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36


Immune response in melanoma: an in-depth analysis of the primary tumor and corresponding sentinel lymph node

Ma, Michelle W; Medicherla, Ratna C; Qian, Meng; Vega-Saenz de Miera, Eleazar; Friedman, Erica B; Berman, Russell S; Shapiro, Richard L; Pavlick, Anna C; Ott, Patrick A; Bhardwaj, Nina; Shao, Yongzhao; Osman, Iman; Darvishian, Farbod
The sentinel lymph node is the initial site of metastasis. Downregulation of antitumor immunity has a role in nodal progression. Our objective was to investigate the relationship between immune modulation and sentinel lymph node positivity, correlating it with outcome in melanoma patients. Lymph node/primary tissues from melanoma patients prospectively accrued and followed at New York University Medical Center were evaluated for the presence of regulatory T cells (Foxp3(+)) and dendritic cells (conventional: CD11c(+), mature: CD86(+)) using immunohistochemistry. Primary melanoma immune cell profiles from sentinel lymph node-positive/-negative patients were compared. Logistic regression models inclusive of standard-of-care/immunological primary tumor characteristics were constructed to predict the risk of sentinel lymph node positivity. Immunological responses in the positive sentinel lymph node were also compared with those in the negative non-sentinel node from the same nodal basin and matched negative sentinel lymph node. Decreased immune response was defined as increased regulatory T cells or decreased dendritic cells. Associations between the expression of these immune modulators, clinicopathological variables, and clinical outcome were evaluated using univariate/multivariate analyses. Primary tumor conventional dendritic cells and regression were protective against sentinel lymph node metastasis (odds ratio=0.714, 0.067; P=0.0099, 0.0816, respectively). Antitumor immunity was downregulated in the positive sentinel lymph node with an increase in regulatory T cells compared with the negative non-sentinel node from the same nodal basin (P=0.0005) and matched negative sentinel lymph node (P=0.0002). The positive sentinel lymph node also had decreased numbers of conventional dendritic cells compared with the negative sentinel lymph node (P<0.0001). Adding sentinel lymph node regulatory T cell expression improved the discriminative power of a recurrence risk assessment model using clinical stage. Primary tumor regression was associated with prolonged disease-free (P=0.025) and melanoma-specific (P=0.014) survival. Our results support an assessment of local immune profiles in both the primary tumor and sentinel lymph node to help guide therapeutic decisions.
PMCID:3882943
PMID: 22425909
ISSN: 0893-3952
CID: 171118

Development of five new melanoma low passage cell lines representing the clinical and genetic profile of their tumors of origin [Letter]

de Miera, Eleazar Vega-Saenz; Friedman, Erica B; Greenwald, Holly S; Perle, Mary A; Osman, Iman
PMCID:3329580
PMID: 22404973
ISSN: 1755-1471
CID: 164344

An analysis of altered melanoma matrix metalloproteinase-23 (MMP-23) expression and response to immune biologic therapy. [Meeting Abstract]

Krogsgaard, M.; Ma, M. W.; Friedman, E. B.; de Miera, E. Vega-Saenz; Darvishian, F.; Perez-Garcia, A.; Berman, R. S.; Shapiro, R. L.; Christos, P. J.; Osman, I.; Pavlick, A. C.
ISI:000208880302400
ISSN: 0732-183x
CID: 3159202

An analysis of sera-based microRNAs as biomarkers of recurrence in melanoma [Meeting Abstract]

Friedman, E. B.; Shang, S.; de Miera, E. Vega-Saenz; Ma, M. W.; Berman, R. S.; Shapiro, R. L.; Pavlick, A. C.; Hernando, E.; Shao, Y.; Osman, I.
ISI:000208880302374
ISSN: 0732-183x
CID: 3159172

Impact of laparoscopic adjustable gastric banding on pregnancy, maternal weight, and neonatal health

Carelli, Allison M; Ren, Christine J; Youn, Heekoung Allison; Friedman, Erica B; Finger, Anne E; Lok, Benjamin H; Kurian, Marina S; Fielding, George A
BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is a proven method for weight reduction. Less is known about pregnancies in patients after LAGB. METHODS: Information was gathered, through database and survey, on women who underwent LAGB at NYU Medical Center between 2001 and 2008 then became pregnant. RESULTS: Pregnancy occurred in 133 women, resulting in 112 babies, including six sets of twins. The average pre-pregnancy body mass index (BMI) was 32.7. Average weight gain was 11.5 kg, but was higher for those with pre-pregnancy BMI <30.0 compared to BMI >30.0 (16.4 vs 8.6 kg). Of singleton pregnancies, 89% were carried to full term, with cesarean section in 45%. Those with pre-pregnancy BMI <30.0 had a lower rate of cesarean section (35.71%), but it was not statistically significant (p = 0.55). Average birth weight was 3,268.6 g. Eight percent of babies from singleton pregnancies were low birth weight (<2,500 g), and seven percent were high birth weight (>4,000 g). Average Apgar scores at 1 and 5 min were 8.89 and 9.17. Four percent of patients developed gestational diabetes, and 5% developed pre-eclampsia. Band adjustments were performed in 71% of patients. Weight gain was higher in those who had their bands loosened in the first trimester (p = 0.063). Three patients had intrapartum band slips; one required surgery during pregnancy. CONCLUSIONS: LAGB is tolerable in pregnancy with rare intrapartum band slips. Weight gain is less in those with higher pre-pregnancy BMI and those who had their bands filled or not adjusted. Babies born to these mothers are as healthy as the general population
PMID: 20835780
ISSN: 1708-0428
CID: 138309

Laparoscopically assisted components separation technique for ventral incisional hernia repair

Milburn, Meghan L; Shah, Paulesh K; Friedman, Erica B; Roth, J Scott; Bochicchio, Grant V; Gorbaty, Benjamin; Silverman, Ronald P
Reconstruction of the abdominal wall to repair ventral hernias continues to pose a challenge to surgeons due to relatively high rates of recurrence and morbidity. In 1990, Ramirez pioneered a technique of components separation of the abdominal wall for ventral hernia repair. Although an effective hernia repair, the mobilization of skin and subcutaneous tissue endangers the blood supply and predisposes midline skin to necrosis. The goal of this study is to determine whether releasing incisions in the transversus abdominis fascia and posterior rectus sheath provide adequate mobilization of the abdominal wall necessary for ventral hernia repair, thus paving the way for a laparoscopic component separation technique. Ten fresh cadavers were used and one side of the abdomen underwent the conventional Ramirez components separation: midline incision, dissection of skin and subcutaneous tissue off the anterior abdominal wall, and incisions in the external oblique aponeurosis and posterior rectus sheath, while the other side received incisions in the transversus abdominis fascia and the posterior rectus sheath with no undermining of the skin. The amount of fascial translation was measured after each incision. Incising only the external oblique aponeurosis produced greater mobilization of the abdominal wall at the level of the umbilicus (P = 0.02) and anterior superior iliac spine (ASIS, P = 0.029) than releasing only transversus abdominis fascia. More importantly, there was no statistically significant difference in the amount of release produced by the complete internal-release components separation versus the conventional technique. In order to test the feasibility of performing the procedure laparoscopically, one additional cadaver underwent a laparoscopic transversus abdominis fascia release. The procedure was successful and resulted in comparable amounts of fascial release as the other 10 cadavers. From this study, it appears technically feasible to perform a laparoscopic components separation to repair a ventral hernia and the procedure produces the same amount of release as the conventional open component separation technique.
PMID: 17216395
ISSN: 1248-9204
CID: 159141