Survival outcomes in patients with advanced hepatocellular carcinoma treated with drug-eluting bead chemoembolization.

OBJECTIVE. The purpose of this study was to determine the overall survival rates in patients with advanced hepatocellular carcinoma (HCC) who undergo treatment with drug-eluting bead (DEB) therapy. MATERIALS AND METHODS. A retrospective review of the clinical HCC database of a single institution was undertaken for patients treated between September 2008 and December 2011. Demographic information, laboratory and imaging findings, procedural details, and outcomes after treatment were obtained. The primary outcome was overall survival, which was stratified by Barcelona Clinic Liver Cancer (BCLC) stage, Child-Pugh class, Eastern Cooperative Oncology Group (ECOG) score, serum bilirubin level, and ethnicity. Multiple secondary independent variables were also measured. RESULTS. Of 239 consecutive patients treated during the prescribed time frame, 43 patients met the inclusion criteria. Thirty patients met the criteria for BCLC stage C, and 13 met the criteria for BCLC stage D based largely on ECOG score. Eight patients had venous invasion or portal venous thrombosis, and four had limited extrahepatic metastases. Eight patients had Child-Pugh class C liver disease but remained candidates for liver transplant based on the Milan criteria. The median overall survival was 596 days; 23 patients are still alive, 12 of whom underwent liver transplant. The only independent variables affecting survival were serum bilirubin value of 2.0 mg/dL or greater (hazard ratio [HR] = 3.96; 95% CI, 1.46-10.7; p = 0.007) and Child-Pugh class B or C disease (HR = 3.33; 95% CI, 1.07-10.34; p = 0.037). CONCLUSION. The use of DEBs for TACE therapy is safe and effective in carefully selected patients with advanced HCC.

Downstaging disease in patients with hepatocellular carcinoma outside of Milan criteria: strategies using drug-eluting bead chemoembolization.

PURPOSE: To assess downstaging rates in patients with United Network for Organ Sharing stage T3N0M0 hepatocellular carcinoma (HCC) treated with doxorubicin-eluting bead transarterial chemoembolization to meet Milan criteria for transplantation. MATERIALS AND METHODS: A single-center retrospective review of 239 patients treated with doxorubicin-eluting bead (DEB) chemoembolization between September 2008 and December 2011 was undertaken. Baseline and follow-up computed tomography or magnetic resonance imaging was assessed for response based on the longest enhancing axial dimension of each tumor (ie, modified Response Evaluation Criteria In Solid Tumors measurements), and medical records were reviewed. Fisher exact tests and exact logistic regression were used to test the association of patient and disease characteristics with downstaging. RESULTS: After exclusions, 22 patients remained in the analysis, 17 of whom (77%) had their HCC downstaged to meet Milan criteria. Among those whose disease was downstaged, seven underwent transplantation, one remained listed for transplantation, six had disease progression beyond Milan criteria, two underwent conventional transarterial chemoembolization, and one underwent radiofrequency ablation. The seven patients who received transplants were still living, but recurrent HCC developed in two. Baseline age (P = .25), Model for End-stage Liver Disease score (P = .77), and α-fetoprotein (AFP) level (P = 1.00) were similar between patients with and without downstaged HCC. No associations were observed between the odds of downstaging and sex (P = .21), Child-Pugh class (P = .14), Child-Pugh class controlling for baseline tumor multiplicity (P = .15), Eastern Cooperative Oncology Group performance status (P = 1.00), tumor burden (P = .31), multiple tumors (P = .31), or hepatitis C virus infection (P = 1.00). Fifteen patients who did not receive transplants were alive at 1 year, with two progression-free. Baseline AFP levels differed between those who survived 1 year and those who did not (P = .02), but did not differ by progression-free survival status (P = .62). CONCLUSIONS: T3N0M0 HCC treatment with DEB chemoembolization has a high likelihood (77%) of downstaging the disease to meet Milan criteria.

Hyperintense white matter lesions in 50 high-altitude pilots with neurologic decompression sickness.

INTRODUCTION: Neurologic decompression sickness (NDCS) can affect high-altitude pilots, causing variable central nervous system symptoms. Five recent severe episodes prompted further investigation. METHODS: We report the hyperintense white matter (HWM) lesion imaging findings in 50 U-2 pilot volunteers, and compare 12 U-2 pilots who experienced clinical NDCS to 38 U-2 pilots who did not. The imaging data were collected using a 3T magnetic resonance imaging scanner and high-resolution (1-mm isotropic) three-dimensional fluid-attenuated inversion recovery sequence. Whole-brain and regional lesion volume and number were compared between groups. RESULTS: The NDCS group had significantly increased whole brain and insular volumes of HWM lesions. The intergroup difference in lesion numbers was not significant. CONCLUSION: A clinical episode of NDCS was associated with a significant increase in HWM lesion volume, especially in the insula. We postulate this to be due to hypobaric exposure rather than hypoxia since all pilots were maintained on 100% oxygen throughout the flight. Further studies will be necessary to better understand the pathophysiology underlying these lesions.

Nonsteroidal anti-inflammatory drugs increase TNF production in rheumatoid synovial membrane cultures and whole blood.

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase activity and hence PG production. However, the ability of NSAIDs to ameliorate pain and tenderness does not prevent disease progression in rheumatoid arthritis, a disease whose pathogenesis is linked to the presence of proinflammatory cytokines, such as TNF-alpha. To understand this observation, we have examined the effect of NSAIDs on the production of clinically validated proinflammatory cytokines. We show that a variety of NSAIDs superinduce production of TNF from human peripheral blood monocytes and rheumatoid synovial membrane cultures. A randomized, double-blinded, crossover, placebo-controlled trial in healthy human volunteers also revealed that the NSAID drug celecoxib increased LPS-induced TNF production in whole blood. NSAID-mediated increases in TNF are reversed by either the addition of exogenous PGE(2) or by a PGE(2) EP2 receptor agonist, revealing that PGE(2) signaling via its EP2 receptor provides a valuable mechanism for controlling excess TNF production. Thus, by reducing the level of PGE(2), NSAIDs can increase TNF production and may exacerbate the proinflammatory environment both within the rheumatoid arthritis joint and the systemic environment.