Background. Noroviruses are enterically transmitted and are a frequent cause of gastroenteritis, affecting 23 million people annually in the United States. We describe a norovirus outbreak and its control in a tertiary care hospital during February-May 2004.Methods. Patients and health care workers met the case definition if they had new onset of vomiting and/or diarrhea during the outbreak period. Selected stool samples were tested for norovirus RNA. We also determined outbreak costs, including the estimated lost revenue associated with unit closures, sick leave, and cleaning expenses.Results. We identified 355 cases that affected 90 patients and 265 health care workers and that were clustered in the coronary care unit and psychiatry units. Attack rates were 5.3% (7 of 133) for patients and 29.9% (29 of 97) for health care workers in the coronary care unit and 16.7% (39 of 233) for patients and 38.0% (76 of 200) for health care workers in the psychiatry units. Thirteen affected health care workers (4.9%) required emergency department visits or hospitalization. Detected noroviruses had 98%-99% sequence identity with representatives of a new genogroup II.4 variant that emerged during 2002-2004 in the United States (e.g., Farmington Hills and other strains) and Europe. Aggressive infection-control measures, including closure of units and thorough disinfection using sodium hypochlorite, were required to terminate the outbreak. Costs associated with this outbreak were estimated to be $657,644.Conclusions. The significant disruption of patient care and cost of this single nosocomial outbreak support aggressive efforts to prevent transmission of noroviruses in health care settings.
PurposeTo evaluate and compare outcome of stereotactic body radiation therapy (SBRT), yttrium-90 radioembolization, radiofrequency ablation (RFA), or transarterial chemoembolization (TACE) as bridge to liver transplant (LT) in patients with hepatocellular carcinoma.Methods and materialsWe retrospectively reviewed patients treated at our institution with SBRT, TACE, RFA, or yttrium-90 as bridge to LT between 2006 and 2013. We analyzed radiologic and pathologic response and rate of failure after bridge therapy. Toxicities were reported using Common Terminology Criteria for Adverse Events, 4.0. Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival after LT.ResultsSixty patients with a median age 57.5 years (range, 44-70) met inclusion criteria. Thirty-one patients (50.7%) had hepatitis C cirrhosis, 14 (23%) alcoholic cirrhosis, and 8 (13%) nonalcoholic steatohepatitis cirrhosis. Patients received a total of 79 bridge therapies: SBRT (n = 24), TACE (n = 37), RFA (n = 9), and Y90 (n = 9). Complete response (CR) was 25% for TACE, 8.6% for SBRT, 22% for RFA, and 33% for Y90. Grade 3 or 4 acute toxicity occurred following TACE (n = 4) and RFA (n = 2). Transplant occurred at a median of 7.4 months after bridge therapy. Pathological response among 57 patients was 100% necrosis (n = 23, 40%), >50% necrosis (n = 20, 35%), <50% necrosis (n = 9, 16%), and no necrosis (n = 5, 9%). Pathologic complete response was as follows: SBRT (28.5%), TACE (41%), RFA (60%), Y90 (75%), and multiple modalities (33%). At a median follow-up of 35 months, 7 patients had recurrence after LT. DFS was 85.8% and overall survival was 79% at 5 years.ConclusionAll bridge therapies demonstrated good pathological response and DFS after LT. SBRT and Y90 demonstrated significantly less grade ≥3 acute toxicity. Choice of optimal modality depends on tumor size, pretreatment bilirubin level, Child-Pugh status, and patient preference. Such a decision is best made at a multidisciplinary tumor board as is done at our institution.
SUMMARY Over 80% of pancreatic ductal adenocarcinoma (PDA) patients are diagnosed with non-resectable late-stage disease that lacks effective neoadjuvant therapies. Stereotactic body radiation therapy (SBRT) has shown promise as an emerging neoadjuvant approach for treating PDA, and here, we report that its combination with local interleukin-12 (IL-12) microsphere (MS) immunotherapy results in marked tumor reduction and cures in multiple preclinical mouse models of PDA. Our findings demonstrate an increase of intratumoral interferon gamma (IFNγ) production following SBRT/IL-12 MS administration that initiates suppressor cell reprogramming and a subsequent increase in CD8 T cell activation. Furthermore, SBRT/IL-12 MS therapy results in the generation of systemic tumor immunity that is capable of eliminating established liver metastases, providing a rationale for follow-up studies in advanced metastatic disease.
Purpose: Stereotactic body radiotherapy (SBRT) is an emerging treatment modality for pancreatic ductal adenocarcinoma (PDAC), which can effectively prime cytotoxic T cells by inducing immunogenic tumor cell death in preclinical models. SBRT effects on human PDAC have yet to be thoroughly investigated; therefore, this study aimed to characterize immunomodulation in the human PDAC tumor microenvironment following therapy. Experimental Design: Tumor samples were obtained from patients with resectable PDAC. Radiotherapy was delivered a median of 7 days prior to surgical resection, and sections were analyzed by multiplex IHC (mIHC), RNA sequencing, and T-cell receptor sequencing (TCR-seq). Results: Analysis of SBRT-treated tumor tissue indicated reduced tumor cell density and increased immunogenic cell death relative to untreated controls. Radiotherapy promoted collagen deposition; however, vasculature was unaffected and spatial analyses lacked evidence of T-cell sequestration. Conversely, SBRT resulted in fewer tertiary lymphoid structures and failed to lessen or reprogram abundant immune suppressor populations. Higher percentages of PD-1+ T cells were observed following SBRT, and a subset of tumors displayed more clonal T-cell repertoires. Conclusions: These findings suggest that SBRT augmentation of antitumor immunogenicity may be dampened by an overabundance of refractory immunosuppressive populations, and support the continued development of SBRT/immunotherapy combination for human PDAC.
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