Dr. Amer Karam is a board-certified, fellowship-trained gynecologic surgeon and clinical professor in the Stanford Medicine Department of Obstetrics & Gynecology, Division of Gynecology Oncology. He specializes in gynecologic oncology, hospice and palliative care, hereditary gynecologic cancers, laparoscopic and robotic gynecologic surgery, and obstetrics and gynecology.

Dr. Karam attended medical school at the American University in Beirut. He completed his internship and residency at the Johns Hopkins Hospital in Baltimore, Maryland, before completing a fellowship in gynecologic oncology at the University of California Los Angeles and a fellowship in breast surgery at the Memorial Sloan-Kettering Cancer Center. Dr. Karam has a vested interest in minimally invasive and robotic surgery with a practice centered on this approach for the treatment of patients with gynecologic malignancy and complicated pelvic surgery. He is currently director of Robotic Surgery and Outreach in the Division of Gynecologic Oncology.

Clinical Focus

  • Cancer > Gynecologic Cancer
  • Gynecologic Oncology

Academic Appointments

Administrative Appointments

  • Unit Medical Director, Stanford University Hospital (2018 - Present)
  • Co-Director, Stanford Robotic Surgery Committee (2016 - Present)
  • Medical Director, Stanford Cancer Center South Bay (2015 - 2018)
  • Director of Robotic Surgery, Stanford Gynecologic Oncology (2013 - Present)
  • Director of Outreach, Stanford Gynecologic Oncolgy (2013 - Present)

Professional Education

  • Board Certification: American Board of Internal Medicine, Hospice and Palliative Medicine (2010)
  • Internship: John Hopkins University-Bayview Medical Center (2001) MD
  • Fellowship: UCLA Medical Center Obstetrics and Gynecology Fellowships (2007) CA
  • Residency: Johns Hopkins University School of Medicine (2004) MD
  • Medical Education: American University of Beirut Office of the Registrar (2000) Lebanon
  • Fellowship: Memorial Sloan-Kettering Cancer Center (2008) NY
  • Board Certification: American Board of Obstetrics and Gynecology, Gynecologic Oncology (2012)
  • Board Certification: American Board of Obstetrics and Gynecology, Hospice and Palliative Medicine (2010)
  • Board Certification: American Board of Obstetrics and Gynecology, Obstetrics and Gynecology (2009)

Clinical Trials

  • A Trial of Robotic Versus Open Hysterectomy Surgery in Cervix Cancer Recruiting

    This is a randomized controlled trial to compare survival for patients who undergoe robotic assisted laparoscopy versus open hysterectomy and lymph node assessment for the treatment of early stage cervical cancer.

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  • Clinical Trial of Lurbinectedin (PM01183) in Platinum Resistant Ovarian Cancer Patients Not Recruiting

    Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate the activity and safety of PM01183 versus PLD or topotecan as control arm in patients with platinum-resistant ovarian cancer. PM01183 will be explored as single agent in the experimental arm (Arm A) versus PLD or topotecan in the control arm (Arm B).

    Stanford is currently not accepting patients for this trial. For more information, please contact Aarti Kale, 650-723-0622.

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  • Concurrent Use Lymphoseek & Indocyanine Green in Sentinel Lymph Node Detection in Endometrial Cancer Not Recruiting

    The goal of this study is to (i) improve detection of sentinel nodes and (ii) reduce additional surgical dissection that is needed in case a sentinel lymph node cannot be detected.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nimna Ranatunga, 650-721-4070.

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  • Health and Recovery Program in Increasing Physical Activity Level in Stage IA-IIIA Endometrial Cancer Survivors Not Recruiting

    This randomized phase II trial studies how well a health and recovery program works in increasing physical activity level in stage IA-IIIA endometrial cancer survivors. Health and recovery program which includes exercise counseling, Fitbit tracker, and phone or email/text communication may increase the level of physical activity in endometrial cancer survivors and promote and maintain behavior change at a lower cost.

    Stanford is currently not accepting patients for this trial. For more information, please contact Melissa Usoz, 650-723-8843.

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  • Heated Intraperitoneal Chemotherapy Followed by Niraparib for Ovarian, Primary Peritoneal and Fallopian Tube Cancer Not Recruiting

    Patients will be registered prior to, during or at the completion of neoadjuvant chemotherapy (Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV on Day 1 every 21 days for 3-4 cycles). Registered patients who progress during neoadjuvant chemotherapy will not be eligible for iCRS and will be removed from the study. Following completion of neoadjuvant chemotherapy, interval cytoreductive surgery (iCRS) will be performed in the usual fashion in both arms. Patients will be randomized at the time of iCRS (iCRS must achieve no gross residual disease or no disease \>1.0 cm in largest diameter) to receive HIPEC or no HIPEC. Patients randomized to HIPEC (Arm A) will receive a single dose of cisplatin (100mg/m2 IP over 90 minutes at 42 C) as HIPEC. After postoperative recovery patients will receive standard post-operative platinum-based combination chemotherapy. Patients randomized to surgery only (Arm B) will receive postoperative standard chemotherapy after recovery from surgery. Both groups will receive an additional 2-3 cycles of platinum-based combination chemotherapy per institutional standard (Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV on Day 1 every 21 days for 2-3 cycles) for a maximum total of 6 cycles of chemotherapy (neoadjuvant plus post-operative cycles) followed by niraparib individualized dosing until progression or 36 months (if no evidence of disease).

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy. Not Recruiting

    Olaparib Monotherapy in Patients with BRCA Mutated Ovarian Cancer following First Line Platinum Based Chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Suzanne Friedrich, 650-725-0426.

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  • Safety and Efficacy of CRS-207 With Epacadostat in Platinum Resistant Ovarian, Fallopian or Peritoneal Cancer Not Recruiting

    This 2-part, Phase 1/2 study will test investigational cancer drugs known as CRS-207, epacadostat (IDO), and pembrolizumab (pembro). The purpose of this study is to find out how safe it is to give the investigational drugs to women with platinum-resistant ovarian, fallopian tube, or peritoneal cancer and if it helps patients with these types of cancer live longer or can help shrink or slow the growth of cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Study of DPX-Survivac Therapy in Patients With Recurrent Ovarian Cancer Not Recruiting

    T cell activating therapy DPX-Survivac, low dose oral cyclophosphamide, and IDO1 inhibitor epacadostat will be tested together for the first time in patients with recurrent ovarian, fallopian tube, or peritoneal cancer to determine the safety and potential immune-modulating activity of the combination of these agents.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer Not Recruiting

    This phase II/III trial studies how well trametinib works and compares it to standard treatment with either letrozole, tamoxifen, paclitaxel, pegylated liposomal doxorubicin, or topotecan in treating patients with low-grade ovarian cancer or peritoneal cavity cancer that has come back (recurrent), become worse (progressive), or spread to other parts of the body. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether trametinib is more effective than standard therapy in treating patients with ovarian or peritoneal cavity cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Madelyn Gutierrez Gomez, 650-723-0298 .

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All Publications

  • Deloyers procedure after left hemicolectomy in Gynecologic Oncology. Gynecologic oncology reports Lang, S. M., Lee, B., Karam, A. 2024; 53: 101367


    •Deloyers procedure is an alternative to ileorectal anastomosis.•Deloyers procedure can be performed after a prior partial colectomy.•Use of this procedure may help achieve complete gross resection during cytoreductive surgery.

    View details for DOI 10.1016/j.gore.2024.101367

    View details for PubMedID 38841265

    View details for PubMedCentralID PMC11150685

  • Surgical Deloyers procedure after left hemicolectomy in Gynecologic Oncology GYNECOLOGIC ONCOLOGY REPORTS Lang, S. M., Lee, B., Karam, A. 2024; 53
  • Controversies in the Surgical Management of Gynecologic Cancer: Balancing the Decision to Operate or Hesitate. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting Somasegar, S., Anastasio, M. K., Karam, A., Rossi, E. C., Obermair, A. 2024; 44 (3): e438550


    Cancer outcomes are largely measured in terms of disease-free survival or overall survival, which is highly dependent on timely diagnosis and access to treatment methods available within the country's existing health care system. Although cancer survival rates have markedly led in the past few decades, any improvement in the 5-year survival of gynecologic cancers has been modest, as in the case of ovarian and cervical cancers, or has declined, as in the case of endometrial cancer. The lack of effective screening options contributes to many women presenting with advanced-stage disease and the need for radical approaches to treatment. Although treatment for early-stage disease can lead to a cure, advanced-stage disease is fraught with a high potential for morbidity and mortality, and recent clinical trials have aimed to assess the noninferiority of minimally invasive options versus aggressive surgical approaches. Of particular interest is fertility-sparing treatments for endometrial and cervical cancers, which have recently been on the rise among younger women. Balancing morbidity with the risk of mortality, and loss of fertility and quality of life requires a targeted patient-centered approach to treatment. This is an ongoing area of intense research and sometimes may challenge current treatment paradigms. In this two-part review, we present an overview of current approaches to gynecologic cancer treatment and the need to de-escalate radical surgical approaches and preserve fertility. We also review the intricacies of ovarian and advanced endometrial cancer treatment, exploring the nuances in surgical debulking timing and its impact on outcomes.

    View details for DOI 10.1200/EDBK_438550

    View details for PubMedID 38815208

  • Trends in ovarian, fallopian tube, and primary peritoneal cancer incidence, mortality, and survival: A 15-year population-based analysis. Gynecologic oncology Somasegar, S., Reddy, R. A., Chow, S., Dorigo, O., Renz, M., Karam, A. 2024; 184: 190-197


    To characterize trends in ovarian, fallopian tube, and primary peritoneal cancer incidence and incidence-based mortality based on histology and site of origin.We obtained age-adjusted incidence and incidence-based mortality for patients with ovarian, fallopian tube, and primary peritoneal cancer from 2000 to 2019 from the US SEER 17 database. Joinpoint was used to characterize log-linear time trends.The incidence and incidence-based mortality of all cancers trended down during the study period. The incidence of epithelial cancers decreased from 2004 to 2019 (AAPC -1.2%, p < 0.001), including that of high-grade (2006-2019: APC -1.2%, p < 0.05) and low-grade (2003-2019: APC -2.4%, p < 0.05) epithelial cancers. There was no change in incidence or incidence-based mortality for ovarian stromal and germ cell cancers.There has been a decrease in the incidence and incidence-based mortality of ovarian, fallopian tube, and primary peritoneal cancer, primarily due to reductions in advanced stage epithelial cancers originating in the ovary, fallopian tube, or peritoneum.

    View details for DOI 10.1016/j.ygyno.2024.01.034

    View details for PubMedID 38330833

  • Aberrant nuclear β-catenin distribution does not prognosticate recurrences of endometrioid endometrial cancers - A retrospective single-institutional study. Gynecologic oncology Beshar, I., Moon, A. S., Darji, H., Liu, C., Jennings, M. T., Dorigo, O., Litkouhi, B., Diver, E. J., Karam, A. K., Howitt, B. E., Renz, M. 2023; 179: 85-90


    Aberrant β-catenin distribution has been theorized as a predictive biomarker for recurrence in early stage, low grade endometrioid endometrial cancer.This retrospective single-institution cohort study reviewed 410 patients with endometrial cancer from May 2018 to May 2022. Only endometrioid histology was included. Demographic and clinicopathological data were collected from the medical records. Univariate and multivariate logistic regressions, and sensitivity analyses for early stage, low grade and no specific molecular profile (NSMP) tumors were performed.297 patients were included for analysis. Most patients were over 60 years old, White, and with a BMI >30 and early stage low grade disease. Aberrant β-catenin distribution was found in 135 patients (45.5%) and wild type membranous β-catenin distribution in 162 (54.5%). While TP53 mutation correlated with endometrial cancer recurrence in this cohort (OR = 4.78), aberrant β-catenin distribution did not correlate in the overall population (OR = 0.75), the early stage low grade cancers (OR = 0.84), or the NSMP group (OR = 1.41) on univariate or multivariate analysis. No correlation between β-catenin distribution and local (OR = 0.61) or distant recurrences (OR = 0.90) was detected.Aberrant β-catenin distribution did not significantly correlate with recurrence in endometrioid endometrial cancer, nor in the early stage, low grade and NSMP sub-cohorts.

