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The effect of preoperative Intestinal microbiota dysbiosis on postoperative recovery of gastrointestinal cancer patients

ABSTRACT: Interventions: Case series:Nil Primary outcome(s): Diarrhea Study Design: Cohort study

DISEASE(S): Gastrointestinal Cancer

PROVIDER: 2679924 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:BackgroundAccumulating evidence suggests a critical role of intestinal dysbacteriosis in surgical site infections and anastomotic leakage after abdominal surgery. However, a direct correlation between pre-existing dysbacteriosis and postoperative infectious complications has not yet been established clinically.MethodsA total of 353 consecutive patients who underwent colorectal cancer (CRC) surgery were enrolled. Gram-stained faecal smears were tested at admission and the first defecation after surgery. Intestinal dysbacteriosis was graded into three groups: normal or slightly decreased intestinal microflora (grade 1), moderate dysbacteriosis (grade 2), and severe dysbacteriosis (grade 3). Clinical outcomes were postoperative infections and anastomotic leakage within 30 days after surgery.ResultsAt the preoperative assessment, 268 (75.9%) patients had normal or slightly decreased intestinal microflora, 58 (16.4%) patients had moderate dysbacteriosis, and 27 (7.6%) patients had severe dysbacteriosis. The patients with preoperative dysbacteriosis had a higher rate of early postoperative diarrhoea (grade 2: OR = 4.53, 95% CI 2.28-9.00, grade 3: OR = 4.52, 95% CI 1.81-11.31), total complications (grade 3 40.7% vs. grade 2 25.9% vs. grade 1 12.7%, P < 0.001), and anastomotic leakage (grade 3 11.1% vs. grade 2 5.2% vs. grade 1 1.5%, P = 0.002). An interaction effect among preoperative dysbacteriosis and early postoperative diarrhoea on total complications was observed in rectal cancer patients (P for interaction = 0.007).ConclusionsAn imbalance of the intestinal microbiome exists in a considerable proportion of CRC patients before surgery. Preoperative dysbacteriosis is associated with higher rates of early postoperative diarrhoea, which further correlates with infectious complications and anastomotic leakage. However, the contribution of preoperative dysbacteriosis to the occurrence of anastomotic leakage needs to be clarified in further studies. Trial registration ChiCTR, ChiCTR1800018755. Registered 8 October 2018-Retrospectively registered, http://www.chictr.org.cn/ChiCTR1800018755 .

Project description:Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with development of postoperative delirium in older surgical patients. We employed a nested case–control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort and the associations between preoperative protein levels and postoperative delirium were assessed using t-test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium (t-test p<0.05). Due to the limited sample size these proteins did not remain significant by multiple hypothesis testing using the Benjamini-Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40/48 case-control samples correctly, principal components analysis separated 43/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80-0.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identifies 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.

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The effect of preoperative Intestinal microbiota dysbiosis on postoperative recovery of gastrointestinal cancer patients

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