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.

scholarly journals The Relationship Between Tumor Budding, Tumor Microenvironment, and Survival in Patients with Primary Operable Colorectal Cancer

2019 ◽  
Vol 26 (13) ◽  
pp. 4397-4404 ◽  
Author(s):  
Hester C. van Wyk ◽  
Antonia Roseweir ◽  
Peter Alexander ◽  
James H. Park ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Evaluation Method ◽  
Venous Invasion ◽  
Staging System ◽  
Consensus Conference ◽  
Tumor Budding ◽  
Inflammatory Cell Infiltrate ◽  
Cancer Specific Survival ◽  
The Relationship

Abstract Background Tumor budding is an independent prognostic factor in colorectal cancer (CRC) and has recently been well-defined by the International Tumour Budding Consensus Conference (ITBCC). Objective The aim of the present study was to use the ITBCC budding evaluation method to examine the relationship between tumor budding, tumor factors, tumor microenvironment, and survival in patients with primary operable CRC. Methods Hematoxylin and eosin-stained slides of 952 CRC patients diagnosed between 1997 and 2007 were evaluated for tumor budding according to the ITBCC criteria. The tumor microenvironment was evaluated using tumor stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumor inflammatory cell infiltrate. Results High budding (n = 268, 28%) was significantly associated with TNM stage (p < 0.001), competent mismatch repair (MMR; p < 0.05), venous invasion (p < 0.001), weak KM grade (p < 0.001), high TSP (p < 0.001), and reduced cancer-specific survival (CSS) (hazard ratio 8.68, 95% confidence interval 6.30–11.97; p < 0.001). Tumor budding effectively stratifies CSS stage T1 through to T4 (all p < 0.05) independent of associated factors. Conclusions Tumor budding effectively stratifies patients’ survival in primary operable CRC independent of other phenotypic features. In particular, the combination of T stage and budding should form the basis of a new staging system for 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 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.

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.

Tumour infiltrating lymphocyte expression of PD-1 as a favourable prognostic factor in patients with mismatch repair competent colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 631-631
Author(s):  
James Hugh Park ◽  
Lauren Grant ◽  
Jean A Quinn ◽  
Campbell SD Roxburgh ◽  
Donald C McMillan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Mismatch Repair ◽  
Tumour Microenvironment ◽  
Therapeutic Benefit ◽  
Clinicopathological Characteristics ◽  
Cancer Specific Survival ◽  
Checkpoint Activation ◽  
The Relationship

631 Background: Immune checkpoint activation is recognised in mismatch repair (MMR) deficient colorectal cancer (CRC), and Programmed Cell Death Protein-1 (PD-1) inhibitors have been shown to have therapeutic benefit in this patient group. However, the role of PD-1 and PD Ligand-1 (PDL-1) in patients with MMR competent CRC remains unclear. The present study examined the relationship between tumor infiltrating lymphocyte (TIL) PD-1 and tumour PDL-1 expression, tumour microenvironment (TME) characteristics and cancer-specific survival (CSS) of patients with MMR competent CRC. Methods: The presence of TIL PD-1 and tumour cell PDL-1 expression was examined in patients who had undergone resection of TNM I-III CRC using a tissue microarray. Relationship with clinicopathological characteristics and the TME (Klintrup-Makinen (KM) grade, Immunoscore, tumour stroma percentage (TSP) and Glasgow Microenvironment Score (GMS)) and CSS was examined. Results: 189 patients were included; 64% were older than 65 and 52% were male. PDL-1 expression was not associated with clinicopathological or TME characteristics. Lymphocyte PD-1 expression was not associated with clinicopathological characteristics, but was associated with a high KM grade ( P< 0.001), high Immunoscore ( P< 0.001), low TSP ( P= 0.068) and a low GMS ( P< 0.001). On multivariate survival analysis, high TIL PD-1 expression was associated with improved CSS (HR 0.60, P= 0.016) independent of Immunoscore (HR 0.74, P= 0.03) and TSP (HR 1.91, P= 0.027). PDL1 expression was not associated with CSS on univariate or multivariate analysis. Pre-operative aspirin use was known for 131 patients. Aspirin use showed a trend towards improved 5-year CSS in patients with low PDL-1 expression (100% vs. 77%, P= 0.103) but worse 5-year CSS in those with high expression (55% vs. 82%, P= 0.045). Conclusions: The presence of PD-1 expressing TILs is a favourable prognostic factor in MMR competent CRC independent of other TME characteristics. Furthermore, the relationship between aspirin and CSS may be dependent on PDL-1 expression. Both PD-1 and PDL-1 may be potential prognostic and predictive markers in patients with MMR competent CRC.

The relationship between tumor location, tumor microenvironment, systemic inflammation, and cancer-specific survival in patients undergoing surgery for colon cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 689-689
Author(s):  
Meera Patel ◽  
James Hugh Park ◽  
Hester Catharina van Wyk ◽  
Joanne Edwards ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Primary Tumour ◽  
Tumour Microenvironment ◽  
Tnm Stage ◽  
Inflammatory Cell Infiltrate ◽  
Curative Surgery ◽  
Cancer Specific Survival ◽  
Tumour Location ◽  
The Relationship

