229 results on '"Goldberg GL"'
Search Results
2. Naive and radiolabeled antibodies to E6 and E7 HPV-16 oncoproteins show pronounced antitumor activity in experimental cervical cancer
- Author
-
Phaëton, R, primary, Gutierrez, J, additional, Jiang, Z, additional, Karabakhtsian, RG, additional, Albanese, J, additional, Sunkara, J, additional, Fisher, DR, additional, Goldberg, GL, additional, and Dadachova, E, additional
- Published
- 2015
- Full Text
- View/download PDF
3. Cone cerclage in pregnancy
- Author
-
Goldberg Gl, Block B, and Altaras Mm
- Subjects
Adult ,Pregnancy ,medicine.medical_specialty ,Invasive carcinoma ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Biopsy ,Obstetrics and Gynecology ,Gestational age ,Uterine Cervical Neoplasms ,medicine.disease ,Cervical intraepithelial neoplasia ,Cervical conization ,Surgery ,Cone biopsy ,Medicine ,Gestation ,Humans ,Female ,business ,Ligation ,Pregnancy Complications, Neoplastic - Abstract
We report a technique of cone cerclage and the results and outcome in 17 patients who required a diagnostic cone biopsy in pregnancy. The mean age of the patients was 30.6 years (range 21-41). The mean gestational age was 18.8 weeks (range 10-32) at the time of the procedure. There were no major complications and hemorrhage was not a significant problem. There were no second-trimester abortions. Two patients required beta-sympathomimetics to suppress uterine activity for longer than 24 hours after the procedure. Six patients had invasive carcinoma, nine had cervical intraepithelial neoplasia (CIN) III, and two had CIN II. In 14 cases, the endocervical and ectocervical margins were negative; two patients with CIN and one with multifocal microinvasion had positive margins. Cone cerclage is a safe and easy method for performing diagnostic cervical conization during pregnancy.
- Published
- 1991
4. The influence of proteasome inhibitor MG132, external radiation, and unlabeled antibody on the tumor uptake and biodistribution of (188)re-labeled anti-E6 C1P5 antibody in cervical cancer in mice.
- Author
-
Phaeton R, Wang XG, Einstein MH, Goldberg GL, Casadevall A, Dadachova E, Phaeton, Rébécca, Wang, Xing Guo, Einstein, Mark H, Goldberg, Gary L, Casadevall, Arturo, and Dadachova, Ekaterina
- Abstract
Background: Human papillomavirus (HPV) infection is considered a necessary step for the development of cervical cancer, and >95% of all cervical cancers have detectable HPV sequences. The authors of this report recently demonstrated the efficacy of radioimmunotherapy (RIT) targeting viral oncoprotein E6 in the treatment of experimental cervical cancer. They hypothesized that the pretreatment of tumor cells with various agents that cause cell death and/or elevation of E6 levels would increase the accumulation of radiolabeled antibodies to E6 in cervical tumors.Methods: HPV type 16 (HPV-16)-positive CasKi cells were treated in vitro with up to 6 grays of external radiation, or with the proteasome inhibitor MG-132, or with unlabeled anti-E6 antibody C1P5; and cell death was assessed. The biodistribution of (188)Re-labeled C1P5 antibody was determined in both control and radiation MG-132-treated CasKi tumor-bearing nude mice.Results: (188)Re-C1P5 antibody demonstrated tumor specificity, very low uptake, and fast clearance from the major organs. The amount of tumor uptake was enhanced by MG-132 but was unaffected by pretreatment with radiation. In addition, in vitro studies demonstrated an unanticipated effect of unlabeled antibody on the amount of cell death, a finding that was suggested by the authors' previous in vivo studies in a CasKi tumor model.Conclusions: The current results indicated that pretreatment of cervical tumors with the proteasome inhibitor MG-132 and with unlabeled antibody to E6 can serve as a means to generate nonviable cancer cells and to elevate the levels of target oncoproteins in the cells for increasing the accumulation of targeted radiolabeled antibodies in tumors. These results favor the further development of RIT for cervical cancers targeting viral antigens. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
5. Virulence of papillary endometrial carcinoma
- Author
-
O'Hanlan, KA, primary, Levine, PA, additional, Harbatkin, D, additional, Feiner, C, additional, Goldberg, GL, additional, Jones, JG, additional, and Rodriguez‐Rodriguez, L, additional
- Published
- 1990
- Full Text
- View/download PDF
6. Current issues regarding tamoxifen and the genital tract: a review.
- Author
-
Sukumvanich P, Khabele D, and Goldberg GL
- Published
- 2004
- Full Text
- View/download PDF
7. Malignant mixed müllerian tumor of the uterus in a patient taking raloxifene.
- Author
-
Goldman NA, de Los Angeles MM, Jones JG, and Goldberg GL
- Published
- 2005
- Full Text
- View/download PDF
8. The role of cancer antigen 125 (CA 125) in the management of ovarian epithelial carcinomas
- Author
-
Altaras, MM, primary, Goldberg, GL, additional, and Levin, W, additional
- Published
- 1989
- Full Text
- View/download PDF
9. Molecular diagnosis of genital human papillomavirus infection: Comparison of two methods used to collect exfoliated cervical cells
- Author
-
Vermund, SH, primary, Schiffman, MH, additional, Goldberg, GL, additional, Ritter, DB, additional, Welman, A, additional, and Burk, RD, additional
- Published
- 1989
- Full Text
- View/download PDF
10. Co-expression of GPR30 and ERbeta and their association with disease progression in uterine carcinosarcoma.
- Author
-
Huang GS, Gunter MJ, Arend RC, Li M, Arias-Pulido H, Prossnitz ER, Goldberg GL, Smith HO, Huang, Gloria S, Gunter, Marc J, Arend, Rebecca C, Li, Maomi, Arias-Pulido, Hugo, Prossnitz, Eric R, Goldberg, Gary L, and Smith, Harriet O
- Abstract
Objective: We sought to evaluate the expression of G protein-coupled receptor 30 (GPR30) and estrogen receptor (ER)beta in uterine carcinosarcoma (CS).Study Design: Immunohistochemistry was performed using antibodies to GPR30, ERbeta, ERalpha, and progesterone receptor (PR). The staining intensity and percentage of positive cells were scored for each tissue section. Expression levels were compared using the Wilcoxon rank sum test. Correlation was evaluated by Spearman rho and logistic regression.Results: Compared with normal endometrium, CS had lower ERalpha and PR expression (both P < .01) but higher GPR30 epithelial expression (P = .03). Advanced-stage CS had higher GPR30 (P < .01) and ERbeta (P = .02) epithelial expression compared with early-stage CS. Expression of GPR30 and ERbeta correlated with each other (P < .01), and not with ERalpha or PR.Conclusion: In uterine CS, GPR30 and ERbeta are coordinately overexpressed and expression levels increase in advanced-stage disease, supporting the involvement of alternative ERs in disease progression. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
11. CA-125: A potential prognostic indicator in patients with cervical cancer?
- Author
-
Goldberg, Gl, Sklar, A, O'Hanlan, Ka, Levine, Pa, and Runowicz, CD
- Published
- 1992
- Full Text
- View/download PDF
12. Safety and efficacy of anticoagulant treatment in patients with ovarian vein thrombosis: a systematic review and meta-analysis of observational studies.
- Author
-
Riva N, Muscat-Baron L, Vassallo C, Ageno W, Rottenstreich A, Sauvé N, Wysokinski WE, Goldberg GL, Salomon O, Labropoulos N, Foulon A, AlSheef M, Gatt A, and Calleja-Agius J
- Abstract
Background: The role of anticoagulation in ovarian vein thrombosis (OVT) is uncertain., Objectives: We aimed to evaluate safety and efficacy of anticoagulant treatment in OVT patients., Methods: A systematic search was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases up to April 2024. Eligible studies included randomized controlled trials and observational studies enrolling at least 10 adult patients with objectively diagnosed OVT and treated with any anticoagulants. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42021270883)., Results: We included 17 observational studies (621 anticoagulated and 376 nonanticoagulated OVT patients); 9 studies enrolled mainly pregnancy/puerperium-related OVT. Most patients received heparins alone (45.7%) or proceeded to vitamin K antagonists (39.2%). The average treatment duration was ≤3 months in 8 studies (47.1%), >3 to ≤6 months in 6 studies (35.3%), and >6 months in 3 studies (17.6%). In treated patients, mortality rate was 2.43% (95% CI, 0.54%-5.41%; I
2 = 53.8%; 12/406 patients; 13 studies), major bleeding was 1.27% (95% CI, 0.48%-2.38%; I2 = 2.5%; 7/583 patients; 15 studies), recurrent venous thromboembolism (VTE) was 3.49% (95% CI, 1.12%-6.95%; I2 = 63.5%; 22/482 patients; 15 studies), and vessel recanalization was 89.4% (95% CI, 74.6%-98.6%; I2 = 80.6%; 163/184 patients; 8 studies). The rate of recurrent VTE in untreated patients was 8.65% (95% CI, 2.61%-17.35%); however, the difference compared with treated patients was not statistically significant (risk ratio, 0.70; 95% CI, 0.36-1.37). At subgroup analyses, the rates of major bleeding and recurrent VTE were 0.80% (95% CI, 0.0-2%.17%) and 3.81% (95% CI, 0.42%-9.63%) in pregnancy/puerperium-related OVT, respectively, and 1.12% (95% CI, 0.32%-2.34%) and 1.78% (95% CI, 0.62%-3.46%), respectively, when analyzing only full-text studies., Conclusion: There is paucity of literature regarding OVT. Our results suggest that anticoagulation is associated with low rates of major bleeding and recurrent VTE., (© 2024 The Authors.)- Published
