Prevalence and significance of anaemia in patients receiving long-course neoadjuvant chemoradiotherapy for rectal carcinoma
ABSTRACT Aim: The study aimed to assess the prevalence and significance of anaemia during long-course neo-adjuvant radiotherapy (LNRT) of rectal cancer at our centre. Method: Hospital coding and a prospective oncology database were used to identify all patients undergoing LNRT for rectal cancer at our centre between 2004-2009. A retrospective review of computerised records was used to extract individual patient data. Anaemia was defined as a haemoglobin (Hb) level <11.5 grammes/decilitre (g/dL) for men and <13 g/dl for women. Downstaging was assessed by comparing radiological (rTNM) to histological stage (ypTNM). Tumour regression after radiotherapy was assessed using the 'Rectal Cancer Regression Group (RCRG)' scores of 1-3. Results were analysed using GnuPSPP statistical software. Results: There were 70 patients (51 male) of median age of 66 (IQR 60-72.75) years. Of these 24 were anaemic. Two (3%) had no Hb recorded and were excluded. Forty-two percent of anaemic patients demonstrated mural (T) downstaging compared with 68% of non-anaemic patients (p=0.03). There was no differences in nodal downstaging between the groups. The RCRG scores showed more tumour regression in non-anaemic than anaemic patients as follows: RCRG 1 59% vs 30%, RCRG 2 11% vs 17%, RCRG 3 38% vs 46% (p< 0.001). Conclusion: The prevalence of anaemia in patients undergoing LNRT was 35%. Anaemia during LNRT was associated with significant reductions in tumour downstaging and regression. © 2012 The Authors Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.
Colorectal Disease 10/2013; 15(10):1199-200. DOI:10.1111/codi.12429 · 2.02 Impact Factor
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ABSTRACT: Background The Wnt/beta-catenin and the Hedgehog (Hh) pathway interact in various cell types while eliciting opposing or synergistic cellular effects. Both pathways are known as exclusive drivers of two distinct molecular subtypes of medulloblastoma (MB).In sonic hedgehog (Shh)-driven MB, activation of Wnt signaling has been shown to suppress tumor growth by either beta-catenin-dependent or -independent inhibition of Shh signaling. However, mechanistic insight in how beta-catenin inhibits the Hh pathway is not known.FindingsHere we show that beta-catenin stabilization by the glycogen synthase kinase 3 inhibitor lithium chloride (LiCl) reduced growth of primary hedgehog-driven MB tumor spheres from patched heterozygous mice (Ptch+/-) in vitro. LiCl treatment of MB spheres down-regulated the Hh target Gli1, whereas the repressive Gli3 protein (Gli3R) was increased. Mechanistically, we show by co-immunoprecipitation and proximity ligation assay that stabilized beta-catenin physically interacts with Gli1, leading to Gli1 sequestration and inhibition of its transcriptional activity. Reduction of Hh signaling upon LiCl stimulation resulted in reduced proliferation, sphere self renewal, a G2/M arrest and induction of a senescent-like state, indicated by p21 upregulation and by increased staining of senescence-associated beta-galactosidase (SA-betaGal). Moreover, LiCl treatment of subcutaneously transplanted MB cells significantly reduced tumor initiation defined as ¿tumor take¿. Although tumor progression was similar, LiCl-treated tumors showed decreased mitotic figures and phospho-histone H3 staining.Conclusion We propose that beta-catenin stabilization increases its physical interaction with Gli1, leading to Gli1 degradation and inhibition of Hh signaling, thereby promoting tumor cell senescence and suppression of ¿tumor take¿ in mice.Molecular Cancer 02/2015; 14(1):17. DOI:10.1186/s12943-015-0294-4 · 5.40 Impact Factor
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ABSTRACT: BackgroundThe relationship between anemia and outcomes after radiotherapy has not been systematically addressed. The study aimed to assess the prevalence and prognostic value of anemia in patients receiving primary radiotherapy for esophageal squamous cell carcinoma (ESCC).MethodsA total of 103 patients with ESCC were retrospectively reviewed. Anemia was defined as a hemoglobin level <12 g/dl for men and <11 g/dl for women. The 3-year and 5-year overall survival (OS) and disease-free survival (DFS) were analyzed between the anemic and non-anemic groups using the Kaplan-Meier method and the Cox proportional hazards model.ResultsNo significant differences were observed in patient characteristics between the anemic and non-anemic groups. The prevalence of anemia was 29.1%. The 3-year and the 5-year OS were 43% and 37%, respectively, in the non-anemic group, and 20% and 17%, respectively, in the anemic group. The 3-year and the 5-year DFS were 37% and 26%, respectively, in the non-anemic group, and 13% and 10%, respectively, in the anemic group. Survival analysis using the Kaplan-Meier method showed that there was significant difference between anemia and non-anemia (P < 0.02). In a multivariate analysis, anemia was identified as a highly significant prognostic factor for 3-year OS (hazard ratio 1.916; P = 0.012) and 3-year DFS (hazard ratio 1.973; P = 0.007), independent of T stage and the status of lymph nodes, and 5-year OS (hazard ratio 1.705; P = 0.027) and 5-year DFS (hazard ratio 1.980; P = 0.005), independent of TNM stage and the status of lymph nodes.ConclusionsAnemia before primary radiotherapy was associated with poor prognosis and an increased risk of relapse, which may serve as a new prognostic factor for ESCC.World Journal of Surgical Oncology 08/2014; 12(1):244. DOI:10.1186/1477-7819-12-244 · 1.20 Impact Factor