Endometrial Evaluation: Are You Still Relying on a Blind Biopsy?

SUPPLEMENT TO

This activity is supported by an educational grant from CooperSurgical, Inc. October 2017 Continuing medical education (CME) credit is awarded upon successful completion of the posttest and evaluation. To access the posttest and evaluation, visit Endometrial Evaluation: www.worldclasscme.com/endometrialevaluation World Class CME is accredited by the Accreditation Council Are You Still Relying on for Continuing Medical Education to provide continuing medical education for physicians. a Blind Biopsy? World Class CME designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate Steven R. Goldstein, MD, CCD, NCMP, FACOG with the extent of their participation in the activity. New York University Medical Center New York, New York Audience: This activity was planned for obstetricians and gynecologists and women’s health care providers. Ted L. Anderson, MD, PhD Faculty Program Director Vanderbilt University Medical School Steven R. Goldstein, MD, CCD, NCMP, FACOG Nashville, Tennessee Professor of Obstetrics and Gynecology New York University School of Medicine Director of Gynecological Ultrasound INTRODUCTION Co-Director of Bone Densitometry One-third of patients who visit a gynecologist are there Department of Obstetrics and Gynecology because of abnormal uterine bleeding (AUB), which New York University Medical Center New York, New York is believed to account for more than 70% of gyneco- logic consults in perimenopausal and postmenopausal Author women.1 Endometrial evaluation has evolved since the Ted L. Anderson, MD, PhD Betty and Lonnie S. Burnett Professor of Obstetrics introduction of suction piston biopsy instruments in the and Gynecology 1980s. Once adequate for evaluation of women with AUB Vice Chair for Gynecology or postmenopausal bleeding, the American College of Vanderbilt University Medical School Obstetricians and Gynecologists (ACOG) Practice Bulle- Nashville, Tennessee tin on AUB now states that a negative blind endometrial Learning Objectives biopsy is not a stopping point in persistent bleeding.1 At the conclusion of this activity, the participant will be able to: Previously, many health care providers avoided in-office 1. See-realize the shortcomings of blind endometrial “point of care“ direct visualization of the endometrial cav- sampling and the history of how that has evolved ity with hysteroscopy for a variety of reasons. However, 2. Understand how to best evaluate women with newer disposable equipment has resulted in a changing abnormal uterine bleeding or postmenopausal bleeding 3. Appreciate how to incorporate direct visualization of landscape that will allow many gynecologists to add such the endometrial cavity with new disposable equipment evaluation to their in-office procedures. 4. Understand what “point of care” evaluation means in abnormal uterine bleeding and how to implement it CAUSES OF ABNORMAL UTERINE BLEEDING 5. Appreciate some “pitfalls and pearls” for evaluating such patients In postmenopausal patients, any bleeding is “uterine cancer until proven otherwise,” although the incidence Date of Original Release: October 1, 2017 2 Date Credits Expire: September 30, 2020 of malignancy will range from 1% to 14%. Indeed, the Conflict of interest disclosure majority of such bleeding actually will be from atrophic Steven R. Goldstein, MD, CCD, NCMP, FACOG changes. In perimenopausal women aged 40 years or Consultant: CooperSurgical—Consulting fees received older, AUB mandates evaluation.1 In fact, in a study of Consultant: Cook OB/GYN—Consulting fees received 433 women aged 40 years to menopause, 79% had no Recipient: Philips Ultrasound—Equipment loan anatomic reason for their bleeding, thus making ovulatory No disclosures to declare dysfunction the most likely final diagnosis.3 Ted L. Anderson, MD, PhD It therefore becomes obvious that the great divide for Heidi M. Wilson, Course Director clinicians is to distinguish between those patients with no

AVAILABLE AT WWW.OBGMANAGEMENT.COM Supplement to OBG Management I October 2017 S1 ENDOMETRIAL EVALUATION: ARE YOU STILL RELYING ON A BLIND BIOPSY?