- 2024
- Full Text
- View/download PDF
13. Racial disparities in the treatment of endometrial intraepithelial neoplasia in postmenopausal women.
- Author
-
Seay K, Katcher A, Hare M, Rahman H, Sison C, Goldberg GL, and Frimer M
- Abstract
Disparities in endometrial cancer has increased during the past decade with Black women more likely to be diagnosed at a later stage and have higher mortality. The majority of research has been focused on cultural barriers, socioeconomic status, lack of access to care, comorbidities, and tumor histology to explain these disparities. Limited studies have been conducted on the disparity in the treatment of endometrial intraepithelial neoplasia(EIN). We sought to analyze the differences in treatment used in the management of postmenopausal women with EIN to evaluate whether race/ethnicity is a contributing factor. An IRB approved retrospective study was conducted amongst women at a single institution diagnosed with EIN. Ethnicity/race was defined as non-Hispanic White, non-Hispanic Black, Hispanic, and Asian. Demographic and clinical data was extracted. Multivariable logistic regression was used to examine the association between ethnicity/race and treatment, adjusted for age, BMI, and underlying medical conditions such as cardiovascular disease and diabetes. In total, 254 patients were analyzed. A significant association between ethnicity/race and treatment with non-Hispanic Black women less likely to be treated with surgical management compared to non-Hispanic White women (OR = 0.326, 95 %CI 0.129-0.827, p = 0.026). Importantly, after adjusting for clinical risk factors(age, BMI, CVD, diabetes), non-Hispanic Black women remained at an increased risk of not undergoing surgical intervention (OR = 0.333, 95 % CI 0.125-0.882, p = 0.027). Future research is imperative to evaluate the root cause of this disparity in the healthcare system., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
14. Author Correction: Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors.
- Author
-
Zakrzewski JL, Suh D, Markley JC, Smith OM, King C, Goldberg GL, Jenq R, Holland AM, Grubin J, Cabrera-Perez J, Brentjens RJ, Lu SX, Rizzuto G, Sant'Angelo DB, Riviere I, Sadelain M, Heller G, Zúñiga-Pflücker JC, Lu C, and van den Brink MRM
- Published
- 2024
- Full Text
- View/download PDF
15. Risk of endometrial polyp and surgical intervention in postmenopausal women with proliferative endometrium.
- Author
-
Rotenberg O, Doulaveris G, Fridman D, Renz M, Kaplan J, Xie X, Goldberg GL, and Dar P
- Subjects
- Pregnancy, Female, Humans, Postmenopause, Retrospective Studies, Endometrium surgery, Endometrium pathology, Uterine Hemorrhage etiology, Hysteroscopy adverse effects, Uterine Neoplasms surgery, Uterine Diseases complications, Uterine Diseases surgery, Uterine Diseases pathology, Leiomyoma surgery, Leiomyoma pathology, Polyps complications, Endometrial Neoplasms surgery, Endometrial Neoplasms complications
- Abstract
Objective: To study the long-term risks of postmenopausal women with proliferative endometrium developing benign uterine pathologies (endometrial polyps and uterine fibroids) and requiring future gynecological interventions, and to compare them with women with atrophic endometrium., Design: Retrospective cohort study of all women aged 55 or over who underwent endometrial biopsy between 1/1997 and 12/2008. Outcome data were available through to 2/2018. Women with proliferative endometrium were compared with those with atrophic endometrium for the presence of endometrial polyps, uterine fibroids, future endometrial biopsy for recurrent vaginal bleeding, and future hysteroscopy or hysterectomy. Logistic regression models were used to evaluate the association of endometrial histology and other covariates with the risk of morbidities., Main Findings: Postmenopausal women with proliferative endometrium are at higher risk of developing endometrial polyps, uterine fibroids and need for surgical intervention. Of 1808 women who underwent endometrial biopsy during the study period, 962 met inclusion criteria: 278 had proliferative and 684 had atrophic endometrium. Length of surveillance was similar in the two groups (11.9 vs. 11.5 years, p = 0.2). Compared with women with atrophic endometrium, women with proliferative endometrium had significantly higher rates of endometrial polyps (17.3 % vs 9.7 % p = 0.001). Multivariable logistic regression confirmed that women with proliferative endometrium had more fibroids on ultrasound (62.1 % vs 50.3 % 3 = 0.02), and had increased risks of developing endometrial polyps (aOR 1.9, 95 % CI 1.28-3.07, p = 0.002), repeat endometrial biopsy (34.9 % vs. 16.8%p < 0.001) and future hysterectomy or hysteroscopy (26.6 % vs 16.2 % p < 0.001)., Conclusions: In addition to the long-term increased risk of cancer, postmenopausal women with proliferative endometrium are more likely to have future bleeding, surgical interventions and diagnosis of endometrial polyps. Medical management to reduce estrogenic activity and associated risks may be considered in these cases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2023
- Full Text
- View/download PDF
16. Development of laparoscopic skills in skills-naïve trainees using self-directed learning with take-home laparoscopic trainer boxes.
- Author
-
Crihfield EG, Uppalapati P, Abittan B, Laibangyang A, Brahmbhatt S, Burlingame M, Goldberg GL, and Rabin JM
- Abstract
Background: To determine if take home laparoscopic trainer boxes with only self-directed learning can develop laparoscopic skills in surgically naive learners., Methods: 74 starting PGY1 OB/Gyn residents and OB/Gyn clerkship medical students volunteered for the study. Learners performed a laparoscopic peg transfer task with only task instructions and no additional training. Initial tasks were recorded and scored. The participants took home a laparoscopic trainer box for 3 weeks to practice without guidance and returned to perform the same task for a second/final score. Initial and final scores were compared for improvement. This improvement was compared to practice and variables such as demographics, surgical interest, comfort with laparoscopy, and past experiences., Results: Mean peg transfer task scores improved from 287 (SD = 136) seconds to 193 (SD = 79) seconds ( p < 0.001). Score improvement showed a positive correlation with number of home practice sessions with a linear regression R
2 of 0.134 ( p = 0.001). More practice resulted in larger increases in comfort levels, and higher comfort levels correlated with better final task scores with a linear regression R2 of 0.152 ( p < 0.001). Interest in a surgical specialty had no impact on final scores or improvement. Playing a musical instrument and having two or more dexterity-based hobbies was associated with a better baseline score ( p = 0.032 and p = 0.033 respectively), but no difference in the final scores or score improvement. No other past experiences impacted scores., Conclusions: Our study demonstrates that the use of home laparoscopic box trainers can develop laparoscopic skills in surgical novices even without formal guidance or curriculum., Competing Interests: Drs. Eric G. Crihfield, Pooja Uppalapati, Baruch Abittan, Anya Laibangyang, Sonam Brahmbhatt, Gary L. Goldberg, Jill M. Rabin, and Ms. Madeleine Burlingame have no conflicts of interest or financial ties to disclose., (© 2023 The Authors.)- Published
- 2023
- Full Text
- View/download PDF
17. Cancer-associated fibroblasts promote cancer stemness by inducing expression of the chromatin-modifying protein CBX4 in squamous cell carcinoma.
- Author
-
Fisher ML, Balinth S, Hwangbo Y, Wu C, Ballon C, Goldberg GL, and Mills AA
- Subjects
- Humans, Interleukin-6 metabolism, Cell Line, Tumor, Cell Proliferation genetics, Chromatin metabolism, Neoplastic Stem Cells pathology, Fibroblasts metabolism, Tumor Microenvironment genetics, Ligases genetics, Ligases metabolism, Polycomb-Group Proteins genetics, Polycomb-Group Proteins metabolism, Cancer-Associated Fibroblasts metabolism, Carcinoma, Squamous Cell pathology
- Abstract
The chromobox-containing protein CBX4 is an important regulator of epithelial cell proliferation and differentiation, and has been implicated in several cancer types. The cancer stem cell (CSC) population is a key driver of metastasis and recurrence. The undifferentiated, plastic state characteristic of CSCs relies on cues from the microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of the microenvironment that can influence the CSC population through the secretion of extracellular matrix and a variety of growth factors. Here we show CBX4 is a critical regulator of the CSC phenotype in squamous cell carcinomas of the skin and hypopharynx. Moreover, CAFs can promote the expression of CBX4 in the CSC population through the secretion of interleukin-6 (IL-6). IL-6 activates JAK/STAT3 signaling to increase ∆Np63α-a key transcription factor that is essential for epithelial stem cell function and the maintenance of proliferative potential that is capable of regulating CBX4. Targeting the JAK/STAT3 axis or CBX4 directly suppresses the aggressive phenotype of CSCs and represents a novel opportunity for therapeutic intervention., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2023
- Full Text
- View/download PDF
18. Stress, anxiety, and illness perception in patients experiencing delay in operative care due to the COVID-19 pandemic.
- Author
-
Soloff MA, Keel T, Nizam A, Goldberg GL, Sakaris A, Diefenbach MA, DePeralta DK, and Frimer M
- Abstract
Background: Amid the height of the COVID-19 pandemic in the US, the US Surgeon General ordered hospitals and healthcare systems to stop all elective surgical procedures. The aim of our study was to evaluate the additional mental health impact of surgical delay on patients awaiting surgery for benign, pre-malignant and malignant conditions within the context of the COVID-19 pandemic., Study Design: All patients over the age of 18 awaiting surgery for benign, pre-malignant or malignant conditions within the gynecologic oncology, surgical oncology and colorectal services across Northwell Health were eligible for participation. Upon successful enrollment, participants completed a baseline questionnaire consisting of the Generalized Anxiety Disorder Questionnaire, the Penn State Worry Questionnaire, and Brief-Illness Patient Questionnaire., Results: The surgical delay was considered moderately to extremely concerning by 72 % of survey respondents, with one third indicating the highest (10/10) level of concern. Fifty-five percent of patients with a pre-operatively suspected/confirmed cancer or pre-malignant condition demonstrated mild to severe anxiety in their completion of the GAD-7 scale. The average time awaiting surgery was 117 days (range 8-292); and 63 % of respondents indicated that the delay had a moderate to severe impact on their daily life., Conclusions: Patients awaiting surgery for confirmed, suspected or pre-malignant conditions expressed decreased sense of control and increased levels of distress compared to patients awaiting procedures for benign conditions (p < 0.05, 95 % CI [-2.65, -0.08]). Future research will focus on the effects of COVID-19 related delays in operative care on clinical outcomes, including cancer morbidity and mortality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No funding/grant provided for this research., (© 2023 The Authors.)
