HER2 testing of gastro-oesophageal adenocarcinoma:a commentary and guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee

The use of biologics targeted to the human epidermal growth factor receptor 2 (HER2) protein is the latest addition to the armamentarium used to fight advanced gastric or gastro-oesophageal junction adenocarcinoma. The decision to treat with the biologic trastuzumab is completely dependent on HER2 testing of tumour tissue. In 2017, the College of American Pathologists, American Society for Clinical Pathology and the American Society of Clinical Oncology jointly published guidelines for HER2 testing and clinical decision making in gastro-oesophageal adenocarcinoma. The Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee has issued the following document as a commentary of these guidelines and, in parallel, to provide guidance on HER2 testing in National Health Service pathology departments within the UK. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such HER2 testing.</jats:p

Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naive Extensive-Stage Small Cell Lung Cancer:A Phase 2 Randomized Study

Purpose: This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naive, extensive-stage small cell lung cancer (ED-SCLC). Patients and Methods: Patients were randomized 1:1:1 to veliparib [240 mg twice daily (BID) for 14 days] plus chemotherapy followed by veliparib maintenance (400 mg BID; veliparib throughout), veliparib plus chemotherapy followed by placebo (veliparib combination only), or placebo plus chemotherapy followed by placebo (control). Patients received 4-6 cycles of combination therapy, then maintenance until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) with veliparib throughout versus control. Results: Overall (N = 181), PFS was improved with veliparib throughout versus control [hazard ratio (HR), 0.67; 80% confidence interval (CI), 0.50-0.88; P = 0.059]; median PFS was 5.8 and 5.6 months, respectively. There was a trend toward improved PFS with veliparib throughout versus control in SLFN11-positive patients (HR, 0.6; 80% CI, 0.36-0.97). Median overall survival (OS) was 10.1 versus 12.4 months in the veliparib throughout and control arms, respectively (HR, 1.43; 80% CI, 1.09-1.88). Grade 3/4 adverse events were experienced by 82%, 88%, and 68% of patients in the veliparib throughout, veliparib combination-only and control arms, most commonly hematologic. Conclusions: Veliparib plus platinum chemotherapy followed by veliparib maintenance demonstrated improved PFS as first-line treatment for ED-SCLC with an acceptable safety profile, but there was no corresponding benefit in OS. Further investigation is warranted to define the role of biomarkers in this setting

The adoption of pottery on Kodiak Island: Insights from organic residue analysis

Pottery technology, originating in Northeast Asia, appeared in Alaska some 2800 years ago. It spread swiftly along Alaska’s coastline but was not adopted on Kodiak Island until around 500 cal BP, as part of the Koniag tradition. While in the southeast pottery was used extensively, people on the northern half of the island did not adopt the technology. What drove these patterns of adoption and non-adoption on Kodiak Island? To better understand the role of ceramic technology in the Koniag tradition we used organic residue analysis to investigate pottery function. Results indicate that pottery was used to process aquatic resources, including anadromous fish, but especially marine species. Based on archaeological and ethnographic data, and spatial analysis of pottery distributions and function, we hypothesize that Koniag pottery was a tool inherent to the rendering of whale oil on the southeast coast of Kodiak Island, supporting previous suggestions by Knecht (1995) and Fitzhugh (2001). When viewed in the broader historical context of major technological and social transformations, we conclude that social identity and cultural boundaries may also have played a role in the delayed and partial adoption of pottery on Kodiak Island

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This article was designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. These guidelines were prepared by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial Committee

Etude de la bioaccumulation des pesticides dans les biofilms de rivière et comparaison avec les cinétiques d’échange dans l’échantillonneur passif POCIS

DoctoralA protocol that enabled the quantification by LC-MS/MS of a group of forty pesticides in periphyton was validated. Furthermore, a laboratory study was undertaken for two weeks, in order to examine the uptake of selected pesticides in biofilm exposed to water at a concentration of 5 µg/L. The quantification indicated a low uptake of pesticides in biofilm compare to Polar Organic Compound Integrative Sampler, during the laboratory experiment and then on the field. Despite the low uptake, the data indicated a biphasic kinetic, with the first part similar to a 1rst order kinetic, which was used as a model for the seven firsts days in order to calculate the uptake and equilibrium constants during this initial period.Un protocole pour la quantification par LC-MS/MS d'un groupe d'une quarantaine de pesticides dans le périphyton a été validé. Une étude en laboratoire sur deux semaines a permis d'examiner l'accumulation de ces pesticides dans le biofilm exposé à une eau dopée à 5 µg/L. La quantification de ces molécules indique une faible accumulation par rapport au POCIS, que ce soit en laboratoire, puis sur le terrain. Malgré cette faible bioaccumulation, les données actuelles semblent indiquer une tendance biphasique avec, durant les premiers jours, l’approximation possible d’une cinétique d’ordre 1. Le modèle associé à cette cinétique d’ordre 1 a permis l’estimation des constantes d'accumulation et de partage des pesticides entre l’eau et le biofilm, durant cette phase initiale de l’exposition

Kinetics and Mechanisms of Substitution Reactions in Group Vii Metal Carbonyl Hydride Complexes

176 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1975.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

A sediment extraction and cleanup method for wide-scope multitarget screening by liquid chromatography-high-resolution mass spectrometry

Previous studies on organic sediment contaminants focused mainly on a limited number of highly hydrophobic micropollutants accessible to gas chromatography using nonpolar, aprotic extraction solvents. The development of liquid chromatography–high-resolution mass spectrometry (LC–HRMS) permits the spectrum of analysis to be expanded to a wider range of more polar and ionic compounds present in sediments and allows target, suspect, and nontarget screening to be conducted with high sensitivity and selectivity. In this study, we propose a comprehensive multitarget extraction and sample preparation method for characterization of sediment pollution covering a broad range of physicochemical properties that is suitable for LC–HRMS screening analysis. We optimized pressurized liquid extraction, cleanup, and sample dilution for a target list of 310 compounds. Finally, the method was tested on sediment samples from a small river and its tributaries. The results show that the combination of 100 °C for ethyl acetate–acetone (50:50, neutral extract) followed by 80 °C for acetone–formic acid (100:1, acidic extract) and methanol–10 mM sodium tetraborate in water (90:10, basic extract) offered the best extraction recoveries for 287 of 310 compounds. At a spiking level of 1 μg mL-1, we obtained satisfactory cleanup recoveries for the neutral extract—(93 ± 23)%—and for the combined acidic/basic extracts—(42 ± 16)%—after solvent exchange. Among the 69 compounds detected in environmental samples, we successfully quantified several pharmaceuticals and polar pesticides