1,736 research outputs found

    Comparison of the prognostic value of measures of the tumor inflammatory cell infiltrate and tumor-associated stroma in patients with primary operable colorectal cancer

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    The aim of the present study was to compare the clinical utility of two measures of the inflammatory cell infiltrate - a H&E-based assessment of the generalised inflammatory cell infiltrate (the Klintrup-Mäkinen (KM) grade), and an immunohistochemistry-based assessment of combined CD3+ and CD8+ T-cell density (the “Immunoscore”), in conjunction with assessment of the tumor stroma percentage (TSP) in patients undergoing resection of stage I-III colorectal cancer (CRC). 246 patients were identified from a prospectively maintained database of CRC resections in a single surgical unit. Assessment of KM grade and TSP was performed using full H&E sections. CD3+ and CD8+ T-cell density was assessed on full sections and the Immunoscore calculated. KM grade and Immunoscore were strongly associated (P<0.001). KM grade stratified cancer-specific survival (CSS) from 88% to 66% (P=0.002) and Immunoscore from 93% to 61% (P<0.001). Immunoscore further stratified survival of patients independent of KM grade from 94% (high KM, Im4) to 60% (low KM, Im0/1). Furthermore, TSP stratified survival of patients with a weak inflammatory cell infiltrate (low KM: from 75% to 47%; Im0/1: from 71% to 38%, both P<0.001) but not those with a strong inflammatory infiltrate. On multivariate analysis, only Immunoscore (HR 0.44, P<0.001) and TSP (HR 2.04, P<0.001) were independently associated with CSS. These results suggest that the prognostic value of an immunohistochemistry-based assessment of the inflammatory cell infiltrate is superior to H&E-based assessment in patients undergoing resection of stage I-III CRC. Furthermore, assessment of the tumor-associated stroma, using TSP, further improves prediction of outcome

    Evaluation of a tumor microenvironment-based prognostic score in primary operable colorectal cancer

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    Purpose: The tumor microenvironment is recognized as an important determinant of progression and outcome in colorectal cancer. The aim of the present study was to evaluate a novel tumor microenvironment–based prognostic score, based on histopathologic assessment of the tumor inflammatory cell infiltrate and tumor stroma, in patients with primary operable colorectal cancer. Experimental Design: Using routine pathologic sections, the tumor inflammatory cell infiltrate and stroma were assessed using Klintrup–Mäkinen (KM) grade and tumor stroma percentage (TSP), respectively, in 307 patients who had undergone elective resection for stage I–III colorectal cancer. The clinical utility of a cumulative score based on these characteristics was examined. Results: On univariate analysis, both weak KM grade and high TSP were associated with reduced survival (HR, 2.42; P = 0.001 and HR, 2.05; P = 0.001, respectively). A cumulative score based on these characteristics, the Glasgow Microenvironment Score (GMS), was associated with survival (HR, 1.93; 95% confidence interval, 1.36–2.73; P < 0.001), independent of TNM stage and venous invasion (both P < 0.05). GMS stratified patients in to three prognostic groups: strong KM (GMS = 0), weak KM/low TSP (GMS = 1), and weak KM/high TSP (GMS = 2), with 5-year survival of 89%, 75%, and 51%, respectively (P < 0.001). Furthermore, GMS in combination with node involvement, venous invasion, and mismatch repair status further stratified 5-year survival (92% to 37%, 93% to 27%, and 100% to 37%, respectively). Conclusions: The present study further confirms the clinical utility of assessment of the tumor microenvironment in colorectal cancer and introduces a simple, routinely available prognostic score for the risk stratification of patients with primary operable colorectal cancer

    Staging the tumor and staging the host: A two centre, two country comparison of systemic inflammatory responses of patients undergoing resection of primary operable colorectal cancer

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    Background: How systemic inflammation-based prognostic scores such as the modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR) differ across populations of patients with colorectal cancer (CRC) remains unknown. The present study examined the mGPS and NLR in patients from United Kingdom (UK) and Japan. Methods: Patients undergoing resection of TNM I-III CRC in two centres in the UK and Japan were included. Differences in clinicopathological characteristics and mGPS (0-CRP≤10 mg/L, 1-CRP>10 mg/L, 2-CRP>10 mg/L, albumin<35 g/L) and NLR (≤5/>5) were examined. Results: Patients from UK (n = 581) were more likely to be female, high ASA and BMI, present as an emergency (all P < 0.01) and have higher T stage compared to those from Japan (n = 559). After controlling for differences in tumor and host characteristics, patients from Japan were less likely to be systemically inflamed (OR: mGPS: 0.37, 95%CI 0.27–0.50, P < 0.001; NLR: 0.53, 95%CI 0.35–0.79, P = 0.002). Conclusion: Systemic inflammatory responses differ between populations with colorectal cancer. Given their prognostic value, reporting of systemic inflammation-based scores should be incorporated into future studies reporting patient outcomes. Summary: Although the systemic inflammatory response is recognised as a prognostic factor in patients with colorectal cancer, it is not clear how these may differ between distinct geographical populations. The present study examines differences in the prevalence of elevated systemic inflammatory responses (modified Glasgow Prognostic Score and neutrophil:lymphocyte ratio) between two populations undergoing resection of colorectal cancer in the United Kingdom and Japan

