To evaluate our experience with more than 500 minimally invasive hepatic procedures. Recent data have confirmed the safety and efficacy of minimally invasive liver surgery. Despite these reports, no programmatic approach to minimally invasive liver surgery has been proposed. We retrospectively reviewed all patients who underwent a minimally invasive procedure for the management of hepatic tumors between January 2001 and April 2008. Patients were divided into 3 groups: laparoscopy with intraoperative ultrasound and biopsy only, laparoscopic radiofrequency ablation (RFA), and minimally invasive resection. To compare the various forms of surgery, we analyzed the incidence of complications, tumor recurrence, mortality, and cost. Statistical analysis was performed using chi(2) analysis, Student t test, Kaplan-Meier survival analysis with the log-rank test, and multivariable Cox models. A total of 590 minimally invasive hepatic procedures were performed during 489 operative interventions. The representative tumor histologies were: hepatocellular carcinoma (HCC; N = 210), colorectal carcinoma (N = 40), miscellaneous liver metastases (N = 42), biliary cancer (N = 20), and benign tumors (N = 176). Thirty-five patients underwent laparoscopic ultrasound and confirmatory biopsy alone; 201 patients underwent 240 laparoscopic RFAs, and 253 patients underwent 306 minimally invasive resections. Conversion rates to open surgery for the RFA and resection group were 2% overall. One hundred ninety-nine (40.6%) patients were cirrhotic; 31 resections were performed in cirrhotic patients. Complication and mortality rates for RFA and resection were comparable (11% vs. 16%, and 1.5% vs. 1.6%). However, complication rates (14% vs. 29%; P = 0.02) and mortality (0.3% vs. 9.7%; P = 0.006) rates were higher in the cirrhotic versus noncirrhotic resection group. Overall recurrence rates for RFA and resection groups were 24% and 23%, respectively. Local recurrence rates were higher in the RFA group (6.3% versus 1.5%; P < 0.06). Overall patient survival differed between HCC patients receiving RFA alone and those receiving RFA and OLT (P < 0.0001). Overall survival for cancer patients receiving RFA versus resection differed significantly when unadjusted for other covariates (P = 0.01), and remained marginally significant in a multivariable model (P = 0.056). Minimally invasive hepatic surgery has become a viable alternative to open hepatic surgery. Our present data are equivalent or superior to those encountered in any large open series. Our experience with RFA confirms a low local recurrence rate and an excellent technique for bridging patients to transplantation. Morbidity and mortality rates for minimally invasive hepatic resections in cirrhotics, is similar to other reported open resection series. This series confirmed excellent interim survival rates after laparoscopic HR and superiority over RFA in the treatment of cancer, with significantly lower local tumor recurrence rate.

A peer-reviewed open access journal published by the National Institute of Environmental Health Sciences

Although nonalcoholic steatohepatitis (NASH) is typically associated with obesity, it has also been reported to occur in lean individuals exposed to industrial chemicals. Occupational exposure to vinyl chloride (VC) is a well-documented risk factor for hemangiosarcoma, but has not previously been associated with steatohepatitis. Here we evaluate liver biopsies from 25 nonobese, highly exposed VC workers for steatohepatitis. Next, we evaluate associated metabolic and cytokine abnormalities in affected workers controlled by 26 chemical workers with no to minimal VC exposures, and 11 unexposed, healthy volunteers. Among highly exposed VC workers the prevalence of steatohepatitis was 80%. Of these, 55% had fibrosis and four had hemangiosarcoma. We have coined the term toxicant-associated steatohepatitis (TASH) to describe this condition, which was not explained by obesity or alcohol. Although mean serum transaminases were normal in TASH, total cytokeratin 18, but not the caspase-cleaved fragment, was elevated. Despite the absence of obesity, workers with TASH had insulin resistance with reduced adiponectin levels. TASH was also associated with markedly elevated serum tumor necrosis factor alpha and interleukins 1β, 6, and 8. Serum antioxidant activity was reduced in TASH. Conclusion: TASH occurred frequently in these nonobese VC workers with high cumulative exposures and normal liver enzymes. Elevated total cytokeratin 18 suggested the presence of necrotic cell death in TASH and may be a useful serologic biomarker. TASH was further characterized by insulin resistance, elevated proinflammatory cytokines, and impaired antioxidant defenses. The threshold VC exposure and the role of other chemical agents in TASH are as yet unknown. (Hepatology 2009.)

Hospital length of stay (LOS) and time for a patient to reach clinical stability (TCS) have increasingly become important outcomes when investigating ways in which to combat Community Acquired Pneumonia (CAP). Difficulties arise when deciding how to handle in-hospital mortality. Ad-hoc approaches that are commonly used to handle time to event outcomes with mortality can give disparate results and provide conflicting conclusions based on the same data. To ensure compatibility among studies investigating these outcomes, this type of data should be handled in a consistent and appropriate fashion.

Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.