- Published
- 2023
- Full Text
- View/download PDF
19. Establishing patient-derived organoids from human endometrial cancer and normal endometrium.
- Author
-
Katcher A, Yueh B, Ozler K, Nizam A, Kredentser A, Chung C, Frimer M, Goldberg GL, and Beyaz S
- Subjects
- Humans, Female, Endometrium pathology, Organoids, Endometrial Neoplasms drug therapy
- Abstract
Endometrial cancer is the most common gynecologic malignancy in the United States and is one of the few malignancies that had an increasing incidence and mortality rate over the last 10 years. Current research models fail to recapitulate actual characteristics of the tumor that are necessary for the proper understanding and treatment of this heterogenous disease. Patient-derived organoids provide a durable and versatile culture system that can capture patient-specific characteristics such as the mutational profile and response to therapy of the primary tumor. Here we describe the methods for establishing, expansion and banking of endometrial cancer organoids to develop a living biobank. Samples of both endometrial tumor tissue and matched normal endometrium were collected from 10 patients. The tissue was digested into single cells and then cultured in optimized media to establish matched patient endometrial cancer and normal endometrial tissue organoids. Organoids were created from all major endometrial cancer histologic subtypes. These organoids are passaged long term, banked and can be utilized for downstream histological and genomic characterization as well as functional assays such as assessing the response to therapeutic drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Katcher, Yueh, Ozler, Nizam, Kredentser, Chung, Frimer, Goldberg and Beyaz.)
- Published
- 2023
- Full Text
- View/download PDF
20. Assessing burnout among Obstetrics & Gynecology residents during night float versus day float in a large academic hospital.
- Author
-
Tarrash M, Nelson D, Gabbur N, and Goldberg GL
- Subjects
- Humans, Cross-Sectional Studies, Prospective Studies, Hospitals, Gynecology education, Burnout, Professional epidemiology, Burnout, Professional psychology
- Abstract
Background: The prevalence estimates of burnout among residents vary widely. Resident physicians working overnight have additional stressors and therefore, may be at higher risk of developing burnout., Objective: To determine the rates of burnout among residents working night rotations versus day rotations., Methods: This is a prospective, cross sectional, survey-based assessment of the prevalence of burnout among Obstetrics and Gynecology (OBGYN) residents on nights versus days rotations conducted at a large academic residency program that spans two separate hospitals in New York. All residents in the residency program were asked to complete the Maslach Burnout Inventory - Human Services Survey for Medical Personnel (MBI-HSS (MP)) after the first rotation of the academic year in 2018, 2019, and 2020. The results for each of the three aspects of the MBI-HSS (MP): emotional exhaustion, depersonalization, and personal accomplishment, were then compared for those on nights versus day rotations using students t-test., Results: A total of 76 responses were received, 13 from residents on night rotations and 63 from residents on day rotations with a response rate of 61.8%. Comparing resident responses for a night versus day rotation, the residents averaged a low level of emotional exhaustion (a score of 17 ± 9) on day shift, compared to a moderate level of emotional exhaustion (a score of 18 ± 14) on nights (p = 0.37). Similarly, 55.6% of respondents reports low personal accomplishment on days, compared to 76.9% while on nights., Conclusions: Emotional exhaustion scores were lower for residents on daytime rotations (mean score 17, SD 9), compared to those on nights rotations (mean 18, SD 14). Although there was no difference in depersonalization when comparing the day and night shift, 45% of the responses indicated high levels of depersonalization regardless of the type of shift. These results highlight the need to continue efforts to minimize burnout in medical training., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
21. The significance of "atrophic endometrium" in women with postmenopausal bleeding.
- Author
-
Rotenberg O and Goldberg GL
- Subjects
- Atrophy complications, Atrophy pathology, Endometrium diagnostic imaging, Endometrium pathology, Female, Humans, Hysteroscopy adverse effects, Postmenopause, Pregnancy, Ultrasonography, Uterine Hemorrhage diagnosis, Uterine Hemorrhage etiology, Uterine Hemorrhage pathology, Endometrial Neoplasms complications, Endometrial Neoplasms diagnosis, Endometrial Neoplasms pathology, Uterine Diseases pathology
- Abstract
We evaluated the interpretation of atrophic endometrium (AE) histology as the most common cause for postmenopausal bleeding (PMB). This theory has been accepted for several generations by gynecologists and gynecologic oncologists and has been published in past and current major gynecology textbooks. In our review of the literature, we did not find sufficient histological or clinical proof for this concept. In our view, AE is not a cause of PMB and we back this up with a review of old and current medical literature. The old studies are based on information which was obtained prior to the existence of transvaginal sonogram, sonohysterogram and hysteroscopy. Focal lesions are notorious for being missed by endometrial sampling and curettage. Recent studies show that focal endometrial lesions are a crucial cause for PMB and some of those lesions can harbor cancer. In our opinion, AE is the most common histology found because it is physiologic and a ubiquitous finding in postmenopausal women, but it is not a cause of PMB. Referring to AE as a cause of PMB may result in misdiagnosis of cancer, management delay and unnecessary intervention. To avoid misdiagnosis of cancer, transvaginal sonogram should be considered in all women with PMB and AE on pathology. If endometrial thickness is found, AE is unlikely to be the cause of the PMB and further workup is warranted to reveal the true etiology for the bleeding., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
- Full Text
- View/download PDF
22. Is minimally invasive surgery for clinical stage I uterine carcinosarcoma safe?
- Author
-
Sinha R, Nizam A, Shan W, Shih KK, Frimer M, Sakaris A, and Goldberg GL
- Subjects
- Female, Humans, Hysterectomy, Minimally Invasive Surgical Procedures, Neoplasm Staging, Retrospective Studies, Carcinosarcoma pathology, Carcinosarcoma surgery, Robotic Surgical Procedures methods, Uterine Neoplasms drug therapy
- Abstract
Minimally invasive surgery (MIS) has been a mainstay of the surgical management of uterine cancer since the mid-2000s. We aim to determine the role and safety of MIS in women with uterine carcinosarcoma (UCS). An Institutional Review Board-approved study identified all patients with UCS between January 2011 and December 2017 at our institution. Demographic and outcome measures were abstracted from the medical records and tumor registry. Cox proportional hazard models, log rank tests, and comparisons of means were used to calculate significance (p < 0.05). 129 women with UCS were identified during the study period. 62 cases (48%) were open procedures and 67 cases (52%) were MIS with the majority of the MIS group having robotic surgery. 55% of the patients had pathological stage 1 disease. Thirty-eight percent of UCS tumors were heterologous. 93% of patients received adjuvant therapy in the form of chemotherapy and/or radiation therapy. There was no difference in the recurrence-free survival (RFS) or overall survival (OS) between the open surgery and the MIS groups as well as between the heterologous and homologous UCS groups (p > 0.05). UCS represents a rare and aggressive subtype of endometrial cancer. Our data suggest that MIS is a safe surgical approach for staging in women with UCS., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)
- Published
- 2022
- Full Text
- View/download PDF
23. Intestinal type adenocarcinoma of the endometrium with signet ring cells, a rare aggressive variant.
- Author
-
Seay K, Bustamante B, Truskinovsky A, Menzin A, and Goldberg GL
- Abstract
Objective: Intestinal type mucinous adenocarcinoma (iMACE) is a rare and unusual variant of mucinous carcinoma of the endometrium that can show focal features of poorly differentiated adenocarcinomas of gastric, pancreatic or intestinal origin by producing signet ring cells. To date, only two reported cases of signet ring cells as a morphological feature of iMACE have been reported. Alterations in E-cadherin expression have been linked to increased metastatic potential, tumor dedifferentiation, and deep myometrial invasion in endometrial carcinomas. The presence or absence of E-cadherin in iMACE with signet-ring cells has not been studied. Thus, we sought to analyze E-cadherin expression in this aggressive variant of endometrial carcinoma., Cases: Diagnosis of iMACE with signet ring cells was rendered with the aid of immunohistochemical staining and histological analysis. Average age of diagnosis was 72 with the presenting complaint of postmenopausal bleeding in all three women. Focal loss or weakly positive E-cadherin expression was seen in areas of signet-rings cell morphology in all three cases., Conclusion: This case report adds to the body of literature that demonstrates the aggressive nature of intestinal differentiation in the endometrium. In addition, this report suggests that the presence of signet-rings cells and loss of E-cadherin expression may render a poorer prognosis as seen in other parts of the body., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
24. Surgeon Attitudes Toward Concurrent Urogynecologic and Gynecologic Oncology Procedures: A Cross-sectional Survey.
- Author
-
Lai E, Goldberg GL, and Shalom D
- Subjects
- Attitude, Cross-Sectional Studies, Female, Humans, Male, United States, Genital Neoplasms, Female surgery, Gynecology methods, Surgeons
- Abstract
Importance: There is increasing overlap in the urogynecologic and gynecologic oncologic patient populations. To improve patient advocacy and access to care, a collaborative surgical approach may benefit this cohort., Objective: The aim of the study was to evaluate surgeon attitudes toward performing concurrent urogynecologic and gynecologic oncology procedures. We hypothesized that most surgeons are amenable to collaboration., Study Design: We conducted a cross-sectional questionnaire of members of the Society of Gynecologic Oncology and the American Urogynecologic Society from August to November 2020. A 23-item online survey was created to assess surgeon demographics, practice and screening patterns, and attitudes toward surgical collaboration. We also evaluated obstacles to performing joint procedures and assessed whether attitudes could be influenced by new information., Results: A total of 338 surveys were included in the analysis, including 158 urogynecologists and 226 gynecologic oncologists (GOs). Most surgeons (77.8%) will recommend concurrent procedures with another specialty, and 97.8% of urogynecologists and 95.7% of oncologists currently perform joint surgical procedures. Male surgeons, regardless of specialty, were more likely to recommend staged procedures (44% vs 31%, P < 0.001), as were GOs (28% vs 10.1%, P < 0.001). However, oncologists were more likely than urogynecologists to initiate referrals for surgical collaboration (33.3% vs 14.4%, P < 0.001)., Conclusions: A total of 22.2% of urogynecologists and oncologists prefer staging surgical procedures. The most common barrier to a combined procedure was logistics. Urogynecologists were more concerned about the effects of cancer treatments on healing, the use of mesh implants, and financial reimbursements as compared with GOs. Treatment delay was a significantly greater concern for the oncologists., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2022 American Urogynecologic Society. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
25. Use of aromatase inhibitors in menopausal deep endometriosis: a case report and literature review.
- Author
-
Rotenberg O, Kuo DYS, and Goldberg GL
- Subjects
- Aromatase therapeutic use, Female, Humans, Letrozole therapeutic use, Menopause, Rectum, Aromatase Inhibitors therapeutic use, Endometriosis drug therapy, Endometriosis surgery
- Abstract
We report and review the clinical effectiveness of aromatase inhibitors in a patient with refractory, recurrent and infiltrating endometriosis. We demonstrate excellent clinical, radiological and endoscopic responses after failure of multiple other modalities. Our case and the literature show that single-agent letrozole is capable to treat deep infiltrative endometriosis involving the rectum and the urinary tract. The use of aromatase inhibitor treatment of endometriosis in postmenopausal women makes sense, is safe and is well tolerated. Difficult cases of deep infiltrative endometriosis might require use of combined surgical and medical treatment modalities. Multidisciplinary involvement of the gynecologist, bowel surgeon, urologist and invasive radiologist might be needed. Aromatase inhibitors should be considered to be an integral part of the armamentarium in the management of women with endometriosis, especially in refractory cases that have failed conventional therapeutic modalities.
