Preoperative MRI and LDH in women undergoing intra-abdominal surgery for fibroids: Effect on surgical route.

Leiomyomas are a common condition with 70–80% of women receiving the diagnosis during their lifetime [ 1 ]. It is estimated that approximately 433,621 hysterectomies and 34,000 myomectomies are performed annually in the United States making these surgeries a significant percentage of the total national operative volume [ 2 , 3 ]. Most of these procedures can be performed via minimally invasive route, decreasing overall morbidity [ 4 , 5 ]. However, in order to do so, an appropriate method for removal of bulky fibroids is required. Preoperative diagnosis of cancer in women presenting with abnormal uterine bleeding remains a challenge [ 6 , 7 ]. Power morcellation was challenged by a recent 2014 U.S. Food and Drug Administration safety communication out of concerns for dissemination of occult leiomyosarcoma (LMS), as well as other cancers, pre-malignant and benign pathologies that could lead to inadvertent spread of malignant and pre-malignant cells throughout the abdominal cavity, and lead to conditions such as iatrogenic leiomyomatosis [ 2 , 8 ]. Several professional societies, including AAGL (Elevating Gynecologic Surgery, founded as American Association of Gynecologic Laparoscopists) and American College of Obstetricians and Gynecologists (ACOG), subsequently followed up with practice guidelines and committee opinions to address this issue, along with updates in the literature [ 9 , 10 ]. In the wake of the FDA advisory, a number of studies have reported rising laparotomy rates, which in turn are associated with increased surgical complications [ 11 , 12 ]. Evidence has consistently supported minimally invasive approaches to myomectomy and hysterectomy to minimize perioperative morbidity [ 3 , 10 ]. A recent decision analysis by Siedhoff et al. incorporating updated leiomyosarcoma incidence estimates continues to suggest that mortality rates are low following hysterectomy for presumed benign fibroids, and that a minimally invasive approach remains a safe option [ 13 ]. A large descriptive study analyzing national trends in hysterectomy surrounding the FDA safety communication found that after an initial reactive decrease in minimally invasive hysterectomies, the effect reversed one year later [ 14 ]. In an attempt to address the morcellation safety concerns regarding LMS while continuing to offer the benefits of minimally invasive options to women, a protocol was instituted in our hospital based on work by Goto el al, requiring pre-operative magnetic resonance imaging (MRI) and serum LDH (lactate dehydrogenase) enzyme levels to identify women at increased risk of LMS [ 15 ]. Our preceding study demonstrated that when this protocol was implemented, MRI alone had a very high negative predictive value; however, it was associated with a high false positive rate and a low positive predictive value [ 16 ]. We are now reporting on the impact of a preoperative protocol on institutional surgical practice patterns at the time of FDA safety communication, and the influence of MRI and LDH results on selection of surgical route and tissue extraction methods.

