Persistent disparities in liver transplantation for patients with hepatocellular carcinoma in the United States, 1998 through 2007.

BACKGROUND: Prior studies have demonstrated that among patients with hepatocellular carcinoma (HCC), African Americans (AAs) and Asian/Pacific Islanders (APIs) are substantially less likely to undergo liver transplantation (LT) compared with whites. The authors examined whether disparities in the receipt of LT among LT-eligible HCC patients changed over a 10-year time period, and whether the disparities might be explained by sociodemographic or clinical factors. METHODS: The National Cancer Data Base, a national hospital-based cancer registry, was used to study 7707 adults with small (≤ 5 cm), nonmetastatic HCC diagnosed between 1998 and 2007. Racial/ethnic patterns in the use of LT were compared during 2 periods of 5 years each: 1998 through 2002 (n = 2412 patients) and 2003 through 2007 (n = 5295 patients). Data regarding comorbid medical conditions were only available during the later time period. RESULTS: Large and persistent racial/ethnic differences in the probability of receiving LT were observed. Compared with whites, hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) for receiving LT from 1998 through 2002 were 0.64 (95% CI, 0.46-0.89) for AA patients, 1.01 (95% CI, 0.79-1.29) for Hispanic patients, and 0.52 (95% CI, 0.39-0.68) for API patients. Analogous results for 2003 through 2007 were 0.64 (95% CI, 0.54-0.76) for AA patients, 0.86 (95% CI, 0.75-0.99) for Hispanic patients, and 0.58 (95% CI, 0.49-0.69) for API patients. AA patients were less likely than whites to undergo any form of surgery, and API patients were more likely than whites to undergo surgical resection. Adjustment for sociodemographic and clinical factors produced only small changes in these HRs. CONCLUSIONS: Between 1998 and 2007, there were large and persistent racial/ethnic disparities noted in the receipt of LT among patients with HCC. These disparities were not explained by sociodemographic or clinical factors.

Direct evidence for rapid and selective induction of tumor neovascular permeability by tumor necrosis factor and a novel derivative, colloidal gold bound tumor necrosis factor.

Tumor necrosis factor (TNF) causes regression of advanced cancers when used in isolation perfusion with melphalan; evidence suggests these effects are mediated via selective yet uncharacterized actions on tumor neovasculature. A novel derivative, colloidal gold bound TNF (cAu-TNF) has been shown to have similar antitumor effects as native TNF with less systemic toxicity in mice. These studies were done to determine their effects on tumor neovasculature, using in vivo video microscopy. Female C57BL/6 mice bearing 20 mm(2) MC38 or LLC tumors that are TNF sensitive and resistant tumors, respectively, had dorsal skinfold chambers implanted. The rate of interstitial accumulation of Texas red fluorescently labeled albumin in tumor and normal vasculature was measured after intravenous TNF, cAu-TNF or PBS. Changes in interstitial fluorescent intensity over time were quantified as a reflection of alterations in vascular permeability. MC38 bearing mice treated with TNF or cAu-TNF demonstrated a rapid, selective and significant increase in tracer accumulation in areas of neovasculature compared to those of normal vasculature. Experiments in LLC tumor bearing mice showed similar results. Monoclonal antibody against tissue factor partially abrogated the effects of TNF on MC38 neovasculature. These data provide direct evidence that TNF and cAu-TNF selectively and rapidly alter permeability in tumor neovasculature; a phenomenon that may be exploited to enhance selective delivery of chemotherapeutics to tumor.

Detection and quantitation of serum mesothelin, a tumor marker for patients with mesothelioma and ovarian cancer.

PURPOSE: To determine whether mesothelin, a cell surface protein highly expressed in mesothelioma and ovarian cancer, is shed into serum and if so to accurately measure it. EXPERIMENTAL DESIGN: We developed a sandwich ELISA using antibodies reacting with two different epitopes on human mesothelin. To quantitate serum mesothelin levels, a standard curve was generated using a mesothelin-Fc fusion protein. Sera from 24 healthy volunteers, 95 random hospital patients, 56 patients with mesothelioma, and 21 patients with ovarian cancer were analyzed. Serum mesothelin levels were also measured before and after surgical cytoreduction in six patients with peritoneal mesothelioma. RESULTS: Elevated serum mesothelin levels were noted in 40 of 56 (71%) patients with mesothelioma and in 14 of 21 (67%) patients with ovarian cancer. Serum mesothelin levels were increased in 80% and 75% of the cases of mesothelioma and ovarian cancer, respectively, in which the tumors expressed mesothelin by immunohistochemistry. Out of the six patients with peritoneal mesothelioma who underwent surgery, four had elevated serum mesothelin levels before surgery. Out of these four patients, three had cytoreductive surgery and the serum mesothelin level decreased by 71% on postoperative day 1 and was undetectable by postoperative day 7. CONCLUSIONS: We developed a serum mesothelin assay that shows that mesothelin is elevated in patients with mesothelioma and ovarian cancer. The rapid decrease in mesothelin levels after surgery in patients with peritoneal mesothelioma suggests that serum mesothelin may be a useful test to monitor treatment response in mesothelin-expressing cancers.

Computer-assisted detection of subcutaneous melanomas: feasibility assessment.

RATIONALE AND OBJECTIVES: Subcutaneous melanomas may be missed on computed tomography because of their peripheral location or perceived unimportance, yet they can have clinical significance. The use of a novel computer-assisted detection scheme to locate subcutaneous melanoma lesions in body CT images was investigated. MATERIALS AND METHODS: The detection software segments subcutaneous fat from the rest of the body and searches for soft tissue density lesions that match a size and shape constraint. Sensitivity and specificity of the proposed method was analyzed by comparing automated lesion detection results in eight patients with 118 subcutaneous melanomas with ground truth data derived from manual tracings of a trained observer. RESULTS: The sensitivity of subcutaneous melanoma detection was 86%. The false-positive rate was 3.1 per slice. Analysis of the false-positives showed that the most common cause was incorrect classification of muscle as a nodule. CONCLUSION: This study showed the feasibility of a fully automatic subcutaneous melanoma lesion detection system having good sensitivity. The false-positive rate was high, but avenues for further reduction were identified.