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Clinical evaluation of the oral gonadotropin-releasing hormone-antagonist elagolix for the management of endometriosis-associated pain

Taylor, Hugh S; Dun, Erica C; Chwalisz, Kristof
Endometriosis is an estrogen-dependent chronic inflammatory disease associated with pelvic pain symptoms that are often severe, mainly dysmenorrhea, nonmenstrual pelvic pain and dyspareunia. This condition is also associated with peripheral and central sensitization. The current medical treatment options for endometriosis-associated pain are limited. Recently, the US FDA approved the novel, oral, nonpeptide gonadotropin-releasing hormone antagonist elagolix for the management of moderate to severe endometriosis-associated pain. Elagolix produces dose-dependent estrogen suppression, from partial suppression at lower doses to nearly full suppression at higher doses. This review article summarizes the current understanding of the pathophysiology of endometriosis, with a focus on the role of estrogen and the mechanisms of pain symptoms, and reviews the clinical development of elagolix in women with endometriosis-associated pain.
PMID: 31434540
ISSN: 1758-1877
CID: 4091822

Elagolix: a promising oral GnRH antagonist for endometriosis-associated pain [Editorial]

Dun, Erica C; Taylor, Hugh S
PMID: 29245894
ISSN: 1949-2553
CID: 3572482

A Comparison of Thermal Plasma Energy Versus Argon Beam Coagulator-Induced Intestinal Injury After Vaporization in a Porcine Model

Tanner, Edward J; Dun, Erica; Sonoda, Yukio; Olawaiye, Alexander B; Chi, Dennis S
OBJECTIVES:Complete cytoreduction of ovarian cancer often requires excision or ablation of bowel serosa implants. Both argon beam coagulator (ABC) and thermal plasma energy (TPE) (PlasmaJet; PlasmaSurgical, Roswell, Ga) have been used to ablate bowel serosa implants. Our objective was to identify comparable power settings as well as determine the rate of bowel perforation, depth of thermal injury, and extent of inflammatory response with ABC versus TPE in a porcine model. MATERIALS AND METHODS:Nine pigs underwent vaporization of small bowel and colon serosa according to assigned treatment group (TPE vs ABC) and settings (ABC: 30, 50, and 70 W; TPE: Cut 10U, 20U, and 30U and Coagulation 10U, 20U, and 30U). Animals underwent necropsy with blinded histomorphologic evaluation on days 0, 3, and 10 postprocedure to assess for presence of bowel perforation, depth of thermal injury, and extent of inflammatory response. RESULTS:At necropsy, bowel perforation was not identified in any animals. Depth of treatment with ABC in the porcine colon was variable and unrelated to power settings whereas TPE was associated with a consistent treatment depth of 1.0 mm regardless of location or power. Treatment with ABC resulted in greater tissue coagulation and desiccation as well as increased rates of mucosal necrosis, especially at higher settings (>50 W). Treatment with TPE primarily resulted in tissue ablation and minimal mucosal necrosis at low settings (Coag 10U-20U). The inflammatory response associated with TPE treatments was interpreted as biologically benign, and less than that observed with the ABC regardless of treatment settings. CONCLUSIONS:Both ABC and TPE effectively ablate bowel serosa in a porcine model. The TPE seems to result in a more predictable tissue effect with less inflammatory response, especially when used at low power settings such as Coag 10U or 20U. These characteristics are appealing for ablation of bowel serosa implants during ovarian cancer surgery and warrant further investigation.
PMID: 27922979
ISSN: 1525-1438
CID: 3567862

Recurrent massive ascites due to mossy endometriosis [Case Report]

Dun, Erica C; Wong, Serena; Lakhi, Nisha A; Nehzat, Ceana H
OBJECTIVE:To report the medical and surgical management of a rare case of recurrent moss-like endometriosis and associated hemorrhagic ascites. DESIGN/METHODS:Video description of the case, demonstration of the surgical technique, discussion of the histology, and review of endometriosis-associated ascites. SETTING/METHODS:Tertiary referral center. PATIENT(S)/METHODS:A 26-year-old nulliparous woman of Nigerian heritage with recurrent hemorrhagic ascites due to endometriosis. Three years previously she underwent an exploratory laparotomy for similar symptoms, and 7 L of hemorrhagic ascites were evacuated from her abdomen. Friable lesions covering the peritoneum of the uterus, bladder, and pouch of Douglas were biopsied and consistent with endometriosis. After her initial surgery, the patient was hormonally suppressed with goserelin for 3 months and oral medroxyprogesterone for 1 year. She then stopped the medications to attempt pregnancy but was unsuccessful. She used clomiphene for 3 months, and the ascites reaccumulated. The patient was started on depot leuprolide and oral norethindrone, but the ascites persisted. INTERVENTION(S)/METHODS:The patient underwent small-diameter laparoscopy using a multipuncture technique, evacuation of 7.8 L of hemorrhagic ascites, enterolysis, appendectomy, chromopertubation, and treatment of the endometriosis. MAIN OUTCOME MEASURE(S)/METHODS:Diffuse olive-green "mossy" endometriosis lesions blanketed the pelvic and abdominal peritoneum. The endometriosis was surgically resected with a combination of peritoneal stripping, excision with carbon dioxide laser, and ablation with neutral argon plasma. Examination of the ascites showed scattered hemosiderin-laden macrophages in a background of red blood cells. Histology of the olive-green mossy lesions revealed dense sheets of hemosiderin-laden macrophages and rare foci of endometriosis. Surgical reports in deidentified patients are exempted from Institutional Review Board approval. The patient gave consent to use photography and images for the video article. RESULT(S)/RESULTS:No postoperative hormone suppression was given to the patient because she desired pregnancy. At 6 months after her second surgery, the patient had not achieved pregnancy, but the ascites had not reaccumulated. She was referred for further infertility care. CONCLUSION(S)/CONCLUSIONS:This rare form of mossy endometriosis often mimics ovarian cancer, pelvic tuberculosis, and other gynecologic conditions, but when identified, the endometriosis can be treated and symptoms can subside with drainage of the ascites, thorough ablation of the diffuse, superficial lesions, and restoration of anatomy.
PMID: 27542707
ISSN: 1556-5653
CID: 3572472

