European and North American guidelines. In this context, faecal microbiota transplantation is beginning to be performed in France in clinical practice, while the rules governing this procedure have been defined in France only for clinical trials. To unify, secure, and evaluate practice in this field in France, the French Group of Faecal microbiota Transplantation (FGFT) was created in October 2014 with the support of the French National Society of Gastroenterology, the French Infectious Disease Society, and the National Academy of Pharmacy. We present here the deliberations of this group regarding the use of faecal microbiota transplantation for recurrent Clostridium difficile infection. The issues addressed are the indications, therapeutic sequence, delivery procedures, donor selection, methods and conditions of specimen preparation, and traceability.