{"paper_id":"e6e89e05-6a02-4c0b-8838-05b136478953","body_text":"This was a retrospective cohort study using American College of Surgeons\nNSQIP data from January 2018 to December 2019 [ 18 ]. Both the general and the procedure targeted (hysterectomy)\nparticipant use files were used. This database includes both inpatient and\noutpatient procedures. This study was deemed exempt by the University of Minnesota\nInstitutional Review Board.\nPostoperative  International Classification of Diseases \n(ICD), 10th Revision, codes were used to identify indications for hysterectomy\n( Supplemental Table 1 ).\nAll patients aged 18 to 55 years who underwent total hysterectomy for the following\nbenign indications were included: endometriosis, abnormal uterine bleeding, myomas,\npelvic organ prolapse, and pelvic pain. These indications were mutually exclusive\ngiven that only a single ICD diagnosis code is available, and other comorbid\ndiagnoses are limited to prespecified variables. Hysterectomies for malignant\nconditions, emergent cases, and cases with preoperative sepsis or blood transfusion\nwere excluded. Current Procedural Terminology (CPT) codes were used to identify the\nroute of total hysterectomy and to exclude nontotal hysterectomy and procedures\ntypically indicated in the presence of malignancy. Robotic hysterectomies are\nincluded in the laparoscopic hysterectomy group, given that information separating\nrobotic laparoscopy from straight stick laparoscopy is not available in this\ndatabase owing to CPT coding. CPT codes were used to identify concurrent\nadhesiolysis procedures.\nCharacteristics from the NSQIP database included year of procedure, patient\nage, race, ethnicity, body mass index, parity, American Society of Anesthesiologists\nclassification, comorbidities (diabetes, current smoker, hypertension, bleeding\ndisorders, pelvic inflammatory disease), and previous abdominal or pelvic surgery.\nEndometriosis characteristics from the NSQIP hysterectomy targeted data file\nincluded presence of endometriosis and location of endometriosis (bowel, genital\ntract, pelvis, urinary, and other). This resulted in information related to the\nprimary study definition of endometriosis as indicated for hysterectomy (by\npostoperative ICD coding), which was used to separate and compare populations, and a\ndesignation of presence of endometriosis from the NSQIP hysterectomy data file,\nwhich was analyzed as a characteristic of the entire study population. These\ndifferent definitions of endometriosis will be referred to as ICD- vs NSQIP-based\nendometriosis in the manuscript. NSQIP data on endometriosis are collected in a\nsimilar fashion to other characteristic data, via certified surgical clinical\nreviewers who receive standardized training to collect data from medical chart\nreview and direct contact with patients. In addition, audits of inter-rater\nreliability are conducted at participating sites.\nPrimary outcomes included 30-day postoperative major morbidity, minor\nmorbidity, or mortality as classified by the validated Clavien-Dindo scale with\ngrade ≥3 complications defined as major and grade ≤2 complications\ndefined as minor [ 19 ]. Minor complications\nincluded only superficial SSI, urinary tract infection, and transfusion requirement.\nSecondary outcomes included the individual components of major and minor morbidity,\nlength of stay, length of operation, reoperation, and readmission.\nDemographics, patient/gynecologic characteristics, and primary/secondary\noutcomes were summarized for all patients and by hysterectomy indication using\ndescriptive statistics. To investigate the association between continuous\ncharacteristics and hysterectomy indication,  t  tests or Wilcoxon\nrank-sum tests were used. Chi-square tests were used for categorical\ncharacteristics. To investigate the effect of hysterectomy indication on primary\noutcomes, unadjusted and adjusted logistic regression models were used. Covariates\nincluded in the adjusted models were age, race, ethnicity, and surgical route. Odds\nratios (ORs), 95% confidence intervals (CIs), and p values were obtained. Unadjusted\nlogistic regression models were used for binary secondary outcomes, and Wilcoxon\nrank-sum tests were used for continuous secondary outcomes due to skewness of these\ndata. Similar analyses were performed to investigate the effect of endometriosis\nlocation. All reported p values are 2 sided, and a significance level of .05 was\nused. Secondary outcomes were adjusted for multiple comparisons using false\ndiscovery rate correction. Statistical analyses were performed using R (v.3.6.1; R\nCore Team, Vienna, Austria) and SAS (v.9.4; SAS Institute Inc., Cary, NC).\n\nA total of 29 742 people underwent hysterectomy during the study period, of\nwhich 3596 (12.1%) were performed for endometriosis. The demographic characteristics\nof the study population are presented in  Table\n1 . Patients undergoing hysterectomy for endometriosis were significantly\nyounger (36.7% vs 23.6% received hysterectomy before the age of 40 years) and more\nlikely to be nulliparous (23.4% vs 19.8%) than those receiving hysterectomy for\nother indications. Patients were predominantly White (84.1% vs 69.7%; p\n<.001) and less likely to be Hispanic (10.5% vs 13.3%; p <.001).