Citations

Key Points Heme, released from hemoglobin, elicits vaso-occlusion in transgenic sickle mice via endothelial TLR4 signaling. Heme/TLR4 signaling activates NF-κB and triggers vaso-occlusion through Weibel-Palade body degranulation and adhesion molecule expression.

Abstract The American Joint Committee on Cancer/Union Internationale Contre le Cancer ( AJCC / UICC ) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression‐based stratification. These parameters rely on tumour‐cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named ‘Immunoscore’ has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC / UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC / UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM ‐I ( TNM ‐Immune). © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Background. Graft pretreatment to limit postoperative damage has the advantage of overcoming a current issue in liver transplantation (LT). The strategic potential of graft pretreatmentin vivoby a specific agonist forγ-aminobutyric acid receptor (GABAR) was investigated in the rat LT model with a small-for-size graft (SFSG).Methods. Recipient rats were divided into three groups according to donor treatments and recipient surgeries: (i) saline and laparotomy, (ii) saline and split orthotopic liver transplantation (SOLT) with 40%-SFSG, and (iii) GABAR agonist and SOLT with 40%-SFSG. Survival was evaluated. Blood and liver samples were collected 6 h after surgery. Immunohistological assessment for apoptotic induction and western blotting for 4-hydroxynonenal, ataxia-telangiectasia mutated kinase (ATM), histone H2AX, phosphatidylinositol-3 kinase (PI3K), Akt, and free radical scavenging enzymes were performed.Results. Pretreatment by GABAR showed improvement in survival, histopathological assessment, and biochemical tests. Apoptotic induction and oxidative stress were observed after SOLT with an SFSG, and this damage was limited by GABAR regulation. GABAR regulation appeared to reduce DNA damage via the ATM/H2AX pathway and to promote cell survival via the PI3K/Akt pathway.Conclusions. Pretreatmentin vivoby GABAR regulation improves graft damage after SOLT with an SFSG. This strategy may be advantageous in LT.

Objective To assess recommendations for prostate‐specific antigen ( PSA ) screening in a national survey of radiation oncologists and urologists following the recent USA P reventive S ervices T ask F orce ( USPSTF ) grade D recommendation. Methods A random sample of 1366 radiation oncologists and urologists were identified from the A merican M edical A ssociation P hysician M asterfile. From N ovember 2011 to A pril 2012, a mail survey was sent to query PSA screening recommendations for men at average risk of prostate cancer for the following age groups: 40–49, 50–59, 60–69, 70–74, 75–79 and ≥80 years. Multivariable logistic regression was used to test for differences in PSA ‐based screening recommendations by physician characteristics. Results Response rates were similar at 52% for radiation oncologists and urologists ( P = 0.92). Overall, 51.5% of respondents recommended PSA ‐based screening for men aged 40–49 years, while nearly all endorsed it for those aged 50–74 years (96.1% for 50–59, 97.3% for 60–69, and 87.7% for 70–74 years). However, screening recommendations decreased to 43.9% and 12.8% for men aged 75–79 and ≥80 years, respectively. On multivariable analysis, urologists were more likely to recommend screening for men aged 40–49 (odds ratio [ OR ] 3.09; P < 0.001) and 50–59 years ( OR 3.81; P = 0.01), but less likely for men aged 75–79 ( OR 0.66; P = 0.01) and ≥80 years ( OR 0.45; P = 0.002) compared with radiation oncologists. Conclusion While radiation oncologists and urologists recommended PSA screening for men aged 50–69 years, there was less agreement about screening for younger (40–49 years old) and older (≥70 years) men at average risk for prostate cancer.

Objectives/HypothesisTo evaluate the utility of positron emission tomography (PET)/computed tomography (CT) for staging the neck in the preoperative setting by comparing it to both CT/magnetic resonance imaging (MRI) and pathologic staging.Study DesignRetrospective review.MethodsSeventy‐one patients with initial diagnosis of head and neck squamous cell carcinoma having preoperative MR or CT imaging and PET/CT with subsequent bilateral neck dissection as part of primary treatment (142 neck dissections). Comparison of cervical nodal metastases based on three separate staging systems: preoperative CT and/or MRI scan, preoperative PET/CT, and pathology.ResultsBoth CT/MRI scans and PET/CT scans statistically predicted pathologic outcomes (P = 0.0001, P = 0.0001, respectively) using Chi square analysis. There was a statistically significant improvement in the prediction of true pathologic disease using PET/CT compared to CT and/or MRI alone (P = 0.005). In a subgroup analysis including only the contralateral neck, this significance persisted (P = 0.013). McNemar's test revealed that subsequent detection of bilateral neck disease by PET/CT scan was significantly superior to MRI or CT alone (P = 0.023).ConclusionIn pathologically positive necks, PET/CT was statistically more reliable at identifying positive disease than CT or MRI alone. Furthermore, such a result is achieved without a statistically significant difference in false positivity between PET/CT and CT or MRI. This suggests that PET/CT positivity, despite negative clinical exam and CT/MRI findings, may be more likely to signify pathologic disease and require appropriate treatment.Level of Evidence4. Laryngoscope, 124:159–164, 2014

Key PointsThe loss of the two most abundant eosinophil granule proteins disrupts the production of blood eosinophils from marrow progenitors. Knockout animals deficient for both MBP-1 and EPX represent a novel strain of mice with a specific and congenital loss of eosinophils.