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Molecular pathogenesis of endometrial intraepithelial neoplasia: Precursor to endometrial cancers
Abstracts / Gynecologic Oncology 141 (2016) 2–208
Conclusions: We propose that the inverse relationship between Snail and let-7 miRNA plays an important role in EOC metastasis. Our collaborators have demonstrated that delivery of mesoporous silica nanoparticles (MSNs) loaded with modified Twist (another EMT TF) siRNA result in smaller breast cancer tumors in xenografts. Further studies are underway to develop a similar experimental set up in our EOC PDX model.
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(4.6%; P = .05) (odds ratio [OR] 0.48, 90% CI 0.24–0.94). However, organ space infections did not differ (3.6% baseline vs 2.9% postintervention, P = .44). SSI after open surgery also decreased by half (20% vs 11%, P = .05) (OR 0.48, 90% CI 0.24–0.95) but not after MIS (2.7% vs 3.6%, P = .52). Postintervention compliance was 61% for preoperative antibacterial soap; 91% for glove change; and 88% for closing instruments. Correct prophylactic antibiotic use was not different (69% baseline vs 75% postintervention, P = .13), but antibiotic redosing improved postintervention (87% baseline vs 94% postintervention, P = .02). Conclusions: This interim analysis of an ongoing QI project found a significant decrease in overall SSI rates using a bundled intervention. The largest decreases were seen in skin infections and SSI after open surgery.
OF
doi:10.1016/j.ygyno.2016.04.210
RO
Objectives: To characterize the relationship between DNA mismatch repair (MMR), ARID1A, and PTEN in endometrial intraepithelial neoplasia (EIN). Background: Type 1 endometrial carcinoma typically develops from a precursor lesion, endometrial hyperplasia, or EIN. The DNA MMR system prevents tumor progression by correcting errors that occur during DNA replication and is present in a proportion of endometrial cancers. Tumor suppressor genes ARID1A and PTEN are also implicated in the molecular pathogenesis of endometrial carcinoma. Previous studies have shown that in endometrial carcinoma, MMR deficiency may be associated with ARID1A mutations. However, in EIN, the relationship between loss of expression (LOE) of MMR, ARID1A, and PTEN has yet to be established. Methods: A retrospective review identified 113 patients with EIN on endometrial biopsy from 2009 to 2014. Tissue microarray blocks were evaluated with immunohistochemical stains using antibodies against MLH1, PMS2, MSH2, MSH6, ARID1A, and PTEN. Statistical analyses were performed using a value of P b .05 as statistically significant. Results: In EIN, LOE rates of MMR, ARID1A, and PTEN were 4.4% (n = 5), 6.2% (n = 7), and 50.4% (n = 57), respectively. LOE of MMR was not significantly associated with expression of ARID1A (P = 1.000) or PTEN (P = .2062). Development of a subsequent invasive malignancy was not significantly associated with LOE of ARID1A (P = .1135), DNA MMR (P = .2424), or PTEN (P = .1670). When combined, LOE of ARID1A and MMR was significantly associated with subsequent cancer (P = .0109). Conclusions: In this series of EIN, the LOE frequency of PTEN (50.4%) agreed with that seen in previous studies. Unlike rates demonstrated in endometrial carcinoma, the proportion of LOE of MMR (4.4%) and ARID1A (6.2%) seen in the precursor lesion were relatively low and thus seems to be nonessential in the development of EIN. There were no cases of concordant LOE of MMR and ARID1A, suggesting independent pathways or differences in temporal patterns in gene expression during the premalignant phase. When combined, LOE of ARID1A and MMR was significantly associated with the development of a subsequent malignancy, suggesting potential prognostic markers, which will require further evaluation.
DP
Fig. 1. Tumor Progression Post Ovarian Bursa Injections of Patient-derived Ovarian Cancer Cells, Control vs. Snail Knockdown.
