Faculty Bibliography

BACKGROUND: Patients who present with stage IV gastric cancer are not commonly managed with surgical resection as effective palliation can usually be accomplished with systemic chemotherapy, endoscopic stenting, or surgical bypass procedures. Given the inherent morbidity and mortality associated with gastrectomy, palliative resection for stage IV gastric cancer should be reserved for ideal surgical candidates who are most likely to benefit from the procedure. The purpose of this study is to review outcomes following resection for stage IV gastric cancer, and to identify criteria predictive of improved outcomes following gastrectomy in this setting. METHODS: A retrospective review of a prospective GI oncology database was conducted. Sixty-three patients with stage IV gastric cancer managed with surgical resection between 1989 and 2001 were identified. Variables including demographic data, patterns of distant spread (ex: peritoneal, lymphatic, hematogenous), location of tumor, and type of gastrectomy were utilized to conduct survival analyses. RESULTS: Actuarial survival for all patients at one and 3-year intervals was 52% and 12%, respectively. Improved survival was observed for patients of East Asian race (median survival 20 vs. 12 months, P < 0.05, students t-test) and age less than 60 years (median survival 15 vs. 12 months, P < 0.05). This trend was also illustrated by Kaplan-Meier survival analysis. Other variables including pattern of distant spread, location of tumor, and type of gastrectomy were not associated with a significant difference in survival. Both East Asian race and age less than 60 years were statistically significant predictors of improved survival when assessed by univariate regression analysis. When variables were analyzed in a multivariate regression analysis, Asian race and age <60 both lost their statistical significance as independent predictors of improved survival. CONCLUSIONS: Long-term survival for patients with stage IV gastric cancer who are managed with surgical resection is achievable. Patient specific variables including East Asian race and age less than 60 years appear to be associated with prolonged survival when assessed by comparison of means, Kaplan-Meier analysis, and univariate regression analysis. However, multivariate regression analysis failed to demonstrate these factors as independent predictors of improved outcome. In conclusion, highly selected acceptable risk surgical candidates with stage IV gastric cancer should be considered for management with surgical resection in clinically appropriate scenarios

BACKGROUND: Overexpression of Neutral Endopeptidase (NEP) has been reported in metastatic carcinomas, implicating NEP in tumor progression and suggesting a role for NEP inhibitors in its treatment. We investigated the role of NEP expression in the clinical progression of cutaneous melanoma. METHODS: We screened 7 melanoma cell lines for NEP protein expression. NEP-specific siRNA was transfected into the lines to examine the role of gene transcription in NEP expression. Immunohistochemistry was done for 93 specimens and correlated with clinicopathologic parameters. Thirty-seven metastatic melanoma specimens were examined for NEP transcript expression using Affymetrix GeneChips. In a subset of 25 specimens for which both transcript and protein expression was available, expression ratios were used to identify genes that co-express with NEP in GeneChip analysis. RESULTS: NEP was overexpressed in 4/7 human melanoma cell lines, and siRNA knock-down of NEP transcripts led to downregulation of its protein expression. NEP protein overexpression was significantly more common in metastatic versus primary tumors (P = 0.002). Twelve of 37 (32%) metastatic tumors had increased NEP transcript expression, and an association was observed between NEP transcript upregulation and protein overexpression (P < 0.0001). Thirty-eight genes were found to significantly co-express with NEP (p < 0.005). Thirty-three genes positively correlated with NEP, including genes involved in the MAP kinase pathway, antigen processing and presentation, apoptosis, and WNT signaling pathway, and 5 genes negatively correlated with NEP, including genes of focal adhesion and the notch signaling pathways. CONCLUSION: NEP overexpression, which seems to be largely driven by increased transcription, is rare in primary melanoma and occurs late in melanoma progression. Functional studies are needed to better understand the mechanisms of NEP regulation in melanoma

BACKGROUND/AIMS: Squamous cell carcinoma of the colon is a rare entity. We report a case of a patient who presented with a perforated squamous cell carcinoma of the sigmoid colon. RESULTS: A 45-year-old female presented with a 2-month history of worsening abdominal pain, bloody diarrhea, and vomiting. She underwent an exploratory laparotomy and was found to have keratinizing squamous cell carcinoma of the sigmoid colon that had perforated forming multiple abscess cavities. The postoperative course was complicated by hypercalcemia and persistent hyperleukocytosis, ultimately resulting in the patient's death. CONCLUSIONS: We present the second reported case of squamous cell carcinoma of the colon associated with hypercalcemia and the first reported case of associated hyperleukocytosis