Résection laparoscopique de 152 cancers colorectaux (résultats à court terme, analyse des facteurs de risque de conversion et de la courbe d'apprentissage)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Preoperative inflammation is an independent factor of worse prognosis after colorectal cancer surgery

International audienceBackground: We know that inflammation is related to colorectal cancer prognosis and to the onset of postoperative infections.Objective: This study aimed to understand the relationship between preoperative inflammation and the prognosis of colorectal cancer and to elucidate whether the impact of inflammation on cancer prognosis was related to an increased risk of surgical infection or was independent of it.Methods: Patients who underwent elective colorectal cancer surgery between November 2011 and April 2014 were included in a prospective database (IMACORS). Preoperative c reactive protein was collected for each patient. Patients were followed up according to the French national guidelines. A cut-off of preoperative CRP of 5mg/L was chosen. Clinical characteristics were compared according to CRP using Chi2 and Mann-Whitney tests. The Overall Survival (OS) and Disease-Free-Survival (DFS) were compared by Kaplan-Meier curves. A Cox proportional hazards regression model was applied to perform a multivariate analysis of OS and DFS's predictors.Results: A total of 254 patients were included. The median age was 68 years old. The median follow up was 41.8 months. The overall median preoperative CRP was 5mg/L. Preoperative CRP was significantly associated with N status; CRP being significantly higher among patients with colonic cancer and with patients who didn't receive a neoadjuvant treatment. Multivariate analyse revealed that preoperative CRP is an independent prognostic factor of OS and DFS respectively (HR=2.34 (1.26-4.31), P=0.006 and HR=1.83 (1.15-2.90), P=0.01).Conclusion: Preoperative inflammation measured by CRP is independently related with overall and disease-free survival of colorectal cancer

Inflammatory markers as early predictors of infection after colorectal surgery: the same cut-off values in laparoscopy and laparotomy?

IF 2.426International audiencePURPOSE:C-reactive protein and procalcitonin are reliable early predictors of infection after colorectal surgery. However, the inflammatory response is lower after laparoscopy as compared to open surgery. This study analyzed whether a different cutoff value of inflammatory markers should be chosen according to the surgical approach.METHODS:A prospective, observational study included consecutive patients undergoing elective colorectal surgery in three academic centers. All infections until postoperative day (POD) 30 were recorded. The inflammatory markers were analyzed daily until POD 4. Areas under the ROC curve and diagnostic values were calculated in order to assess their accuracy as a predictor of intra-abdominal infection.RESULTS:Five-hundred-one patients were included. The incidence of intra-abdominal infection was 11.8%. The median levels of C-reactive protein (CRP) and procalcitonin (PCT) were lower in the laparoscopy group at each postoperative day (p < 0.0001). In patients without intra-abdominal infection, they were also lower in the laparoscopy group (p = 0.0036) but were not different in patients presenting with intra-abdominal infections (p = 0.3243). In the laparoscopy group, CRP at POD 4 was the most accurate predictor of overall and intra-abdominal infection (AUC = 0.775). With a cutoff of 100 mg/L, it yielded 95.7% negative predictive value, 75% sensitivity, and 70.3% specificity for the detection of intra-abdominal infection.CONCLUSION:The impact of infection on inflammatory markers is more important than that of the surgical approach. Defining a specific cutoff value for early discharge according to the surgical approach is not justified. A patient with CRP values lower than 100 mg/L on POD 4 can be safely discharged

Diagnostic Accuracy of Inflammatory Markers As Early Predictors of Infection After Elective Colorectal Surgery

IF 8.569International audienceBackground:Intra-abdominal infections are frequent and life-threatening complications after colorectal surgery. An early detection could diminish their clinical impact and permit safe early discharge.Objective:This study aimed to find the most accurate marker for the detection of postoperative intra-abdominal infection and the appropriate moment to measure it.Methods:A prospective, observational study was conducted in 3 centers. Consecutive patients undergoing elective colorectal surgery with anastomosis were included. C-reactive protein and procalcitonin were measured daily until the fourth postoperative day. Postoperative infections were recorded according to the definitions of the Centres for Diseases Control. The areas under the receiver operating characteristic curve were analyzed and compared to assess the diagnostic accuracy of each marker.Results: :Five-hundred and one patients were analyzed. The incidence of intra-abdominal infection was 11.8%, with 24.6% of patients presenting at least one infectious complication. Overall mortality was 1.2%. At the fourth postoperative day, C-reactive protein was more discriminating than procalcitonin for the detection of intra-abdominal infection (areas under the ROC curve: 0.775 vs 0.689, respectively, P = 0.03). Procalcitonin levels showed wide dispersion. For the detection of all infectious complications, C-reactive protein was also significantly more accurate than procalcitonin on the fourth postoperative day (areas under the ROC curve: 0.783 vs 0.671, P = 0.0002).Conclusions:C-reactive protein is more accurate than procalcitonin for the detection of infectious complications and should be systematically measured at the fourth postoperative day. It is a useful tool to ensure a safe early discharge after elective colorectal surgery