    View details for DOI 10.1016/j.ygyno.2023.10.025

    View details for PubMedID 37944330

  • Does lymph node assessment change the prognostic significance of substantial LVSI and p53 status in endometrial endometrioid carcinoma? Gynecologic oncology Hui, C., Mendoza, M. G., von Eyben, R., Dorigo, O., Litkouhi, B., Renz, M., Karam, A., Hammer, P. M., Howitt, B. E., Kidd, E. 2023; 177: 150-156


    The PORTEC-2 update suggested that substantial lymphovascular space invasion (LVSI) and abnormal p53 expression (p53abnl) predict for poorer outcomes and that these patients should be treated with external beam radiation therapy (EBRT). We aim to determine if patients with these risk factors who undergo a lymph node (LN) assessment show similar outcomes.We retrospectively reviewed 126 patients with FIGO 2009 stage IA grade 3, stage IB grade 1-2, and stage IIIC (positive LN but no other stage II/III risk factors) endometrioid endometrial cancer who underwent LN assessment. Local (LR), regional recurrences (RR), and distant metastases were analyzed using competing risk methods, and overall survival (OS) was analyzed using Kaplan-Meier.Median follow-up time was 37.2 months. OS was significantly different between patients with and without p53abnl expression (16.7% versus 3.1% deceased), and between patients with and without LVSI (11.1% versus 1.5% deceased; p < 0.01 for both). The 2-year cumulative incidence of LR for patients with p53abnl versus wild type p53 and LVSI versus no LVSI was 11.1% (95% CI 0-25.6) versus 2.2% (95% CI 0-5.25; p = 0.04), and 11.4% (95% CI 2.0-20.9) versus 0%, respectively (p < 0.01). The 2-year cumulative RR in patients with LVSI versus no LVSI was 6.9% (95% CI 0-14.4) versus 0% (p = 0.05). No patients who completed pelvic RT experienced an in-field recurrence.Despite LN assessment, patients with high-intermediate risk early-stage or stage IIIC (with positive lymph nodes only but no other stage II or III risk factors) endometrial cancer with p53abnl expression and/or LVSI have worse outcomes. These patients may derive benefit from intensification with EBRT to improve local and pelvic control.

    View details for DOI 10.1016/j.ygyno.2023.09.001

    View details for PubMedID 37696217

  • Surgical outcomes for robotic-assisted single-site hysterectomy in risk-reducing, precancerous, and malignant gynecological disease: A single institution retrospective study Reddy, R., Somasegar, S., Karam, A. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2023: S151-S152
  • Graduate and Continuing Medical Education of Placenta Accreta Spectrum. American journal of perinatology Feltmate, C., Easter, S. R., Gilner, J. B., Karam, A. K., Khourry-Callado, F., Fox, K. A. 2023; 40 (9): 1002-1008


    Surgical training experience in obstetrics-gynecology (OB-GYN) residency and fellowship training, particularly in open abdominal surgeries has declined over the last 2 decades. This is due, in part, due to a universal trend toward non-invasive treatments for gynecologic conditions once treated surgically. Management of placenta accreta spectrum (PAS) often requires complex surgical skills, including, but not limited to highly complex hysterectomy. The decline in surgical case numbers has fallen as the incidence of PAS has risen, which we anticipate will lead to a gap in critical skills needed for graduating obstetrician-gynecologists to able to safely care for people with PAS.

    View details for DOI 10.1055/s-0043-1761640

    View details for PubMedID 37336218

  • Surgical Techniques for the Management of Placenta Accreta Spectrum. American journal of perinatology Khoury-Collado, F., Newton, J. M., Brook, O. R., Carusi, D. A., Shrivastava, V. K., Crosland, B. A., Fox, K. A., Khandelwal, M., Karam, A. K., Bennett, K. A., Sandlin, A. T., Shainker, S. A., Einerson, B. D., Belfort, M. A. 2023; 40 (9): 970-979


    The surgical management of placenta accreta spectrum (PAS) is often challenging. There are a variety of techniques and management options described in the literature ranging from uterine sparing to cesarean hysterectomy. Following the inaugural meeting of the Pan-American Society for Placenta Accreta Spectrum a multidisciplinary group collaborated to describe collective recommendations for the surgical management of PAS. In this manuscript, we outline individual components of the procedure and provide suggested direction at key points of a cesarean hysterectomy in the setting of PAS. KEY POINTS: · The surgical management of PAS requires careful planning and expertise.. · Multidisciplinary team care for pregnancies complicated by PAS can decrease morbidity and mortality.. · Careful surgical techniques can minimize risk of significant hemorrhage by avoiding pitfalls..

    View details for DOI 10.1055/s-0043-1761636

    View details for PubMedID 37336214

  • Trends in ovarian cancer incidence and incidence-based mortality: A 15-year populationbased analysis Somasegar, S., Reddy, R. A., Karam, A. LIPPINCOTT WILLIAMS & WILKINS. 2023
  • Adjuvant radiation therapy in early-stage endometrial cancer with abnormal beta-catenin expression is associated with improved local control. Gynecologic oncology Hui, C., Mendoza, M. G., Snyder, J., Dorigo, O., Litkouhi, B., Renz, M., Karam, A., Devereaux, K., Howitt, B. E., Kidd, E. A. 2023; 174: 42-48


    Emerging data suggests that abnormal (nuclear) β-catenin expression in some settings is associated with poorer outcomes. Our study aimed to verify the significance of abnormal β-catenin expression in early-stage endometrial cancer patients and determine if adjuvant radiation therapy (RT) improves local control.We identified 213 patients with FIGO 2018 stage I-II endometrioid endometrial cancer who underwent surgery from 2009 to 2021 with β-catenin expression assessed. Vaginal, regional, and distant recurrences were analyzed using competing risk methods, and overall survival was analyzed using Kaplan-Meier.Median follow up was 53.2 months; 6.9% experienced vaginal, 8.2% regional, and 7.4% distant recurrence. For the entire cohort, abnormal β-catenin expression was significantly associated with vaginal recurrence and remained significant on multivariate analysis (p = 0.03). There were 114 patients in the no specific molecular profile (NSMP) subgroup, and abnormal β-catenin expression was present in 46.5%. In the NSMP subgroup, abnormal β-catenin expression was associated with increased rates of vaginal recurrence (p = 0.06). Abnormal β-catenin expression in the NSMP subgroup was significant on multivariate analysis for vaginal recurrence (p = 0.04). RT significantly decreased vaginal recurrences in the entire cohort in patients with abnormal β-catenin expression (0%) versus wild type expression (17.5%; p = 0.03). In the NSMP subgroup 0% of patients who received RT versus 20.9% of patients who did not receive RT experienced a vaginal recurrence (p = 0.03).Use of adjuvant RT for stage I-II NSMP endometrial cancer with abnormal β-catenin expression improved local control. RT should be considered in these patients to decrease risk of vaginal recurrences.

    View details for DOI 10.1016/j.ygyno.2023.04.018

    View details for PubMedID 37149904

  • NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022. Journal of the National Comprehensive Cancer Network : JNCCN Armstrong, D. K., Alvarez, R. D., Backes, F. J., Bakkum-Gamez, J. N., Barroilhet, L., Behbakht, K., Berchuck, A., Chen, L. M., Chitiyo, V. C., Cristea, M., DeRosa, M., Eisenhauer, E. L., Gershenson, D. M., Gray, H. J., Grisham, R., Hakam, A., Jain, A., Karam, A., Konecny, G. E., Leath Iii, C. A., Leiserowitz, G., Liu, J., Martin, L., Matei, D., McHale, M., McLean, K., Miller, D. S., Percac-Lima, S., Remmenga, S. W., Schorge, J., Stewart, D., Thaker, P. H., Vargas, R., Hendrickson, A. W., Werner, T. L., Zsiros, E., Dwyer, M. A., Hang, L. 2022; 20 (9): 972-980


    Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.

    View details for DOI 10.6004/jnccn.2022.0047

    View details for PubMedID 36075393

  • Technetium Tc 99m tilmanocept fails to detect sentinel lymph nodes in endometrial cancer. Gynecologic oncology reports Reddy, R. A., Moon, A. S., Chow, S., Heilbroner, L., Howitt, B., Diver, E., Dorigo, O., Litkouhi, B., Renz, M., Karam, A. 2022; 43: 101054


    Technetium Tc 99m tilmanocept is a synthetic radiotracer specifically designed for sentinel lymph node (SLN) mapping that has been FDA-approved in breast cancer, melanoma, and head and neck cancer. No published studies exist for the use of this radiotracer in endometrial cancer.The primary objective was to determine the detection rate of bilateral SLNs in endometrial cancer with the concurrent use of technetium Tc 99m tilmanocept and ICG.An open-label, single cohort, prospective feasibility study was conducted with participants receiving preoperative cervical injections of technetium Tc 99m tilmanocept followed by subsequent imaging and SPECT/CT. Intraoperative ICG injections were administered for all patients with near-infrared imaging used to visualize lymphatic vessels and nodes. A laparoscopic gamma counter was used to detect radioactive SLN intraoperatively.All six evaluated patients had FIGO grade 1 or 2 endometrioid histology. Stage IA/IB were in 33% and 66% of patients, respectively. Tilmanocept did not map any SLN in the first six patients but instead showed retention of the tracer in the cervical stroma, leading to study discontinuation for futility. ICG mapped bilateral SLN in all patients with the most common location being the external iliac region, followed by the obturator and common iliac areas. All patients had CD206 positive staining throughout the full wall thickness of ectocervix, transformation zone, endocervix, and lymphatic vessels. No patients experienced adverse events.Technetium Tc 99m tilmanocept did not detect SLN in early stage endometrial cancers and is unlikely to improve bilateral detection rate compared to ICG alone. ICG remains a standard technique for SLN detection in low stage, low grade endometrial cancer.

    View details for DOI 10.1016/j.gore.2022.101054

    View details for PubMedID 35958955

    View details for PubMedCentralID PMC9361318

  • Role of sentinel lymph node biopsy for gynecologic cancers. Current opinion in obstetrics & gynecology Chow, S., Karam, A. 1800; 34 (1): 15-19


    PURPOSE OF REVIEW: To provide an overview of the current knowledge and recent advances of sentinel lymph node (SLN) assessment in uterine, cervical, vulvar, and ovarian cancers.RECENT FINDINGS: In endometrial cancer, SLN evaluation has become increasingly utilized as part of the treatment of early-stage disease, with data showing improved detection of pelvic lymph node metastasis. In cervical cancer, SLN biopsy has also gained increasing traction with studies demonstrating the feasibility and accuracy of SLN detection. Evaluation with frozen section, however, remains limited in the detection of metastases. The prognostic significance of positive SLN in vulvar cancer is currently being investigated, with preliminary data showing lower recurrence rates in patients receiving adjuvant radiation.SUMMARY: SLN evaluation remains standard of care to detect lymph node metastasis in early-staged endometrial cancer. In cervical cancer, SLN biopsy has been shown to be reliable, while decreasing morbidity without impacting disease-free survival in select patients. The technique and high sensitivity of SLN biopsy in vulvar cancer has been demonstrated in large prospective trials. There are no randomized controlled trials in ovarian cancer that evaluate the role of SLN biopsy on treatment and outcome; current SLN evaluation remains investigational.