A total of 1,678 women undergoing intra-abdominal fibroid surgery (myomectomies and hysterectomies) were identified during the study period. Of these, a total of 593 women were excluded for having a benign non-leiomyoma indication for surgery or for a history of prior uterine malignant or pre-malignant uterine conditions (i.e., endometrial hyperplasia or endometrial cancer). A total of 1,085 women were included in the study, 479 women in the pre-protocol group and 606 in the post-protocol group. Patient demographics are shown in Table 1 . BMI = Body Mass Index. Age and BMI are listed as average (range). Other characteristics are listed as N (%). P -values determined by exact Mann-Whitney tests (for BMI and age) and by Fisher exact tests (for the rest of the characteristics listed in this table). The pre-protocol group had more women who were white, post-menopausal, and on tamoxifen when compared to the women in the post-protocol group. The post-protocol group had more Hispanic women. No differences were noted in age, BMI, cancer history, or history of pelvic radiation. Details on MRI and LDH test accuracy were described in our preceding study; in brief, most abnormal MRI results in the post-protocol cohort was noted to be false-positive [ 16 ]. There were no differences between pre- and post-protocol groups in the incidence of leiomyomas, uterine malignancies or atypical uterine tumors. Only the incidence of benign non-leiomyoma diagnoses, including adenomyosis and endometrial polyps, as diagnosed on surgical pathology, differed between the two groups: 33% vs 56% in the pre- and post-protocol groups for open hysterectomies, and 36% vs 46% in MIS hysterectomies, respectively (p = 0.05 for both) ( Table 2 ). Data are summarized as N; %. All Fisher’s exact P-values for association equal to 1.0 except for the association between benign non-fibroids and pre/post protocol in open and MIS hysterectomies (p = 0.05 for both, in bold). a “Benign Non-fibroid” includes adenomyosis, ademonyoma, endometrial polyp, chronic endometritis, denuded endometrium, polypoid adenomyoma, endometriosis, fibrosis, infarctive endometrium, endometrium with cystic degeneration, atrophic endometrium, focal compression atrophy, tubal metaplasia, glandular crowding, proliferative endometrium, foreign body giant cell reaction, and chronic serosal inflammation b “Other Gynecological Cancer” includes aggressive angiomyxoma, mullerian adenocarcinoma, and endometrial stromal sarcoma c “Non-Gynecological Cancer” includes metastatic breast adenocarcinoma d “Smooth Muscle Tumor Variant” includes adenostromyoma, smooth muscle tumor of uncertain malignant potential, symplastic leiomyoma, cellular leiomyoma, adenomatoid tumor, mitotically active leiomyoma, lipoleiomyoma, leiomyoma with atypia, and mitotically active smooth muscle tumor with atypia Since our cohorts were based on the timing of protocol initiation, we compared surgical routes and methods of tissue extraction in both pre- and post-protocol cohorts (Tables 3 and 4 ). MIS-Minimally invasive surgery P = 0.406, Fisher’s exact test for association. All values are N (%) unless otherwise indicated. MIS-Minimally invasive surgery. * “Unknown”—cases in tissue extraction method was not stated in the operative report. Vaginal without containment bag—includes intact and fragmented specimen removal. Contained tissue extraction methods include “mini-laparotomy with containment bag” and “vaginal with containment bag.” Uncontained tissue extraction methods include “power morcellation,” “mini-laparotomy without containment bag” and “vaginal without containment bag.” A significant increase in the use of containment bags for tissue extraction was seen in the post-protocol group, from 1% to 19% (P<0.001) ( Table 4 ). There was no significant difference between pre- and post-protocol groups with regards to the proportion of open versus minimally invasive route of surgery (14% vs. 12% open procedure rates in pre- and post-protocol groups, respectively, P = 0.406). Open hysterectomy rates (19% vs. 16% in pre- and post-protocol groups, respectively, P = 0.463) and open myomectomy rates (10% vs. 9% in pre- and post-protocol groups, respectively, P = 0.776) in either cohort did not differ when broken down by the type of surgery. There was a significant decrease in the rate of power morcellation use over the study period: 66% pre-protocol vs. 50% post-protocol (P<0.001) ( Table 4 ). Similar trends with regard to decreased use of power morcellation and increased use of containment bags for tissue extraction were noted for both hysterectomies and myomectomies ( Table 5 ). Data are summarized as N; %. *Corresponds to Fisher’s Exact test of association between pre and post-protocol and each extraction route. a Includes intact and fragmented specimen removals b “Unknown” refers to cases in which MIS tissue extraction method was not mentioned in the operative report. Contained tissue extraction methods include “mini-laparotomy with containment bag” and “vaginal with containment bag.” Uncontained tissue extraction methods include “power morcellation,” “mini-laparotomy without containment bag” and “vaginal without containment bag.” In the post-protocol cohort of 606 cases, 358 women had both MRI and LDH performed prior to surgery, a protocol compliance rate of 59% ( S1 Table ). Out of the 358 women with full protocol testing, only six women had abnormal pathology (two had leiomyosarcoma, one endometrial adenocarcinoma, one other smooth muscle cancer, and two had smooth muscle tumor variants) [ 16 ]. Sub-group analysis was performed by MRI and LDH results with regard to subsequent surgical route. Of those 358 women who had both MRI and LDH completed preoperatively, 203 had both negative MRI and negative LDH results; in this group, only 3% of women had an open procedure. In contrast, in the 23 women with both abnormal MRI and abnormal LDH, 17% underwent open surgery (P = 0.01 when compared to the group that had both normal results), while the rest underwent a minimally invasive procedure. Furthermore, 132 women had discordant results. A combination of an abnormal MRI with normal LDH was significantly more likely to be associated with an open procedure (9.3%; P = 0.02 when compared to group with both normal results), while normal MRI and abnormal LDH combination did not show statistically significant increase in open route. Abnormal MRI alone, regardless of LDH results, was associated with higher rates of open approach (13.4% when abnormal vs. 3.4% when normal, P = 0.001). Abnormal LDH results alone did not significantly influence route (P = 0.19). Subgroup size was too small to perform analysis by procedure type (myomectomy and hysterectomy) within each subgroup.

