No abstract

In the case of Legionnaires' disease described, severe respiratory problems necessitated mechanical ventilatory support, tracheal intubation, and positive end-expiratory pressure. Fever was eliminated with erythromycin therapy but returned after five days, and lung infiltrates spread. After supplementary treatment with other antibiotics and methylprednisolone sodium succinate, both the fever and the infiltrates disappeared. We feel that the multisystem involvement and the recrudescence of fever in our patient emphasize the wide spectrum of characteristics of Legionnaires' disease and the importance of continuation of antibiotics for a prolonged period to eradicate infection.

A 63-year-old white male was in good health until 1975, when (Fig. 2). The hilar lymph nodes were not enlarged and were unaffected by cancer. The skin lesions regressed fol lowing surgery. The patient was followed with periodic chest radiograms.Radiologic examination of the chest performed four years after the initial operation revealed an irregular density superimposing the left border of the aor tic knuckle (Fig. 3)

Early detection is a major goal for reducing mortality of human cancer. However, non-invasive detection of early stage tumors has remained a challenge. We have developed an approach called Targeted Error Correction Sequencing (TEC-Seq) for ultra-sensitive analyses of circulating cell-free tumor DNA (ctDNA). This methodology involves in-solution targeted capture of multiple regions of the genome and deep sequencing (~30,000x) of cell-free DNA fragments. Laboratory and bioinformatic methods were optimized to enrich for rare ctDNA molecules and to reduce potential amplification, sequencing, and contamination errors. We have used this approach to examine 58 cancer related genes, and demonstrated a limit of detection of mutant to wild-type DNA of 0.05% and a specificity >99.999% across targeted regions of interest. We applied this method to analyze plasma from healthy individuals as well as over 200 individuals with breast, lung, colorectal and ovarian cancers. Analysis of plasma from 44 healthy individuals revealed no tumor-related somatic mutations and identified alterations in genes related to myelodysplasia in a subset of cases. Among patients with cancer, we detected measurable ctDNA in 56%, 71%, 57%, and 56% of patients with early stage (I and II) breast, colorectal, lung and ovarian cancer. Over three quarters of patients with late stage (III and IV) disease had detectable ctDNA among all cases analyzed. Analyses of mutations in the circulation revealed a high concordance with alterations in the independently analyzed tumors of these patients. These analyses provide a widely applicable, ultra-sensitive, and non-invasive method for detection of ctDNA, and have important implications for detection of early stage disease and management of patients with cancer. Citation Format: Jillian A. Phallen, Mark Sausen, Vilmos Adleff, Alessandro Leal, Jacob Fiksel, Carolyn Hruban, Savannah Speir, Eniko Papp, Valsamo Anagnostou, Mai-Britt W. Orntoft, Thomas Reinert, Brian D. Woodward, Derek Murphy, Sonya Parpart-Li, David Riley, Monica Nesselbush, Naomi Sengamalay, Andrew Georgiadis, Rob Scharpf, Qing K. Li, Sian Jones, Samuel Angiuoli, Joost Huiskens, Cornelis Punt, Nicole van Grieken, Remond Fijneman, Gerrit Meijer, Hatim Husain, Luis Diaz, Torben Ørntoft, Hans J. Nielsen, Claus L. Anderson, Victor E. Velculescu. Detection of circulating tumor DNA in early stage cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-246. doi:10.1158/1538-7445.AM2017-LB-246