    View details for DOI 10.1097/GCO.0000000000000766

    View details for PubMedID 34967810

  • Phase II Trial Evaluating Efficacy of a Fitbit Program for Improving the Health of Endometrial Cancer Survivors Rahimy, E., Usoz, M., von Eyben, R., Fujimoto, D., Watanabe, D., Karam, A., Jairam-Thodla, A., Mills, M., Dorigo, O., Diver, E., Teng, N., English, D., Kidd, E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S13
  • Rapid Response of a BRCA2/TP53/PTEN-Deleted Metastatic Uterine Leiomyosarcoma to Olaparib: A Case Report. The Permanente journal Pan, M., Ganjoo, K., Karam, A. 2021; 25


    None: Patients with metastatic uterine leiomyosarcoma (uLMS) have poor prognosis due to limited treatment options, especially when disease progresses on doxorubicin and gemcitabine-docetaxel regimens. Here we report a patient whose metastatic uLMS contains a BRCA2 deep deletion as well as TP53 and PTEN deep deletion. The patient responded rapidly to olaparib, a poly (ADP-ribose) polymerase inhibitor, after progressing on gemcitabine-docetaxel, doxorubicin, and temozolomide regimens. This case report shall be helpful to the treatment of other patients with metastatic uLMS that harbors a BRCA2 mutation or deletion.

    View details for DOI 10.7812/TPP/20.251

    View details for PubMedID 33970096

  • When to Operate, Hesitate and Reintegrate: Society of Gynecologic Oncology Surgical Considerations During the COVID-19 Pandemic OBSTETRICAL & GYNECOLOGICAL SURVEY Fader, A. N., Huh, W. K., Kesterson, J., Pothuri, B., Wethington, S., Wright, J. D., Bakkum-Gamez, J. N., Soliman, P. T., Sinno, A. K., Leitao, M., Martino, M. A., Karam, A., Rossi, E., Brown, J., Blank, S., Burke, W., Goff, B., Yamada, S., Uppal, S., Dowdy, S. C. 2021; 76 (2): 88–90
  • Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Armstrong, D. K., Alvarez, R. D., Bakkum-Gamez, J. N., Barroilhet, L., Behbakht, K., Berchuck, A., Chen, L., Cristea, M., DeRosa, M., Eisenhauer, E. L., Gershenson, D. M., Gray, H. J., Grisham, R., Hakam, A., Jain, A., Karam, A., Konecny, G. E., Leath, C. A., Liu, J., Mahdi, H., Martin, L., Matei, D., McHale, M., McLean, K., Miller, D. S., O'Malley, D. M., Percac-Lima, S., Ratner, E., Remmenga, S. W., Vargas, R., Werner, T. L., Zsiros, E., Burns, J. L., Engh, A. M. 2021; 19 (2): 191–226


    Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country's fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.

    View details for DOI 10.6004/jnccn.2021.0007

    View details for PubMedID 33545690

  • Prospective molecular classification of endometrial carcinomas: institutional implementation, practice, and clinical experience. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Devereaux, K. A., Weiel, J. J., Pors, J., Steiner, D. F., Ho, C., Charu, V., Suarez, C. J., Renz, M., Diver, E., Karam, A., Litkouhi, B., Dorigo, O., Kidd, E. A., Yang, E. J., Folkins, A. K., Longacre, T. A., Howitt, B. E. 2021


    The comprehensive genomic analysis of endometrial carcinoma (EC) by The Cancer Genome Atlas (TCGA) led to the discovery of four distinct and prognostically significant molecular subgroups. Molecular classification has the potential to improve risk-stratification when integrated with clinicopathologic features and has recently been included in national and international patient management EC guidelines. Thus, the adoption of molecular classification into routine pathologic and clinical practice is likely to grow significantly in the upcoming years. Establishing an efficient and standardized workflow for performing molecular classification on ECs, and reporting both the molecular and histologic findings in an integrative manner, is imperative. Here we describe our effort to implement rapid and routine molecular classification on all ECs diagnosed at our institution. To this effect, we performed immunohistochemistry as a surrogate marker for identifying genetic and/or epigenetic alterations in DNA mismatch repair (e.g., MLH1, PMS2, MSH6, MSH2), and TP53 genes. In addition, we have developed and employed a single-gene POLE SNaPshot assay, which is a rapid and analytically sensitive method for detecting select POLE exonuclease domain mutations (EDMs). We report our molecular testing workflow and integrative reporting system as well as the clinicopathologic and molecular features of 310 ECs that underwent routine molecular classification at our institution. The 310 ECs were molecularly classified as follows: 15 (5%) POLE mutant (POLEmut), 79 (25%) mismatch repair-deficient (MMRd), 135 (44%) no specific molecular profile (NSMP), and 81 (26%) p53 abnormal (p53abnl). This work provides an initial framework for implementing routine molecular classification of ECs.

    View details for DOI 10.1038/s41379-021-00963-y

    View details for PubMedID 34743187

  • Phase II trial evaluating efficacy of a Fitbit program for improving the health of endometrial cancer survivors. Gynecologic oncology Rahimy, E. n., Usoz, M. n., von Eyben, R. n., Fujimoto, D. n., Watanabe, D. n., Karam, A. n., Jairam-Thodla, A. n., Mills, M. n., Dorigo, O. n., Diver, E. J., Teng, N. n., English, D. n., Kidd, E. n. 2021


    Despite the favorable prognosis of early stage endometrial cancer, mortality from cardiovascular disease is high. We aimed to evaluate the efficacy of a Fitbit program to improve physical activity in endometrial cancer survivors.Eligible patients were diagnosed with stage IA-IIIA endometrial adenocarcinoma, ≥3 months out from treatment. Participants received a Fitbit Alta and were randomized to receive communication via telephone or electronic methods (email/text). Communication was every two weeks for two months, then once during months four and five. Average daily steps were assessed weekly for nine months.The 46 analyzable patients demonstrated a baseline of 5641 median daily average steps. Average steps increased by 22% at 6 months but decreased to baseline by nine months. Baseline activity level (daily steps and walks per week) was the greatest predictor of activity level. Only the telephone intervention participants demonstrated increased activity level at several timepoints, although not maintained by nine months. BMI was unchanged. There was mild improvement in physical and social well-being in those with low baseline well-being (p = 0.009 and 0.014, respectively), regardless of intervention group. Emotional well-being correlated with step count (p = 0.005).Activity level was low and mildly improved on the Fitbit program with the telephone intervention, but effects did not persist by study completion. The program had the greatest impact on a select group of telephone intervention patients with high baseline walking frequency and low baseline step count. Others may require more intense intervention to promote more robust/persistent lifestyle changes.

    View details for DOI 10.1016/j.ygyno.2021.01.033

    View details for PubMedID 33551199

  • Minimally Invasive Surgery for Gynecologic Cancers-A Cautionary Tale. JAMA oncology Karam, A., Dorigo, O. 2020

    View details for DOI 10.1001/jamaoncol.2020.1617

    View details for PubMedID 32525507

  • Sentinel Lymph Node Biopsies in Endometrial Cancer: Practice Patterns among Gynecologic Oncologists in the United States JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY Renz, M., Diver, E., English, D., Kidd, E., Dorigo, O., Karam, A. 2020; 27 (2): 482–88
  • Vulvar sarcoma outcomes by histologic subtype: a Surveillance, Epidemiology, and End Results (SEER) database review. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society Johnson, S. n., Renz, M. n., Wheeler, L. n., Diver, E. n., Dorigo, O. n., Litkouhi, B. n., Behbakht, K. n., Howitt, B. n., Karam, A. n. 2020


    Vulvar cancers account for 5% of all gynecologic malignancies; only 1%-3% of those vulvar cancers are primary vulvar sarcomas. Given the rarity of vulvar sarcomas, outcome data specific to histopathologic subtypes are sparse. The aim of this study was to identify clinical and pathologic factors of primary vulvar sarcomas that are associated with survival and may inform treatment decisions.The Surveillance, Epidemiology, and End Results (SEER) database was searched for women diagnosed with vulvar sarcoma between 1973 and 2018. We identified 315 patients and reviewed their demographic, clinicopathologic, surgical, and survival information. Statistical analyses included χ2 and t-tests, Kaplan-Meier survival, and Cox regression analyses.The most common histopathologies of vulvar sarcomas were dermatofibrosarcomas (85/315, 27%) and leiomyosarcomas (72/315, 22.9%). Rhabdomyosarcomas (18/315, 5.7%), liposarcomas (16/315, 5.1%), and malignant fibrous histiocytomas (16/315, 5.1%) were less frequent. The majority of patients underwent surgery (292/315, 92.7%), which included lymph node dissections in 21.6% (63/292). Survival and lymph node involvement varied significantly with histologic subtype. The 5-year disease-specific survival for dermatofibrosarcomas, liposarcomas, and fibrosarcomas was 100% and only 60.3% and 62.5% for malignant fibrous histiocytomas and rhabdomyosarcomas, respectively. None of the patients with (dermato)fibrosarcomas, liposarcomas, or leiomyosarcomas had positive lymph nodes, in contrast to rhabdomyosarcomas and malignant fibrous histiocytomas with 77.8% and 40% positive lymph nodes, respectively. The 5-year disease-specific survival for women with positive lymph nodes was 0%.Vulvar sarcomas are heterogeneous with survival highly dependent on the histopathologic subtype. While surgical excision is the mainstay of treatment for all vulvar sarcomas, staging lymphadenectomy should be deferred for (dermato)fibrosarcomas, liposarcomas, and leiomyosarcomas as there were no cases of lymph nodes metastases.

    View details for DOI 10.1136/ijgc-2020-001516

    View details for PubMedID 32641392

  • Two Patient Studies of a Companion Diagnostic Immuno-Positron Emission Tomography (PET) Tracer for Measuring Human CA6 Expression in Cancer for Antibody Drug Conjugate (ADC) Therapy. Molecular imaging Natarajan, A., Srinivas, S. M., Azevedo, C., Greene, L., Bauchet, A., Jouannot, E., Lacoste-Bourgeacq, A., Guizon, I., Cohen, P., Naneix, A., Ilovich, O., Cisneros, J., Rupanarayan, K., Chin, F. T., Iagaru, A., Dirbas, F. M., Karam, A., Gambhir, S. S. 2020; 19: 1536012120939398


    An antigen binding fragment (BFab) derived from a tumor-associated mucin 1-sialoglycotope antigen (CA6) targeting antibody (huDS6) was engineered. We synthesized a companion diagnostic positron emission tomography (PET) tracer by radiolabeling BFab with [64Cu] to measure CA6 expression on cancer tissues prior to anti-human CA6 (huDS6-DM4 antibody-drug conjugate) therapy for ovarian and breast cancer patients. After chemotherapy, the ovarian patient received PET scan with 18F-2-fluoro-2-deoxyglucose ([18F]FDG: 10 mCi), followed by [64Cu]-DOTA-BFab ([64Cu]BFab; 5.5 mCi) 1 week later for PET scanning of CA6 expression and subsequent surgery. The breast cancer patient was treated with chemotherapy before primary tumor resection and subsequent [18F]FDG-PET scan. 4 weeks later the patient received of [64Cu]BFab (11.7 mCi) for CA6 PET scan. Whole body [18F]FDG-PET of the breast cancer patient indicated FDG-avid tumor metastases to the liver, bilateral hila and thoracic spine, but no uptake was observed for the ovarian patient. Each patient was also imaged by PET/CT with [64Cu]BFab at 1 and 24 hours after tracer administration. The [64Cu]BFab tracer was well tolerated by both patients without adverse effects, and no significant tracer uptake was observed in both patients. Immunohistochemistry (IHC) data indicated CA6 expressions were weak to intermediate and matched with the [64Cu]BFab-PET signals.