We conducted a retrospective chart review of a convenience sample of women who underwent intra-abdominal surgery for symptomatic fibroids at New York University Langone Health (NYULH) from April 23, 2013 to April 23, 2015, one year prior and one year after protocol implementation. An institution-wide protocol requiring preoperative MRI with diffusion weighted imaging, serum LDH isoenzyme 3, and total LDH was implemented on April 23, 2014 to determine eligibility for uncontained power morcellation based on pre-operative assessment of LMS risk. Our preceding publication describes this protocol in detail [ 16 ]. We included women between the ages of 18–99 with symptomatic fibroid uterus who underwent intra-abdominal surgery for leiomyomas. This included myomectomies (laparoscopic, robotic and open approaches) and hysterectomies (both total and supracervical, with laparoscopic, robotic, vaginal, laparoscopically-assisted vaginal and open approaches). We excluded hysteroscopic myomectomies. Patients were screened by a review of the operating room schedule during the study period. Eligible patients’ charts were reviewed to extract relevant data including: patient demographics, preoperative workup, type of surgery and method of tissue extraction. We reviewed our internal institutional gynecologic cancer database (created and maintained for the purposes of tumor board treatment planning) to confirm that all cases of LMS were captured in our study. In brief, a patient was eligible for uncontained laparoscopic power morcellation if all three results (MRI, total LDH, and LH3) were normal. If one of the results was abnormal, the surgeon was restricted from using the power morcellator; clinical management, as well as the resultant mode of surgery, and method of specimen removal was left to the surgeon’s discretion. Alexis ® contained extraction system bags (Applied Medical) became available at the time of protocol implementation; other types of containment systems including those that allow contained laparoscopic morcellation, were not. Operating room schedules were reviewed to identify eligible women during the study period, and charts were reviewed to extract relevant data, including patient demographics, preoperative work-up, pathology results, type of surgery, and method of tissue extraction. The outcome metrics for this report include: The impact of the protocol on institutional surgical practice patterns (including route, type, and extraction method), and The influence of MRI and LDH results on surgical route. Fischer exact tests were used to compare binary demographic parameters, pre- and post-protocol surgical patterns, uterine pathology incidence, and protocol adherence; Mann Whitney tests were used to compare continuous variables. Statistical analysis was performed using SAS software version 9.3 (SAS Institute, Cary, NC). We obtained approval from the NYU School of Medicine IRB (i15-01220) with a waiver of consent prior to data collection on June 15, 2015.

Although earlier studies have suggested an overall decrease in minimally invasive hysterectomies in response to the FDA warning on power morcellation, there was no change in rates of minimally invasive hysterectomies and myomectomies at our institution during a similar time period. More studies are needed to describe effect of pre-operative MRI and LDH testing on surgical route, referral patterns to gynecologic oncology, and patient perceptions of how those results affected their experience. Further research is needed to guide practices that will consistently identify the highest risk patients preoperatively and minimize the impact of unexpected cancers while affording the appropriate patients the benefits of minimally invasive surgery.

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