- Published
- 2022
- Full Text
- View/download PDF
26. Intraoperative Indocyanine Green Dye Use in Ovarian Torsion: A Feasibility Study.
- Author
-
Nicholson K, Urh A, Demertzis K, Holubyeva A, LaPier Z, Cisneros-Camacho A, Goldberg GL, and Schwartz B
- Subjects
- Adnexa Uteri, Adolescent, Adult, Feasibility Studies, Female, Humans, Middle Aged, Prospective Studies, Young Adult, Indocyanine Green, Ovarian Torsion
- Abstract
Study Objective: To determine the feasibility of intravenous indocyanine green (ICG) dye use in patients with adnexal torsion to intraoperatively evaluate ovarian perfusion after detorsion., Design: A prospective multicenter single-arm feasibility study., Setting: A teaching hospital., Patients: A total of 12 nonpregnant patients, 18 to 45 years old with surgically confirmed adnexal torsion., Interventions: Torsion was surgically confirmed, the involved adnexa were untwisted laparoscopically, and ICG dye was injected intravenously. The absence or presence of ICG perfusion was documented, and the clinical decision for ovarian conservation or removal was determined by the surgeon., Measurements and Main Results: The primary outcome was feasibility of using ICG dye including measures such as time to visualized perfusion and operative time. Secondary outcomes included presence or absence of ovarian preservation and postoperative follow-up measures. Intraoperative visualization of ICG perfusion to the detorsed adnexa was achieved in 10 patients (83%) in a median time of 1 minute (0, 2), resulting in entire (n = 9) or partial (n = 1) ovarian conservation. Perfusion was absent in 2 cases, and postoophorectomy histologic necrosis was confirmed in one case. Median operative time was 74 minutes (48, 94). There were no adverse events related to ICG dye use., Conclusion: Intraoperative ICG dye use in this study was logistically feasible and conservation of the entire or partial ovary was observed in 83% of patients, including one case where preoperative Doppler flow was absent., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
27. Minimally invasive versus open surgery for women with stage 1A1 and stage 1A2 cervical cancer: A retrospective database cohort study.
- Author
-
Hayek J, Mowzoon M, Demissie S, Palileo A, Serur E, Goldberg GL, and Alagkiozidis I
- Abstract
Background: Recent studies comparing minimally invasive versus open radical hysterectomy in patients with early-stage cervical cancer have reported a worse overall survival with minimally invasive surgery (MIS). However, in the patients with microscopic disease, there was no survival difference and the optimal surgical approach for microscopic cervical cancer remains unclear., Methods: Using the National Cancer Database, we identified a cohort of women who underwent hysterectomy as the primary treatment for stage IA1/IA2 cervical cancer between January 2010 and December 2016. Using multivariable logistic regression, our primary outcome was to compare overall survival between the open and MIS groups. The data was stratified for simple and radical hysterectomies. Secondary endpoint was comparison of readmission rates and length of stay (LOS)., Results: We identified 6230 patients with stage IA1 and IA2 cervical cancer that underwent hysterectomy as primary treatment. 4054 of these women (65%) underwent MIS. There was no difference in age, lympho-vascular invasion, number of lymph nodes retrieved and histology between the two groups. In the overall cohort, there was no difference in survival between the open and the MIS group (Hazard ratio for the open group 1.23; CI 0.92-1.63). Post-operative radiation therapy was more common in the open group (5.24% vs 4.09%, p value < 0.02). The mean LOS (1.35 days vs 3.08 days) was shorter in MIS group ( p value < 0.0001). No difference was found in the readmission rates (60% for the MIS group vs 55% for the open group; p value 0.14)., Conclusions: Our data suggest that MIS is associated with similar overall survival and shorter length of hospital stay compared to the open hysterectomy in women with stage IA cervical cancer. Based on this large data set, MIS appears to be a safe and effective surgical approach for women with stage IA1/IA2 cervical cancer., Competing Interests: There is no conflict of interest., (© 2022 The Authors.)
- Published
- 2022
- Full Text
- View/download PDF
28. Nosocomial COVID-19 infection in women undergoing elective cesarean delivery: a prospective cohort study.
- Author
-
Nizam A, Nimaroff ML, Menzin AW, Goldberg GL, Miyara SJ, and Molmenti E
- Subjects
- Cohort Studies, Female, Humans, Pandemics, Pregnancy, Prospective Studies, SARS-CoV-2, COVID-19, Cross Infection epidemiology, Cross Infection etiology
- Abstract
Background: The COVID-19 pandemic placed obstetricians in a difficult position of continuing to perform elective cesarean delivery without the knowledge of the risk of the spread of nosocomial infection of the COVID-19 virus., Objective: This study aimed to determine the nosocomial infection rate in women undergoing elective cesarean delivery at 2 academic institutions., Study Design: This nonrandomized prospective cohort trial evaluated patients undergoing elective cesarean delivery during the reopening phase of the COVID-19 pandemic in the state of New York at 2 large volume labor and delivery units. Eligible patients with a negative preoperative reverse transcriptase-polymerase chain reaction test and immunoglobulin G antibody test for COVID-19 were retested 6 to 9 days after discharge. The primary objective was the COVID-19 test conversion rate defined as a positive polymerase chain reaction test for SARS-CoV-2 after discharge with a negative preoperative test. This was used as a proxy for the nosocomial infection rate., Results: A total of 136 patients were screened for participation. Of these patients, 2 tested positive for COVID-19 on preoperative testing, and 25 declined to participate. Overall, 111 patients consented to participate, and 96 patients underwent both preoperative and postoperative testing. No patient with a negative polymerase chain reaction test preoperatively, had a positive polymerase chain reaction test for the COVID-19 virus postoperatively., Conclusion: With strict and methodical perioperative and postpartum protocols, we can limit nosocomial COVID-19 infection in women undergoing elective cesarean delivery., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
29. BRD4 Regulates Transcription Factor ΔNp63α to Drive a Cancer Stem Cell Phenotype in Squamous Cell Carcinomas.
- Author
-
Fisher ML, Balinth S, Hwangbo Y, Wu C, Ballon C, Wilkinson JE, Goldberg GL, and Mills AA
- Subjects
- Animals, Apoptosis, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Cell Cycle Proteins genetics, Cell Proliferation, Enhancer of Zeste Homolog 2 Protein genetics, Humans, Mice, Mice, Nude, Neoplastic Stem Cells metabolism, STAT3 Transcription Factor genetics, Transcription Factors genetics, Tumor Cells, Cultured, Tumor Suppressor Proteins genetics, Xenograft Model Antitumor Assays, Carcinoma, Squamous Cell pathology, Cell Cycle Proteins metabolism, Enhancer of Zeste Homolog 2 Protein metabolism, Gene Expression Regulation, Neoplastic, Neoplastic Stem Cells pathology, STAT3 Transcription Factor metabolism, Transcription Factors metabolism, Tumor Suppressor Proteins metabolism
- Abstract
Bromodomain containing protein 4 (BRD4) plays a critical role in controlling the expression of genes involved in development and cancer. Inactivation of BRD4 inhibits cancer growth, making it a promising anticancer drug target. The cancer stem cell (CSC) population is a key driver of recurrence and metastasis in patients with cancer. Here we show that cancer stem-like cells can be enriched from squamous cell carcinomas (SCC), and that these cells display an aggressive phenotype with enhanced stem cell marker expression, migration, invasion, and tumor growth. BRD4 is highly elevated in this aggressive subpopulation of cells, and its function is critical for these CSC-like properties. Moreover, BRD4 regulates ΔNp63α, a key transcription factor that is essential for epithelial stem cell function that is often overexpressed in cancers. BRD4 regulates an EZH2/STAT3 complex that leads to increased ΔNp63α-mediated transcription. Targeting BRD4 in human SCC reduces ΔNp63α, leading to inhibition of spheroid formation, migration, invasion, and tumor growth. These studies identify a novel BRD4-regulated signaling network in a subpopulation of cancer stem-like cells, elucidating a possible avenue for effective therapeutic intervention. SIGNIFICANCE: This study identifies a signaling cascade driven by BRD4 that upregulates ΔNp63α to promote cancer stem-like properties, which has potential therapeutic implications for the treatment of squamous cell carcinomas., (©2021 American Association for Cancer Research.)
