Objective: Sentinel lymph node (SLN) biopsy has emerged as a viable alternative to complete lymph node dissection in women with endometrial cancer. This technique’s high negative predictive value (NPV) and accuracy have been demonstrated. However, research has also suggested SLN mapping is less successful in obese women. Because obesity is a direct risk factor for endometrial cancer, it is imperative this technique be thoughtfully evaluated in obese women. We sought to define the rate of successful SLN mapping in women with a BMI <30 versus ≥30 among a large cohort.
Objective: Isolated tumor cells (ITC) are tumor deposits measuring ≤0.2 mm, whereas micrometastasis (MM) is defined as a metastatic deposit measuring >0.2 to ≤2 mm. While the characterization of these findings and their significance have been discussed in breast cancer literature, less is known about these results in endometrial cancer. We sought to determine whether patient and disease characteristics correlate with the finding of ITC or MM on sentinel lymph node (SLN) biopsy for endometrial cancer.
Video Objective The objective of this video is to demonstrate the technique of performing an ovarian transposition using robotic assistance in order to preserve ovarian function in a patient who is planning to undergo pelvic radiation therapy. Setting The patient is a 29 y/o nulligravida with a history of stage 3B rectal adenocarcinoma. She is s/p neoadjuvant chemotherapy using Folfox and Capecitabine and is planning for pelvic radiation therapy. She elects to undergo a transposition procedure in order to reduce her risk of premature ovarian failure. Interventions The robotic trocars are placed in the standard gynecologic oncology robotic fashion in order to mobilize the ovaries above the pelvic brim and out of the radiation field. To avoid comprising the ovarian vasculature, retroperitoneal tunnels are created in the pelvic sidewalls bilaterally and the adnexa are pulled through. The ovaries are sutured in place superior to the anterior superior iliac spine and lateral to the psoas muscle. Surgical clips are placed at the border of each ovary for identification during radiation planning. Conclusion Pelvic radiation therapy is often required in the management of gynecologic and nongynecologic malignancies. The ovaries are extremely radiosensitive and very low doses can be associated with a high risk of ovarian failure. Premature menopause results in long-term deprivation of estrogen and can lead to increased risk of all-cause mortality, cardiovascular risk, and osteoporosis. Research indicates that many female patients diagnosed with cancer do not receive adequate information regarding ovarian preservation. One study reports that 50% of oncologists reported moderate to high confidence in knowledge of female fertility preservation. Laparoscopic ovarian transposition is a great surgical option for reproductive age women undergoing gonadotoxic radiation. Robotic assisted ovarian transposition has the advantage of improved visualization and articulation of wrist movements. Robotics can help to overcome the limitations of laparoscopy, especially in complicated procedures. The objective of this video is to demonstrate the technique of performing an ovarian transposition using robotic assistance in order to preserve ovarian function in a patient who is planning to undergo pelvic radiation therapy. The patient is a 29 y/o nulligravida with a history of stage 3B rectal adenocarcinoma. She is s/p neoadjuvant chemotherapy using Folfox and Capecitabine and is planning for pelvic radiation therapy. She elects to undergo a transposition procedure in order to reduce her risk of premature ovarian failure. The robotic trocars are placed in the standard gynecologic oncology robotic fashion in order to mobilize the ovaries above the pelvic brim and out of the radiation field. To avoid comprising the ovarian vasculature, retroperitoneal tunnels are created in the pelvic sidewalls bilaterally and the adnexa are pulled through. The ovaries are sutured in place superior to the anterior superior iliac spine and lateral to the psoas muscle. Surgical clips are placed at the border of each ovary for identification during radiation planning. Pelvic radiation therapy is often required in the management of gynecologic and nongynecologic malignancies. The ovaries are extremely radiosensitive and very low doses can be associated with a high risk of ovarian failure. Premature menopause results in long-term deprivation of estrogen and can lead to increased risk of all-cause mortality, cardiovascular risk, and osteoporosis.
