Acetaminophen (APAP) overdose is one of the most frequent causes of acute liver failure in the United States and is primarily mediated by toxic metabolites which accumulate in the liver upon depletion of glutathione stores. However, cells of the innate immune system, including NK cells, neutrophils, and Kupffer cells, have also been implicated in the centrilobular liver necrosis associated with APAP. We have recently shown that dendritic cells (DC) regulate intra-hepatic inflammation in chronic liver disease and, therefore, postulated that DC may also modulate the hepatotoxic effects of APAP. We found that DC immune-phenotype was markedly altered after APAP challenge. In particular, liver DC expressed higher MHC II, co-stimulatory molecules, and Toll-like Receptors, and produced higher IL-6, MCP-1, and TNF-α. Conversely, spleen DC were unaltered. However, APAP-induced centrilobular necrosis, and its associated mortality, was markedly exacerbated upon DC depletion. Conversely, endogenous DC expansion using FMS-like tyrosine kinase 3 ligand (Flt3L) protected mice from APAP injury. Our mechanistic studies showed that APAP liver DC had the particular capacity to prevent NK cell activation and induced neutrophil apoptosis. Nevertheless, the exacerbated hepatic injury in DC depleted mice challenged with APAP was independent of NK cells and neutrophils or numerous immune modulatory cytokines and chemokines. Conclusions Taken together, these data indicate that liver DC protect against APAP toxicity while their depletion is associated with exacerbated hepatotoxicity.

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Use of nipple-sparing mastectomy (NSM) for risk-reduction and therapeutic breast cancer resection is growing. The role for intraoperative frozen section of the nipple-areolar complex remains controversial. Records of patients undergoing NSM at our institution from 2006 to 2013 were reviewed. Records from 501 nipple-sparing mastectomies were reviewed (216 therapeutic, 285 prophylactic). Of the 480 breasts with sub-areolar biopsies, 307 had intraoperative frozen sections and 173 were evaluated with permanent paraffin section only. Among the 307 intraoperative frozen sections, 12 biopsies were positive on permanent paraffin section (3.9% or 12/307). Of the 12 positive permanent biopsies, five were false negative and the remaining seven concordant intraoperatively. Sensitivity and specificity of sub-areolar frozen section were 0.58 and 1, respectively. Positive sub-areolar biopsies consisted primarily of ductal carcinoma in situ (62% or 13/21). The nipples or nipple-areolar complex were resected in a separate procedure following mastectomy (10/21), intraoperatively following frozen section results (7/21) or during second-stage breast reconstruction (3/21; 1 additional scheduled). Only 30% (6/20) of resected specimens had abnormal residual pathology. Intraoperative frozen section is highly specific and moderately sensitive for the detection of positive sub-areolar biopsies in NSM. Its use can help guide intraoperative reconstructive planning. The presence of positive sub-areolar biopsies in both contralateral and high-risk prophylactic mastectomy specimens emphasizes the need to perform sub-areolar biopsies in all nipple-sparing mastectomies.

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Massive HCC represents a tumour subtype that is associated with young, chronic hepatitis B carriers with non-cirrhotic livers. The clinical implications of this finding are that patients with massive HCC are typically excellent resection candidates barring the presence of gross vascular invasion or distant metastases.

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We report the utility of office-based, nonimaged guided fine needle aspiration of palpable axillary lymph nodes in breast cancer patients. We examine the sensitivity and specificity of this procedure, and examine factors associated with a positive fine needle aspiration biopsy result. Although the utility of ultrasound-guided fine needle aspiration biopsy (FNA) of axillary lymph nodes is well established, there is little data on nonimage guided office-based FNA of palpable axillary lymphadenopathy. We investigated the sensitivity and specificity of nonimage-guided FNA of axillary lymphadenopathy in patients presenting with breast cancer, and report factors associated with a positive FNA result. Retrospective study of 94 patients who underwent office-based FNA of palpable axillary lymph nodes between 2004 and 2008 was conducted. Cytology results were compared with pathology after axillary sentinel node or lymph node dissection. Nonimage-guided axillary FNA was 86% sensitive and 100% specific. On univariate analysis, patients with positive FNA cytology had larger breast tumors (p = 0.007), more pathologic positive lymph nodes (p < 0.0001), and were more likely to present with a palpable breast mass (p = 0.006) or with radiographic lymphadenopathy (p = 0.002). FNA-positive patients had an increased presence of lymphovascular invasion (p = 0.001), higher stage of disease (p < 0.001), higher N stage (p < 0.0001), and higher rate of HER2/neu expression (p = 0.008). On multivariate analysis, radiographic lymphadenopathy (p = 0.03) and number of positive lymph nodes (p = 0.04) were associated with a positive FNA result. Nonimage-guided FNA of palpable axillary lymphadenopathy in breast cancer patients is an inexpensive, sensitive, and specific test. Prompt determination of lymph node positivity benefits select patients, permitting avoidance of axillary ultrasound, sentinel lymph node biopsy, or delay in receiving neoadjuvant therapy. This results in time and cost savings for the health care system, and expedites definitive management.

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