    The Constraint of a General Effective Potential in Vector Torsion Coupled Conformally Induced Gravity

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    It is found that the deviation of an effective potential from the quartic form is related to the metric and vector torsion dependencies of the effective potential in the vector torsion coupled conformally induced gravity.Comment: 3pages Revtex 3.0, no figur

    Bundle and annulus CHF correlations applicable for near critical pressure region

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    Paper presented at the 8th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Mauritius, 11-13 July, 2011.Bundle and annulus CHF correlations are developed by using CHF experimental data from the Freon R-134a Thermal Hydraulic Experimental Loop developed at KAERI. The CHF data are in the range of the pressure of 3200 ~ 4030 kPa (Critical pressure of R-134a = 4059 kPa), the mass flux 150∼1500 kg/m2s, and the inlet subcooling 40 ~ 70 kJ/kg. We obtained local T/H values using a subchannel analysis code and produced CHF correlations for the matrix subchannel, coldwall subchannel and annulus channel, respectively. A subchannel code, The MATRA-α IBM PC version, is used to obtain the local conditions in a hot subchannel (CHF observed channel) in the 5x5 bundle geometry. All the CHF experimental data are successfully calculated by the present correlations with good prediction performance. The prediction accuracy of the correlations is not distorted by much in any of the ranges of the independent parameters. The bundle CHF correlations could help one to conceptually design a SCWR, by adopting a fluidto- fluid modeling technique for a CHF near a critical pressure.mp201

    TOXOPLASMOSIS OF THE CENTRAL NERVOUS SYSTEM IN HIV PATIENTS

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    Currently HIV infection in Kazakhstan is mainly spread among population groups with risk taking behavior (injection drug users – IDUs, sex workers – SWs). The lesions and fatalities in patients with HIV infection are mainly caused by complications, i.e. the development of opportunistic infections and secondary diseases. Timely diagnosis of these conditions determines the success of treatment and life expectancy of patients. Among superinfections the following ones take the lead: mycoses (pneumocystosis, candidiasis, cryptococcosis, coccidioidosis), diseases caused by a group of herpes viruses (herpes simplex, herpes zoster, cytomegalovirus infection, Epstein-Barr virus infection, Kaposi’s sarcoma), bacterial infection (tuberculosis, atypical mycobacteriosis, salmonellosis), protozoosis (toxoplasmosis, cryptosporidiosis). Multi-infections are common as well. Opportunistic infections are insidious in humans and take the form of endogenous infections; they as well are activated with the development of clinical manifestations along with formation of immunodeficiency and, accordingly, cause severe and even fatal diseases

    Pre-operative, biopsy-based assessment of the tumour microenvironment in patients with primary operable colorectal cancer

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    The tumour microenvironment (TME) is recognised as an important prognostic characteristic and therapeutic target in patients with colorectal cancer (CRC). However, assessment generally utilises surgically resected specimens, precluding neoadjuvant targeting. The present study investigated the feasibility of intra‐epithelial CD3+ T‐lymphocyte density and tumour stroma percentage (TSP) assessment using preoperative colonoscopic biopsies from 115 patients who had undergone resection of stages I–III CRC, examining the relationship between biopsy and surgically resected specimen‐based assessment, and the relationship with cancer‐specific survival (CSS). High biopsy CD3+ density was associated with high CD3+ density in the invasive margin, cancer stroma and intra‐epithelial compartments of surgically resected specimens (area under the curve > 0.62, p < 0.05 for all) and with high Immunoscore. High biopsy TSP predicted high TSP in resected specimens (p = 0.001). Intra‐class correlation coefficient for both measures was >0.7 (p < 0.001), indicating excellent concordance between individuals. Biopsy CD3+ density (hazard ratio [HR] 0.23, p = 0.002) and TSP (HR 2.23, p = 0.029) were independently associated with CSS; this was comparable to the prognostic value of full section assessment (HR 0.21, p = 0.004, and HR 2.25, p = 0.033 respectively). These results suggest that assessment of the TME is comparable in biopsy and surgically resected specimens from patients with CRC, and biopsy‐based assessment could allow for stratification prior to surgery or commencement of therapy targeting the TME
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