- Published
- 2021
- Full Text
- View/download PDF
30. Clinical Implications of Genomic Loss of Heterozygosity in Endometrial Carcinoma.
- Author
-
Bustamante B, Sinha R, Rice B, Nizam A, Shan W, Goldberg GL, John V, Lin DI, Danziger N, Pavlick DC, Elvin JA, and Frimer M
- Subjects
- Aged, Endometrial Neoplasms pathology, Female, Genomics, Humans, Middle Aged, Retrospective Studies, Survival Rate, DNA Copy Number Variations, Endometrial Neoplasms genetics, Loss of Heterozygosity
- Abstract
Purpose: Homologous recombination deficiency, identified by homologous recombination deficiency gene alterations or high percentage of genome-wide loss of heterozygosity (gLOH), is associated with improved prognosis, platinum sensitivity (PS), and poly (ADP-ribose) polymerase inhibitor response in high-grade ovarian cancer. Since the copy number-high (CN-H) endometrial cancer molecular subtype (EC-MS) shares molecular features with high-grade ovarian cancer, our aim was to assign EC-MS on the basis of comprehensive genomic profiling (CGP) results and evaluate the gLOH status with clinical behavior of EC., Methods: Eighty-two epithelial EC tumor tissues were sequenced by hybrid capture-based CGP, and results were used to assign EC-MS (ultramutated, microsatellite instability-high, CN-low; CN-high). Retrospective chart review established clinical characteristics, including PS. Relationships of PS, EC-MS, gene alterations, and gLOH were assessed statistically., Results: PS and EC-MS of CN-H showed statistically significant difference in overall survival (OS). Most notably, when the CN-H EC-MS was subcategorized by gLOH status, there was a significant difference in OS with gLOH-H being associated with longer survival. Cox semi-proportional hazard modeling showed that gLOH, stage, and race were significant in modeling OS., Conclusion: The method of assigning EC-MS by CGP demonstrates similar clinical features to previous reports of EC-MS assigned by other methods. CGP can also assess gLOH status with gLOH-H most commonly seen in CN-H tumors. CN-H, gLOH-H patients showed significantly improved OS (hazard ratio, 0.100 [0.02-0.51 95% CI]). Thus, gLOH status may be a meaningful prognostic biomarker within the CN-H tumors and possibly across EC-MS., Competing Interests: Doug I. Lin Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Pharma AG Natalie Danziger Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Dean C. Pavlick Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Julia A. Elvin Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Marina Frimer Research Funding: GlaxoSmithKline No other potential conflicts of interest were reported. Doug I. Lin Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Pharma AG Natalie Danziger Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Dean C. Pavlick Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Julia A. Elvin Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Marina Frimer Research Funding: GlaxoSmithKline No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)
- Published
- 2021
- Full Text
- View/download PDF
31. Yolk sac tumor of the endometrium in a post-menopausal woman: Case report and review of the literature.
- Author
-
Sinha R, Bustamante B, Truskinovsky A, Goldberg GL, and Shih KK
- Abstract
•Seven of eighteen postmenopausal female endometrial YST cases were pure YST.•IHC supports somatic tumor cell retro -differentiation yielding extra-gonadal YST.•Studying genetic alterations in endometrial YST may elucidate its histiogenesis., (© 2021 The Authors.)
- Published
- 2021
- Full Text
- View/download PDF
32. Malignant Female Adnexal Tumor of Probable Wolffian Origin (FATWO): A case report and review for the literature.
- Author
-
Sinha R, Bustamante B, Tahmasebi F, and Goldberg GL
- Abstract
•Of the fewer than 100 FATWO case reports published, at least 25 reports have metastatic quality.•Very little information regarding optimal management of FATWO is known; immunohistochemical stains may help guide therapy.•FATWO may be more of a low malignant potential entity, and patients with the diagnosis should be followed closely., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Inc.)
- Published
- 2021
- Full Text
- View/download PDF
33. Long-term outcome of postmenopausal women with proliferative endometrium on endometrial sampling.
- Author
-
Rotenberg O, Doulaveris G, Fridman D, Renz M, Kaplan J, Xie X, Goldberg GL, and Dar P
- Subjects
- Black or African American, Age Factors, Aged, Aged, 80 and over, Asian, Atrophy, Body Mass Index, Female, Hispanic or Latino, Humans, Logistic Models, Middle Aged, Multivariate Analysis, Retrospective Studies, Risk Factors, White People, Cell Proliferation, Endometrial Hyperplasia epidemiology, Endometrial Neoplasms epidemiology, Endometrium pathology, Postmenopause
- Abstract
Background: Proliferative endometrium has been reported in 15% of endometrial biopsies of women aged 50 years and older. Contrary to endometrial hyperplasia, proliferative endometrium has not been associated with the risk of endometrial cancer., Objective: This study aimed to report on the long-term outcome of postmenopausal women who received a diagnosis of proliferative endometrium., Study Design: This is a retrospective cohort study of 1808 women aged 55 years and older who underwent endometrial sampling between January 1997 and December 2008. Outcome data were available through February 2018. Women with a proliferative endometrium were compared with those with an atrophic endometrium for future development of endometrial hyperplasia or cancer. A subanalysis was performed for those who presented with postmenopausal bleeding. Uni- and multivariable logistic regression analyses were used to assess for confounders., Results: In this study, 297 women (16.4%) received a diagnosis of proliferative endometrium. Furthermore, 962 women met the inclusion criteria. Among those women, 278 had a proliferative endometrium, and 684 had an atrophic endometrium. Women with a proliferative endometrium were younger (61.2 vs 64.5 years; P<.0001) and had a higher body mass index (33.9 vs 30.6 kg/m
2 ; P<.0001). More African American women had a proliferative endometrium. Both groups had a similar length of surveillance (11.9 vs 11.5 years; P=.27). Women with a proliferative endometrium had a higher risk of developing endometrial hyperplasia or cancer (11.9% vs 2.9%; P<.0001), any endometrial cancer (5.8% vs 1.8%; P=.002), atypical endometrial hyperplasia (2.2% vs 0.4%; P=.02), and nonatypical endometrial hyperplasia (2.0% vs 0.7%; P=.001). The risk of developing endometrial cancer and endometrial hyperplasia remained similar after excluding cases on hormonal replacement therapy (12.2% vs 3%; P=.001). On logistic regression analysis, proliferative endometrium histology (odds ratio, 3.89; 95% confidence interval, 2.03-7.49; P<.0001), age >60 years (odds ratio, 1.98; 95% confidence interval, 1.03-3.82; P=.04), and body mass index >35 kg/m2 (odds ratio, 2.3; 95% confidence interval, 1.09-4.83; P<.0001) remained significant risk factors for progression to cancer., Conclusion: One of the 6 postmenopausal women who underwent endometrial sampling had a proliferative endometrium. Furthermore, 11.9% of women developed endometrial hyperplasia or cancer, a 4-fold greater incidence than women with an atrophic endometrium. The findings of this study suggest that long-term monitoring is warranted for women with postmenopausal bleeding and a proliferative endometrium histology. Further studies are needed to examine if a treatment is required to negate the risk of unopposed estrogen., (Copyright © 2020. Published by Elsevier Inc.)- Published
- 2020
- Full Text
- View/download PDF
34. Utility of a custom designed next generation DNA sequencing gene panel to molecularly classify endometrial cancers according to The Cancer Genome Atlas subgroups.
- Author
-
Miller EM, Patterson NE, Gressel GM, Karabakhtsian RG, Bejerano-Sagie M, Ravi N, Maslov A, Quispe-Tintaya W, Wang T, Lin J, Smith HO, Goldberg GL, Kuo DYS, and Montagna C
- Subjects
- Aged, Carcinoma, Endometrioid genetics, DNA Copy Number Variations, DNA Mismatch Repair genetics, DNA Polymerase II genetics, Endometrial Neoplasms genetics, Endometrial Neoplasms mortality, Endometrial Neoplasms therapy, Female, Humans, INDEL Mutation, Middle Aged, Molecular Sequence Annotation, Neoplasms, Second Primary genetics, Poly-ADP-Ribose Binding Proteins genetics, Polymorphism, Single Nucleotide, DNA, Neoplasm genetics, Endometrial Neoplasms classification, High-Throughput Nucleotide Sequencing, Mutation, Neoplasm Proteins genetics
- Abstract
Background: The Cancer Genome Atlas identified four molecular subgroups of endometrial cancer with survival differences based on whole genome, transcriptomic, and proteomic characterization. Clinically accessible algorithms that reproduce this data are needed. Our aim was to determine if targeted sequencing alone allowed for molecular classification of endometrial cancer., Methods: Using a custom-designed 156 gene panel, we analyzed 47 endometrial cancers and matching non-tumor tissue. Variants were annotated for pathogenicity and medical records were reviewed for the clinicopathologic variables. Using molecular characteristics, tumors were classified into four subgroups. Group 1 included patients with > 570 unfiltered somatic variants, > 9 cytosine to adenine nucleotide substitutions per sample, and < 1 cytosine to guanine nucleotide substitution per sample. Group 2 included patients with any somatic mutation in MSH2, MSH6, MLH1, PMS2. Group 3 included patients with TP53 mutations without mutation in mismatch repair genes. Remaining patients were classified as group 4. Analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, North Carolina, USA)., Results: Endometrioid endometrial cancers had more candidate variants of potential pathogenic interest (median 6 IQR 4.13 vs. 2 IQR 2.3; p < 0.01) than uterine serous cancers. PTEN (82% vs. 15%, p < 0.01) and PIK3CA (74% vs. 23%, p < 0.01) mutations were more frequent in endometrioid than serous carcinomas. TP53 (18% vs. 77%, p < 0.01) mutations were more frequent in serous carcinomas. Visual inspection of the number of unfiltered somatic variants per sample identified six grade 3 endometrioid samples with high tumor mutational burden, all of which demonstrated POLE mutations, most commonly P286R and V411L. Of the grade 3 endometrioid carcinomas, those with POLE mutations were less likely to have risk factors necessitating adjuvant treatment than those with low tumor mutational burden. Targeted sequencing was unable to assign samples to microsatellite unstable, copy number low, and copy number high subgroups., Conclusions: Targeted sequencing can predict the presence of POLE mutations based on the tumor mutational burden. However, targeted sequencing alone is inadequate to classify endometrial cancers into molecular subgroups identified by The Cancer Genome Atlas.
- Published
- 2020
- Full Text
- View/download PDF
35. Mesonephric-like adenocarcinoma of the ovary with co-existent endometriosis: A case report and review of the literature.
