Hazar Michael

Multiple Antibiotic Changes during the First 72 Hours of Hospitalization

Background: Increasing concern about inappropriate antibiotic use prompted us to examine whether our patients were receiving frequent and perhaps unwarranted changes of antibiotic therapy. Methods: We evaluated antibiotic prescribing by the physicians in the Emergency Department and by those on the inpatient medical service during the first 72 hours of hospitalization in 119 patients admitted with suspected serious infections to an acute care, university‐affiliated, municipal teaching hospital. The appropriateness of antibiotic prescriptions was assessed independently and retrospectively by 2 infectious disease specialists (each based at a different hospital) using a 4‐grade scale (from 1=wrong choice to 4=appropriate). Of their evaluations of the 427 antibiotic regimens given to the 119 patients during 4 defined intervals during their first 72 hours of hospitalization, 90% agreed with each other within 1 grade. Their evaluations were then compared with the selections that had been made at each interval by the prescribing physicians. Results: Successive prescribing physicians changed the antibiotic regimens in 77% of cases during the first 24 hours and in 56% during the next 48, often without apparent clinical or microbiologic indications. By 72 hours, the 119 patients had received a mean of 3.1±1.3 (±SD) different antibiotics, and 40 received between 4 and 7. Only 7% of the patients had no change in the regimen prescribed originally. Conclusions: Many patients had multiple changes of antibiotics, often unnecessarily, resulting in exposure to too many agents.

The Accuracy of Endoscopic Ultrasound (EUS)-Guided Fine Needle Aspiration (FNA) for Diagnosing Solid Pancreatic Lesions Using a New 25-Gauge Needle System

The Accuracy of Endoscopic Ultrasound (EUS)-Guided Fine Needle Aspiration (FNA) for Diagnosing Solid Pancreatic Lesions Using a New 25-Gauge Needle System Sammy Ho, Robert Bonasera, Hazar Michael, Bonnie Pollack, James Grendell, Mala Gupta, Martin Feuerman, Simcha Pollack, Frank Gress Introduction: EUS-FNA has enhanced our ability to diagnose pancreatic masses. Most of the published data is based on the use of a 22-gauge needle. The aim of this study was to evaluate our center’s experience with a new disposable 25-gauge needle system in the diagnosis of solid pancreatic lesions.Methods: Our institution began utilizing this FDA approved 25-gauge EUS-FNA needle system (Echotip, Wilson Cook, Winston Salem, NC) in 2/2001. All patients referred for EUS evaluation of solid pancreatic mass between 2/2001 and 12/2002 were reviewed. Patient demographics, clinical history including follow-up, and pathology findings were recorded. Cytopathology was compared with operative histopathology in patients who had surgery. Patients who did not have surgery were followed clinically. Results: A total of 163 patients (mean age 66, 88 M/75 F) underwent EUS-FNA for solid pancreatic lesions using the 25-gauge needle. FNA was consistent with pancreatic malignancy in 48% (78/163) while 45% (74/163) had no evidence of malignancy. In the remaining 7% (11/163), biopsy was inconclusive. No complications were reported. Of the pancreatic cancer patients, 96% (75/78) had adenocarcinoma and 4% (3/78) had other malignancies. In the group with a definitive FNA diagnosis, 14% (23/163) underwent surgery and operative histopathology was compared with FNA cytopathology. There was one falsenegative and no false-positive diagosis; and the sensitivity, specificity, PPV, and NPV were 94%, 100%, 100%, and 86% respectively. In the false-negative case, patient had cytologic evidence of chronic pancreatitis. In patients with an inconclusive FNA, 27% (3/11) had surgery and 2 had adenocarcinoma. The remaining 84% (137/163) of patients who did not undergo surgery were followed clinically. The mean survival for patients with a positive, negative, and inconclusive FNA was 11, 23, and 14 months respectively. Conclusions: 1. EUSFNA using a 25-gauge needle system can accurately and safely provide a cytologic diagnosis of pancreatic masses. 2. The patient who had a false-negative FNA diagnosis had chronic pancreatitis, confirming previous reports that cytologic evaluation of pancreatic tissue in the setting of chronic inflammation can be difficult. 3. Studies with larger sample size and randomized arms are now needed to further assess the accuracy and complication rate of this smaller needle system.