689 Background: Evidence from clinical trials and cohort studies suggest primary tumour location is a prognostic factor in patients with advanced colorectal cancer and that right and left colonic tumours should be considered as distinct clinical and biological entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), and cancer-specific survival (CSS) in patients undergoing surgery for colon cancer. Methods: Clinicopathological characteristics were extracted from a prospective database of patients who underwent potentially curative surgery for colon cancer between 1997 and 2016, at a single centre. The tumour microenvironment was assessed retrospectively using routine H&E pathological sections. Results: 722 patients were included. The majority of patients were over the age of 65 years (69%), were male (52%), had right-sided (RS) tumour location (63%), had TNM stage I/II disease (64%) and 25% received adjuvant chemotherapy. RS location was associated with poor tumour differentiation ( p =< 0.001) and high venous invasion ( p =0.003) but not with TNM stage (p= 0.310), perineural invasion ( p= 0.286), tumour budding ( p= 0.568), margin involvement ( p= 0.424), peritoneal involvement ( p= 0.689), tumour necrosis ( p= 0.423) or tumour cell proliferation ( p= 0.605). RS location was not associated with tumour inflammatory cell infiltrate at the margin (CD3+ p= 0.103, CD8+ p= 0.620) or in the tumour (CD3+ p= 0.540, CD8+ p= 0.713) or with tumour stroma percentage ( p= 0.843). RS location was associated with high mGPS ( p =0.007) and neutrophil:platelet score ( p =0.001) but not NLR ( p= 0.387). Finally, there was no difference between RS and left sided tumour location in the administration of adjuvant chemotherapy (p= 0.901) or CSS ( p= 0.951). Conclusions: Few clinicopathological features were associated with tumour location in patients undergoing surgery for colon cancer. However, RS tumour location was consistently associated with a higher SIR. This may account for the poor prognosis associated with RS tumours in patients with advanced colon cancer.

scholarly journals Oncological evaluation in the perioperative period using cfDNA with BRAF V600E mutation in patients with colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Keita Tanaka ◽  
Yoichiro Yoshida ◽  
Teppei Yamada ◽  
Takaomi Hayashi ◽  
Hideki Shimaoka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Perioperative Period ◽  
Radical Resection ◽  
Braf V600e ◽  
Tumor Diameter ◽  
Prognostic Information ◽  
A Prospective Study ◽  
Digital Polymerase Chain Reaction ◽  
The Relationship

AbstractThe detection of circulating cell-free DNA (cfDNA) by liquid biopsy is reported to provide prognostic information in colorectal cancer (CRC). Although the frequency of BRAF V600E mutation in CRC is less than 10%, it is associated with poor responses to conventional chemotherapy. We conducted a prospective study to investigate the relationship between the perioperative mutant allele frequency (MAF) of BRAF V600E and tumor recurrence, and to evaluate the possibility of early detection of recurrence. Among 362 patients who underwent radical resection, cfDNA was extracted from the perioperative blood of 11 CRC patients with BRAF V600E mutation and analyzed using the digital polymerase chain reaction (dPCR) system. The median follow-up time was 22 months, and there were four cases of recurrence. Although there was no correlation between recurrence and the perioperative MAF of BRAF V600E, tumor diameter was correlated with the MAF (p = 0.024), and the MAF increased with time in two patients from whom additional samples were obtained prior to recurrence. In this study, we identified a correlation between the pathological tumor diameter and the MAF, but it was difficult to predict recurrence by measuring cfDNA with BRAF V600E mutation in the perioperative period of radical resection of 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.

Identification of stage I/II colorectal cancer patients at risk of recurrence: The role of elastica stains to detect venous invasion.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14117-e14117
Author(s):  
Campbell SD Roxburgh ◽  
Alan K Foulis ◽  
Manal Atwan ◽  
Paul G Horgan ◽  
Donald C. Mcmillan
Keyword(s):  
Colorectal Cancer ◽  
At Risk ◽  
High Risk ◽  
Venous Invasion ◽  
Stage I ◽  
Low Grade ◽  
Cancer Specific Survival ◽  
Node Negative ◽  
Risk Of Recurrence

e14117 Background: Venous invasion (VI) is a high-risk characteristic in colorectal cancer (CRC) and in stage II disease guides provision of adjuvant therapy. However, reported rates vary in published studies from 10-90%. We recently reported use of elastica stains improve reproducibility of reporting, increasing rates to >50% (Roxburgh, Ann Surg, 2010). Furthermore, compared to H&E alone, elastica detected VI provided superior prediction of 3yr cancer survival in an unselected cohort of CRC patients. The present study aims to examine how the approach could be used in patients with node negative CRC. Methods: We retrieved pre-2003 tumour blocks, sectioned and stained them with elastica. Post-2003, elastica detected VI was routinely reported. A minimum of 3 blocks was required for analysis. Those who died within 30 days of surgery or had neoadjuvant therapy were excluded. Results: 244 stage I/II patients underwent surgery between 1997-2006. 65 cases pre-2003 were analyzed retrospectively. The rate of elastica detected VI was 54%. Elastica detected VI related to other high-risk pathology including T stage (p<0.001), serosal invasion (p<0.01), tumour grade (p<0.05) and low-grade lymphocytic infiltrate (P<0.05). Minimum follow-up was 5 yrs; mean follow-up 99 months (60-178), during which there were 99 deaths, 48 from cancer. Absence of VI related to improved 5-yr cancer specific survival (93% vs 66%). On multivariate analysis, VI independently related to cancer specific survival (HR=5.5,95%CI 2-13,p<0.001) with margin involvement (HR=2.4,95%CI 1-6,p=0.067) and serosal involvement (HR=2.2,95%CI1-4, p=0.015). For CRC mortality, the area under the receiver operator curve was highest for VI compared with other pathology (AUC 0.69, 95%CI 0.6-0.8, P<0.001). Absence of VI related to 5-yr survivals of 92% and 97% in colon and rectal cancer respectively. Conclusions: More objective assessment of VI with routine elastica staining provides accurate prediction of survival in stage I/II CRC. Presence of VI was associated with a 5.5 fold increased risk of cancer death at 5 yrs. Such results support routine use of elastica stains to identify patients with node negative disease at risk of recurrence.

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