anatomic abnormality (best treated hormonally or expec- setting, especially in a point-of-care fashion—where the tantly) versus those with anatomic pathology (who will patient is initially examined—rather than at a separate time often be in need of more definitive diagnosis and thera- (and possibly separate location) with additional personnel. peutic intervention). IMAGING TECHNIQUES SHORTCOMINGS OF BLIND BIOPSY Transvaginal ultrasound (TV U/S) has become integral After a single study by Stovall et al, blind endometrial to virtually all gynecologic practice. However, it is all too sampling with disposable suction piston devices became often performed by other personnel (sonographers, radi- the standard approach for patients with AUB.4 Stovall per- ologists) and at a different time and location than when formed such outpatient biopsy on 40 patients with known the patient has presented to the gynecologic provider. carcinoma the week prior to scheduled hysterectomy and The limitations of TV U/S in distinguishing global from obtained endometrial carcinoma in 39 of the 40 samples; focal pathologies is well established.3,9 The addition of he reported a 97.5% accuracy. This was widely publicized, fluid enhancement, known as saline infusion sonohys- marketed, and promoted, and was rapidly accepted as terography (SIS), improves the sensitivity and specificity standard of care. In a similar study by Guido et al, research- of unenhanced TV U/S to approach that of diagnostic ers performed blind endometrial sampling in 65 patients hysteroscopy.10 It has been our observation, however, that with known carcinoma in the operating room just prior to the majority of SIS is not done by the clinician at the time hysterectomy.5 These blind biopsies missed 11 of 65 can- of patient presentation, but rather all too often, as men- cers (a sensitivity of only 83%). Importantly, upon opening tioned, at another time, in another location, and with the removed uteri for visual inspection of the endome- additional personnel. Thus, it has not evolved into the sat- trium it was determined that, when the cancers occupied isfactory point-of-care option that would allow the major- at least 50% of the endometrial surface, the biopsy was ity of patients with AUB to be evaluated at the time of 100% accurate. In similar studies of women with known presentation. In the setting of AUB, TV U/S has not allowed carcinomas, the sensitivities of blind sampling were only gynecologists or their patients to optimize economy of 84% and 68%, yielding false negative rates of 16% and time, effort, and finances. 32%, respectively.6,7 Again, these were blind biopsies per- Furthermore, many gynecologists have not added formed on women with known carcinoma. office hysteroscopy to their armamentarium of evaluation In 2012, the ACOG Practice Bulletin acknowledged, “the tools because of the complex and expensive equipment primary role of endometrial sampling in patients with AUB involved, the space required, the need for sterilization and is to determine if carcinoma or pre-malignant lesions are maintenance of equipment, and concerns about issues of present.”1 The bulletin also states that endometrial biopsy patient discomfort. Newer disposable office hysteroscopes has “high overall accuracy in diagnosing endometrial can- have the ability to completely change that aspect of prac- cer when an adequate specimen is obtained and when tice and truly make the evaluation “point of care.” the endometrial process is global.” In trying to understand why such biopsies failed in nonglobal pathology, one ADVANTAGES OF HYSTEROSCOPY need look no further than Guido’s studies demonstrating Clearly hysteroscopy can distinguish no pathology from that blind biopsy can miss cancers that occupy less than global pathology from focal abnormalities. It can deter- 50% of the surface area. Further, a prehysterectomy study mine which patients may need to go to the operating by Rodriguez et al demonstrated that Pipelle endometrial room as well as optimize preoperative surgical planning. biopsy sampled an average of only 4% (range, 0%-12%) of Ideally this would be done in an office setting when the the endometrial surface area.8 Therefore, these tests only patient first presents (point of care). The cost-effective- can be considered an endpoint when they reveal cancer ness of office hysteroscopy in identifying patients who or atypical complex hyperplasia. do not need to go to the operating room for operative These findings have tremendous ramifications for hysteroscopy interventions has been well established. clinical practice. Certainly health care providers, espe- Moawad et al reported that almost 60% of women who cially in low resource areas, can begin the evaluation with underwent diagnostic office hysteroscopy for AUB were a blind biopsy. But if the results do not indicate cancer or able to avoid the need for intervention in the operative atypical hyperplasia, the evaluation cannot be consid- suite, saving almost $1500 per patient.11 Given the inci- ered adequate, much less definitive, especially if bleeding dence of AUB in reproductive age and postmenopausal persists. Thus, the concept of distinguishing “global” from women, as described above, the cost savings of this “focal” pathologies is becoming increasingly understood strategy to overall health care expenditures is stagger- and important. Providing patients who have no anatomic ing. Even in those cases in which there is a known or abnormality with a diagnosis is best done in an office suspected anatomic abnormality (eg, polyps or fibroids),

S2 October 2017 I Supplement to OBG Management ENDOMETRIAL EVALUATION: ARE YOU STILL RELYING ON A BLIND BIOPSY?

