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Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma.

ABSTRACT: Background. Tumor necrosis as well as tumor-associated macrophages (TAMs) in the tumor invasive front (TIF) have been suggested to have a prognostic value in selected solid tumors, inclusive hilar cholangiocarcinoma. However, little is known regarding their influence on tumor progression and prognosis in intrahepatic cholangiocarcinoma (iCC). Methods. We analyzed surgically resected tumor specimens of human iCC (n = 88) for distribution and localization of TAMs, as defined by expression of CD68, formation of necrosis and extent of peritumoral fibrosis. Abundance of TAMs, tumor necrosis and grade of fibrosis were assessed immunohistochemically and histologically and correlated with clinicopathological characteristics, tumor recurrence and patients' survival. Statistical analysis was performed using SPSS software. Results. Patients with tumors characterized by low levels of TAMs in TIF or necrosis showed a significantly decreased 1-, 3- and 5-y recurrence-free survival and a significantly decreased overall survival, when compared with patients with tumors showing high levels of TAMs in TIF or no necrosis. Patients with high density of TAMs in TIF showed significantly lower incidence of tumor recurrence, as well (p < 0.05). Absence of tumor necrosis and TAMs in TIF were confirmed as independent prognostic variables in the multivariate survival analysis (all p < 0.05). Conclusions. High levels of TAMs in TIF or absence of histologic tumor necrosis are associated with a significantly improved recurrence-free and overall survival of patients with iCC. These results suggest TAMs and necrosis as valuable prognostic markers in routine histopathologic evaluation, and might indicate more individualized therapeutic strategies.

SUBMITTER: Atanasov G

PROVIDER: S-EPMC5593714 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma.

Atanasov Georgi G Dietel Corinna C Feldbrügge Linda L Benzing Christian C Krenzien Felix F Brandl Andreas A Mann Elli E Englisch Julianna Paulina JP Schierle Katrin K Robson Simon C SC Splith Katrin K Morgul Mehmet Haluk MH Reutzel-Selke Anja A Jonas Sven S Pascher Andreas A Bahra Marcus M Pratschke Johann J Schmelzle Moritz M

Oncoimmunology 20170628 8

<b>Background</b>. Tumor necrosis as well as tumor-associated macrophages (TAMs) in the tumor invasive front (TIF) have been suggested to have a prognostic value in selected solid tumors, inclusive hilar cholangiocarcinoma. However, little is known regarding their influence on tumor progression and prognosis in intrahepatic cholangiocarcinoma (iCC). <b>Methods</b>. We analyzed surgically resected tumor specimens of human iCC (n = 88) for distribution and localization of TAMs, as defined by expre ...[more]

PMID: 28919993

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Project description:Inflammation has a critical role in the development and progression of cancers. We developed a novel systemic inflammation score (SIS) based on lymphocyte, monocyte, and CA19-9 and explored its prognostic value in intrahepatic cholangiocarcinoma (ICC). From January 2005 to December 2011, 322 consecutive ICC patients who underwent curative resection in our center were included in this study, and validated in a retrospective study of 126 patients enrolled from 2012 to 2014. Clinicopathological variables including preoperative serum CA19-9 and LMR were analyzed. The cutoff values of CA19-9 and LMR were determined based on receiver operating characteristics curve analysis in the primary cohort. Kaplan-Meier curves and multivariate Cox-regression analyses were calculated for time to recurrence (TTR) and overall survival (OS). In univariate analysis of all patients, all three inflammatory and tumor marker including NLR ? 2.49 (P<0.001), LMR ? 4.45 (P=0.002), and CA19-9?89 (P<0.001) were associated with poor prognoses. When omitting SIS in multivariate analysis, preoperative LMR (P =0.006) and serum CA19-9 (P<0.001) were independent predictors of OS. In addition, elevated CA19-9 (P=0.001), multiple tumors (P<0.001), and lymph node metastasis (P<0.001) were significant predictors of worse recurrence free survival. Moreover, high SIS was significantly associated with aggressive tumor behaviours including large tumor size (P<0.001), multiple tumors (P=0.033), lymphonodus node metastasis (P=0.001), and high TNM stage (P<0.0001). Finally, univariate and multivariate analyses revealed the SIS was an independent predictor for TTR (HR=2.077, 95% CI, 1.365-3.162, P=0.001) and OS (HR=3.133 95% CI, 2.058-4.769, P<0.001). These results were further confirmed in the validation cohort. In conclusions, our findings demonstrate that the SIS as a potentially powerful prognostic biomarker in ICC that predicts poor clinical outcomes and is a promising tool for ICC treatment strategy decisions.

Project description:ImportanceAdrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined.ObjectivesTo define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction.Design, setting, and participantsNomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015.Main outcomes and measuresThe discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves.ResultsIn total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63-5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47-15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95-3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27-4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02-3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00-3.17; P = .05), positive nodal status (HR, 5.89; 95% CI, 2.05-16.87; P = .001), and R1 margin (HR, 2.83; 95% CI, 1.51-5.30; P = .001). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.74 for RFS and 0.70 for OS).Conclusions and relevanceIndependent predictors of survival and recurrence risk after curative-intent surgery for ACC were selected to create nomograms predicting RFS and OS. The nomograms were able to stratify patients into prognostic groups and performed well on internal validation.

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Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma.

Publications

Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma.

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