The host inflammatory responses, tumor stroma percentage, and survival in colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 549-549
Author(s):  
James Hugh Park ◽  
Colin H. Richards ◽  
Donald C. Mcmillan ◽  
Paul G. Horgan ◽  
Campbell S. D. Roxburgh
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Response ◽  
Inflammatory Cell ◽  
Inflammatory Responses ◽  
Tumor Stroma ◽  
Inflammatory Cell Infiltrate ◽  
Cell Infiltrate ◽  
Local Inflammatory Response ◽  
Invasive Margin ◽  
N Stage

549 Background: The role of host inflammatory responses in determining colorectal cancer (CRC) outcome is increasingly recognised. In particular, a marked local inflammatory response is associated with improved survival. However, determinants of this response are not clear. A plausible factor in the density, location and type of the inflammatory cell infiltrate is the extent of tumor stroma. The aim of the present study was to examine the relationship between tumor stroma percentage (TSP), tumor inflammatory infiltrate and survival in patients undergoing elective CRC resection. Methods: 335 patients who had undergone elective resection for stage I-III CRC at a single institution between 1997-2008 were included. TSP at the invasive margin (IM) was assessed on H and E sections and grouped as low (≤50%) or high (>50%). Local inflammatory response was assessed at the IM using Klintrup-Mäkinen (K-M) score and at the IM, tumor stroma and cancer cell nests (CCNs) using the following T-cell markers: CD3, CD8, CD45R0, FOXP3. Systemic inflammatory response was assessed using modified Glasgow Prognostic Score (mGPS). Results: Eighty-three patients (25%) had high TSP. High TSP was associated with increased T stage, N stage (both p < 0.01), margin and serosal involvement (both p < 0.05), an infiltrative invasive margin (p < 0.001) and tumor necrosis (p = 0.001). TSP was associated with decreased infiltration by CD3+ and CD8+ cells at the CCNs (p < 0.01 and p < 0.05 respectively) but not at the IM or stroma. K-M score showed a trend towards an inverse association with TSP (p = 0.067). CD45R0+ and FOXP3+cell infiltration and mGPS were not associated with TSP. On multivariate analysis, TSP was associated with poorer cancer-specific survival (HR 1.93, 95% CI 1.15-3.23, p = 0.012), independent of N stage, VI (both p < 0.05), low CD8 at the IM and CCNs (both p < 0.01) and mGPS (p = 0.001). Conclusions: TSP was associated with the presence of high risk pathological characteristics and down-regulation of host intra-tumoral immune responses and was independently associated with poorer cancer survival. The extent of tumor stroma is an important factor in the nature of the tumor inflammatory cell infiltrate and outcome in patients undergoing elective surgery for CRC.

The relationship between tumour necrosis, circulating IL-6 concentrations, and inflammatory responses in patients undergoing curative resection for colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 404-404
Author(s):  
Graeme JK Guthrie ◽  
Campbell SD Roxburgh ◽  
Colin H Richards ◽  
Paul G. Horgan ◽  
Donald C. Mcmillan
Keyword(s):  
Colorectal Cancer ◽  
Skeletal Muscle ◽  
Inflammatory Response ◽  
Interleukin 6 ◽  
Tumour Necrosis ◽  
Curative Resection ◽  
Inflammatory Cell ◽  
Inflammatory Responses ◽  
Inflammatory Cell Infiltrate ◽  
Cell Infiltrate