    View details for DOI 10.1177/1536012120939398

    View details for PubMedID 33104454

  • In Reply to Vitiello et al.: Acute Optic Neuritis Diagnosed by Bedside Ultrasound in an Emergency Department: Follow-Up and Clarification. The Journal of emergency medicine Saigh, M. P., Plauché, H. M., Butts, C. n., Karam, A. K., Suau, S. J., Moreno-Walton, L. n. 2020; 59 (3): 449–51

    View details for DOI 10.1016/j.jemermed.2020.06.062

    View details for PubMedID 33126962

  • Society of gynecologic oncology surgery considerations during when to operate, hesitate and reintegrate the COVID-19 pandemic. Gynecologic oncology Fader, A. N., Huh, W. K., Kesterson, J. n., Pothuri, B. n., Wethington, S. n., Wright, J. D., Bakkum-Gamez, J. N., Soliman, P. T., Sinno, A. K., Leitao, M. n., Martino, M. A., Karam, A. n., Rossi, E. n., Brown, J. n., Blank, S. n., Burke, W. n., Goff, B. n., Yamada, S. D., Uppal, S. n., Dowdy, S. C. 2020


    The COVID-19 pandemic has challenged our ability to provide timely surgical care for our patients. In response, the U.S. Surgeon General, the American College of Srugeons, and other surgical professional societies recommended postponing elective surgical procedures and proceeding cautiously with cancer procedures that may require significant hospital resources and expose vulnerable patients to the virus. These challenges have particularly distressing for women with a gynecologic cancer diagnosis and their providers. Currently, circumstances vary greatly by region and by hospital, depending on COVID-19 prevalence, case mix, hospital type, and available resources. Therefore, COVID-19-related modifications to surgical practice guidelines must be individualized. Special consideration is necessary to evaluate the appropriateness of procedural interventions, recognizing the significant resources and personnel they require. Additionally, the pandemic may occur in waves, with patient demand for surgery ebbing and flowing accordingly. Hospitals, cancer centers and providers must prepare themselves to meet this demand. The purpose of this white paper is to highlight all phases of gynecologic cancer surgical care during the COVID-19 pandemic and to illustrate when it is best to operate, to hestitate, and reintegrate surgery. Triage and prioritization of surgical cases, preoperative COVID-19 testing, peri-operative safety principles, and preparations for the post-COVID-19 peak and surgical reintegration are reviewed.

    View details for DOI 10.1016/j.ygyno.2020.06.001

    View details for PubMedID 32532460

  • Coexistence of BRAF V600E and TERT Promoter Mutations in Low-grade Serous Carcinoma of Ovary Recurring as Carcinosarcoma in a Lymph Node: Report of a Case INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY Tavallaee, M., Steiner, D. F., Zehnder, J. L., Folkins, A. K., Karam, A. K. 2019; 38 (4): 386–92
  • Transesophageal Echocardiographic Observation of Caval Thrombus Followed by Intraoperative Placement of Inferior Vena Cava Filter for Presumed Pulmonary Embolism During Cesarean Hysterectomy for Placenta Percreta: A Case Report A & A PRACTICE Nanji, J. A., Ansari, J. R., Yurashevich, M., Ismawan, J. M., Lyell, D. J., Karam, A. K., Hovsepian, D. M., Riley, E. T. 2019; 12 (2): 37–40
  • Acute Optic Neuritis Diagnosed by Bedside Ultrasound in an Emergency Department. The Journal of emergency medicine Saigh, M. P., Plauché, H. M., Butts, C. n., Karam, A. K., Suau, S. J., Moreno-Walton, L. n. 2019


    Transorbital ultrasound was used to diagnose acute optic neuritis (AON) at bedside in an emergency department (ED).A 59-year-old female patient presented to an ED after 7 days of progressive unilateral visual loss while she was receiving outpatient treatment for relapsing-remitting multiple sclerosis. Transorbital ultrasound revealed a disparity between the optic nerve sheath diameters of the affected and nonaffected eyes and striking optic nerve edema in the affected eye. These findings led to a diagnosis of AON and early definitive treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Given an absence of reliable diagnostic criteria for AON, comorbidity with multiple sclerosis, and limitations inherent to magnetic resonance imaging, transorbital sonography may facilitate diagnosis of this condition in emergent presentations.

    View details for DOI 10.1016/j.jemermed.2019.04.032

    View details for PubMedID 31229301

  • Advanced communication: A critical component of high quality gynecologic cancer care: A Society of Gynecologic Oncology evidence based review and guide. Gynecologic oncology Littell, R. D., Kumar, A. n., Einstein, M. H., Karam, A. n., Bevis, K. n. 2019


    Effective communication between gynecologic oncology providers and patients is vital to patient-centered care. Skilled communication improves the patient's knowledge retention, builds trust in providers, enhances shared decision-making, and alleviates anxiety of both patients and caregivers. Effective communication is also associated with reduced provider burnout due to improved comfort from possessing the skills to handle emotionally charged situations. Therefore, training in serious illness communication skills is critically important to gynecologic oncology practice and benefits patients, providers, and the healthcare system. Like surgical skills, communication skills can be learned and improved upon, particularly by making use of communication skills courses and other resources. While the purpose of each conversation will vary based on the medical setting, most communication roadmaps incorporate four basic components: 1) Assess patient knowledge and understanding, 2) inform patient in accordance with her communication preferences, 3) recognize and respond to emotion 4) elicit patient values, and create a plan that aligns with those values. Improved patient outcomes associated with addressing patient emotions underscore a critical need to recognize and address emotional cues during difficult conversations. We present strategies for delivering serious news, and for discussing prognosis and goals of care. In each strategy, we highlight skills for recognizing and responding to patient and family emotional cues.

    View details for DOI 10.1016/j.ygyno.2019.07.026

    View details for PubMedID 31422857

  • Sentinel lymph node biopsies in endometrial cancer - practice patterns among Gynecologic Oncologists in the United States. Journal of minimally invasive gynecology Renz, M. n., Diver, E. n., English, D. n., Kidd, E. n., Dorigo, O. n., Karam, A. n. 2019


    To evaluate practice patterns among gynecologic oncologists with regards to sentinel lymph node injection and biopsy in endometrial cancer.Observational study with no control group.Active members of the Society of Gynecologic Oncology.After IRB approval, we performed an online survey amongst active members of the Society of Gynecologic Oncology. Members were contacted via email and their answers anonymously captured. Study data were collected using REDCap.318 of 1216 listed members completed the online survey, The majority of respondents (82.7%) perform sentinel lymph node sampling for endometrial cancer staging. Most technical aspects of sentinel lymph node sampling were consistently applied by the vast majority of respondents, including the choice of indocyanine green (ICG) as lymphatic tracer (97.3%) and its injection into the cervix (100%). Other technical aspects of sentinel lymph node sampling, such as the depth of injection, varied amongst respondents. While 50.9% of the respondents perform an intraoperative assessment of the uterus by frozen section, only 17.9% assess sentinel lymph nodes by frozen section and/or touch prep. Some of the respondents' approaches are based on limited data, including (i) the use of sentinel lymph node injection and biopsy for high-risk histologies (performed by 69 - 75% of the respondents dependent upon the histology), (ii) omitting side-specific completion lymphadenectomy in the absence of sentinel node mapping (in up to 57.8%) or (iii) when lymph node metastases are present (in 39.9%).In summary, despite the growing use of sentinel lymph node injection and biopsy in endometrial cancer, practice patterns vary considerably among providers sampled by this survey. Some of the decisions are based on limited evidence and, in some instances, deviate from current published guidelines.

    View details for PubMedID 30980995

  • Case of Metastatic Extramammary Paget Disease of the Vulva Treated Successfully With Trastuzumab Emtansine. JCO precision oncology Hsieh, G. L., English, D. P., Tu, P., Folkins, A. K., Karam, A. K. 2018; 2: 1-8

    View details for DOI 10.1200/PO.17.00204

    View details for PubMedID 35135119

  • Racial disparities in outcomes for high-grade uterine cancer: A California cancer registry study CANCER MEDICINE Baskovic, M., Lichtensztajn, D. Y., Trung Nguyen, Karam, A., English, D. P. 2018; 7 (9): 4485–95

    View details for DOI 10.1002/cam4.1742

    View details for Web of Science ID 000444945200030

  • Transesophageal Echocardiographic Observation of Caval Thrombus Followed by Intraoperative Placement of Inferior Vena Cava Filter for Presumed Pulmonary Embolism During Cesarean Hysterectomy for Placenta Percreta: A Case Report. A&A practice Nanji, J. A., Ansari, J. R., Yurashevich, M., Ismawan, J. M., Lyell, D. J., Karam, A. K., Hovsepian, D. M., Riley, E. T. 2018


    During a cesarean hysterectomy for placenta percreta, transesophageal echocardiography was used to monitor volume status and guide resuscitation. After delivery of the neonate but before massive surgical hemorrhage, a thrombus appeared in the inferior vena cava. Roughly 3 hours later, the patient had hemodynamic changes consistent with an intraoperative pulmonary embolism. Boluses of epinephrine stabilized the patient. An inferior vena cava filter was placed via an in situ internal jugular central venous cannula to prevent further embolic events. We believe transesophageal echocardiography is a useful monitor during surgery for placenta percreta.

    View details for PubMedID 30020106

  • Case of Metastatic Extramammary Paget Disease of the Vulva Treated Successfully With Trastuzumab Emtansine JCO PRECISION ONCOLOGY Hsieh, G. L., English, D. P., Tu, P., Folkins, A. K., Karam, A. K. 2018; 2
  • Coexistence of BRAF V600E and TERT Promoter Mutations in Low-grade Serous Carcinoma of Ovary Recurring as Carcinosarcoma in a Lymph Node: Report of a Case. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists Tavallaee, M., Steiner, D. F., Zehnder, J. L., Folkins, A. K., Karam, A. K. 2018


    Low-grade serous carcinomas only rarely coexist with or progress to high-grade tumors. We present a case of low-grade serous carcinoma with transformation to carcinosarcoma on recurrence in the lymph node. Identical BRAF V600E and telomerase reverse transcriptase promoter mutations were identified in both the original and recurrent tumor. Given that telomerase reverse transcriptase promotor mutations are thought to play a role in progression of other tumor types, the function of telomerase reverse transcriptase mutations in BRAF mutated low-grade serous carcinoma deserves investigation.

    View details for PubMedID 29620581

  • Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: first-line interventions ANNALS OF ONCOLOGY Karam, A., Ledermann, J. A., Kim, J., Sehouli, J., Lu, K., Gourley, C., Katsumata, N., Burger, R. A., Nam, B., Bacon, M., Ng, C., Pfisterer, J., Bekkers, R. L., Casado Herraez, A., Redondo, A., Fujiwara, H., Gleeson, N., Rosengarten, O., SCAMBIA, G., Zhu, J., Okamoto, A., Stuart, G., Ochiai, K. 2017; 28 (4): 711-717


    The consensus statements regarding first-line therapies in women with ovarian cancer, reached at the Fifth Ovarian Cancer Consensus Conference held in Tokyo, Japan, in November 2015 are reported. Three topics were reviewed and the following statements are recommended: (i) Surgery: the subgroups that should be considered in first-line ovarian cancer clinical trials should be (a) patients undergoing primary debulking surgery and (b) patients receiving neo-adjuvant chemotherapy. The amount of residual disease following surgery should further stratify patients into those with absent gross residual disease and others. (ii) Control arms for chemotherapy: for advanced stage ovarian cancer the standard is intravenous 3-weekly carboplatin and paclitaxel. Acceptable alternatives, which should be stratified variables in trials when more than one regimen is offered, include weekly paclitaxel plus 3-weekly carboplatin, the addition of bevacizumab to 3-weekly carboplatin and paclitaxel, and intraperitoneal therapy. (iii) Trial Endpoints: overall survival is the preferred primary endpoint for first-line clinical trials with or without a maintenance component. Progression-free survival (PFS) is an alternative primary endpoint, but if PFS is chosen overall survival must be measured as a secondary endpoint and PFS must be supported by additional endpoints, including predefined patient reported outcomes and time to first or second subsequent therapy. For neoadjuvant therapy, additional 'window of opportunity' endpoints should be included.