- Author
-
Seay K, Akanbi T, Bustamante B, Chaudhary S, and Goldberg GL
- Abstract
Introduction: Mesonephric-like adenocarcinoma (MLA) is a rare malignant gynecologic neoplasm occurring in the uterine corpus and ovary. The morphological and immunohistochemical characteristics of MLA closely resemble that of cervical mesonephric adenocarcinomas, but whether they share a common histogenesis remains unclear. Two main theories for histogenesis of MLAs include the origination of these neoplasms from mesonephric remnants, as is the case for cervical mesonephric adenocarcinoma, versus the differentiation along a mesonephric pathway from Mullerian lesions., Case: A 67-year-old presented after a right salpingo-oophorectomy for a complex ovarian mass revealed a mesonephric-like adenocarcinoma of the ovary and endometriosis. She underwent a total abdominal hysterectomy, pelvic lymphadenectomy, and infra-colic omentectomy, and diagnosed with Stage IA mesonephric-like adenocarcinoma of the ovary. At 18 months post-operatively, the patient developed flank and abdominal pain and was found to have multiple sites of recurrent disease. She was referred to medical oncology for chemotherapy as she was not a candidate for surgical cytoreduction., Discussion: This case demonstrates the aggressive nature of ovarian MLA and the need for a multidisciplinary approach when determining the treatment. In addition, this case provides further evidence to support the theory that at least a subset of MLAs arises from a Mullerian lesion which then differentiates down a mesonephric pathway., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)
- Published
- 2020
- Full Text
- View/download PDF
36. Risk factors associated with delayed discharge following robotic assisted surgery for gynecologic malignancy.
- Author
-
Tymon-Rosario JR, Miller DT, Novetsky AP, Goldberg GL, Nevadunsky NS, Makhija SK, Kuo DY, and Van Arsdale AR
- Subjects
- Female, Humans, Male, Middle Aged, Patient Discharge, Prospective Studies, Risk Factors, Genital Neoplasms, Female complications, Genital Neoplasms, Female surgery, Postoperative Complications etiology, Robotic Surgical Procedures adverse effects
- Abstract
Background: The risk factors for extended length of stay (LOS) have not been examined in a cohort of patients with complex social and medical barriers who undergo robotic assisted (RA) surgery for gynecologic malignancies. We sought to identify those patients with a LOS > 24 h after robotic surgery and the risk factors associated with delayed discharge. Then we aimed to develop a predictive model for clinical care and identify modifiable pre-operative risk factors., Methods: After IRB approval, data was abstracted from medical records of all patients with a gynecologic malignancy who underwent a RA laparoscopic surgery from 2010 to 2015. Univariable and multivariable logistic regression was performed to identify independent risk factors associated with delayed discharge defined as LOS > 24 h. A multi-variable logistic regression model was performed using a stepwise backward selection for the final prediction model. All testing was two-sided and a p-value < 0.05 was considered statistically significant., Results: Of the 406 eligible and evaluable patients, 194 (48%) had a LOS > 24 h. Age ≥ 60 years, a higher usage of narcotic medication, a longer surgical time, and a larger estimated blood loss were all associated with LOS > 24 h (p < 0.05). Many of these women had a social work consultation and went home with home care services despite no surgical or post-operative complications. Our prediction model has the potential to correctly classified 75% of the patients discharged within 24 h., Conclusions: The development of a pre-hospitalization risk stratification and anticipating the possible need for home care services pre-operatively shows promise as a strategy to decrease LOS in patients classified as high-risk. These findings warrant prospective validation through the use of this prediction model in our institution., Competing Interests: Declaration of competing interest All authors fulfill the conditions required for authorship and declare that they have no conflicts of interest to disclose., (Published by Elsevier Inc.)
- Published
- 2020
- Full Text
- View/download PDF
37. Long-term outcome of postmenopausal women with non-atypical endometrial hyperplasia on endometrial sampling.
- Author
-
Rotenberg O, Fridman D, Doulaveris G, Renz M, Kaplan J, Gebb J, Xie X, Goldberg GL, and Dar P
- Subjects
- Aged, Atrophy, Disease Progression, Endometrial Neoplasms epidemiology, Endometrial Neoplasms pathology, Female, Humans, Hysterectomy statistics & numerical data, Logistic Models, Middle Aged, Retrospective Studies, Risk Factors, Uterine Neoplasms epidemiology, Uterine Neoplasms pathology, Endometrial Hyperplasia pathology, Endometrium pathology, Postmenopause
- Abstract
Objective: To assess the long-term outcome of postmenopausal women diagnosed with non-atypical endometrial hyperplasia (NEH)., Methods: This was a retrospective study of women aged 55 or older who underwent endometrial sampling in our academic medical center between 1997 and 2008. Women who had a current or recent (< 2 years) histological diagnosis of NEH were included in the study group and were compared with those diagnosed with atrophic endometrium (AE). Outcome data were obtained until February 2018. The main outcomes were risk of progression to endometrial carcinoma and risk of persistence, recurrence or new development of endometrial hyperplasia (EH) ('persistent EH'). Logistic regression analysis was used to identify covariates that were independent risk factors for progression to endometrial cancer or persistent EH., Results: During the study period, 1808 women aged 55 or older underwent endometrial sampling. The median surveillance time was 10.0 years. Seventy-two women were found to have a current or recent diagnosis of NEH and were compared with 722 women with AE. When compared to women with AE, women with NEH had significantly higher body mass index (33.9 kg/m
2 vs 30.6 kg/m2 ; P = 0.01), greater endometrial thickness (10.00 mm vs 6.00 mm; P = 0.01) and higher rates of progression to type-1 endometrial cancer (8.3% vs 0.8%; P = 0.0003) and persistent NEH (22.2% vs 0.7%; P < 0.0001). They also had a higher rate of progression to any type of uterine cancer or persistent EH (33.3% vs 3.5%; P < 0.0001). Women with NEH had a significantly higher rate of future surgical intervention (51.4% vs 15.8%; P < 0.0001), including future hysterectomy (34.7% vs 9.8%; P < 0.0001). On multivariable logistic regression analysis, only NEH remained a significant risk factor for progression to endometrial cancer or persistence of EH., Conclusions: Postmenopausal women with NEH are at significant risk for persistent EH and progression to endometrial cancer, at rates higher than those reported previously. Guidelines for the appropriate management of postmenopausal women with NEH are needed in order to decrease the rate of persistent disease or progression to cancer. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)- Published
- 2020
- Full Text
- View/download PDF
38. Correction: Septin 9 isoforms promote tumorigenesis in mammary epithelial cells by increasing migration and ECM degradation through metalloproteinase secretion at focal adhesions.
- Author
-
Marcus J, Bejerano-Sagie M, Patterson N, Bagchi S, Verkhusha VV, Connolly D, Goldberg GL, Golden A, Sharma VP, Condeelis J, and Montagna C
- Abstract
The original version of this Article contained an error in the author affiliations. Vladislav V. Verkhusha was incorrectly associated with the School of Mathematics, Statistics & Applied Mathematics, National University of Ireland Galway, Galway, Ireland. The correct affiliation is Anatomy and Structural Biology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA.
- Published
- 2020
- Full Text
- View/download PDF
39. Overall Survival and Adjuvant Therapy in Women with Ovarian Carcinosarcoma: A Single-Institution Experience.
- Author
-
Nizam A, Bustamante B, Shan W, Shih KK, Whyte JS, Sakaris A, Dos Santos L, Frimer M, Menzin AW, Truskinovsky A, and Goldberg GL
- Abstract
Background: Carcinosarcoma of the ovary (CSO) is a rare and aggressive variant of ovarian cancer. Due to the rare nature of the disease there is insufficient evidence to make recommendations regarding standard management and overall prognosis., Methods: An Institutional Review Board-approved study identified all our patients with CSO between January 2011 and May 2018. Demographic and outcome measures were abstracted from the medical records and tumor board files. Cox proportional hazard models, log rank tests, and comparisons of means were used to calculate significance ( p < 0.05)., Results: 27 women with CSO were identified. The median age at diagnosis was 65 years (range 48-91). Five women (18%) presented with early stage disease (Stage I or II) and 22 patients (82%) presented with late stage III or IV disease. Twenty patients (74%) received intravenous platinum-based combination chemotherapy. Seven patients did not receive chemotherapy during their treatment course. The median overall survival was 23 months (range 2-68 months). Overall survival was not significantly worsened by the stage of disease at diagnosis. There was no difference in survival based on the age at diagnosis, tobacco status or ethnicity ( p > 0.05)., Conclusion: This is one of the largest single institution experiences with CSO. The majority of our patients presented with advanced stage disease and received adjuvant platinum-based chemotherapy after cytoreductive surgery. The median overall survival of 23 months was not affected by the stage of the disease. The optimal management of this rare disease needs further study with collaborative, prospective multi-institutional trials.
- Published
- 2019
- Full Text
- View/download PDF
40. Necessity of routine cardiac evaluation in patients receiving pegylated liposomal doxorubicin for gynecologic cancer.
- Author
-
Dioun SM, Vilardo N, Goldberg GL, and Gressel GM
- Subjects
- Doxorubicin adverse effects, Drug Substitution, Echocardiography methods, Female, Heart Diseases physiopathology, Heart Diseases prevention & control, Humans, Middle Aged, Multimodal Imaging methods, Polyethylene Glycols adverse effects, Radionuclide Angiography methods, Retrospective Studies, Stroke Volume drug effects, Antibiotics, Antineoplastic administration & dosage, Doxorubicin analogs & derivatives, Genital Neoplasms, Female drug therapy, Heart Diseases chemically induced
- Abstract
Objective: Pegylated liposomal doxorubicin (PLD) has similar reported clinical efficacy compared with conventional doxorubicin with less cardiotoxicity. The manufacturer of PLD advises that cardiac function should be evaluated with endomyocardial biopsy, echocardiography or multigated radionucleotide scan (MUGA) pre-treatment and during therapy. This study was designed to assess the necessity of pre-treatment cardiac evaluation in patients receiving PLD., Methods: After IRB approval, a retrospective study of all women with gynecologic cancer who received PLD from 2006 to 2018 was performed. Demographic information, treatment records, cardiac risk factors, and cardiac surveillance testing were examined. Wilcoxon signed rank sum test and logistic regression were used to evaluate the association of cumulative PLD exposure with cardiotoxicity., Results: A total of 235 patients received PLD for gynecologic cancer. Patients received a median of 3 cycles of PLD with a cumulative dosage of 237 mg over a median follow-up time of 24 months. Sixteen patients in the cohort (7%) had no cardiac surveillance at all. Of the remaining patients who underwent cardiac testing, 183 (84%) received MUGA scans and 36 (16%) had echocardiography. Of the 56 patients who had both pre- and post-treatment cardiac testing, there was no significant difference in median ejection fraction (p = 0.17). Three patients developed PLD-associated cardiac toxicity but only one patient had severe manifestations requiring discontinuation of PLD therapy., Conclusions: Routine cardiac testing before, during or after treatment with PLD may be unnecessary. Cardiac testing may be more appropriate for individual patients for whom the clinical suspicion of PLD-related cardiac toxicity is high., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
