Objective To compare outcomes for patients with hepatocellular carcinoma (HCC) treated with either liver resection or transplantation. Methods A retrospective, single institution analysis of 413 HCC patients from 1999–2009. Results 413 patients with HCC underwent surgical resection (n=106), transplantation (n=270), or were listed without receiving transplantation (n=37). Excluding transplanted patients with incidental tumors (n=50), 257 patients with suspected HCC were listed with the intent to transplant (ITT). The median diameter of the largest tumor by radiography was 6.0 cm in resected, 3.0 cm in transplanted, and 3.4 cm in the listed-but-not-transplanted patients. Median time to transplant was 48 days. Recurrence rates were 19.8% for resection and 12.1% for all ITT patients. Overall, patient survival for resection vs. ITT patients was similar (5-year survival of 53.0% vs. 52.0%, NS). However, for HCC patients with MELD scores <10 and who radiologically met Milan or UCSF criteria, 1-year and 5-year survival rates were significantly improved in resected patients. For patients with MELD <10 and who met Milan criteria, 1-year and 5-year survival were 92.0% and 63.0% for resection (n=26) vs. 83.0% and 41.0% for ITT (n=73, p=0.036). For those with MELD <10 and met UCSF criteria, 1-year and 5-year survival was 94.0% and 62.0% for resection (n=33) vs. 81.0% and 40.0% for ITT (n=78, p=0.027). Conclusions Among known HCC patients with preserved liver function, resection was associated with superior patient survival versus transplantation. These results suggest surgical resection should remain the first line therapy for patients with HCC and compensated liver function who are candidates for resection.

Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die on basis of high IL-6 levels. Am J Physiol Regul Integr Comp Physiol 289: R1048 -R1053, 2005. First published June 9, 2005; doi:10.1152/ajpregu.00312.2005.-Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels Ͼ14,000 pg/ml drawn 6 h after cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 h after septic insult. Our first aim was to see whether earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die on the basis of high IL-6 levels. Mice (n ϭ 184) were subjected to CLP, had IL-6 levels drawn 6 h later, and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning 6 or 12 h postoperatively. Overall 1-wk survival improved from 25.5 to 35.9% with earlier administration of antibiotics (P Ͻ 0.05). In mice with IL-6 levels Ͼ14,000 pg/ml, 25% survived if imipenem was started at 6 h, whereas none survived if antibiotics were started later (P Ͻ 0.05). On the basis of these results, we examined whether targeted antibody therapy could improve survival in mice with elevated IL-6 levels. A different cohort of mice (n ϭ 54) had blood drawn 6 h after CLP, and then they were randomized to receive either monoclonal anti-IL-6 IgG or irrelevant rat IgG. Anti-IL-6 antibody failed to improve either overall survival or outcome in mice with IL-6 levels Ͼ14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6. cecal ligation and puncture; cytokine; imipenem; critical illness; interleukin-6 DESPITE AGGRESSIVE TREATMENT, between 120,000 and 210,000 people die of sepsis annually in the United States (2, 15). Early goal-directed therapy in sepsis is associated with a marked improvement in overall patient outcome (22), although there is currently no way to know which specific patients will have the most favorable response to this therapy. The pro-and antiinflammatory cytokine interleukin (IL)-6 is associated with increased mortality in patients with sepsis (7,10,11,17,23). In addition, IL-6 levels drawn 6 h after the onset of sepsis predict mortality with high specificity in mice subjected to either cecal ligation and puncture (CLP) (20,26,27,29) or Pseudomonas aeruginosa pneumonia (5).Although IL-6 levels correlate with mortality in sepsis, its role as a mediator of the septic response is more complicated. Mice have improved survival if given anti-IL-6 antibody immediately after CLP (21) or 2 or 4 h after gavage with Escherichia coli and thermal injury (9). These effects are time dependent, because mortality is unaffected if anti-IL-6 is given 4 h after CLP (21) or 8 h after bacterial gavage and burn ...

The association between malignancy and thrombosis has long been appreciated but remains incompletely understood. This is the first of a two-part review of the complex, integral relationship between these two entities, and addresses the mechanisms and pathogenesis of this relationship and the clinical risk factors for thromboembolism in cancer patients.J. Surg. Oncol. 2011;104:316-322. ß 2011 Wiley-Liss, Inc.KEY WORDS: thromboembolism; cancer biology; thrombophilic state; risk factorsThe association of thrombophilia with cancer has long been recognized. In 1868, Trousseau described this in presenting a series of patients with gastrointestinal neoplasms to the New Sydenham Society in London. In 1878, Theodor Billroth lectured on his observation of cancer cells within intravascular thrombi to the same Society, postulating that distant metastasis of cancer occurs primarily through venous thromboembolism (VTE) [1,2]. Rudolf Virchow made the seminal observation of the association of stasis, hypercoagulability, and endothelial damage in VTE. Morrison [3] was the first to report specific prothrombotic humoral abnormalities in cancer patients, publishing his findings in 1932.The clinical incidence of VTE in cancer patients ranges from 10% to 20%. The incidence in autopsy series exceeds 50%, with pulmonary embolism being present in 26% (range 13-42%). The clinical incidence of VTE in cancer patients is roughly fourfold higher than that in those with non-malignant diagnoses [4,5].The prevalence of malignancy among all patients with VTE ranges from 4% to 20%. There is a 4-to 5-fold increase in postoperative VTE in cancer patients as compared to patients with other diagnoses undergoing the same surgical procedures. VTE remains the second commonest proximate cause of death in cancer patients overall [6][7][8][9]. This is the first part of a two-part review of the thrombophilic state in cancer. The focus of this part is on the biochemical and clinical prevalence of hemostatic derangements in cancer, their role in cancer biology, and risk factors for thromboembolism in cancer patients. The second part will address thromboembolism and cancer outcomes, anticoagulation and cancer outcomes, suppression and prevention, VTE and occult malignancy, and progress in antithrombotic therapy, and possibilities in future cancer treatment.

Objective-Pathogens that cause pneumonia may be treated in a targeted fashion by antibiotics, but if this therapy fails, treatment involves only non-specific supportive measures, independent of the inciting infection. The purpose of this study was to determine whether host response is similar following disparate infections with similar mortalities.Design-Prospective, randomized controlled study.Setting-Animal laboratory in a university medical center.Interventions-Pneumonia was induced in FVB/N mice by either Streptococcus pneumoniae or two different concentrations of Pseudomonas aeruginosa. Plasma and bronchoalveolar lavage fluid from septic animals was assayed by a microarray immunoassay measuring 18 inflammatory mediators at multiple timepoints.Measurements and Main Results-The host response was dependent upon the causative organism as well as kinetics of mortality, but the pro-and anti-inflammatory response was independent of inoculum concentration or degree of bacteremia. Pneumonia caused by different concentrations of the same bacteria, Pseudomonas aeruginosa, also yielded distinct inflammatory responses; however, inflammatory mediator expression did not directly track the severity of infection. For all infections, the host response was compartmentalized, with markedly different concentrations of inflammatory mediators in the systemic circulation and the lungs. Hierarchical clustering analysis resulted in the identification of 5 distinct clusters of the host response to bacterial infection. Principal components analysis correlated pulmonary MIP-2 and IL-10 with progression of infection while elevated plasma TNFsr2 and MCP-1 were indicative of fulminant disease with >90% mortality within 48 hours.