The high rate of mortality and frequent incidence of recurrence associated with hepatocellular carcinoma (HCC) reveal the need for new therapeutic approaches. In this report, we evaluated the efficacy of a novel chemo-immunotherapeutic strategy to control HCC and investigated the underlying mechanism that increased the antitumor immune response. We developed a novel orthotopic mouse model of HCC through seeding of tumorigenic hepatocytes from SV40 T antigen (Tag) transgenic MTD2 mice into the livers of syngeneic C57BL/6 mice. These MTD2-derived hepatocytes form Tag expressing HCC tumors specifically within the liver. This approach provides a platform to test therapeutic strategies and antigen specific immune-directed therapy in an immunocompetent murine model. Using this model, we tested the efficacy of a combination of oral sunitinib, a small molecule multi-targeted receptor tyrosine kinase (RTK) inhibitor, and adoptive transfer of tumor antigen-specific CD8+ T cells to eliminate HCC. Sunitinib treatment alone promoted a transient reduction in tumor size. Sunitinib treatment combined with adoptive transfer of tumor antigen-specific CD8+ T cells led to elimination of established tumors without recurrence. In vitro studies revealed that HCC growth was inhibited through suppression of STAT3 signaling. In addition, sunitinib treatment of tumor-bearing mice was associated with suppression of STAT3 and a block in T cell tolerance. Conclusion These findings indicate that sunitinib inhibits HCC tumor growth directly through the STAT3 pathway and prevents tumor antigen-specific CD8+ T cell tolerance, thus defining a synergistic chemo-immunotherapeutic approach for HCC.

The outcome of patients with colorectal liver metastases (CLM) undergoing surgical resection in the era of effective chemotherapy is not widely reported. In addition, factors associated with disease-specific survival (DSS) in a contemporary series of patients are not well defined. Clinical, pathologic, and outcome data for 64 patients with CLM treated by a single surgeon in a multidisciplinary setting from February 2002 to October 2007 were examined. Hepatic resection was combined with radiofrequency ablation (RFA) in 23 (36%) cases. Secondary or tertiary resection was undertaken in 12 (19%) patients. Synchronous CLM were noted in 25 (39%) cases. Neoadjuvant chemotherapy was given to 41 (64%) patients. Following hepatic resection, adjuvant chemotherapy was administered in 52 (81%) cases. There was one (2%) operative mortality. One or more complications were noted in 24 (38%) patients. Median length of hospital stay was 7 (2-7) days. Five-year DSS and overall survival were 72% and 69%, respectively. Bilobar disease (p < 0.001), local tumor extension (p = 0.02), response to neoadjuvant chemotherapy (p = 0.005), preoperative portal vein embolization (p = 0.05), number of hepatic lesions (p = 0.03), positive resection margin (p < 0.001), and node-positive primary disease (p = 0.001) were prognostically significant factors on univariate analysis. On multivariate analysis, bilobar disease (p = 0.02) and local tumor extension (p = 0.02) were the only two independent prognostic factors. We conclude that, in patients with CLM, a multidisciplinary approach encompassing an aggressive surgical policy achieves excellent 5-year survival results with acceptable operative morbidity and mortality. Bilobar disease and local extrahepatic extension of cancer appear to be independent prognostic factors for long-term survival.

Nonpuerperal subareolar mastitis and abscess is a benign breast entity often associated with prolonged morbidity. Through better understanding of the underlying disease process the imaging, physical, and clinical findings of this rare process can be more readily recognized and treatment options expedited, improving patient care.

A classic PD combined with an antecolic anastomosis and retrogastric vascular omental patch results in a significant reduction in DGE.