Preoperative inflammation increases the risk of infection after elective colorectal surgery: results from a prospective cohort.

International audienceBackgroundSeptic complications after colorectal surgery are frequent and sometimes life-threatening. It is well-known that inflammation impairs the healing process. It has been suggested that preoperative ongoing inflammation could increase the risk of postoperative infections. This study aimed to elucidate the role of preoperative inflammation on postoperative infectious complications and to understand if, through biological markers, it is possible to identify preoperatively patients at higher risk of infection. MethodsA prospective, observational study was conducted in three centers from November 2011 to April 2014. Consecutive patients undergoing elective colorectal surgery with anastomosis were included. Any ongoing infection was an exclusion criterion. C-reactive protein, albumin, prealbumin and procalcitonin plasma levels were measured preoperatively. Postoperative infections were recorded according to the definitions of the Centers for Diseases Control. The areas under the receiver operating characteristic curve were analyzed and compared to assess the accuracy of each preoperative marker. ResultsFour-hundred and seventy two patients were analyzed. Infectious complications occurred in 118 patients (25%) and mortality in 6 patients (1.3%). In the univariate analysis, preoperative C-reactive protein and albuminemia were found significantly associated with postoperative infectious complications (P = 0.008 and P = 0.0002, respectively). Areas under the ROC curve for preoperative C-reactive protein and albuminemia were 0.57and 0.62, respectively. ConclusionsThis study confirms the association between preoperative inflammatory activity, hypoalbuminemia and the onset of infections after surgery. Trials aiming to decrease the inflammatory activity before surgery in order to prevent postoperative complications are warranted

Development of a Highly Selective Allosteric Antagonist Radioligand for the Type 1 Cholecystokinin Receptor and Elucidation of Its Molecular Basis of Binding

Understanding the molecular basis of ligand binding to receptors provides insights useful for rational drug design. This work describes development of a new antagonist radioligand of the type 1 cholecystokinin receptor (CCK1R), (2-fluorophenyl)-2,3-dihydro-3-[(3-isoquinolinylcarbonyl)amino]-6-methoxy-2-oxo-l-H-indole-3-propanoate (T-0632), and exploration of the molecular basis of its binding. This radioligand bound specifically with high affinity within an allosteric pocket of CCK1R. T-0632 fully inhibited binding and action of CCK at this receptor, while exhibiting no saturable binding to the closely related type 2 cholecystokinin receptor (CCK2R). Chimeric CCK1R/CCK2R constructs were used to explore the molecular basis of T-0632 binding. Exchanging exonic regions revealed the functional importance of CCK1R exon 3, extending from the bottom of transmembrane segment (TM) 3 to the top of TM5, including portions of the intramembranous pocket as well as the second extracellular loop region (ECL2). However, CCK1R mutants in which each residue facing the pocket was changed to that present in CCK2R had no negative impact on T-0632 binding. Extending the chimeric approach to ECL2 established the importance of its C-terminal region, and site-directed mutagenesis of each nonconserved residue in this region revealed the importance of Ser(208) at the top of TM5. A molecular model of T-0632-occupied CCK1R was consistent with these experimental determinants, also identifying Met(121) in TM3 and Arg(336) in TM6 as important. Although these residues are conserved in CCK2R, mutating them had a distinct impact on the two closely related receptors, suggesting differential orientation. This establishes the molecular basis of binding of a highly selective nonpeptidyl allosteric antagonist of CCK1R, illustrating differences in docking that extend beyond determinants attributable to distinct residues lining the intramembranous pocket in the two receptor subtypes