41. Neutrophilia and mortality in women with uterine carcinosarcoma.
- Author
-
Arend R, Van Arsdale A, Gojayev A, Roane BM, Doo D, Leath C, Goldberg GL, and Huang G
- Subjects
- Aged, Alabama epidemiology, Carcinosarcoma pathology, Female, Humans, Leukocyte Count, Leukocyte Disorders pathology, Middle Aged, Neoplasm Staging, Neutrophils pathology, Prognosis, Proportional Hazards Models, Retrospective Studies, Uterine Neoplasms pathology, Carcinosarcoma blood, Carcinosarcoma mortality, Leukocyte Disorders blood, Leukocyte Disorders mortality, Uterine Neoplasms blood, Uterine Neoplasms mortality
- Abstract
Objective: The objective of this study was to investigate the relationship between pre-treatment absolute neutrophil count and clinical outcomes in patients with uterine carcinosarcoma., Methods: In an Institutional Review Board approved, retrospective cohort study of 103 patients with uterine carcinosarcoma, the pre-treatment absolute neutrophil count data were obtained from the medical records, along with clinical, pathologic, treatment, and outcome data. Kaplan-Meier survival estimates were calculated and compared by the log rank test. Univariable and multivariable Cox proportional hazard regression models were used to examine the relationship of pre-treatment absolute neutrophil count with progression-free survival and overall survival., Results: Uterine carcinosarcoma patients in the highest quartile of pre-treatment absolute neutrophil count had significantly reduced progression-free survival (p<0.001, log rank test), and overall survival (p<0.001, log rank test), compared with patients in the lower absolute neutrophil count quartiles. On multivariable analysis, high absolute neutrophil count was an independent poor prognostic factor for disease recurrence, HR 2.97 (95% CI 1.35 to 6.53, p=0.007) for highest versus lowest quartile absolute neutrophil count, and for mortality, HR 4.43 (95% CI 1.64 to 12.00, p= 0.003)., Conclusions: High pre-treatment absolute neutrophil count is an independent poor prognostic factor in patients with uterine carcinosarcoma and may be useful as a potential biomarker in clinical trials. The mechanistic relationship of neutrophilia and uterine carcinosarcoma progression merits further investigation., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2019
- Full Text
- View/download PDF
42. The association of sexual dysfunction with race in women with gynecologic malignancies.
- Author
-
Frimer, Turker LB, Shankar V, Cardaci R, Van Arsdale AR, Rosenthal E, Kuo DYS, Goldberg GL, and Nevadunsky N
- Abstract
Gynecologic cancer survivors report sexual health among their highest concerns. The aim of this study was to identify the prevalence of sexual dysfunction (SD) in survivors of gynecologic malignancies and to evaluate the association of sexual function with race, ethnicity and treatment modality. In this study, survivors of endometrial, cervical, vaginal, and vulvar cancer who presented to the gynecologic oncology practice were asked to self-administer the Female Sexual Function Index (FSFI) survey to evaluate their sexual function. The prevalence of SD was estimated and its association with demographic and clinical co-variates was analyzed. Of the 155 participants, the prevalence of SD was 44.5% (95%CI: 36.7-52.7). Patients were significantly more likely to report SD if they did not currently have a partner (69% vs 22% p < .01). Abstinence within six months of their cancer diagnosis was also associated with SD (72% vs 26% p < .01). Patients who self-identified as black race compared to white race were three times more likely to have SD (OR = 3.9, 95% CI 1.1-14.3). Patients who received adjuvant chemotherapy and radiation therapy compared to those who did not among the entire cohort had an increased risk of SD (OR = 3.4, 95% CI 1.2-9.6). In our diverse population, almost half of our patients were identified to have SD. Black as compared to white race reported significantly higher sexual dysfunction. An increased risk for sexual dysfunction was observed among those women who received chemotherapy and radiation with or without surgery., Precis: Survivorship is an important issue for women with gynecologic malignancies. This study addresses the high rates of sexual dysfunction in a racially diverse patient population., (© 2019 The Authors.)
- Published
- 2019
- Full Text
- View/download PDF
43. Septin 9 isoforms promote tumorigenesis in mammary epithelial cells by increasing migration and ECM degradation through metalloproteinase secretion at focal adhesions.
- Author
-
Marcus J, Bejerano-Sagie M, Patterson N, Bagchi S, Verkhusha VV, Connolly D, Goldberg GL, Golden A, Sharma VP, Condeelis J, and Montagna C
- Subjects
- Breast Neoplasms enzymology, Breast Neoplasms metabolism, Extracellular Matrix enzymology, Humans, MCF-7 Cells, Mammary Glands, Human metabolism, Neoplasm Invasiveness, Septins genetics, Tumor Microenvironment, Up-Regulation, Breast Neoplasms pathology, Carcinogenesis, Cell Movement, Extracellular Matrix metabolism, Focal Adhesions, Mammary Glands, Human pathology, Matrix Metalloproteinases metabolism, Protein Isoforms physiology, Septins physiology
- Abstract
The cytoskeletal interacting protein Septin 9 (SEPT9), a member of the septin gene family, has been proposed to have oncogenic functions. It is a known hot spot of retroviral tagging insertion and a fusion partner of both de novo and therapy-induced mixed lineage leukemia (MLL). Of all septins, SEPT9 holds the strongest link to cancer, especially breast cancer. Murine models of breast cancer frequently exhibit SEPT9 amplification in the form of double minute chromosomes, and about 20% of human breast cancer display genomic amplification and protein over expression at the SEPT9 locus. Yet, a clear mechanism by which SEPT9 elicits tumor-promoting functions is lacking. To obtain unbiased insights on molecular signatures of SEPT9 upregulation in breast tumors, we overexpressed several of its isoforms in breast cancer cell lines. Global transcriptomic profiling supports a role of SEPT9 in invasion. Functional studies reveal that SEPT9 upregulation is sufficient to increase degradation of the extracellular matrix, while SEPT9 downregulation inhibits this process. The degradation pattern is peripheral and associated with focal adhesions (FAs), where it is coupled with increased expression of matrix metalloproteinases (MMPs). SEPT9 overexpression induces MMP upregulation in human tumors and in culture models and promotes MMP3 secretion to the media at FAs. Downregulation of SEPT9 or chemical inhibition of septin filament assembly impairs recruitment of MMP3 to FAs. Our results indicate that SEPT9 promotes upregulation and both trafficking and secretion of MMPs near FAs, thus enhancing migration and invasion of breast cancer cells.
- Published
- 2019
- Full Text
- View/download PDF
44. Adjuvant Pelvic Radiation "Sandwiched" Between Paclitaxel/Carboplatin Chemotherapy in Women With Completely Resected Uterine Serous Carcinoma: Long-term Follow-up of a Prospective Phase 2 Trial.
- Author
-
Frimer M, Miller EM, Shankar V, Girda E, Mehta K, Smith HO, Kuo DYS, Goldberg GL, and Einstein MH
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carboplatin administration & dosage, Carboplatin adverse effects, Chemoradiotherapy adverse effects, Chemoradiotherapy methods, Chemotherapy, Adjuvant, Cystadenocarcinoma, Serous pathology, Cystadenocarcinoma, Serous surgery, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Neoplasm Staging, Paclitaxel administration & dosage, Paclitaxel adverse effects, Progression-Free Survival, Radiotherapy, Adjuvant, Survival Rate, Uterine Neoplasms pathology, Uterine Neoplasms surgery, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Cystadenocarcinoma, Serous drug therapy, Cystadenocarcinoma, Serous radiotherapy, Uterine Neoplasms drug therapy, Uterine Neoplasms radiotherapy
- Abstract
Objective: We prospectively evaluated patients with completely resected uterine serous carcinoma (USC) treated with radiation "sandwiched" between carboplatin/paclitaxel (C/T). The primary objective was to determine the safety profile, and the secondary outcome was to evaluate progression-free and overall survival., Methods: Surgically staged patients with completely resected USC were enrolled to receive 3 cycles of paclitaxel 175 mg/m and carboplatin (area under the curve, 6-7.5) every 21 days, followed by radiotherapy and an additional 3 cycles of T/C at area under the curve of 5-6 (6 cycles + radiotherapy). Toxicity was graded according to National Cancer Institute Common Toxicity Criteria, version 4.03. Kaplan-Meier and log-rank tests were used to compare survival probabilities., Results: One hundred forty patients were enrolled, of which 132 were evaluable, completed at least 3 cycles of chemotherapy and radiation. One hundred seven (81%) completed 6 cycles of chemotherapy and radiation. Patients with early-stage (I/II) disease have survival probabilities of 0.96 and 0.81 at 2 and 5 years. Patients with stage I USC and lymphovascular invasion have considerably worse overall survival, with 2.7 times' higher risk of death than those without lymphovascular invasion. Patients with late-stage (III/IV) disease had overall survival probabilities of 0.64 and 0.18 at 2 and 5 years, which is far higher survival than what has been reported in single-modality trials. Interestingly, and different than what is reported in other studies, there is no difference in survival in African Americans versus whites/other races who were evaluable. Of the 779 cycles administered, 22% and 14% of cycles were associated with grades 3 and 4 hematologic toxicities, respectively. Grades 3 and 4 nonhematologic toxicities occurred in 6.9% of cycles., Conclusions: The long-term follow-up in this study demonstrates that "sandwich" therapy is an efficacious, well-tolerated treatment approach with acceptable toxicities. Lymphovascular invasion (LVSI) is a significantly poor prognostic factor in stage I USC. Multimodal "sandwich" therapy should be considered in all USC patients who have undergone complete surgical resection and staging.
- Published
- 2018
- Full Text
- View/download PDF
45. Insulin-like growth factor 2: a poor prognostic biomarker linked to racial disparity in women with uterine carcinosarcoma.
