Perioperative Glycemic Control During Colorectal Surgery.

Hyperglycemia occurs frequently among patients undergoing colorectal surgery and is associated with increased risk of poor clinical outcomes, especially related to surgical site infections. Treating hyperglycemia has become a target of many enhanced recovery after surgery programs developed for colorectal procedures. There are several unique considerations for patients undergoing colorectal surgery including bowel preparations and alterations in oral intake. Focused protocols for those with diabetes and those at risk of hyperglycemia are needed in order to address the specific needs of those undergoing colorectal procedures.

Fecal microbiota transplantation: current clinical efficacy and future prospects.

Fecal microbiota transplantation (FMT) has gained mainstream attention with its remarkable efficacy in treating recurrent Clostridium difficile infection (RCDI) when there are no other effective therapies. Methods of selecting donors and routes of administration vary among studies, but there are now randomized controlled trials showing efficacy of FMT in treating RCDI. Ongoing trials of FMT for other disease such as inflammatory bowel disease are underway; this therapy should not be used for these conditions unless there is strong evidence for efficacy. Long-term safety data are sorely needed, as well as clarification of regulatory concerns.

Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome.

BACKGROUND: Alterations in gastrointestinal (GI) permeability and immune measures are present in some patients with irritable bowel syndrome (IBS) but the relationship to symptoms is poorly defined. In adults with IBS, we compared permeability, unstimulated peripheral blood monocyte (PBMC) interleukin-10 (IL-10) levels, IBS life interference, and GI and psychological distress symptoms. METHODS: In 88 women and 18 men with IBS, GI permeability was quantitated as percent recovery of urinary sucrose and the lactulose/mannitol (L/M) ratio. IL-10 was measured in supernatants from 72-h incubated, unstimulated PBMCs. Participants completed a 4-week daily diary recording IBS life interference on daily activities and work, IBS symptoms, and psychological distress symptoms. They also completed the Brief Symptom Inventory. RESULTS: The L/M ratio but not percent sucrose recovery was significantly correlated with IBS interference with activities and work and retrospectively measured anxiety and depression. Unstimulated PBMC production of IL-10 correlated significantly with IBS interference with daily work, IBS symptom score, and abdominal pain. We identified a subgroup of IBS subjects with higher IL-10 and/or higher L/M ratio who had substantially higher IBS interference and IBS symptom scores. CONCLUSIONS: Our findings suggest a distinct subgroup of IBS patients with alterations in gut barrier function. This subgroup is characterized by increased GI permeability and/or increased PBMC production of IL-10. These physiologic alterations reflect more severe IBS as measured by interference of IBS with daily activities and daily IBS symptoms.

Alteration of the intestinal microbiome: fecal microbiota transplant and probiotics for Clostridium difficile and beyond.

Clostridium difficile infection is increasingly common with a high risk of recurrence despite antibiotic treatment. In cases of recurrent C. difficile infection, fecal microbiota transplant (FMT) is a highly effective treatment option promoting the restoration of normal gut microbiota. Furthermore, preliminary uncontrolled evidence demonstrates possible benefit of FMT in the management of some cases of inflammatory bowel disease and chronic constipation. In addition to presenting an overview of FMT, we discuss the role of probiotics, a more common approach to modifying the intestinal microbiome. Probiotics have been utilized broadly for many disease processes, including gastrointestinal, cardiovascular and allergic disease settings, although with limited and inconsistent results. Multiple potential areas for research are also identified.

Identification of putative immunologic targets for colon cancer prevention based on conserved gene upregulation from preinvasive to malignant lesions.

The length of time required for preinvasive adenoma to progress to carcinoma, the immunogenicity of colorectal cancer (CRC), and the identification of high-risk populations make development and testing of a prophylactic vaccine for the prevention of CRC possible. We hypothesized that genes upregulated in adenoma relative to normal tissue, which maintained increased expression in CRC, would encode proteins suitable as putative targets for immunoprevention. We evaluated existing adenoma and CRC microarray datasets and identified 160 genes that were ≥2-fold upregulated in both adenoma and CRC relative to normal colon tissue. We further identified 23 genes that showed protein overexpression in colon adenoma and CRC based on literature review. Silencing the most highly upregulated genes, CDH3, CLDN1, KRT23, and MMP7, in adenoma and CRC cell lines resulted in a significant decrease in viability (P < 0.0001) and proliferation (P < 0.0001) as compared to controls and an increase in cellular apoptosis (P < 0.05 for CDH3, KRT23). Results were duplicated across cell lines representing microsatellite instability, CpG island methylator, and chromosomal instability phenotypes, suggesting immunologic elimination of cells expressing these proteins could impact the progression of all CRC phenotypes. To determine whether these proteins were immunogens, we interrogated sera from early stage CRC patients and controls and found significantly elevated CDH3 (P = 0.006), KRT23 (P = 0.0007), and MMP7 (P < 0.0001) serum immunoglobulin G in cases as compared to controls. These data show a high throughput approach to the identification of biologically relevant putative immunologic targets for CRC and identified three candidates suitable for vaccine development.

Probiotics and prebiotics in clinical practice.

Probiotics are living organisms that have a beneficial therapeutic effect on the host when ingested. The bacteria Lactobacillus GG and the yeast Saccharomyces boulardii have been shown in controlled trials to prevent antibiotic-associated diarrhea. Prebiotics are non-living, indigestible polysaccharides metabolized in the intestine that induce physical and bacteriologic musocal modifications. Rather than introducing exogenous bacteria into the intestinal millieu, prebiotics stimulate certain indigenous bacteria already resident in the gut.