179 – Poster Molecular pathogenesis of endometrial intraepithelial neoplasia: Precursor to endometrial cancers J.W.H. Wong. John A. Burns School of Medicine at the University of Hawaii, Honolulu, HI, USA
doi:10.1016/j.ygyno.2016.04.209
TE
178 – Poster The DISINFECT initiative: Decreasing the incidence of surgical INFECTions in gynecologic oncology J.S. Taylor, C.A. Marten, D.C. Bodurka, J.K. Burzawa, M.F. Munsell, K. Potts, A.M. Nick, L.A. Meyer, C.F. Levenback, K.M. Schmeler. The University of Texas MD Anderson Cancer Center, Houston, TX, USA
UN
CO
RR
EC
Objectives: To evaluate the impact of a bundled intervention on surgical site infection (SSI) rates after surgery for gynecologic cancer. Methods: We performed a quality improvement (QI) project to decrease SSI rates after open and minimally invasive surgery (MIS) using the following interventions: patient education; preoperative antibacterial soap; appropriate antibiotic prophylaxis with redosing; change of gloves and use of clean instruments at surgical closure; surgical dressing for 48 hours; and a postdischarge phone call to assess for infection. SSI was defined as an infection of the surgical incision or organ space requiring antibiotics. Baseline SSI rate within 30 days of surgery was obtained from chart review (May 1, 2014, to June 30, 2014) and compared with postintervention (April 16, 2015, to July 15, 2015) data. Patient demographics, clinical characteristics, compliance, and SSI rates were compared between groups using the Fisher exact and Mann-Whitney tests. Results: A total of 166 baseline cases were compared with 241 postintervention cases. Median body mass index for the baseline and postintervention groups was 27.6 and 28.2 kg/m2, respectively (P = .66). Seventy-five baseline MIS surgeries (45%) were performed versus 138 (58%) in the postintervention cases (P = .02). Disease sites in the baseline and postintervention groups included the ovary (51% vs 33%), uterus (22% vs 25%), cervix (4% vs 9%), and benign disease (23% vs 34%). Chemotherapy and/or radiotherapy was given preoperatively in 37 (22%) baseline cases compared with 36 (15%) postintervention cases (P = .07). Bowel resection was performed in 44 (27%) and 58 (24%) baseline and postintervention cases, respectively (P = .64). Overall SSI rate decreased from baseline to postintervention (12% vs 6.6%, P = .04). Skin infections (superficial and deep) decreased by half from baseline (9%) to postintervention
doi:10.1016/j.ygyno.2016.04.211
Conclusions: We propose that the inverse relationship between Snail and let-7 miRNA plays an important role in EOC metastasis. Our collaborators have demonstrated that delivery of mesoporous silica nanoparticles (MSNs) loaded with modified Twist (another EMT TF) siRNA result in smaller breast cancer tumors in xenografts. Further studies are underway to develop a similar experimental set up in our EOC PDX model.
73
(4.6%; P = .05) (odds ratio [OR] 0.48, 90% CI 0.24–0.94). However, organ space infections did not differ (3.6% baseline vs 2.9% postintervention, P = .44). SSI after open surgery also decreased by half (20% vs 11%, P = .05) (OR 0.48, 90% CI 0.24–0.95) but not after MIS (2.7% vs 3.6%, P = .52). Postintervention compliance was 61% for preoperative antibacterial soap; 91% for glove change; and 88% for closing instruments. Correct prophylactic antibiotic use was not different (69% baseline vs 75% postintervention, P = .13), but antibiotic redosing improved postintervention (87% baseline vs 94% postintervention, P = .02). Conclusions: This interim analysis of an ongoing QI project found a significant decrease in overall SSI rates using a bundled intervention. The largest decreases were seen in skin infections and SSI after open surgery.