- Author
-
Van Arsdale AR, Arend RC, Cossio MJ, Erickson BK, Wang Y, Doo DW, Leath CA, Goldberg GL, and Huang GS
- Subjects
- Aged, Aged, 80 and over, Carcinosarcoma pathology, Female, Humans, Prognosis, Race Factors, Uterine Neoplasms pathology, Biomarkers, Tumor metabolism, Carcinosarcoma epidemiology, Insulin-Like Growth Factor II metabolism, Uterine Neoplasms epidemiology
- Abstract
The objective of this study was to investigate the relationship of insulin-like growth factor 2 (IGF2) expression and survival in women with uterine carcinosarcoma (UCS). Insulin-like growth factor 2 protein expression was determined by immunohistochemical staining of tumor tissues from 103 patients with UCS. The H-score (product of staining intensity and percentage positive cells) was quantified for the epithelial cytoplasmic (EC), epithelial nuclear (EN), and malignant stromal compartments. Multivariable Cox proportional hazard regression models were used to examine the relationship of IGF2 levels with progression-free survival (PFS) and overall survival (OS). Adjusting for stage, race, and adjuvant therapy, PFS and OS were reduced in patients with high IGF2 (H-score ≥ median) in the EC and EN compartments. Black race was independently associated with reduced PFS and OS in patients with early-stage disease, and IGF2 levels in the EC were higher in black than in white patients (P = 0.02, Wilcoxon test). In a race-stratified multivariable analysis, high IGF2 in the epithelial compartments more than doubled the risk of death in black women; HR = 2.43 (95% CI: 1.18-5.01, P = 0.02) for high IGF2 in the EC; and HR = 2.34 (95% CI: 1.25-4.39, P = 0.008) for high IGF2 in the EN. In conclusion, high tumor IGF2 expression is an independent risk factor for reduced PFS and OS in UCS. Black women have elevated tumor IGF2 compared with white women, and decreased survival associated with high IGF2. These findings identify IGF2 as a candidate biomarker for survival linked to racial disparity in women with UCS., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
46. Female Sex Hormone Receptor Profiling in Uterine Adenosarcomas.
- Author
-
Marcus JZ, Klobocista M, Karabakhtsian RG, Prossnitz E, Goldberg GL, and Huang GS
- Subjects
- Estrogen Receptor alpha biosynthesis, Estrogen Receptor beta biosynthesis, Female, Humans, Middle Aged, Adenosarcoma metabolism, Receptors, Estrogen biosynthesis, Receptors, G-Protein-Coupled biosynthesis, Receptors, Progesterone biosynthesis, Uterine Neoplasms metabolism
- Abstract
Objective: This study aimed to identify the hormonal receptor status in uterine adenosarcoma (AS) and uterine AS with sarcomatous overgrowth (AS + SO), including those with high-grade histologic features (nuclear pleomorphism, atypical mitoses, necrosis), with or without heterologous elements. Estrogen receptor (ER) status, including estrogen receptor α (ERα), estrogen receptor β (ERβ), and G protein-coupled estrogen receptor (GPER), and progesterone receptor (PgR) status were examined., Methods: From August 2001 to November 2013, 11 patients with histologic diagnosis of uterine AS were identified. Tumor tissue sections were stained for ERα, ERβ, GPER, and PgR and examined both for percentage of overall cells stained and for intensity of staining. Descriptive statistics were calculated using clinicopathologic data abstracted from the medical record., Results: Eight cases of AS and 3 cases of AS with high-grade features were identified. Seven of 8 tumor samples of AS showed strong or moderate intensity immunostaining for ERα; all AS + SO tumor samples showed minimal to no immunoreactivity for ERα. There was a significant decrease in ERα H scores in high-grade tumors when compared with AS (P = 0.01). Lower PgR H scores were observed in high-grade tumors compared with those in AS (P = 0.04). Estrogen receptor β immunostaining was variable, and GPER immunostaining was absent in the majority of tumor samples., Conclusions: Higher expression of ERα and PgR was observed in AS when compared with those with AS + SO and high-grade features. Both tumor subtypes showed similar levels of ERβ and GPER expression, although significant differences in ERβ and GPER expression were not detected. In contrast to our previous findings in uterine carcinosarcoma, ERs ERβ and GPER do not seem to play a significant role in AS in this study.
- Published
- 2018
- Full Text
- View/download PDF
47. Malignant Endometrial Polyps in Uterine Serous Carcinoma: The Prognostic Value of Polyp Size and Lymphovascular Invasion.
- Author
-
Ouyang C, Frimer M, Hou LY, Wang Y, Goldberg GL, and Hou JY
- Subjects
- Aged, Female, Humans, Lymphatic Metastasis, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Prognosis, Survival Rate, Cystadenocarcinoma, Serous pathology, Polyps pathology, Uterine Neoplasms pathology
- Abstract
Objectives: Uterine serous carcinoma (USC) involving an endometrial polyp and concurrent extrauterine disease is associated with poor prognosis. We examined the clinicopathological profiles of patients with stage 1A USC with and without polyp involvement and the role of polyp size and lymphovascular invasion (LVI) as prognostic indicators for extrauterine disease in patients with early USC., Methods/materials: From 2002 to 2014, 242 patients with pure USC were identified. Fisher exact test was used for categorical variables. The student t test was used for means. Logistic regression was used to compute the odds ratio for continuous and categorical variables., Results: Among stage 1A patients, the odds ratio of developing extrauterine disease for every 1 cm increase in polyp size is 1.368 (95% confidence interval, 1.034-1.810). Polyp size is only significantly associated with advanced stage disease for patients with myometrial invasion. A higher percent of LVI was found in stage 4 patients (31%). There is no survival or recurrence difference for stage 1 patients regardless of treatment or observation., Conclusions: Polyp size does not predict extrauterine disease for USC patients with disease in polyp only or disease in polyp and endometrium. Further study is needed to investigate whether presence of LVI is a prognostic factor.
- Published
- 2018
- Full Text
- View/download PDF
48. Physical activity-related differences in body mass index and patient-reported quality of life in socioculturally diverse endometrial cancer survivors.
- Author
-
Rossi A, Garber CE, Kaur G, Xue X, Goldberg GL, and Nevadunsky NS
- Subjects
- Body Mass Index, Cross-Sectional Studies, Culture, Endometrial Neoplasms pathology, Female, Humans, Middle Aged, Sociological Factors, Surveys and Questionnaires, Survivors statistics & numerical data, Endometrial Neoplasms psychology, Exercise psychology, Quality of Life psychology
- Abstract
Purpose: The purpose of this study was to describe physical activity-related differences in body composition, quality of life, and behavioral variables among a socioculturally diverse sample of endometrial cancer survivors., Methods: Ambulatory, English-speaking endometrial cancer survivors (6 months to 5 years post-treatment), who were residents of Bronx, NY, were recruited to complete questionnaires about physical activity (PA), quality of life (QoL), and psychosocial characteristics. Body weight and height were obtained from medical records to determine body mass index (BMI). ANOVA and independent sample t tests were used to determine differences between racial/ethnic groups and active versus insufficiently active, respectively., Results: Sixty-two participants enrolled in the study. Recruitment rate was 7% for mailed questionnaires and 92% in clinic. Mean age was 63 ± 10 years. Sixty-five percent of the sample was obese (mean BMI: 34.2 ± 8.6 kg·m
-2 ). BMI was significantly higher in non-Hispanic black women (37.8 ± 10.2 kg·m-2 ) than non-Hispanic white women (31.2 ± 7.8 kg·m-2 ; d = 0.73, p = 0.05). Forty-seven percent reported being physically active, with no differences by race/ethnicity. Physically active endometrial cancer survivors had higher QoL scores (d = 0.57, p = 0.02). There was a moderate effect size for BMI for the active (32.4 ± 5.6 kg·m-2 ) compared to the insufficiently active group (35.7 ± 10.2 kg·m-2 ; d = 0.40, p = 0.06). Walking self-efficacy was a significant predictor of physical activity (χ2 = 13.5, p = 0.02)., Conclusions: Physically active endometrial cancer survivors reported higher QoL, lower BMI, and more positive walking self-efficacy. These data suggest that a physically active lifestyle has a benefit in socioculturally diverse endometrial cancer survivors.- Published
- 2017
- Full Text
- View/download PDF
49. The gynecologic oncology fellowship interview process: Challenges and potential areas for improvement.
- Author
-
Gressel GM, Van Arsdale A, Dioun SM, Goldberg GL, and Nevadunsky NS
- Abstract
The application and interview process for gynecologic oncology fellowship is highly competitive, time-consuming and expensive for applicants. We conducted a survey of successfully matched gynecologic oncology fellowship applicants to assess problems associated with the interview process and identify areas for improvement. All Society of Gynecologic Oncology (SGO) list-serve members who have participated in the match program for gynecologic oncology fellowship were asked to complete an online survey regarding the interview process. Linear regression modeling was used to examine association between year of match, number of programs applied to, cost incurred, and overall satisfaction. Two hundred and sixty-nine eligible participants reported applying to a mean of 20 programs [range 1-45] and were offered a mean of 14 interviews [range 1-43]. They spent an average of $6000 [$0-25,000], using personal savings (54%), credit cards (50%), family support (12%) or personal loans (3%). Seventy percent of respondents identified the match as fair, and 93% were satisfied. Interviewees spent a mean of 15 [0-45] days away from work and 37% reported difficulty arranging coverage. Linear regression showed an increase in number of programs applied to and cost per applicant over time ( p < 0.001) between 1993 and 2016. Applicants who applied to all available programs spent more ( p < 0.001) than those who applied to programs based on their location or quality. The current fellowship match was identified as fair and satisfying by most respondents despite being time consuming and expensive. Suggested alternative options included clustering interviews geographically or conducting preliminary interviews at the SGO Annual Meeting.
- Published
- 2017
- Full Text
- View/download PDF
50. Uterine sarcoma with ambiguous histomorphology: A case report.
- Author
-
Miller EM, Fu Y, Vera RB, Goldberg GL, and Karabakhtsian RG
- Abstract
Background: Leiomyosarcomas (LMS) and endometrial stromal sarcomas (ESS) may display overlapping histomorphology, which may challenge diagnostic accuracy. Since LMS and ESS have vastly different clinical behavior and adjuvant therapy recommendations, accurate diagnosis is critical., Case: We present the case of an 83-year-old female with postmenopausal bleeding who underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy for clinically atypical appearing leiomyomata. Histologically, dual populations of cells with morphologic features of low-grade ESS and high-grade spindle cell sarcoma were seen. Immunohistochemistry and molecular studies revealed the cells to be of smooth muscle derivation, rendering a diagnosis of high-grade LMS with heterogeneous morphology (stage IB). The patient received adjuvant gemcitabine plus docetaxel. She recurred 8 months after completion of chemotherapy and was transferred to hospice care., Conclusion: Ancillary studies, such as immunohistochemistry and molecular testing, aid in accurate subcategorization of uterine sarcomas with ambiguous histomorphology.
- Published
- 2017
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.