Excision of an epidermal inclusion cyst: Correction of a long-term complication of female genital circumcision [Case Report]

Dun, Erica C; Ackerman, Christina; Cutler, Abigail; Lakhi, Nisha A
Epidermal inclusion cysts are a late complication of female genital circumcision, which is a practice that affects 125 million women primarily from Africa and the Middle East. A 30-year-old woman, gravida 4, para 1, presented to our clinic with an 8-year history of a slowly enlarging periclitoral mass. The patient had undergone female genital circumcision at the age of 5 years. We describe and video-illustrate the surgical technique of excising the 8-cm epidermal inclusion cyst. Using this technique, the entire cyst was resected intact, excess vulvar skin removed, and defect repaired. Postoperatively, she had minimal pain, no dyspareunia, and good cosmesis. Restoration of anatomy for this late complication of female genital circumcision is achievable with knowledge of anatomy, adherence to basic surgical principles that include tension-free closure, and close postoperative follow up.
PMID: 27001220
ISSN: 1097-6868
CID: 3572462

Endometriosis in Adolescents: Referrals, Diagnosis, Treatment, and Outcomes

Dun, E C; Kho, K A; Kearney, S; Nezhat, C H
PMID: 27678955
ISSN: 1553-4669
CID: 3572492

Endometriosis in adolescents

Dun, Erica C; Kho, Kimberly A; Morozov, Vadim V; Kearney, Susan; Zurawin, Jonathan L; Nezhat, Ceana H
BACKGROUND AND OBJECTIVES/OBJECTIVE:Women with endometriosis often report onset of symptoms during adolescence; however, the diagnosis of endometriosis is often delayed. The aim of this study was to describe the experience of adolescents who underwent laparoscopy for pelvic pain and were diagnosed with endometriosis: specifically, the symptoms, time from onset of symptoms to correct diagnosis, number and type of medical professionals seen, diagnosis, treatment, and postoperative outcomes. METHODS:We reviewed a series of 25 females ≤21 years of age with endometriosis diagnosed during laparoscopy for pelvic pain over an 8-year period. These patients were followed up for 1 year after surgery. RESULTS:The mean age at the time of surgery was 17.2 (2.4) years (range, 10-21). The most common complaints were dysmenorrhea (64%), menorrhagia (44%), abnormal/irregular uterine bleeding (60%), ≥1 gastrointestinal symptoms (56%), and ≥1 genitourinary symptoms (52%). The mean time from the onset of symptoms until diagnosis was 22.8 (31.0) months (range, 1-132). The median number of physicians who evaluated their pain was 3 (2.3) (range, 1-12). The adolescents had stage I (68%), stage II (20%), and stage III (12%) disease. Atypical endometriosis lesions were most commonly observed during laparoscopy. At 1 year, 64% reported resolved pain, 16% improved pain, 12% continued pain, and 8% recurrent pain. CONCLUSIONS:Timely referral to a gynecologist experienced with laparoscopic diagnosis and treatment of endometriosis is critical to expedite care for adolescents with pelvic pain. Once the disease is diagnosed and treated, these patients have favorable outcomes with hormonal and nonhormonal therapy.
PMID: 26005317
ISSN: 1938-3797
CID: 3572452

Laparoscopically-assisted, hysteroscopic removal of an interstitial pregnancy with a fertility-preserving technique [Case Report]