    View details for DOI 10.1093/annonc/mdx011

    View details for Web of Science ID 000397622100010

    View details for PubMedID 28327917

  • Breast Cancer Posttreatment Surveillance: Diagnosis and Management of Recurrent Disease. Clinical obstetrics and gynecology Karam, A. K. 2016; 59 (4): 772-778


    There has been a steady decline in breast cancer mortality that has led to a significant increase in the number of patients surviving breast cancer. We will review in this manuscript the evidence and guidelines for posttreatment surveillance of patients with breast cancer as well as the management options for patients who are diagnosed with local-regional and distant recurrences.

    View details for PubMedID 27681690

  • Risk-Reducing Surgery in Hereditary Breast and Ovarian Cancer NEW ENGLAND JOURNAL OF MEDICINE Karam, A. 2016; 374 (24): 2403

    View details for PubMedID 27305205

  • Pilot prospective evaluation of F-18-FPPRGD(2) PET/CT in patients with cervical and ovarian cancer EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Minamimoto, R., Karam, A., Jamali, M., Barkhodari, A., Gambhir, S. S., Dorigo, O., Iagaru, A. 2016; 43 (6): 1047-1055


    We report the effect of antiangiogenic therapy on the biodistribution of (18)F-FPPRGD2 (a surrogate biomarker of integrin αvβ3 expression), and the potential of (18)F-FPPRGD2 to predict the prognosis in patients with cervical cancer and ovarian cancer in this clinical scenario.Data from six women, age range 30 - 59 years (mean ± SD 44.0 ± 12.5 years), who had undergone a (18)F-FPPRGD2 PET/CT scan and bevacizumab-containing therapy were prospectively collected and analyzed. We compared baseline (18)F-FPPRGD2 and (18)F-FDG uptake in the lesions and tumor-to-background (T/B) ratios. The maximum and mean (18)F-FPPRGD2 standardized uptake values (SUVmax and SUVmean) were recorded for 13 normal organs, as well as in all the identified malignant lesions on the pretreatment scan and the 1-week post-treatment scan. We also measured changes in (18)F-FPPRGD2 uptake from before to 1 week after treatment, and compared them to the changes in (18)F-FDG uptake from before to 6 weeks after treatment. Treatment outcomes were correlated with these changes.The uptake in lesions and T/B ratio of (18)F-FPPRGD2 were lower than those of (18)F-FDG (SUVmax 3.7 ± 1.3 vs. 6.0 ± 1.8, P < 0.001; SUVmean 2.6 ± 0.7 vs. 4.2 ± 1.3, P < 0.001; T/B ratio based on SUVmax 2.4 ± 1.0 vs. 2.6 ± 1.0, P < 0.04; T/B ratio based on SUVmean 1.9 ± 0.6 vs. 2.4 ± 1.0, P < 0.003). One patient did not return for the follow-up scan and in another patient no lesions were identified on the pretreatment scan. (18)F-FPPRGD2 uptake in lesions in the remaining four patients had significantly changed 1 week after treatment (SUVmean 3.3 ± 1.0 vs. 2.7 ± 1.0, P < 0.001), while uptake in all normal tissues analyzed was not affected by treatment. One patient with clinical disease progression had a decrease in lesional (18)F-FPPRGD2 SUVmean of 1.6 % and in (18)F-FDG SUVmean of 9.4 %. Two patients with a clinical complete response to treatment had decreases in lesional (18)F-FPPRGD2 SUVmean of 25.2 % and 25.0 % and in (18)F-FDG SUVmean of 6.1 % and 71.8 %. One patient with a clinical partial response had a decrease in lesional (18)F-FPPRGD2 SUVmean of 7.9 % and in (18)F-FDG SUVmean of 76.4 %.This pilot study showed that (18)F-FPPRGD2 and (18)F-FDG provide independent information about the biology of ovarian and cervical cancers. Bevacizumab-containing therapy does not affect (18)F-FPPRGD2 uptake in normal organs, but does result in statistically significant changes in lesions. In addition, (18)F-FPPRGD2 may have potential for early prediction of response to such treatments. These preliminary findings have to be confirmed in larger studies.

    View details for DOI 10.1007/s00259-015-3263-7

    View details for Web of Science ID 000374972900008

    View details for PubMedID 26611425

  • Adenocarcinoma With Breast/Adnexal and Upper Gastrointestinal Differentiation Arising in an Ovarian Mature Cystic Teratoma: A Case Report and Review of the Literature INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY Wheeler, L., Westhoff, G. L., O'Keefe, M. C., Kong, C. S., Karam, A. 2016; 35 (1): 72-77


    Mature cystic teratomas are the most common type of ovarian germ cell tumors. In about 1% of cases, usually among postmenopausal women, a mature cystic teratoma can undergo malignant transformation. Among malignant transformations, squamous cell carcinoma is the most common histology, comprising approximately 80% of cases. In this report, we present the unique case of a 55-yr-old woman with a pelvic mass found to be a mature cystic teratoma with malignant transformation to adenocarcinoma with breast/adnexal, upper gastrointestinal, and neuroendocrine differentiation. The predominant malignant component was the adenocarcinoma exhibiting breast/skin adnexal differentiation, which was found to involve the omentum and a right para-aortic node. We provide an in-depth review of the pathologic findings, as well as a review of the current literature on malignant transformation to adenocarcinoma. This report aims to open a conversation regarding the management of these patients, with a specific focus on the role of molecular analysis and targeted therapies.

    View details for DOI 10.1097/PGP.0000000000000218

    View details for Web of Science ID 000366942300012

    View details for PubMedID 26352552

  • Video-based Peer Feedback Through Social Networking for Robotic Surgery Simulation A Multicenter Randomized Controlled Trial ANNALS OF SURGERY Carter, S. C., Chiang, A., Shah, G., Kwan, L., Montgomery, J. S., Karam, A., Tarnay, C., Guru, K. A., Hu, J. C. 2015; 261 (5): 870-875


    To examine the feasibility and outcomes of video-based peer feedback through social networking to facilitate robotic surgical skill acquisition.The acquisition of surgical skills may be challenging for novel techniques and/or those with prolonged learning curves.Randomized controlled trial involving 41 resident physicians performing the Tubes (Da Vinci Intuitive Surgical, Sunnyvale, CA) simulator exercise with versus without peer feedback of video-recorded performance through a social networking Web page. Data collected included simulator exercise score, time to completion, and comfort and satisfaction with robotic surgery simulation.There were no baseline differences between the intervention group (n = 20) and controls (n = 21). The intervention group showed improvement in mean scores from session 1 to sessions 2 and 3 (60.7 vs 75.5, P < 0.001, and 60.7 vs 80.1, P < 0.001, respectively). The intervention group scored significantly higher than controls at sessions 2 and 3 (75.5 vs 59.6, P = 0.009, and 80.1 vs 65.9, P = 0.019, respectively). The mean time (seconds) to complete the task was shorter for the intervention group than for controls during sessions 2 and 3 (217.4 vs 279.0, P = 0.004, and 201.4 vs 261.9, P = 0.006, respectively). At the study conclusion, feedback subjects were more comfortable with robotic surgery than controls (90% vs 62%, P = 0.021) and expressed greater satisfaction with the learning experience (100% vs 67%, P = 0.014). Of the intervention subjects, 85% found that peer feedback was useful and 100% found it effective.Video-based peer feedback through social networking appears to be an effective paradigm for surgical education and accelerates the robotic surgery learning curve during simulation.

    View details for DOI 10.1097/SLA.0000000000000756

    View details for Web of Science ID 000352326900033

    View details for PubMedID 24887970

  • Does Omentectomy in Epithelial Ovarian Cancer Affect Survival? An Analysis of the Surveillance, Epidemiology, and End Results Database INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER McNally, L., Teng, N. N., Kapp, D. S., Karam, A. 2015; 25 (4): 607-615


    Although omentectomy is part of the staging and treatment of epithelial ovarian cancer (EOC), its performance in a patient with a grossly normal omentum—acknowledging its role in debulking gross tumor deposits—has never been definitively shown to improve survival.Using Surveillance, Epidemiology, and End Results data from 1998 to 2010, we identified patients with EOC and assessed their age, race, year of diagnosis, tumor grade, histologic subtype, International Federation of Gynecology and Obstetrics stage, lymph node dissection, nodal findings, and performance of omentectomy. We compared disease-specific survival (DSS) based on the presence or absence of omentectomy using log-rank univariate analysis, Cox multivariate analysis, and Kaplan-Meier survival curves.A total of 20,975 patients with invasive EOC underwent surgical treatment. Initial univariate analysis indicated a lower mean DSS with performance of omentectomy. However, multivariate analysis demonstrated no significant association between DSS and performance of omentectomy (hazard ratio, 0.978; P = 0.506). The DSS was improved if lymphadenectomy was performed (hazard ratio, 0.60; P < 0.001). In recent years, there was a trend toward decreased performance of omentectomy.To look specifically at patients without bulky omental disease, a subset analysis was done looking at patients with stage I-IIIA disease who had had lymphadenectomy performed. There were 5454 patients in the group who underwent an omentectomy and 2404 patients in the group who did not. No difference in DSS was seen between the groups based on performance of omentectomy (P = 0.89). However, the analysis was limited by the lack of Surveillance, Epidemiology, and End Results data on the extent of omentectomy, amount of residual disease, and adjuvant chemotherapy.In this analysis, performance of omentectomy in patients with EOC without bulky disease (≤stage IIIA) did not seem to confer improvement in survival. A randomized control trial would be needed to fully address this question.

    View details for DOI 10.1097/IGC.0000000000000412

    View details for Web of Science ID 000354103000011

    View details for PubMedID 25756404

  • Estimating the Risk of Abnormal Cervical Papanicolaou Test (PAP) in Female Renal Transplant Recipients (RTR) as Compared With Age-Matched Controls Chang, S., Tarin, M., Fung, P., Karam, A., Rao, J. NATURE PUBLISHING GROUP. 2015: 85A
  • Estimating the Risk of Abnormal Cervical Papanicolaou Test (PAP) in Female Renal Transplant Recipients (RTR) as Compared With Age-Matched Controls Chang, S., Tarin, M., Fung, P., Karam, A., Rao, J. NATURE PUBLISHING GROUP. 2015: 85A
  • Increased risk and pattern of secondary malignancies in patients with invasive extramammary Paget disease. British journal of dermatology Karam, A., Dorigo, O. 2014; 170 (3): 661-671


    Extramammary Paget disease (EMPD) is often associated with underlying or distant synchronous malignancies. The prognosis for affected patients is generally favourable; however, the risk of secondary malignancies is unknown.The goal of the study was to analyse the incidence, prognosis and pattern of secondary malignancies for patients with invasive EMPD using data from the Surveillance, Epidemiology and End Results (SEER) Program.We searched the SEER Program database for patients diagnosed with invasive EMPD between 1973 and 2008. Demographic data, outcome and secondary malignancies more than 1 year after the initial diagnosis of invasive EMPD were included in the analysis. We calculated the standardized incidence ratio (SIR) and estimated the excess absolute risk (EAR) per 10 000 person-years (PY).There were 1439 patients who were diagnosed with invasive EMPD. Most patients (80·4%) had localized disease, while 17·1% had locoregional spread and 2·5% presented with distant disease. The SIR for secondary malignancies in patients with invasive EMPD was significantly elevated with an EAR of 97·4 additional malignancies per 10 000 PY. The excess risk was mostly due to a significantly increased incidence of colorectal and anal malignancies. The initial site of disease predicted the site of the secondary malignancies, with patients with colorectal, anal, vulvar and scrotal disease showing an increased risk of colorectal, anal, vulvar and scrotal malignancies, respectively.Our study identified a long-term increased risk of developing secondary malignancies in patients with invasive EMPD that are mainly related to the site of origin of this disease. Patients with invasive EMPD require prolonged follow-up and screening for these malignancies.