\nPatients with endometriosis were more likely to be current smokers (16.5% vs 15.1%;\np <.029), but were less likely to have comorbid diabetes (5.0% vs 6.5%; p\n<.001) or hypertension (16.5% vs 21.5%; p <.001). They had slightly\nlower body mass index than patients with other benign disease (median 29.6\nkg/m 2  vs median 30.5 kg/m 2 ; p <.001).\nGynecologic characteristics of the study population are presented in  Table 2 . Patients with endometriosis were more\nlikely to undergo any minimally invasive route of surgery (87.6% vs 77.8%) than\npatients with other benign indications, with the majority (66.3% vs 50.8%) being\nlaparoscopic. Patients with endometriosis were much less likely to undergo vaginal\nhysterectomy (5.4% vs 12.6%; p <.001). Overall rates of previous abdominal\n(27.4%) and pelvic surgery (60.4%) were high; however, they were higher for those\nwith hysterectomy for endometriosis (31.2% vs 26.9% [p <.001] and 67.5% vs\n59.5% [p <.001], respectively). A total of 2513 cases included various\nconcurrent lysis of adhesion procedures. Those with endometriosis were more likely\nto undergo concurrent lysis of adhesions with fulguration or excision (9.4% vs 2.0%;\np <.001) and ureterolysis (3.1% vs 0.9%; p <.001) at the time of\nhysterectomy.\nOf all patients in the study population, 18% (n = 5347) had endometriosis at\nthe time of surgery designated by NSQIP rather than by ICD diagnosis. More patients\nreceiving hysterectomy for endometriosis (ICD definition) had designated\nendometriosis by NSQIP than those with other benign disease (64.3% vs 11.6%; p\n<.001), although not all did (35.7% receiving hysterectomy for endometriosis\n(ICD definition) did not have endometriosis by NSQIP designation). Most of these\npatients also had the location of endometriosis noted (n = 5346). Those with\nendometriosis indication for hysterectomy were more likely to have bowel (9.1% vs\n3.5%; p <.001), urinary tract (6.4% vs 3.6%; p <.001), and pelvic\nlesions (57.1% vs 44.7%; p <.001); however, they had similar amounts of\ngenital tract (56.2% vs 57.0%; p = .558) or “other” endometriosis\nlesions (7.5% vs 7.1%; p = .612) as those with other benign indications.\nPrimary outcomes are summarized in  Table\n3 . The overall incidence of major morbidity (3.4%) and mortality (n = 2,\n0.0%) in the study population was rare. Major morbidity was more likely in patients\nundergoing hysterectomy for endometriosis (adjusted OR, 1.25; 95% CI,\n1.02–1.54; p = .033). On analysis of secondary outcomes, deep SSI/\norgan-space infection was also more likely in patients undergoing hysterectomy for\nendometriosis (adjusted OR, 1.42; 95% CI, 1.12–1.80; p = .024), whereas other\nmorbidity outcomes were the same in both populations (with the exception of\ntransfusion being more likely in patients with other benign indications [OR, 0.58;\n95% CI, 0.45–0.75; p <.001]). Overall length of stay (73.1% vs 78.6%\n≥1 day; p = .983) and operative time (median 118.0 minutes [Q1–Q3,\n87.0–157.0] vs median 125.0 minutes [Q1–Q3, 93.0–169.0]; p\n<.001) were clinically similar in patients undergoing hysterectomy for\nendometriosis vs other benign disease.\nOutcomes by NSQIP designated location of endometriosis regardless of ICD\nindication for hysterectomy are shown in  Fig. 1 \nand in  Supplemental Table\n2 . Length of stay was clinically similar for patients undergoing hysterectomy\nwith endometriosis lesions of the bowel (82.1%; ≥1 day) vs those with lesions\nof the urinary tract (69.3%; ≥1 day) or genital tract, pelvic, or other\nlesions (75.1% ≥1 day; p =.202). Operating time was increased for patients\nwith bowel lesions (median 163.0 minutes [Q1–Q3, 119.2–223.0]) vs\nurinary tract (median 129.0 minutes [Q1–Q3, 93.5–182.0]) or other\nlesions (median 120.0 minutes [Q1–Q3, 90.0–164.0]; p = .001).\n\nThis represents one of the largest studies comparing severe postoperative\nmorbidity (Clavien-Dindo grade ≥3) after hysterectomy for patients with\nendometriosis vs other benign disease. Consistent with previous findings, we\nidentified that patients undergoing hysterectomy for endometriosis were at higher\nodds of major morbidity (3.8%; adjusted OR, 1.25), likely driven by increased risk\nof deep SSI/organ-space infection (2.3%; OR, 1.42), despite the use of minimally\ninvasive approach in most cases (87.6%). The minority of patients with endometriosis\nlesions of the bowel (5.9%) were at particularly high risk of major morbidity (OR,\n1.65) and deep SSI/organ-space infection (OR, 2.18) and sepsis (OR, 5.94). Despite\nthese increased risks, no other differences were found including presence of any\nother type of infection, wound disruption, thromboembolism, single organ failure,\nreoperation, readmission, length of stay, or length of operation.