Maureen A. Lemens

Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer

OBJECTIVE Preoperative thrombocytosis has been implicated as a negative prognostic marker for epithelial ovarian cancer (EOC). We assessed whether thrombocytosis is an independent risk factor for EOC recurrence and death. METHODS Perioperative patient characteristics and process-of-care variables (National Surgical Quality Improvement Program (NSQIP)-defined) were retrospectively abstracted from 587 women who underwent EOC staging between 1/2/03-12/29/08. Thrombocytosis was defined as platelet count > 450 × 10(9)/L. Disease-free survival (DFS) and overall survival (OS) were determined using Kaplan-Meier methods. Associations were evaluated with Cox proportional hazards regression and hazard ratios (HR). RESULTS The incidence of preoperative thrombocytosis was 22.3%. DFS was 70.8% and 36.0% at 1 and 3 years. OS was 83.3% and 54.3% at 1 and 3 years. Ascites, lower hemoglobin, advanced disease, and receipt of perioperative packed red blood cell transfusion were independently associated with thrombocytosis. Older age and the presence of coronary artery disease were associated with lower likelihood of thrombocytosis. Overall, thrombocytosis was an independent predictor of increased risk of recurrence. Among early stage (I/II) cases, there was a 5-fold increase in the risk of death and nearly 8-fold risk of disease recurrence independently associated with thrombocytosis. CONCLUSION Preoperative thrombocytosis portends worse DFS in EOC. In early stage disease, thrombocytosis is a potent predictor of worse DFS and OS and further assessment of the impact of circulating platelet-derived factors on EOC survival is warranted. Thrombocytosis is also associated with extensive initial disease burden, measurable residual disease, and postoperative sequelae. Preoperative platelet levels may have value in primary cytoreduction counseling.

Incidence of and risk factors for postoperative ileus in women undergoing primary staging and debulking for epithelial ovarian carcinoma

OBJECTIVE Thorough primary cytoreduction for epithelial ovarian carcinoma (EOC) improves survival. The incidence of postoperative ileus (POI) in these patients may be underreported because of varying POI definitions and the evolving, increasingly complex contemporary surgical approach to EOC. We sought to determine the current incidence of POI and its risk factors in women undergoing debulking and staging for EOC. METHODS We retrospectively identified the records of women who underwent primary staging and cytoreduction for EOC between 2003 and 2008. POI was defined as a surgeons diagnosis of POI, return to nothing-by-mouth status, or reinsertion of a nasogastric tube. Perioperative patient characteristics and process-of-care variables were analyzed. Univariate analyses were used to identify POI risk factors; variables with P ≤.20 were included in multivariate analysis. RESULTS Among 587 women identified, the overall incidence of POI was 30.3% (25.9% without bowel resection, 38.5% with bowel resection; P=.002). Preoperative thrombocytosis, involvement of bowel mesentery with carcinoma, and perioperative red blood cell transfusion were independently associated with increased POI. Postoperative ibuprofen use was associated with decreased POI risk. Women with POI had a longer length of stay (median, 11 vs 6 days) and increased time to recovery of the upper (7.5 vs 4 days) and lower (4 vs 3 days) gastrointestinal tract (P<.001 for each). CONCLUSIONS The rate of POI is substantial among women undergoing staging and cytoreduction for EOC and is associated with increased length of stay. Modifiable risk factors may include transfusion and postoperative ibuprofen use. Alternative interventions to decrease POI are needed.

Surgical site infection after primary surgery for epithelial ovarian cancer: Predictors and impact on survival