Abstract B100: Panvac-F and Panvac-V: Phase I study of intratumoral and systemic vaccination

Patients with adenocarcinoma of the pancreas were treated using a combination of EUS-guided intrapancreatic tumor injection and systemic boost using PANVAC-F and PANVAC-V in this first-in-man Phase I trial. The study represents the translation of our unique demonstration in murine models of bladder and orthotopic mammary tumors that anergy to systemic immunization using antigen encoding vaccinia recombinants could be overcome by immunization into the tumor microenvironment. Consented patients with locally advanced or minimally metastatic pancreatic cancer received EUS-guided intrapancreatic injections (IT) of recombinant Panvac-F (Fowlpox encoding MUC-1, CEA, TRICOM), systemic subcutaneous (SC) Panvac-V (vaccinia) and SC Panvac-F boosts. Systemic SC vaccines were accompanied by subcutaneous rH-GM-CSF, 100 mcg X 4 days. Patients received 2 intrapancreatic injections of Panvac-F (2 weeks apart) with systemic Panvac-V and Panvac-F boosts given with GMCSF extending to day 71 (total of 2 IT Panvac-F, 1 SC Panvac-V, 4 SC Panvac-F). Patients were allowed to transition to standard care at day 31. Patients were evaluated for toxicity and tumor progression. Follow-up care was provided by referring oncologists. In this dose escalation study, the first cohort of 6 pts received IT Panvac-F (10 8 PFU), SC Panvac-V (2 X 10 8 PFU), and SC Panvac-F (10 9 PFU). The second dose cohort of 8 pts received IT Panvac-F (10 9 PFU), SC Panvac-V (2 X 10 8 PFU), and SC Panvac-F (10 9 PFU ). At dose level 1, two of six patients were removed from study after approximately two weeks due to rapid disease progression and died one and six months after trial initiation. At dose level 2, one patient was removed due to rapidly progressive disease and died at 1 mo and a second patient withdrew following 1 IT inoculation and died at month 16. Of the remaining 10 pts, 3 presented with distant metastatic disease (Median Survival 7 mos, range 1-25) and 7 presented without distant metastases (Median Survival 16 mos, range 3-35). Of note, none of the 7 patients presenting without metastatic disease developed distant visceral metastases, by imaging available to us but died of sequellae associated with progressive local disease. Of the above 10 pts, all but one transitioned initially to treatment with gemcitabine-based therapy. (the remaining pt did not begin systemic treatment). Initial RNAseq transcriptome analysis of Fine Needle Aspirate (FNA) comparing Day 1 and Day 14 samples demonstrated a significant increase in a series of chemokines associated with the induction of an immune response in the tumor microenvironment. A planned series of immunologic and genetic analyses are underway. Results demonstrate that the “first in man” intrapancreatic administration of recombinant poxvirus was well tolerated with the complete regimen suggesting an encouraging period of stable disease. The finding that none of the patients who presented without distant visceral metastases developed such would be consistent with the generation of a systemic immune response with effects on seeded metastatic cells. Analysis of local and systemic immune responses is currently proceeding and may provide further insights. This study is supported by the NCI Cancer Therapeutics Evaluation Program (CTEP) and by NCI U01-CA07031 and P30-CA72720. Citation Format: Elizabeth A. Poplin, David A. August, Rebecca A. Moss, Tamir Ben-Menachem, Hazar Michael, Aparna Repaka, Renee Artymyshyn, Chang Chan, James L. Gulley, Robert S. DiPaola, Edmund C. Lattime. Panvac-F and Panvac-V: Phase I study of intratumoral and systemic vaccination. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B100.