    View details for DOI 10.1111/bjd.12635

    View details for PubMedID 24617434

  • Update on breast cancer surgery approaches CURRENT OPINION IN OBSTETRICS & GYNECOLOGY Karam, A. 2013; 25 (1): 74–80


    This review seeks to review the latest developments in breast cancer surgery.The manuscript will cover the latest developments in breast conservation therapy such as oncoplastic surgery, partial, and accelerated breast irradiation as well as nipple and areola sparing mastectomies, breast reconstruction, and recent developments in axillary staging.At the conclusion of this article the reader will have a comprehensive overview of the latest developments and principles of breast cancer surgical management.

    View details for DOI 10.1097/GCO.0b013e32835c03fa

    View details for Web of Science ID 000313550200012

    View details for PubMedID 23254625

  • Down-Regulation of Vitamin D Receptor in Mammospheres: Implications for Vitamin D Resistance in Breast Cancer and Potential for Combination Therapy PLOS ONE Pervin, S., Hewison, M., Braga, M., Lac Tran, Chun, R., Karam, A., Chaudhuri, G., Norris, K., Singh, R. 2013; 8 (1): e53287


    Vitamin D signaling in mammary cancer stem cells (MCSCs), which are implicated in the initiation and progression of breast cancer, is poorly understood. In this study, we examined vitamin D signaling in mammospheres which are enriched in MCSCs from established breast cancer cell lines. Breast cancer cells positive for aldehyde dehydrogenase (ALDH(+)) had increased ability to form mammospheres compared to ALDH(-) cells. These mammospheres expressed MCSC-specific markers and generated transplantable xenografts in nude mice. Vitamin D receptor (VDR) was significantly down-regulated in mammospheres, as well as in ALDH(+) breast cancer cells. TN aggressive human breast tumors as well as transplantable xenografts obtained from SKBR3 expressed significantly lower levels of VDR but higher levels of CD44 expression. Snail was up-regulated in mammospheres isolated from breast cancer cells. Inhibition of VDR expression by siRNA led to a significant change in key EMT-specific transcription factors and increased the ability of these cells to form mammospheres. On the other hand, over-expression of VDR led to a down-regulation of Snail but increased expression of E-cad and significantly compromised the ability of cells to form mammospheres. Mammospheres were relatively insensitive to treatment with 1,25-dihydroxyvitamin D (1,25D), the active form of vitamin D, compared to more differentiated cancer cells grown in presence of serum. Treatment of H-Ras transformed HMLE(HRas) cells with DETA NONOate, a nitric oxide (NO)-donor led to induction of MAP-kinase phosphatase -1 (MKP-1) and dephosphorylation of ERK1/2 in the mammospheres. Combined treatment of these cells with 1,25D and a low-concentration of DETA NONOate led to a significant decrease in the overall size of mammospheres and reduced tumor volume in nude mice. Our findings therefore, suggest that combination therapy using 1,25D with drugs specifically targeting key survival pathways in MCSCs warrant testing in prospective clinical trial for treatment of aggressive breast cancer.

    View details for DOI 10.1371/journal.pone.0053287

    View details for Web of Science ID 000314759400039

    View details for PubMedID 23341935

    View details for PubMedCentralID PMC3544824

  • MMPs in Ovarian Cancer as Therapeutic Targets ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY Karam, A., Dorigo, O. 2012; 12 (7): 764-772


    In the United States, about 22,000 women will be diagnosed with ovarian cancer in 2011, and an estimated 14,000 patients will succumb to the disease. Surgery and chemotherapy present the main treatment modalities, but despite the development of novel therapies, the overall 5 years survival for ovarian cancer patients with advanced disease at diagnosis remains at only about 30%. Novel therapeutic strategies are needed to prolong survival and achieve greater cure rates. Matrix metalloproteinases (MMPs) are frequently expressed in ovarian cancer, and play an important role in the metastatic process. MMPs mediate degradation of the basement membrane as a crucial step in epithelial transformation, ovarian tumorigenesis and intraperitoneal metastasis. Various preclinical and clinical studies have demonstrated that MMPs might provide a suitable therapeutic target. This review summarizes important observations regarding the expression of MMPs in ovarian cancer, their biological role, and data from clinical trials targeting MMPs in ovarian cancer patients.

    View details for Web of Science ID 000310052900009

    View details for PubMedID 22292752

  • Treatment outcomes in a large cohort of patients with invasive Extramammary Paget's disease GYNECOLOGIC ONCOLOGY Karam, A., Dorigo, O. 2012; 125 (2): 346-351


    The outcome of patients with invasive Extramammary Paget's disease (EMPD) is poorly studied. The goal of the current study was to analyze the incidence, treatment approaches and outcome of patients with invasive EMPD.We searched the SEER program database for patients diagnosed with invasive EMPD between 1973 and 2007. Demographic data, outcome and therapeutic modalities were included in the analysis. Disease specific survival (DSS) was calculated from the time of original diagnosis.1439 patients were diagnosed with invasive EMPD. Most patients (80.4%) had localized disease, while 17.1% had locoregional spread, and 2.5% had distant disease. 1230 (86.4%) patients underwent site directed surgery, and 92 (6.4%) patients radiotherapy. 139 (9.7%) patients did not undergo any surgery or radiation therapy. The 5-year DSS was 94.9% for localized disease, 84.9% for regional disease and 52.5% for distant disease. Multivariate analysis showed a significantly shorter DSS associated with older age and advanced stage treatment modality (HR for death 1.07 and 2.5). Site directed surgery was associated with a significantly improved outcome when compared to patients who underwent no intervention (HR 0.44). Patients who received radiation, alone or in combination with site directed surgery, did not fare any better than patients who underwent surgery alone.The DSS of patients with invasive EMPD is generally favorable. A poor outcome was associated with older age, advanced stage and treatment modality. The association between a shortened DSS and the use of radiotherapy, alone or in combination with surgery, is surprising and warrants further investigation.

    View details for DOI 10.1016/j.ygyno.2012.01.032

    View details for Web of Science ID 000303227500014

    View details for PubMedID 22293043

  • Genital rhabdomyoma of the urethra in an infant girl HUMAN PATHOLOGY Lu, D. Y., Chang, S., Cook, H., Alizadeh, Y., Karam, A. K., Moatamed, N. A., Dry, S. M. 2012; 43 (4): 597-600


    Extracardiac rhabdomyomas are rare benign entities that usually occur in the head and neck region. Although genital rhabdomyoma is known to occur in the lower genital tract of young and middle-aged women, involvement of the anatomically adjacent urethra by rhabdomyoma is exceedingly rare. We present a case of genital rhabdomyoma arising from the urethra of an infant girl. The tumor was characterized by the submucosal presence of mature-appearing rhabdomyoblastic cells containing conspicuous cross-striations, with the cells set in a collagenous stroma. Necrosis and mitoses were absent. Skeletal muscle differentiation of the tumor cells was supported by positive immunohistochemical staining for desmin and myogenin. To our knowledge, this is the first case of urethral genital-type rhabdomyoma in a child.

    View details for DOI 10.1016/j.humpath.2011.06.012

    View details for Web of Science ID 000301894300015

    View details for PubMedID 21992817

  • Determinants of outcome in elderly patients with positive sentinel lymph nodes AMERICAN JOURNAL OF SURGERY Karam, A. K., Hsu, M., Patil, S., Stempel, M., Traina, T. A., Ho, A. Y., Cody, H. S., Morrow, M., Gemignani, M. L. 2011; 201 (6): 734–40


    Older women are less likely to receive standard of care treatment for breast cancer.We examined variables that affected the outcome of elderly patients ≥70 years old among 1,470 patients with invasive cancer with positive sentinel lymph nodes (SLNs).Elderly patients were less likely to undergo mastectomy, completion axillary node dissection (ALND), adjuvant chemotherapy, and radiotherapy (RT) following breast-conserving therapy (BCT) compared with patients <70 years old. The 5-year risk of disease progression and cumulative incidence of breast cancer-specific deaths were not significantly different for both groups. On multivariate analysis, hormone receptor-negative status, number of metastatic lymph nodes, high nuclear grade, and tumor size were the factors independently associated with increased risk of disease progression.Tumor factors were the primary determinants of breast cancer outcomes in our cohort. Elderly patients are less likely to receive aggressive surgical interventions and adjuvant therapy because of perceived life expectancy.

    View details for DOI 10.1016/j.amjsurg.2010.02.005

    View details for Web of Science ID 000293183800008

    View details for PubMedID 20619395

  • Breast Cancer Posttreatment Surveillance: Diagnosis and Management of Recurrent Disease CLINICAL OBSTETRICS AND GYNECOLOGY Karam, A. K. 2011; 54 (1): 157–63


    Invasive breast cancer is the most common malignancy diagnosed in American women. The use of screening mammography and progress in adjuvant therapy has led to a steady decline in breast cancer mortality, and as the number of breast cancer survivors increases, there has been a marked increase in the number of patients enrolled in posttreatment surveillance programs.The majority of breast cancer recurrences occurs during the first decade after initial diagnosis with a peak incidence 2 to 5 years after diagnosis, although the number of recurrences for endocrine responsive cancer continues to rise afterward. The goal of posttreatment follow-up programs in patients with breast cancer is to detect potentially curable locoregional recurrences, second primary tumors, and the detection of systemic relapses. However, contrary to the long-held belief, most recurrences are symptomatic and occur during the interval between scheduled visits.

    View details for DOI 10.1097/GRF.0b013e318208393b

    View details for Web of Science ID 000286656300022

    View details for PubMedID 21278515

  • Cisplatin and PI3kinase Inhibition Decrease Invasion and Migration of Human Ovarian Carcinoma Cells and Regulate Matrix-Metalloproteinase Expression CYTOSKELETON Karam, A. K., Santiskulvong, C., Fekete, M., Zabih, S., Eng, C., Dorigo, O. 2010; 67 (8): 535-544


    Targeting of the PI3K (phosphoinositide3-kinase)/Akt/mTOR pathway in human ovarian cancer cells is a promising novel therapeutic strategy. We investigated the effects of cisplatin and the PI3K inhibitor LY294002 on invasion, migration and the expression of essential matrix metalloproteinases (MMPs) in ovarian cancer cells. SKOV3, OVCAR5 and IGROV1 human ovarian cancer cell lines were treated with cisplatin, LY294002 and a combination of both drugs. Invasion and migration of treated cells was assessed using Matrigel and uncoated PET membrane assays. Expression levels of pro-MMP2, MMP2, TIMP1, TIMP2 and MT1-MMP were determined using Western Blotting. Gel zymography was used to quantitate the functional levels of active MMP2. All three cell lines showed significantly reduced invasion and migration after treatment with cisplatin, LY294002, and the combination of both drugs compared to untreated controls. In SKOV3 cells, cisplatin alone and in combination with LY294002 resulted in a 6.3 and 7.1-fold reduction in the total amount of activated MMP2. TIMP1 expression decreased by 5.0, 6.6 and 28.4-fold with cisplatin, LY294002 and the combination respectively (P < 0.05). In contrast, only cisplatin and the combination of both drugs resulted in a significant, 3.7 and 5.1-fold reduction in the level of TIMP2. Expression levels of MT1-MMP remained unchanged. These observations were corroborated in IGROV1 cell lines that showed similar changes of activated MMP2 and TIMP2 expression, but no significant decrease in TIMP1 levels. Our data suggests that inhibition of ovarian cancer cell motility is mediated via down-regulation of activated MMP2, TIMP1 and TIMP2 expression under these treatment conditions.