Nezhat, Ceana H; Dun, Erica C
Described is a novel surgical management of an unruptured interstitial pregnancy with preservation of the ipsilateral fallopian tube and uterine cornua. The patient was a 34-year-old woman, gravida 3, para 1, with an unruptured left interstitial pregnancy at 9 weeks' gestation, who desired preservation of fertility. The ectopic pregnancy was entirely removed via laparoscopically assisted hysteroscopy with a fertility-preserving surgical technique, with minimal blood loss, preservation of reproductive organs, restoration of anatomy, a patent ipsilateral fallopian tube, and expedient return to normal reproductive function. After the procedure, serial human chorionic gonadotropin levels were obtained until they were <5 mIU/mL. A hysterosalpingogram obtained 2 months after the procedure showed normal uterine and fallopian tube contour and bilateral tubal patency. We conclude that this laparoscopically assisted hysteroscopic technique is a safe and efficient fertility-preserving approach to management of an unruptured interstitial pregnancy.
PMID: 24768982
ISSN: 1553-4669
CID: 3572422

Hematoureter due to endometriosis [Case Report]

Lakhi, Nisha; Dun, Erica C; Nezhat, Ceana H
OBJECTIVE:To report the laparoscopic management of a rare case of hematoureter due to endometriosis in a young woman with multiple genitourinary anomalies. DESIGN/METHODS:Video demonstration of a surgical technique and review of genitourinary endometriosis. SETTING/METHODS:Hospital. PATIENT(S)/METHODS:A 17-year-old nulliparous woman with multiple genitourinary anomalies presented with pelvic pain and unilateral retroperitoneal mass. The patient had uterine didelphys, a history of left nephrectomy, and partial ureter resection as an infant. She had a partial resection of a left transverse vaginal septum due to hematocolpos at age 12. A preoperative magnetic resonance imaging (MRI) scan revealed a left retroperitoneal mass with extension to the paravesical region, reaccumulation of the hematocolpos behind the partially resected left transverse vaginal septum, and a dilated left uterine horn with hematometra. INTERVENTION(S)/METHODS:Laparoscopic management of hematoureter due to intrinsic endometriosis. MAIN OUTCOME MEASURE(S)/METHODS:Intraoperative findings showed uterus didelphys with dilated left horn, normal right horn, and normal right and left fallopian tubes and ovaries. The left transverse vaginal septum was resected vaginally, and the hematocolpos and hematometra drained. The left uterine horn and cervix were laparoscopically resected. The left-side serpiginous retroperitoneal mass was dissected from the pelvic sidewall, ligated, and transected, with spillage of thick, brown liquid. The pathology of the mass wall was smooth muscle and transitional epithelium consistent with ureter, in addition to hemorrhage and glandular structures consistent with endometriosis. Endometriosis was also present in the serosa of the left uterine horn. Thus, the left retroperitoneal mass was the left ureter remnant, which acquired endometriosis and collected menstrual debris, resulting in hematoureter. CONCLUSION(S)/CONCLUSIONS:Two major pathologic types of ureteral endometriosis have been described: intrinsic, as occurred in this patient, and extrinsic. Women with müllerian anomalies, vaginal obstruction, or imperforate hymen are at higher risk of endometriosis. Prior urogenital surgery can further complicate and distort the anatomy. Thus, a preoperative understanding of the patient's urogenital anomalies is important to consider the differential diagnoses and anticipate surgical needs.
PMID: 24680366
ISSN: 1556-5653
CID: 3572412

Office visceral slide test compared with two perioperative tests for predicting periumbilical adhesions

Nezhat, Ceana H; Dun, Erica C; Katz, Adi; Wieser, Friedrich A
OBJECTIVE:To determine whether the office visceral slide test is an effective screening test for predicting obliterating periumbilical adhesions compared with two ultrasound tests performed in the operating room. METHODS:Women undergoing benign laparoscopic gynecologic surgery between July 2012 and August 2013 were invited to participate. All participants had an office-based ultrasound test at their preoperative visit (the office visceral slide test), two operating room ultrasound tests (the preoperative examination with visceral slide and the periumbilical ultrasound-guided saline infusion test), and then their scheduled laparoscopic procedure. We measured the ability of the three screening tests to detect obliterating periumbilical adhesions. RESULTS:Eighty-two women completed the study; 12 women were excluded because they had no history of surgery and 70 women with a history of abdominal and pelvic surgery were analyzed in the study group. The study group (n=70) had a median of two (range, 1-6) previous abdominal surgeries. The median number of previous laparotomies was 0 (range, 0-5). The median number of previous laparoscopies was 1 (range, 0-6). At laparoscopy, 6 of 70 women (8.6%) had periumbilical adhesions diagnosed; 18 of 70 women (25.7%) had any adhesions located in the abdomen or pelvis. The office visceral slide test had a sensitivity of 83.3%, specificity of 100%, positive predictive value of 100%, negative predictive value of 98.5% and diagnostic accuracy of 98.6%. CONCLUSION/CONCLUSIONS:The office visceral slide test is a simple and reliable test for detecting obliterating periumbilical adhesions in the outpatient setting. LEVEL OF EVIDENCE/METHODS:II.
PMID: 24785858
ISSN: 1873-233x
CID: 3572432