404 Background: Cancer-associated inflammation, in the form of systemic and local inflammation, and tumour necrosis are known to have prognostic value in colorectal cancer (CRC). In addition, recent work has reported a direct relationship between the systemic inflammatory response and loss of skeletal muscle in patients with CRC. However, the inter-relationships between these inflammatory responses, tumour necrosis, metabolic upset and circulating biochemical mediators are unclear in CRC. Interleukin-6 and its downstream signalling cascades have been implicated in both cancer-associated inflammation and cancer-associated muscle wasting. The aim of the present study was to examine whether circulating IL-6 concentrations may link tumour necrosis, local and systemic inflammatory responses, and metabolic upset in patients undergoing curative resection for colorectal cancer. Methods: The study included 118 patients undergoing surgery for CRC between 2004 and 2009. Data were collected from pre-operative blood tests. Routine pathology specimens were scored for Klintrup criteria and tumour necrosis. Results: Tumour necrosis was associated with increased T-stage (p<0.01), reduced inflammatory cell infiltrate (p<0.05), increased IL-6 (p<0.001), IL-10 (p<0.01), and VEGF (p<0.001) and with markers of the systemic inflammatory response: mGPS (p<0.001), anaemia (p<0.05); increased white cell (p<0.001), neutrophil (p<0.05) and platelet (p<0.001) counts. Circulating IL-6 was associated with increased IL-10 (p<0.01), VEGF (p<0.001), increased mGPS (p<0.001), increased white cell (p<0.01) and platelet (p<0.01) counts and low skeletal muscle index (p<0.01). On Spearman rank correlation there were significant associations between circulating concentrations of IL-6 and IL-10 (rs= 0.39, p<0.001) and CRP (r= 0.42, p<0.001). Conclusions: Interleukin-6 appears to be associated with systemic inflammation, tumour necrosis, and sarcopenia in colorectal cancer. However, the lack of an association between IL-6 and the local inflammatory response suggests a more complex relationship with the tumour inflammatory cell infiltrate.

Assessment of the tumor inflammatory cell infiltrate in preoperative colonoscopic biopsies of patients with primary operable colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 637-637
Author(s):  
James Hugh Park ◽  
David Mansouri ◽  
Clare Orange ◽  
Paul G. Horgan ◽  
Donald C. Mcmillan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Cell ◽  
Tumor Resection ◽  
Inflammatory Cell Infiltrate ◽  
Cell Infiltrate ◽  
Elective Resection ◽  
Reliable Assessment ◽  
Resected Tumor ◽  
Tumor Biopsies ◽  
Independent Cohort

637 Background: The tumor inflammatory cell infiltrate is an important and potentially modifiable determinant of outcome in colorectal cancer (CRC). Although a weak inflammatory infiltrate is associated with poor prognosis independent of TNM stage, identifying such patients prior to surgery is problematic. The aim of the present study was to compare the tumor inflammatory cell infiltrate in matched preoperative colonoscopic tumor biopsies and resected tumor specimens from patients undergoing primary elective resection of CRC. Methods: Using an automated scoring system (nuclear h-score) CD3+ T-lymphocyte density was quantified in preoperative tumor biopsies of 76 patients undergoing elective resection of stage I-III CRC and compared to pathological characteristics and manual semi-quantitative (high vs. low) scoring of CD3+density within the invasive margin (IM) intraepithelial (IE) and cancer stroma (CS) compartments of resected tumor specimens. Results: The median h-score was 41 (range 14-85). Patients with a high tumor resection IM, IE and CS CD3+ density had a higher biopsy CD3+ density than patients with a low IM, IE and CS CD3+ density (median h-score: IM – 47 vs. 37, p=0.011; IE – 50 vs. 38, p=0.014, CS – 46 vs. 37, p=0.014). Patients with mismatch repair deficient tumors showed a trend towards a higher biopsy CD3+ density (57 vs. 40, p=0.169). No other pathological factors were associated with biopsy CD3+ density. When biopsy CD3+ density was categorised as high (h-score ≥41) or low (h-score<41), high biopsy CD3+ density was associated with CD3+ density within the IM, IE (both p≤0.05) and CS (p<0.01) and showed a trend towards greater 5-year survival (high – 80% (SE 7), low – 67% (SE 8), p=0.122). Conclusions: The results of the present study suggest that assessment of the inflammatory cell infiltrate in preoperative colonoscopic biopsies may provide reliable assessment of the inflammatory cell infiltrate within resected CRC tumors. Although requiring validation in an independent cohort, this has significant implications for the provision of neoadjuvant therapy, particularly targeting the inflammatory cell infiltrate, in patients with primary operable CRC.