    View details for DOI 10.1002/cm.20465

    View details for Web of Science ID 000280543100006

    View details for PubMedID 20607860

    View details for PubMedCentralID PMC3001291

  • Ovarian cancer: the duplicity of CA125 measurement NATURE REVIEWS CLINICAL ONCOLOGY Karam, A. K., Karlan, B. Y. 2010; 7 (6): 335–39


    Since it was first described in 1981, CA125 has held an important role in monitoring patients with ovarian cancer. CA125 is elevated in 80% of patients with epithelial ovarian cancer at initial diagnosis and correlates well with response to therapy. CA125 monitoring is used for the follow up of patients with epithelial ovarian cancer, and elevations in CA125 measurements often antedate any signs, symptoms or radiographic evidence of disease by several months. Unfortunately, data favoring early therapeutic intervention for recurrent ovarian cancer is lacking, especially in patients with isolated CA125 elevations. In asymptomatic patients, elevations in CA125 have been associated with considerable anxiety and deterioration in quality of life without any significant gains in survival. Patients with ovarian cancer should, therefore, be counseled regarding the advantages and shortcomings of intensive CA125 testing. While some patients may benefit from early detection of recurrent disease and be candidates for secondary cytoreductive surgery, others may choose to delay therapy until they develop symptoms of disease recurrence. The results of a clinical trial suggest that withholding treatment in the event of isolated rising CA125 levels will not negatively impact these patients overall survival, highlighting the need for improved salvage therapies for recurrent ovarian cancer.

    View details for DOI 10.1038/nrclinonc.2010.44

    View details for Web of Science ID 000278718200010

    View details for PubMedID 20368726

  • Predictors of Completion Axillary Lymph Node Dissection in Patients With Immunohistochemical Metastases to the Sentinel Lymph Node in Breast Cancer ANNALS OF SURGICAL ONCOLOGY Pugliese, M. S., Karam, A. K., Hsu, M., Stempel, M. M., Patil, S. M., Ho, A. Y., Traina, T. A., Van Zee, K. J., Cody, H. S., Morrow, M., Gemignani, M. L. 2010; 17 (4): 1063–68


    Axillary lymph node dissection (ALND) in patients with immunohistochemistry (IHC)-determined metastases to the sentinel lymph node (SLN) is controversial. The goal of this study was to examine factors associated with ALND in IHC-only patients.Retrospective review of an institutional SLN database from July 1997 to July 2003 was performed. We compared sociodemographic, pathologic, and therapeutic variables between IHC-only patients who had SLN biopsy alone and those that had ALND.Our study group consisted of 171 patients with IHC-only metastases to the SLN. Young age, estrogen receptor negative status, high Memorial Sloan-Kettering Cancer Center nomogram score, and chemotherapy were associated with ALND. Among patients who had ALND (n = 95), 18% had a positive non-SLN. Rates of systemic therapy were similar between those with and without positive non-SLNs at ALND. No axillary recurrences were observed in this series with a median follow-up of 6.4 years. The percentage of patients who were recurrence-free after 5 years was 97% (95% confidence interval, 92.1-98.6).On the basis of our findings and the lack of prospective randomized data, the practice of selectively limiting ALND to IHC-only patients thought to be at high risk and to patients for whom the identification of additional positive nodes may change systemic therapy recommendations seems to be a safe and reasonable approach.

    View details for DOI 10.1245/s10434-009-0834-5

    View details for Web of Science ID 000275709500015

    View details for PubMedID 20033325

  • Vascular endothelial growth factor and its relationship to the prognosis and treatment of breast, ovarian, and cervical cancer ANGIOGENESIS Carpini, J., Karam, A. K., Montgomery, L. 2010; 13 (1): 43–58


    Tumor neovascularization is a complex process that plays a crucial role in the development of many different types of cancer. Vascular endothelial growth factor (VEGF) is a potent mitogen that is involved with mitogenesis, angiogenesis, endothelial survival, and the induction of hematopoiesis. By increasing vascular permeability in endothelial cells, it helps tumors recruit wound-healing proteins fibrin and fibrinogen from the plasma, suggesting that tumor formation is a process of abnormal wound healing dependent on the ability to generate a blood supply. The human female reproductive tract is highly dependent on VEGF for normal functions such as endometrial proliferation and development of the corpus luteum. The unique influence of female sex steroid hormones on the expression and activity of VEGF deems angiogenesis an important facet of the development of breast and ovarian cancer. Additionally, the up-regulation of VEGF by the E6 oncoprotein of the human papillomavirus suggests that VEGF plays an important role in the development of cervical cancer. Clinical trials have investigated the humanized monoclonal antibody bevacizumab as potential treatment for all three forms of cancer; the data show that in breast cancer, the use of bevacizumab may lengthen the disease-free survival for women with advanced breast cancer, but does not appear to change their overall survival. It may have a role as salvage chemotherapy for ovarian and cervical cancer, though further research is needed to establish it as a definitive form of treatment.

    View details for DOI 10.1007/s10456-010-9163-3

    View details for Web of Science ID 000276046200004

    View details for PubMedID 20229258

  • Extreme drug resistance assay does not influence survival in women with epithelial ovarian cancer GYNECOLOGIC ONCOLOGY Karam, A. K., Karlan, B. Y. 2010; 116 (1): 149-150
  • Extreme drug resistance assay results do not influence survival in women with epithelial ovarian cancer GYNECOLOGIC ONCOLOGY Karam, A. K., Chiang, J., Fung, E., Nossov, V., Karlan, B. Y. 2009; 114 (2): 246–52


    Extreme drug resistance (EDR) assays have been used to identify chemotherapy regimens that are least likely to be of clinical benefit in the treatment of epithelial ovarian cancer (EOC). We sought to examine the impact of EDR assay-guided therapy on the outcome of patients with EOC in the primary and recurrent settings.We conducted a retrospective review of demographic, pathologic, EDR assay and clinical outcome data from 377 patients with EOC who had an assay sent at the time of their primary or subsequent cytoreductive surgeries. Multivariate analyses were performed using Cox proportional hazards method to identify and estimate the impact of independent prognostic factors on time to progression (TTP), overall survival (OS) and survival after recurrence (RS).Increasing age was associated with a worse OS and RS (HR=1.34; 95% CI, 1.14-1.58 and HR=1.14; 95% CI, 1.00-1.31, respectively for each decade increase in age). Surgical outcome in the setting of primary or secondary cytoreduction remained an important predictor of survival. Compared with patients with microscopic residual disease, patients who were left with 0.1 to 1.0 cm and >1.0 cm residual disease had an increased risk of recurrence (HR=1.94; 95% CI, 1.33 to 2.84 and HR=3.61; 95% CI; 2.07 to 6.39, respectively) and death (HR=1.59; 95% CI, 1.03 to 2.45; and HR=2.14; 95% CI, 1.09 to 4.20, respectively). For patients who recurred, those who did not undergo secondary cytoreductive surgery and patients who were left with >1.0 cm residual had an increased risk of death compared to patients with microscopic residual (HR=2.13; 95% CI, 1.28 to 3.54; and HR=2.84; 95% CI, 1.71 to 4.71, respectively). EDR assay results analyzed for single agents or combinations of chemotherapies failed to independently predict patient outcomes no matter if the assay was performed at the time of the primary surgery or recurrence.EDR assay results do not independently predict or alter the outcomes of patients with EOC who are treated with the current standards of primary cytoreductive surgery followed by platinum and taxane combination chemotherapy.

    View details for DOI 10.1016/j.ygyno.2009.02.022

    View details for Web of Science ID 000267971400019

    View details for PubMedID 19500821

  • Predictors of Completion Axillary Lymph Node Dissection in Patients with Positive Sentinel Lymph Nodes ANNALS OF SURGICAL ONCOLOGY Karam, A. K., Hsu, M., Patil, S., Stempel, M., Traina, T. A., Ho, A. Y., Cody, H. S., Port, E. R., Morrow, M., Gemignani, M. L. 2009; 16 (7): 1952–58


    Completion axillary lymph node dissection (CALND) is routinely performed in breast cancer patients with positive sentinel lymph nodes (SLN). We sought to determine the sociodemographic, pathologic, and therapeutic variables that were associated with CALND.From 7/1997 to 7/2003, 1,470 patients with invasive breast cancer were SLN positive by intraoperative frozen section or final pathologic exam by hematoxylin-eosin and/or immunohistochemistry (IHC). A comorbidity score was assigned using Adult Comorbidity Evaluation-27 system. Fisher's exact, Wilcoxon tests, and multivariate logistic regression analysis were used.CALND was performed less often in patients with age >or= 70 years compared with age < 70 years, moderate or severe comorbidities compared with no or mild, IHC-only positive SLN and breast conservation therapy (BCT compared with mastectomy. Patients who did not undergo CALND were less likely than CALND patients to have grade III disease, lymphovascular invasion multifocal disease, tumor size > 2 cm or to receive adjuvant chemotherapy. However, they were more likely to undergo axillary radiotherapy (RT). On multivariate analysis, age >or= 70 years [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.26-0.63], IHC-only positive SLN (OR 0.13, 95%CI 0.09-0.19), presence of moderate to severe comorbidities (OR 0.64, 95%CI 0.41-0.99), tumor size

    View details for DOI 10.1245/s10434-009-0440-6

    View details for Web of Science ID 000266982900033

    View details for PubMedID 19381724

  • Patients with a history of epithelial ovarian cancer presenting with a breast and/or axillary mass GYNECOLOGIC ONCOLOGY Karam, A. K., Stempel, M., Barakat, R. R., Morrow, M., Gemignani, M. L. 2009; 112 (3): 490–95


    A breast and/or axillary mass in a patient with epithelial ovarian cancer (EOC) may be due to an EOC breast metastasis or a second primary breast cancer. We sought to review our experience with patients with a history of EOC presenting with a breast and/or axillary mass to determine if clinical features differed between these entities.Between 1/90 and 10/07, 29 women with epithelial EOC presented with a breast or axillary mass, including 10 patients with EOC metastatic to the breast and/or axilla and 19 patients with a second primary breast cancer following their original EOC diagnosis. Clinicopathologic factors/survival were retrospectively abstracted from medical records.The mean EOC disease-free survival (DFS) was 14.9 mo versus 77.4 mo (P<0.001) for patients with recurrent epithelial ovarian cancer metastatic to the breast and/or axilla and patients with a second primary breast cancer, respectively. Similarly, the mean interval between diagnosis of EOC and the breast and/or axillary event was 31.2 mo versus 70.7 mo for those patients who had metastatic recurrent EOC and those patients with breast cancer (P=0.02). Patients with a second primary breast cancer were more likely to be diagnosed on mammogram and have a family history of breast and ovarian carcinoma than patients with metastatic EOC to the breast and/or axilla (14/19 [73.7%] versus 2/9 [22.8%], P=0.02; and 12/18 [66.7%] versus 2/10 [20%], P=0.05, respectively). Median overall survival for patients with EOC metastasis was 26 mo but was not yet reached for those patients with a second primary breast cancer. On univariate analysis, an ovarian cancer DFS of 12 mo or more and the performance of breast/axillary surgery were associated with a significantly longer overall survival (P=0.01 and 0.02, respectively), whereas an elevated CA125 level at the time of the breast/axilla event and the presence of EOC metastases to the breast and axilla were significant negative predictors of survival (P=0.01 and 0.05, respectively).The interval between EOC diagnosis and the breast and/or axilla event, an elevated CA125 level, and a family history of breast and/or ovarian cancer may help differentiate patients with metastatic EOC to the breast and/or axilla from those patients with a second primary breast cancer. The presence of a metastatic EOC portends a poor prognosis.

    View details for DOI 10.1016/j.ygyno.2008.11.006

    View details for Web of Science ID 000264162800011

    View details for PubMedID 19101713

  • HER-2/neu targeting for recurrent vulvar Paget's disease A case report and literature review GYNECOLOGIC ONCOLOGY Karam, A., Berek, J. S., Stenson, A., Rao, J., Dorigo, O. 2008; 111 (3): 568-571


    The treatment of Paget's disease of the vulva particularly for recurrences can be challenging. Overexpression of the HER-2/neu protein has been found in about 30% of vulvar Paget's cases therefore presenting a potential therapeutic target.We report the case of a 52-year-old patient with persistent Paget's disease of the vulva despite eight surgical excisions over a 15-year period. Immunohistochemistry demonstrated overexpression of the HER-2/neu protein in the vulva resection specimen. Treatment with Trastuzumab resulted in a significant regression of her disease and resolution of symptoms.Based on our case report, therapeutic targeting of HER-2/neu for patients with Paget's disease of the vulva using for example Trastuzumab is a potentially effective, alternative approach, and warrants further investigation.