\nPrevious large cohort studies comparing complication rates by route of\nhysterectomy sometimes include risks in the setting of endometriosis. These data are\nconflicting on the significance of endometriosis and risk of morbidity and are\nlikely outdated (most patients undergoing abdominal hysterectomy) [ 13 , 20 , 21 ]. Recent studies have evaluated\nperioperative outcomes for various minimally invasive procedures for endometriosis\nin patients with predominantly American Society for Reproductive Medicine stage III\nand IV disease [ 7 , 8 , 14 , 16 , 17 , 22 – 24 ]. Few studies evaluate definitive surgery with\nhysterectomy [ 15 ]. Although the definition of\nmorbidity varied, major morbidity ranged from 1.5% [ 22 ] up to 9.3% to 11.8% [ 7 , 16 , 24 ]\nin patients with any concurrent rectal procedure or up to 16% for patients with\nureteral nodules [ 8 ]. Most studies identified\na major morbidity rate of 4.5% to 5.4%, slightly higher than in our population\n(3.8%) [ 7 , 14 , 17 , 23 ]. The largest prospective cohort study by Byrne et al\n[ 25 ] (n = 5162) of patients with deep\nrectovaginal endometriosis primarily focused on pain and quality of life measures\npostoperatively, but did identify a complication rate of 6.8%. These studies were\nperformed with smaller numbers of patients (n = 80−568) in single-site\nhigh-referral centers, where procedures were often performed by high-volume,\nfellowship-trained surgeons. Our cohort more similarly represents the general\npopulation of patients undergoing hysterectomy with nonspecialized gynecologists,\nlikely with less severe disease than those at referral centers. Although in our\nstudy morbidity was indeed greater for patients with endometriosis, there was no\ndifference in other important outcomes such as readmission and, surprisingly, length\nof operation. Similarly, despite risk of deep SSI, risk of wound disruption or\nreoperation was not increased. Based on our findings, we agree with Vallée et\nal [ 17 ] that patients with endometriosis\nwithout involvement of the digestive or urinary tract generally have an overall low\nrisk of morbidity and may undergo hysterectomy safely. Special attention should\nfocus on identifying patients at risk of higher stage endometriosis preoperatively\nand monitoring for SSI within the first postoperative month. Furthermore, referral\nto high volume surgeons should be considered for patients at risk of higher stage\nendometriosis with digestive or urinary tract involvement.\nStrengths of this study include the large national data set used, increasing\ngeneralizability of results. The NSQIP data set also allows detection of infrequent\nsignificant morbidity outcomes that may not be captured by single institution\nstudies. However, the large size of the population cohort and multiple comparisons\ndoes increase the risk of type I errors; false discovery rate correction was used to\nadjust for this risk. Postoperative outcomes within the NSQIP database are limited\nto 30 days and NSQIP participating institutions. In addition, information related to\nrobotic surgery separate from laparoscopy and surgeon training as a minimally\ninvasive gynecologist is not available. There are several other limitations of this\ndata set, including its retrospective design, information limited to prespecified\ndiagnosis and procedure coding, and a lack of insight into details of NSQIP coding\nof endometriosis-related variables. Discrepancies between ICD and NSQIP designated\nendometriosis could be caused by several factors: true presence of endometriosis in\npatients undergoing hysterectomy for other primary disease, endometriosis not\npreviously diagnosed but present at the time of surgery, and inaccuracy of ICD\ncoding, NSQIP coding, or both. Neither the ICD coding nor the NSQIP designation of\nendometriosis includes a pathology-proven diagnosis, and information on American\nSociety for Reproductive Medicine endometriosis staging is not available. Specific\ndetails of how the definition of deep incisional or organ-space infection was met\nwere not available. Improvements to ICD and CPT coding of endometriosis will improve\nlarger population-based study of this disease. Future study may investigate risk\nfactors for deep SSI and morbidity in patients undergoing definitive surgery for\nendometriosis and explore the relationship between location of endometriosis lesions\nor concurrent procedures and other complications such as organ injury and repair\nusing a large data set.\nIn conclusion, this retrospective study of morbidity after hysterectomy for\nbenign disease using a large national data base in the United States identified\npatients with endometriosis to be at risk of major morbidity likely driven by deep\nSSI/organ-space infection compared with their peers. Those with endometriosis\nlesions of the bowel were at particularly high risk. Overall risk of morbidity was\nlow in the general population, and other postoperative complications were the same\nbetween groups. These results confirm previous findings that patients with\nendometriosis may be at higher risk of postoperative complications; however,\nsignificant morbidity is rare, and hysterectomy among the general population\nregardless of indication is safe.","source_license":"CC0","license_restricted":false}