FIGURE 2 Hysteroscope image showing endometrial atrophy FIGURE 1 The reposable hysteroscopy system consists of a in a 61-year-old woman with postmenopausal bleeding reusable hand-held unit and a disposable cannula Image courtesy of Steven R. Goldstein, MD, CCD, NCMP, FACOG

diagnostic hysteroscopy can help the physician make a single-use cannulas are approximately 11 in long and more accurate diagnosis, which is valuable for optimizing 4 mm in diameter, have a slightly curved tip (25˚), and con- operative planning.12 tain a miniature camera and a LED light source. The can- nula snaps securely onto a receptacle on the hand-held POINT-OF-CARE OFFICE HYSTEROSCOPY monitor and contains a channel for infusion of saline dis- Office hysteroscopy remains grossly underutilizedtension medium. The cannula can be inserted in a similar because of the complexity and expense of acquiring and fashion as an endometrial biopsy device. The cannula can maintaining the necessary equipment. Additionally, tradi- then be attached to a 3.7 x 3.5 in LCD screen. tional systems require a dedicated cart and are not typi- A base unit allows battery recharging (full battery cally small enough or mobile enough to transport among gives about 2 hours of continuous use) and USB transfer examination rooms. Thus, the space requirement is not of images or videos to a laptop. Such a system eliminates insignificant. Further, there are issues of cleaning, sterile the need for a tower with separate cameras, light sources, processing, and storage, as well as training of staff to aid and monitors and cords to assemble. It also eliminates the in these tasks. Accordingly, the thought of incorporat- ing office hysteroscopy into the typical practice can be a bit overwhelming. Handheld systems like the Wireless Digital Endoscope Camera (WiCAM, The Prometheus Group, Dover, NH) and the EndoSee hysteroscope (Cooper Surgical, Trumbull, CT) can radically change direct intrauterine evaluation in the office. Each has its own distinct advantages. The WiCam battery powered 4.7 x 2.2 inch wireless camera connects to any standard hysteroscope and trans- mits images to your laptop using HIPAA-compliant soft- ware. A rechargeable LED light source connects to the light post of the hysteroscope. This gives a high-quality image without the need for a tower or the multiple wired connections it entails, but you still need a hysteroscope to connect (not included). The EndoSee hysteroscope (FIGURE 1) is a self- FIGURE 3 Hysteroscope image of submucous myoma in a contained system approximately the size of an iPhone, perimenopausal woman attached to a single-use disposable cannula contain- Image courtesy of Ted L. Anderson, MD, PhD ing both camera and light source at the tip. Sterile

Supplement to OBG Management I October 2017 S3 ENDOMETRIAL EVALUATION: ARE YOU STILL RELYING ON A BLIND BIOPSY?

