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

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

Tumor infiltration by Tbet+ effector T cells and CD20+ B cells is associated with survival in gastric cancer patients

International audienceTumor-infiltrating T and B lymphocytes could have the potential to affect cancer prognosis. The objective of this study was to investigate the prognostic significance of tumor infiltration by CD8 and CD4 T cells, and B lymphocytes in patients with localized gastric cancer. In a retrospective cohort of 82 patients with localized gastric cancer and treated by surgery we quantitatively assessed by immunohistochemistry on surgical specimen, immune infiltrates of IL-17(+), CD8(+), Foxp3(+), Tbet(+) T cells and CD20(+) B cells both in the tumor core and at the invasive margin via immunohistochemical analyses of surgical specimens. We observed that CD8(+) and IL17(+) T-cell densities were not significantly associated with gastric cancer prognosis. In contrast, high infiltration of Tbet(+) T cells, high numbers of CD20(+) B-cell follicles, and low infiltration of Foxp3(+) T cells, were associated with better relapse-free survival. Interestingly, treatment with neoadjuvant chemotherapy or histological tumor type (diffuse versus intestinal) did not influence type and density of immune infiltrates or their prognostic value. Immunohistochemical analysis of the gastric cancer stromal microenvironment revealed organized T and B cell aggregates, with strong structural analogies to normal secondary lymphoid organs and which could be considered as tertiary lymphoid structures. Using transcriptomic data from an independent cohort of 365 localized gastric cancer, we confirmed that a coordinated Th1, and B cell stromal gene signature is associated with better outcome. Altogether, these data suggest that tumor infiltration by B and Th1 T cells could affect gastric cancer prognosis and may be used to better define the outcome of patients with localized gastric cancer

L’organisation de cellules T effectrices Th1 (Tbet+) et de cellules B (CD20+) en structures lymphoïdes tertiaires constitue un facteur pronostique dans le cancer de l’estomac localisé

International audienceObjectifsL’étude de l’infiltrat tumoral par les cellules du système immunitaire constitue un facteur pronostique favorable dans plusieurs variétés de pathologies cancéreuses. L’objectif de notre étude est de décrire l’organisation intra- et péri-tumorale de différentes populations lymphocytaires, et d’explorer leur éventuel rôle pronostique chez des patients atteints d’un cancer de l’estomac localisé.MéthodesNous avons étudié de manière rétrospective par méthode immunohistochimique l’infiltrat immunitaire de différentes sous-populations lymphocytaires T (Th17 : IL-17+, T CD8+, T régulateurs : Foxp3+ et Th1 : Tbet+) et lymphocytaires B (CD20+) en périphérie tumorale, et au sein même de la tumeur sur les pièces opératoires gastriques d’une cohorte de 82 patients atteints d’un cancer de l’estomac localisé et réséqué.RésultatsLa teneur de l’infiltrat en lymphocytes T cytotoxiques et en lymphocytes Th17 ne semble pas avoir de valeur pronostique dans notre étude. Les caractéristiques de l’infiltrat immunitaire ne sont ni influencées par l’administration d’une chimiothérapie néoadjuvante, ni par le grade histopathologique de la tumeur. En revanche, nous avons pu déceler que la présence d’infiltrats riches en cellules lymphocytaires Th1 (Tbet+) et en follicules lymphocytaires B (CD20+), associés à une faible proportion de lymphocytes T régulateurs était associée à une meilleure survie sans récidive des patients. De plus, nous mettons en évidence que ces infiltrats lymphocytes Th1/B s’organisent histologiquement en structure s’apparentant à des structures lymphoïdes tertiaires, où des lymphocytes B proliférant sont entourés de lymphocytes T eux-mêmes en contact avec des cellules présentatrices d’antigènes matures (cellules dendritiques DC-lamp+).L’analyse transcriptomique d’une série indépendante de 365 cancers de l’estomac localisés confirme le pronostic favorable conféré par une signature stromale de coopération immune lymphocytaire B et Th1.ConclusionNos résultats démontrent l’importance pronostique d’une signature immunohistochimique et génomique Th1/réponse B dans le cancer de l’estomac