The relationship between tumor and host factors and survival in patients undergoing adjuvant chemotherapy for colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 525-525
Author(s):  
James Hugh Park ◽  
Colin H. Richards ◽  
Donald C. Mcmillan ◽  
Paul G. Horgan ◽  
Campbell S. D. Roxburgh
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Tumor Microenvironment ◽  
Inflammatory Responses ◽  
Prognostic Score ◽  
Glasgow Prognostic Score ◽  
Cancer Specific Survival ◽  
Local Inflammatory Response ◽  
Invasive Margin ◽  
The Relationship

525 Background: The tumor microenvironment and host inflammatory responses are important determinants of outcome in colorectal cancer (CRC), however their impact on survival in patients receiving adjuvant chemotherapy remains unclear. The aim of the present study was to examine the relationship between these factors, clinicopathological characteristics and survival in patients receiving adjuvant chemotherapy for CRC. Methods: 365 patients who had undergone CRC resection at a single institution between 1997-2008 were included; 88 patients subsequently received chemotherapy. Tumor stroma percentage (TSP) and necrosis were assessed on H and E sections and graded as low or high. Local inflammatory response was assessed using the Klintrup-Mäkinen (K-M), Galon and revised Immunoscore (CD45RO+ /CD8+, and CD3+/CD8+at the invasive margin and tumor center, respectively). Systemic inflammation was assessed using modified Glasgow Prognostic Score (mGPS). Results: Patients receiving adjuvant chemotherapy were younger with a lower ASA (both P<0.05), had advanced T- and N-stage (P<0.05 and P<0.001, respectively), poor tumor differentiation (P<0.05), venous invasion (VI) (P<0.01), margin involvement, infiltrative invasive margin (both P<0.05) and high TSP (P<0.01). In those patients who received adjuvant chemotherapy, on multivariate analysis of clinicopathological factors, VI (HR 3.00, 95%CI 1.22-7.37, P=0.017), TSP (HR 3.00, 95%CI 1.26-7.12, P=0.013), K-M score (HR 5.24, 95%CI 1.21-22.68, P=0.027) and mGPS (HR 3.10 95%CI 1.47-6.55, P=0.003) were independently associated with cancer-specific survival. When the interrelationships between factors independently associated with cancer survival were examined, VI, mGPS, K-M score and TSP were independent of each other (all P>0.05). Conclusions: Compared to standard CRC pathological staging, the present results suggest that assessment of both tumor microenvironment and host inflammatory responses may have superior prognostic value compared with TNM in patients receiving adjuvant chemotherapy.

The relationship between the non-canonical NF-κB pathway, tumour microenvironment, systemic inflammation and survival in patients undergoing surgery for colorectal caner.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 631-631
Author(s):  
Meera Patel ◽  
Lindsay Bennett ◽  
Jean A Quinn ◽  
Hester Catharina van Wyk ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Responses ◽  
Venous Invasion ◽  
Tumour Microenvironment ◽  
Braf V600e ◽  
High Expression ◽  
Inflammatory Cell Infiltrate ◽  
Cancer Specific Survival ◽  
Local Inflammatory Response ◽  
The Relationship

631 Background: In patients with colorectal cancer (CRC) the local and systemic inflammatory responses (LIR and SIR) are important determinants of disease progression. The present study examines the association of transcription factor RelB, a key member of the non-canonical NF-κB pathway and its association with LIR and SIR in patients undergoing resection of CRC. Methods: Patients with stage I-III CRC who underwent curative resection in a single institution and were in a previously constructed tissue microarray were studied. IHC was utilised to examine cytoplasmic and nuclear RelB expression. The relationship between RelB, clinicopathological characteristics, LIR (Klintrup-Mäkinen (KM) grade, CD3+ and CD8+T-cell density), SIR and cancer-specific survival (CSS) was examined. Results: 208 patients were included in the analysis. Cytoplasmic RelB (cyto-RelB) was associated with nuclear RelB ( p=0.006). High expression of cyto-RelB was associated with MMR competence ( p=0.010) but not with TNM stage ( p=0.468), venous invasion ( p=0.973), tumour budding ( p=0.068), tumour necrosis ( p=0.786), tumour cell proliferation ( p=0.907), BRAF V600E mutation ( p=0.585) or administration of adjuvant chemotherapy ( p=0.853). High cyto-RelB was inversely associated with mGPS (mGPS >1: low cyto-RelB – 19% vs. high cyto-RelB – 8%, p=0.017). Also, cyto-RelB was inversely associated with tumour inflammatory cell infiltrate at the margin, Klintrup-Mäkinen grade ( p=0.059), (CD3+ p=0.010, CD8+ p=0.007) and in the tumour (CD3+ p=0.002) and a trend with tumour stroma percentage ( p=0.079). High expression of cyto-RelB was not significantly associated with CSS ( p=0.052). Conclusions: In patients undergoing CRC resection, high expression of cyto-RelB was associated with an adverse host local inflammatory response. Up-regulation of the non-canonical NF- κB pathway may be an important mechanism whereby the tumour deregulates local inflammatory responses and evades host immunosurveillance. Further investigation of inflammation based signal transduction pathways in patients with colorectal cancer is warranted.