need for cleaning and sterile processing of equipment REFERENCES between uses. In addition, it does not require a dedicated 1. Committee on Practice Bulletins—Gynecology. Practice bulletin no. procedure room or storage space. Its use draws many par- 128: diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol. 2012;120(1):197-206. allels to office endometrial biopsy. 2. Goldstein SR. Modern evaluation of the endometrium. Obstet Gynecol. Minimal patient preparation is necessary with the 2010;116(1):168-176. portable video hysteroscope devices. If the procedure is 3. Goldstein SR, Zeltser I, Horan CK, Snyder JR, Schwartz LB. Ultrasonog- scheduled, such as timing a cycling patient to just after raphy-based triage for perimenopausal patients with abnormal uter- ine bleeding. Am J Obstet Gynecol. 1997;177(1):102-108. the bleeding ends, the operator might consider misopros- 4. Stovall TG, Photopulos GJ, Poston WM, Ling FW, Sandles LG. Pipelle tol preparation of the cervix, but cervical dilation is almost endometrial sampling in patients with known endometrial carci- never required. After connecting the sterile cannula, the noma. Obstet Gynecol. 1991;77(6):954-956. 5. Guido RS, Kanbour-Shakir A, Rulin MC, Christopherson WA. Pipelle fluid distension medium is delivered via intravenous endometrial sampling. Sensitivity in the detection of endometrial extension tubing. Distension fluid can aid in cervical dila- cancer. J Reprod Med. 1995;40(8):553-555. tion and passage of the catheter into the uterine cavity 6. Larson DM, Krawisz BR, Johnson KK, Broste SK. Comparison of the under visualization. The contours of the uterine cavity can Z-Sampler and Novak endometrial biopsy instruments for in-office diagnosis of endometrial cancer. Gynecol Oncol. 1994;54(1):64-67. be explored by gentle turning, taking advantage of the 7. Ferry J, Farnsworth A, Webster M, Wren B. The efficacy of the pipelle curved tip for optimal visualization. Multiple reports have endometrial biopsy in detecting endometrial carcinoma. Austn N Z described the portable video hysteroscope to be easy to J Obstet Gynaecol. 1993;33(1):76-78. use and well tolerated by patients while providing excel- 8. Rodriguez MH, Platt LD, Medearis AL, Lacarra M, Lobo RA. The use of transvaginal sonography for evaluation of postmenopausal ovarian lent evaluation of the uterine cavity and producing high size and morphology. Am J Obstet Gynecol. 1988;159(4):810-814. 13,14 quality images and videos. 9. Grimbizis GF, Tsolakidis D, Mikos T, et al. A prospective comparison of transvaginal ultrasound, saline infusion sonohysterography, and diag- SUMMARY nostic hysteroscopy in the evaluation of endometrial pathology. Fertil Steril. 2010;94(7):2720-2725. AUB in women aged 40 years and older with any post- 10. Kelekci S, Kaya E, Alan M, Alan Y, Bilge U, Mollamahmutoglu L. Com- menopausal bleeding requires evaluation. The utilization parison of transvaginal sonography, saline infusion sonography, and of TV U/S, often needing fluid enhancement (with SIS), has office hysteroscopy in reproductive-aged women with or without a role but is too often sent for evaluation by imaging spe- abnormal uterine bleeding. Fertil Steril. 2005;84(3):682-686. 11. Moawad NS, Santamaria E, Johnson M, Shuster J. Cost-effectiveness of cialists. Blind endometrial sampling, which has previously office hysteroscopy for abnormal uterine bleeding. JSLS. 2014;18(3): been the mainstay of diagnosis, is only a stopping point doi: 10.4293/JSLS.2014.00393. when cancer or atypical hyperplasia is found. Office hys- 12. Shinar S, Bibi G, Barzilay L Rubens P, Almog B, Levin I. The value of teroscopy, previously underutilized, is now increasingly diagnostic hysteroscopy before operative hysteroscopy for sus- pected abnormal intrauterine findings. J Minim Invasive Gynecol. possible because of the introduction of small devices 2014;21(2):228-232. containing disposable camera-holding cannulas. For the 13. Wortman M. The EndoSee hysteroscope: Initial experience with a self- many providers who never were able to do office-based, contained hand-held hysteroscopy system [abstract]. J Minim Invasive point-of-care hysteroscopy, these small devices now offer Gynecol. 2013;20(6 suppl):S68. 14. Munro M. Pilot evaluation of the EndoSee hand-held hysteroscopic the ability to do so. This will have tremendous advantages system for diagnostic hysterocopy [abstract]. J Minim Invasive Gynecol. for patients and providers in terms of cost and time. 2013;20(6 suppl):S68-S69.

Continuing medical education (CME) credit is awarded upon successful completion of this posttest and evaluation. To access the posttest and evaluation, visit: WWW.WORLDCLASSCME.COM/ENDOMETRIALEVALUATION World Class CME 6201 Fairview Road, Suite 200 Charlotte, North Carolina 28210 888-207-9105 www.worldclasscme.com [email protected]

S4 October 2017 I Supplement to OBG Management