OF
doi:10.1016/j.ygyno.2016.04.210
RO
Objectives: To characterize the relationship between DNA mismatch repair (MMR), ARID1A, and PTEN in endometrial intraepithelial neoplasia (EIN). Background: Type 1 endometrial carcinoma typically develops from a precursor lesion, endometrial hyperplasia, or EIN. The DNA MMR system prevents tumor progression by correcting errors that occur during DNA replication and is present in a proportion of endometrial cancers. Tumor suppressor genes ARID1A and PTEN are also implicated in the molecular pathogenesis of endometrial carcinoma. Previous studies have shown that in endometrial carcinoma, MMR deficiency may be associated with ARID1A mutations. However, in EIN, the relationship between loss of expression (LOE) of MMR, ARID1A, and PTEN has yet to be established. Methods: A retrospective review identified 113 patients with EIN on endometrial biopsy from 2009 to 2014. Tissue microarray blocks were evaluated with immunohistochemical stains using antibodies against MLH1, PMS2, MSH2, MSH6, ARID1A, and PTEN. Statistical analyses were performed using a value of P b .05 as statistically significant. Results: In EIN, LOE rates of MMR, ARID1A, and PTEN were 4.4% (n = 5), 6.2% (n = 7), and 50.4% (n = 57), respectively. LOE of MMR was not significantly associated with expression of ARID1A (P = 1.000) or PTEN (P = .2062). Development of a subsequent invasive malignancy was not significantly associated with LOE of ARID1A (P = .1135), DNA MMR (P = .2424), or PTEN (P = .1670). When combined, LOE of ARID1A and MMR was significantly associated with subsequent cancer (P = .0109). Conclusions: In this series of EIN, the LOE frequency of PTEN (50.4%) agreed with that seen in previous studies. Unlike rates demonstrated in endometrial carcinoma, the proportion of LOE of MMR (4.4%) and ARID1A (6.2%) seen in the precursor lesion were relatively low and thus seems to be nonessential in the development of EIN. There were no cases of concordant LOE of MMR and ARID1A, suggesting independent pathways or differences in temporal patterns in gene expression during the premalignant phase. When combined, LOE of ARID1A and MMR was significantly associated with the development of a subsequent malignancy, suggesting potential prognostic markers, which will require further evaluation.
DP
Fig. 1. Tumor Progression Post Ovarian Bursa Injections of Patient-derived Ovarian Cancer Cells, Control vs. Snail Knockdown.
179 – Poster Molecular pathogenesis of endometrial intraepithelial neoplasia: Precursor to endometrial cancers J.W.H. Wong. John A. Burns School of Medicine at the University of Hawaii, Honolulu, HI, USA
doi:10.1016/j.ygyno.2016.04.209
TE
178 – Poster The DISINFECT initiative: Decreasing the incidence of surgical INFECTions in gynecologic oncology J.S. Taylor, C.A. Marten, D.C. Bodurka, J.K. Burzawa, M.F. Munsell, K. Potts, A.M. Nick, L.A. Meyer, C.F. Levenback, K.M. Schmeler. The University of Texas MD Anderson Cancer Center, Houston, TX, USA
UN
CO
RR
EC
Objectives: To evaluate the impact of a bundled intervention on surgical site infection (SSI) rates after surgery for gynecologic cancer. Methods: We performed a quality improvement (QI) project to decrease SSI rates after open and minimally invasive surgery (MIS) using the following interventions: patient education; preoperative antibacterial soap; appropriate antibiotic prophylaxis with redosing; change of gloves and use of clean instruments at surgical closure; surgical dressing for 48 hours; and a postdischarge phone call to assess for infection. SSI was defined as an infection of the surgical incision or organ space requiring antibiotics. Baseline SSI rate within 30 days of surgery was obtained from chart review (May 1, 2014, to June 30, 2014) and compared with postintervention (April 16, 2015, to July 15, 2015) data. Patient demographics, clinical characteristics, compliance, and SSI rates were compared between groups using the Fisher exact and Mann-Whitney tests. Results: A total of 166 baseline cases were compared with 241 postintervention cases. Median body mass index for the baseline and postintervention groups was 27.6 and 28.2 kg/m2, respectively (P = .66). Seventy-five baseline MIS surgeries (45%) were performed versus 138 (58%) in the postintervention cases (P = .02). Disease sites in the baseline and postintervention groups included the ovary (51% vs 33%), uterus (22% vs 25%), cervix (4% vs 9%), and benign disease (23% vs 34%). Chemotherapy and/or radiotherapy was given preoperatively in 37 (22%) baseline cases compared with 36 (15%) postintervention cases (P = .07). Bowel resection was performed in 44 (27%) and 58 (24%) baseline and postintervention cases, respectively (P = .64). Overall SSI rate decreased from baseline to postintervention (12% vs 6.6%, P = .04). Skin infections (superficial and deep) decreased by half from baseline (9%) to postintervention
doi:10.1016/j.ygyno.2016.04.211