Faculty Bibliography

BACKGROUND: In patients with T1b-T3b cutaneous melanoma the utility of radiologic imaging at the time of diagnosis is unclear. Whether initial imaging led to a change in stage or treatment plan was investigated. METHODS: The melanoma database was searched for patients with T1b-T3b primary lesions, clinically N0, and asymptomatic for metastatic disease. Radiologic studies conducted before wide local excision +/- sentinel lymph node biopsy as well as all further imaging and investigations were analyzed. Outcome measures included upstaging, change in initial surgical management, true-positive, false-positive, true-negative, and false-negative rates of each imaging modality. RESULTS: In all, 344 preoperative imaging studies (chest x-ray [CXR], computed tomography [CT], positron emission tomography [PET]/CT) were performed on 158 patients, resulting in 49 findings suspicious for metastatic melanoma and 134 findings suggestive of nonmelanoma pathology. Only 1 of 344 (0.3%) studies, a PET/CT, correlated with confirmed metastatic melanoma. The false-positive rates were CXR 5 of 7 (71.4%), chest CT 21 of 24 (87.5%), abdomen/pelvis CT 10 of 11 (90.9%), head CT 2 of 2 (100.0%), PET/CT 3 of 5 (60.0%). No patient was upstaged or had a change in initial surgical management based on preoperative imaging. The cost of all initial imaging and imaging to follow-up abnormal findings was estimated as $555,308 for the 158 patients studied. CONCLUSIONS: Imaging at the time of initial diagnosis of T1b-T3b, clinically N0, M0 melanoma was of low yield with a high false-positive rate, and did not lead to upstaging or change in initial surgical management. These findings suggest that imaging of asymptomatic patients at the time of diagnosis may not be warranted

The authors report and discuss a case of a mucinous carcinoma of the appendix, a rare entity with a distinct natural history that poses diagnostic and therapeutic challenges. Mucinous peritoneal carcinomatosis is most commonly associated with primary tumors of the appendix and colon. Typically, spread remains confined to the abdominal cavity. Imaging assessment of these mucinous lesions is difficult, while tumor markers (CEA and CA19.9) may be surrogates for extent of disease. Treatment consists of surgical debulking, sometimes coupled with intraperitoneal drug delivery, but recurrence is universal. New treatment approaches are needed. Mucin genes are regulated in part by epidermal growth factor receptor signaling. Therefore, we initiated a phase II study of cetuximab for mucinous peritoneal carcinomatosis, that was part of this patient's treatment

Cancer/testis (CT) antigens are potential targets for cancer immunotherapy, with NY-ESO-1 being among the most immunogenic. In several clinical trials in malignant melanoma (MM) patients, NY-ESO-1 protein/peptides showed clear evidence of inducing specific immunity. However, little is known about NY-ESO-1 expression in primary and metastatic MM and its relationship to disease progression. We analyzed NY-ESO-1 expression immunohistochemically in a series of primary and metastatic MMs and its relation to prognostic parameters and survival. We studied 61 primary and 63 metastatic MM specimens (from 61 and 56 patients, respectively). The prevalence of NY-ESO-1 expression was significantly higher in metastatic versus primary tumors [18/56 (32%) versus 8/61 (13%), P = 0.015]. There was a significant association between initial stage at presentation and NY-ESO-1 expression [stage I (3.45%), stage II (9.52%) and stage III (45.45%), P = 0.0014]. Primary MMs expressing NY-ESO-1 were significantly thicker than NY-ESO-1 negative cases (median thickness 4.7 mm versus 1.53 mm respectively, P = 0.03). No significant difference was seen in overall survival. In conclusion, NY-ESO-1 is more frequently expressed in metastatic than in primary MM and its expression is associated with thicker primary lesions and a higher frequency of metastatic disease, indicative of a worse prognosis. Our study suggests that patients with metastatic MM who express NY-ESO-1 may benefit from NY-ESO-1-based immunotherapy

BACKGROUND: Sustainable international surgery expertise is more frequently being discussed in the US surgical community. At the resident level, there is discussion about incorporating international experience into residency training, but current opportunities for residents are limited and often require personal funding and use of vacation time. This study analyzed resident interest in acquiring international experience. STUDY DESIGN: A structured questionnaire was administered anonymously to all New York University general surgery residents. The questionnaire elicited demographic information and information about interest in an international surgery elective and future volunteerism. Descriptive statistics and chi-square analyses were performed for the completed data. RESULTS: Fifty-two of 63 residents (82.5%) completed surveys. Fifty-one residents (98%) were interested in an international elective, and 38 residents (73%) would prioritize such an elective over all other electives. Twenty-three (44%) and 25 (48%) residents would be willing to use vacation and finance the elective, respectively. The most frequent expectations of international training were acquiring technical and clinical skills (94% of residents) and cultural skills (88%). Residents believed financial difficulties and scheduling conflicts were the most significant barriers to international training (82% and 53%, respectively). Thirty-two residents (62%) planned to incorporate volunteer work into their future practice. Chi-square analyses revealed a significant relationship between residents who would prioritize international training and those who planned to incorporate volunteerism into their future practice (p<0.01). CONCLUSIONS: International training represents an opportunity for US surgical education to provide residents with broader clinical expertise and increased cultural awareness. Our data suggest that surgical residents at NYU are strongly interested in acquiring this experience and that international training may provide an opportunity to encourage lifelong volunteerism. National study of US residents and faculty is warranted to further investigate these conclusions

Mutations in the BRAF oncogene at amino acid 600 have been reported in 40 to 70% of human metastatic melanoma tissues, and the critical role of BRAF in the biology of melanoma has been established. Sampling the blood compartment to detect the mutational status of a solid tumor represents a highly innovative advance in cancer medicine, and such an approach could have advantages over tissue-based techniques. We report the development of a fluorescence-based polymerase chain reaction (PCR) assay to detect mutant BRAF alleles in plasma. A mutant-specific PCR assay was optimized to specifically amplify the mutant BRAF allele without amplifying the wild-type allele. Experiments mixing DNA from a BRAF mutant melanoma cell line with wild-type human placental DNA in varying proportions were performed to determine the threshold of this assay and to compare it with routine DNA sequencing. The assay was then applied to tissue and plasma specimens from patients with metastatic melanoma. The assay detected 0.1 ng of mutant DNA mixed in 100 ng of wild-type DNA and was 500-fold more sensitive than DNA sequencing. The assay detected mutant BRAF alleles in plasma samples from 14 of 26 (54%) metastatic melanoma patients. These data demonstrate the feasibility of blood-based testing for BRAF mutations in metastatic melanoma patients

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