Abstract Objective: To determine the effect of HE4 on expression of immune-related genes in CD8+ T cells and explore the role of HE4 in immunosuppression and angiogenesis in epithelial ovarian cancer (EOC). Methods: Tissue HE4 levels and T cell counts were determined by immunohistochemistry (IHC). Recombinant HE4 (rHE4)-mediated gene expression in CD8+ T cells was measured by qPCR array. Cytokine levels were determined using a human cytokine array. Cell viability of ovarian cancer cells co-cultured with pooled peripheral blood mononuclear cells (PBMC) in the presence or absence of rHE4 was determined using MTS cell viability reagent. P-values were determined by unpaired 2-tailed student t test. Activation of STAT3 was evaluated by Western blot, and the interaction of STAT3 and HE4 was queried by immunoprecipitation of STAT3. Finally, HE4 and IL8 levels were measured by IHC in a microarray of human EOC and normal adjacent tissue (NAT), and levels were correlated using Spearman Rank test. Results: Tissue HE4 levels correlated with CD8+ T cell counts in EOC. rHE4 treatment of CD8+ T cells upregulated expression of a panel of immunosuppressive and proangiogenic genes, including VEGF, HIF1A, STAT3, IDO1, FOXP3, and IL8. IL8 was most robustly upregulated (99-fold vs control). HE4 also resulted in alterations in cytokine levels in ovarian cancer cells co-cultured with PBMCs. OVCAR8 and SKOV3 ovarian cancer cell lines were treated with rHE4, and levels of phospho-STAT3—a known regulator of IL8—were measured. HE4 was found to activate STAT3 in a time-dependent manner, which occurred in the absence of a physical interaction between HE4 and STAT3. rHE4 treatment of OVCAR8 and SKOV3 cells co-cultured with PBMCs suppressed PBMC-mediated cytotoxicity. Finally, IL8 and HE4 mean levels were elevated in EOC tissue compared to NAT and significantly correlated (R=0.49332; p=0.00142). Conclusions: HE4 upregulates expression of genes involved in promoting a proangiogenic and immunosuppressive microenvironment in EOC, which may play a role in reduced cytotoxic ability of immune cells. Upregulation of IL8 may occur via HE4 regulation of STAT3 signaling. Future directions include testing the effect of HE4 on endothelial cell angiogenesis and determining if STAT3 and VEGF inhibitors modulate HE4 suppression of immune cell cytotoxicity. Citation Format: Nicole James, Jenna Emerson, Ashley Borgstadt, Lindsey Beffa, Anze Urh, Kyukwang Kim, Rakesh Singh, Richard Moore, Paul DiSilvestro, Jennifer Ribeiro. Genomic analysis of immunosuppressive and proangiogenic genes in recombinant HE4 treated immune cells and implications for T-cell cytotoxicity in ovarian cancer cell co-culture [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B33.
Objective: Our objective was to evaluate the learning curve for surgeons in identification of sentinel lymph nodes.
Objective: Sentinel node biopsy is the standard of care for the assessment of nodal status in breast and skin cancers. The National Comprehensive Cancer Network guidelines now include sentinel lymph node dissection (SLND) as an option for nodal evaluation in women with endometrial cancer. The objective of this study was to evaluate the surgical learning curve, describe our experience with high-grade tumors, and examine the performance characteristics of SLND.
Introduction: The biomarker HE4 is overexpressed in EOC and is associated with chemoresistance and decreased survival. Tumor infiltrating lymphocytes (TIL) by CD8+ cells is correlated with improved overall and progression-free survival and inversely correlates with programmed death ligand 1 (PD-L1) expression. The objective of this study was to evaluate the role HE4 plays in modulating immune functions in EOC through its effect on PD-L1 expression and CD8+ TIL.
Objectives: Determining which endometrial and cervical cancer patients will benefit from nodal staging is controversial. Sentinel lymph node (SLN) biopsy can be useful as an adjunct to lymphadenectomy in high-risk patients, but more importantly is employed as an alternative method of nodal evaluation for patients with low-risk tumors. The objectives of this study were to evaluate the surgical learning curve and to examine the performance characteristics of SLN dissection.