    View details for DOI 10.1016/j.ygyno.2007.12.014

    View details for Web of Science ID 000261758000037

    View details for PubMedID 18252264

  • Reoperative Sentinel Lymph Node Biopsy after Previous Mastectomy JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Karam, A., Stempel, M., Cody, H. S., Port, E. R. 2008; 207 (4): 543–48


    Sentinel lymph node (SLN) biopsy is the standard of care for axillary staging in breast cancer, but many clinical scenarios questioning the validity of SLN biopsy remain. Here we describe our experience with reoperative-SLN (re-SLN) biopsy after previous mastectomy.Review of the SLN database from September 1996 to December 2007 yielded 20 procedures done in the setting of previous mastectomy. SLN biopsy was performed using radioisotope with or without blue dye injection superior to the mastectomy incision, in the skin flap in all patients. In 17 of 20 patients (85%), re-SLN biopsy was performed for local or regional recurrence after mastectomy.Re-SLN biopsy was successful in 13 of 20 patients (65%) after previous mastectomy. Of the 13 patients, 2 had positive re-SLN, and completion axillary dissection was performed, with 1 having additional positive nodes. In the 11 patients with negative re-SLN, 2 patients underwent completion axillary dissection demonstrating additional negative nodes. One patient with a negative re-SLN experienced chest wall recurrence combined with axillary recurrence 11 months after re-SLN biopsy. All others remained free of local or axillary recurrence. Re-SLN biopsy was unsuccessful in 7 of 20 patients (35%). In three of seven patients, axillary dissection was performed, yielding positive nodes in two of the three. The remaining four of seven patients all had previous modified radical mastectomy, so underwent no additional axillary surgery.In this small series, re-SLN was successful after previous mastectomy, and this procedure may play some role when axillary staging is warranted after mastectomy.

    View details for DOI 10.1016/j.jamcollsurg.2008.06.139

    View details for Web of Science ID 000260274000012

    View details for PubMedID 18926457

  • Her2neu over-expression and PI3kinase/Akt pathway activation in Paget's disease of the vulva. 55th Annual Meeting of the Society-for-Gynecologic-Investigation Stenson, A., Behjatnia, B., Shamonki, J., Rao, J., Karam, A., Berek, J., Dorigo, O. SAGE PUBLICATIONS INC. 2008: 307A–307A
  • Neoadjuvant cisplatin and radical cesarean hysterectomy for cervical cancer in pregnancy NATURE CLINICAL PRACTICE ONCOLOGY Karam, A., Feldman, N., Holschneider, C. H. 2007; 4 (6): 375–80


    A 28-year-old Hispanic gravida 1 was found to have a 4-5 cm cervical mass when she presented at 23 weeks gestation. On pelvic examination, the tumor was shown to encompass the entire circumference of the cervix without parametrial or vaginal involvement. A biopsy of the mass revealed a poorly differentiated squamous-cell carcinoma of the cervix. An MRI study of the abdomen and pelvis showed a 4 cm cervical mass that was suspicious for left parametrial and rectovaginal septal involvement. No hydronephrosis or lymphadenopathy was noted. The patient elected to proceed with her pregnancy.General physical and gynecological examinations, cervical biopsy, pelvic and obstetric ultrasound, histopathological examination, MRI of the abdomen and pelvis without and with gadolinium, neonatal hearing test and renal function studies.Poorly differentiated stage IB2 squamous-cell carcinoma of the cervix with MRI imaging suggestive of parametrial and rectovaginal septal involvement.Neoadjuvant chemotherapy using weekly cisplatin from 24 to 30 weeks, bed rest and oral terbutaline at 31 weeks because of premature contractions, and a course of antenatal steroids to promote fetal lung maturity. At 33 weeks radical cesarean hysterectomy, bilateral pelvic and para-aortic lymphadenectomy and bilateral ovarian transposition were carried out, followed by adjuvant pelvic radiation therapy with cisplatin chemosensitization 4 weeks postpartum.

    View details for DOI 10.1038/ncponc0821

    View details for Web of Science ID 000246725100012

    View details for PubMedID 17534393

  • Secondary cytoreductive surgery for isolated nodal recurrence in patients with epithelial ovarian cancer GYNECOLOGIC ONCOLOGY Santillan, A., Karam, A. K., Li, A. J., Gluntoli, R., Gardner, G. J., Cass, I., Karlan, B. Y., Bristow, R. E. 2007; 104 (3): 686–90


    To evaluate the feasibility and associated survival outcome of secondary cytoreductive surgery in patients with isolated lymph node recurrence of epithelial ovarian cancer.Twenty-five patients with epithelial ovarian cancer who underwent secondary cytoreductive surgery for isolated lymph node recurrence were identified from tumor registry databases. Demographic, diagnostic, operative, pathologic, and follow-up data were abstracted retrospectively. Overall survival was calculated using the Kaplan-Meier method.The median age at time of primary surgery for ovarian cancer was 55 years; 72% of patients had FIGO III/IV disease, and all had high-grade tumors. All patients received platinum-based chemotherapy following primary surgery. The median time from completion of primary chemotherapy to nodal recurrence surgery was 16 months (range=6 to 40 months). The distribution of nodal involvement was pelvic=12% (n=3), para-aortic=60% (n=15), inguinal=20% (n=5), peri-cardiac=4% (n=1), and pelvic plus para-aortic=4% (n=1). The maximal nodal tumor diameter ranged from 1.5 cm to 14 cm, with a median of 3.0 cm. Optimal secondary cytoreductive surgery (residual disease

    View details for DOI 10.1016/j.ygyno.2006.10.020

    View details for Web of Science ID 000244796500032

    View details for PubMedID 17141302

  • Tertiary cytoreductive surgery in recurrent ovarian cancer: Selection criteria and survival outcome GYNECOLOGIC ONCOLOGY Karam, A. K., Santillan, A., Bristow, R. E., Giuntoli, R., Gardner, G. J., Cass, I., Karlan, B. Y., Li, A. J. 2007; 104 (2): 377–80


    Studies of tertiary cytoreductive surgery (TCS) in recurrent epithelial ovarian cancer are limited, and appropriate patient selection remains a clinical challenge. We sought to evaluate the impact of TCS on survival and to determine predictors of optimal tertiary resection.Between January 1997 and July 2004, 47 women with recurrent epithelial ovarian cancer underwent TCS at two institutions. All patients received initial platinum and taxane-based chemotherapy following primary cytoreductive surgery. Clinico-pathologic factors and survival were retrospectively abstracted from medical records. Optimal TCS was defined as microscopic residual disease.Thirty of 47 (64%) patients underwent optimal TCS. Size of tumor implants<5 cm on preoperative imaging was the only significant predictor of achieving optimal TCS. Overall survival after TCS was statistically longer in patients with microscopic versus macroscopic residual disease (24 versus 16 months, p=0.03). After controlling for age, time to progression and optimal TCS, only the presence of diffuse disease at tertiary exploration remained a significant poor predictor of survival. However, in a cohort of patients with limited disease implants, multivariate analysis indicated that optimal TCS retained prognostic significance as a positive predictor of survival. Twelve patients (26%) experienced severe postoperative complications, including six with pulmonary embolism, four with fistulae and two with postoperative myocardial infarctions.Size of disease implants on preoperative imaging may guide the selection of candidates for TCS. In those patients with limited disease implants at laparotomy, optimal TCS is associated with improved survival.

    View details for DOI 10.1016/j.ygyno.2006.08.037

    View details for Web of Science ID 000244101200018

    View details for PubMedID 17014899

  • Argon beam coagulation facilitates management of placenta percreta with bladder invasion OBSTETRICS AND GYNECOLOGY Karam, A. K., Bristow, R. E., Bienstock, J., Montz, F. J. 2003; 102 (3): 555–56


    Placenta percreta with bladder invasion is a rare but potentially lethal complication of pregnancy.A multigravida, with a history of two prior cesarean deliveries, presented with complaints of heavy vaginal bleeding near term. She had been previously diagnosed with an anterior placenta previa. A placenta percreta with bladder invasion was confirmed on cystoscopy. The patient underwent a successful cesarean hysterectomy using the argon beam coagulator.Argon beam coagulation may successfully help manage placenta percreta with bladder invasion while minimizing blood loss.

    View details for DOI 10.1016/S0029-7844(03)00164-9

    View details for Web of Science ID 000185007400024

    View details for PubMedID 12962942

  • Factors associated with fetal demise in fetal echogenic bowel Al-Kouatly, H. B., Chasen, S. T., Karam, A. K., Ahner, R., Chervenak, F. A. MOSBY, INC. 2001: 1039–43


    The purpose of this study was to determine risk factors associated with intrauterine fetal demise in fetuses with unexplained echogenic bowel that is diagnosed in the second trimester.A retrospective case-control study compared fetuses with echogenic bowel and fetal demise with fetuses with echogenic bowel who were live born. Fetuses affected with cystic fibrosis, aneuploidy, or congenital infection and fetuses diagnosed with major anomalies were excluded. Variables examined in the determination of risk factors for intrauterine fetal demise included intrauterine growth restriction, oligohydramnios, elevated maternal serum alpha-fetoprotein levels, and elevated maternal serum beta-hCG levels. Statistical analysis was performed with the Fisher exact test, Student t test, and logistic regression analysis.One hundred fifty-six fetuses met the inclusion criteria. There were 9 cases of intrauterine fetal demise and 147 live born control fetuses. The median gestational age of intrauterine fetal demise was 22.0 weeks (range, 17-39 weeks). Intrauterine growth restriction occurred more frequently in cases of intrauterine fetal demise than in live born infants (22.2% vs 0.7%; P =.009), as did oligohydramnios (44.4% vs 2.0%; P <.001) and elevated maternal serum alpha-fetoprotein levels (80.0% vs 7.7%; P: =.001). With the use of logistic regression analysis, elevated maternal serum alpha-fetoprotein was the strongest independent risk factor that was associated with intrauterine fetal demise (odds ratio, 39.48; 95% CI, 11.04%-141.25%).In our series, there was a 5.8% incidence of intrauterine fetal demise in fetuses with unexplained echogenic bowel. Elevated maternal serum alpha-fetoprotein is the strongest predictor of fetal demise in fetal echogenic bowel.

    View details for DOI 10.1067/mob.2001.117641

    View details for Web of Science ID 000172396100007

    View details for PubMedID 11717629

  • Endometriosis Malignant Transformation Review: Rhabdomyosarcoma Arising From an Endometrioma. JSLS : Journal of the Society of Laparoendoscopic Surgeons Nezhat, C. n., Vu, M. n., Vang, N. n., Ganjoo, K. n., Karam, A. n., Folkins, A. n., Nezhat, A. n., Nezhat, F. n. ; 23 (4)


    Endometriosis is a widely known benign disease, but 0.5%-1% of cases are associated with malignancy. It has been linked with ovarian neoplasms, particularly endometrioid and clear cell adenocarcinoma histology. Rhabdomyosarcomas are rarely associated with endometriosis.A 35-year-old patient underwent surgical management of endometriomas to optimize infertility treatment. She later developed abdominal pain with rapid recurrence of ovarian masses. This prompted additional surgery with biopsies diagnosing ovarian rhabdomyosarcoma. Retroactive review of pathologic specimens from her prior surgery demonstrated the neoplasm originated from her prior endometrioma. Focal areas suggested possible underlying ovarian adenosarcoma with stromal overgrowth.The incidence of rhabdomyosarcoma arising from endometriosis is exceedingly rare. The accuracy of diagnosing endometriosis and ruling out neoplasm requires coordinated efforts of a multidisciplinary team, involving radiologists, pathologists, oncologists, and gynecologic surgeons.

    View details for DOI 10.4293/JSLS.2019.00038

    View details for PubMedID 31624455

    View details for PubMedCentralID PMC6791399