The relationship between the local inflammatory response and postoperative infective complications following resection for colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 413-413
Author(s):  
Michelle Leana Ramanathan ◽  
Campbell S. D. Roxburgh ◽  
Paul G. Horgan ◽  
Donald C. Mcmillan
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Response ◽  
Curative Resection ◽  
Inflammatory Responses ◽  
Surgical Site Infections ◽  
Local Inflammation ◽  
Elective Resection ◽  
Local Inflammatory Response ◽  
The Relationship ◽  
Infective Complications

413 Background: In patients with colorectal cancer, the presence of both systemic and/ or local inflammatory responses are predictors of survival independent of tumour stage. The relationship between a raised perioperative systemic inflammatory response and the development of postoperative infective complications is also well established. The aim of the present study was to examine the relationship between the local inflammatory response and the development of postoperative infective complications, in patients undergoing resection for colorectal cancer. Methods: Patients with histologically proven colorectal cancer who, on the basis of laparotomy findings and preoperative abdominal computed tomography, were considered to have undergone potentially curative resection were included in the study (n = 310). Patient characteristics and postoperative complications within 30 days were recorded in a prospective surgical database. Local inflammation was analysed using Klintrup-Makinen criteria and Jass scoring on routine hematoxylin and eosin slides. Results: The majority of patients were 65 or older (66%), male (57%), had colonic tumours (68%) and node negative disease (60%). Most patients underwent elective resection (87%) and were from a deprived area (55%). During follow up 109 (35%) patients developed a postoperative complication; 88 (81%) of which had infective complications. There were no significant associations between local inflammation, as evidenced by Klintrup-Makinen criteria and Jass score, and all infective complications (p = 0.929, p = 0.317), surgical site infections (p = 0.956, p = 0.115), or anastomotic leak (p = 0.771, p = 0.157). Conclusions: The results of the present study show that there is no significant relationship between the degree of local inflammation, as evidenced by Klintrup-Makinen criteria and Jass score, and the development of postoperative infective complications following potentially curative resection for colorectal cancer.

scholarly journals Higher Number of EBI3 Cells in Mucosal Chronic Hyperplastic Candidiasis May Serve to Regulate IL-17-Producing Cells

2021 ◽  
Vol 7 (7) ◽  
pp. 533
Author(s):  
Ailish Williams ◽  
Helen Rogers ◽  
David Williams ◽  
Xiao-Qing Wei ◽  
Damian Farnell ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Oral Lichen Planus ◽  
Inflammatory Cell ◽  
Candida Infection ◽  
Inflammatory Cell Infiltrate ◽  
T Helper ◽  
Cell Infiltrate ◽  
High Prevalence ◽  
Squamous Cell Papilloma ◽  
Oral Lichen

Previous research into the inflammatory cell infiltrate of chronic hyperplastic candidosis (CHC) determined that the immune response is primarily composed of T cells, the majority of which are T helper (CD4+) cells. This present investigation used immunohistochemistry to further delineate the inflammatory cell infiltrate in CHC. Cells profiled were those expressing IL-17A cytokine, EBI3 and IL-12A subunits of the IL-35 cytokine, and FoxP3+ cells. Squamous cell papilloma (with Candida infection) and oral lichen planus tissues served as comparative controls to understand the local immune responses to Candida infection. The results demonstrated that Candida-induced inflammation and immune regulation co-exist in the oral mucosa of CHC and that high prevalence of cells expressing the EBI3 cytokine subunit may play an important role in this regulation. This balance between inflammation and immune tolerance toward invading Candida in the oral mucosa may be critical in determining progress of infection.

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