OBJECTIVE Surgical site infection (SSI) following epithelial ovarian cancer (EOC) primary surgery (PS) occurs in 10-15% of women. Perioperative factors associated with SSI and impact of SSI on survival were determined. METHODS EOC cases that underwent PS from 1/2/2003 to 12/30/2011 were retrospectively reviewed. SSIs were defined according to ACS NSQIP. Logistic regression models were fit to identify factors associated with SSI. Cox proportional hazards models were utilized to evaluate the association of patient and perioperative characteristics with overall survival (OS) and disease-free survival (DFS). RESULTS Among 888 cases, 96 (10.8%) developed SSI: 32 superficial, 2 deep, and 62 organ/space. Factors independently associated with superficial SSI were increasing BMI (odds ratio 1.41 [95% confidence interval, 1.12, 1.76] per 5kg/m(2)), increasing operative time (1.24 [1.02, 1.50] per hour), and advanced stage (III/IV) (10.22 [1.37, 76.20]). Factors independently associated with organ/space SSI were history of gastroesophageal reflux disease (2.13 [1.23, 3.71]), surgical complexity (intermediate 3.11 [1.02, 9.49]; high 8.07 [2.60, 25.09]; referent: low), and residual disease (RD) (measureable ≤1cm 1.77 [0.96, 3.27]; suboptimal >1cm (3.36 [1.48, 7.61]; referent: microscopic). Occurrence of superficial (hazard ratio 1.69 [1.12, 2.57]) or organ/space (1.46 [1.07, 2.00]) SSI was independently associated with worse OS. SSI occurrence was not independently associated with DFS. CONCLUSIONS SSI after PS is associated with decreased OS. Most risk factors for SSI are not modifiable. Alternative measures to lower rates of SSIs are needed as this may improve OS. Preoperative identification of SSI risk factors may assist in risk-assessment and operative planning.

Incidence and predictors of venous thromboembolism after debulking surgery for epithelial ovarian cancer.

Objective The aim of this study was to determine the incidence and the risk factors of venous thromboembolism (VTE) within 30 days after primary surgery for epithelial ovarian cancer (EOC). Methods In a historical cohort study, we estimated the postoperative 30-day cumulative incidence of VTE among consecutive Mayo Clinic patients undergoing primary cytoreduction for EOC between January 2, 2003, and December 29, 2008. We tested perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program, >130 variables) as potential predictors of postoperative VTE using the Cox proportional hazards modeling. Results Among 569 cases of primary EOC cytoreduction and/or staging and no recent VTE, 35 developed symptomatic VTE within 30 days after surgery (cumulative incidence = 6.5%; 95% confidence interval, 4.4%–8.6%). Within the cohort, 95 (16.7%) received graduated compression stockings (GCSs), 367 (64.5%) had sequential compression devices + GCSs, and 69 (12.1%) had sequential compression devices + GCSs + postoperative heparin, with VTE rates of 1.1%, 7.4%, and 5.8%, respectively (P = 0.07, χ2 test). The remaining 38 (6.7%) received various other chemical and mechanical prophylaxis regimens. In the multivariate analysis, current or past tobacco smoking, longer hospital stay, and a remote history of VTE significantly increased the risk for postoperative VTE. Conclusions Venous thromboembolism is a substantial postoperative complication among women with EOC, and the high cumulative rate of VTE within 30 days after primary surgery suggests that a more aggressive strategy is needed for VTE prevention. In addition, because longer hospital stay is independently associated with a higher risk for VTE, methods to decrease length of stay and minimize factors that contribute to prolonged hospitalization are warranted.

The impact of perioperative packed red blood cell transfusion on survival in epithelial ovarian cancer

Objective Perioperative packed red blood cell transfusion (PRBCT) has been implicated as a negative prognostic marker in surgical oncology. There is a paucity of evidence on the impact of PRBCT on outcomes in epithelial ovarian cancer (EOC). We assessed whether PRBCT is an independent risk factor of recurrence and death from EOC. Methods Perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program) were retrospectively abstracted from 587 women who underwent primary EOC staging between January 2, 2003, and December 29, 2008. Associations with receipt of PRBCT were evaluated using univariate logistic regression models. The associations between receipt of PRBCT and disease-free survival and overall survival were evaluated using multivariable Cox proportional hazards models and using propensity score matching and stratification, respectively. Results The rate of PRBCT was 77.0%. The mean ± SD units transfused was 4.1 ± 3.1 U. In the univariate analysis, receipt of PRBCT was significantly associated with older age, advanced stage (≥IIIA), undergoing splenectomy, higher surgical complexity, serous histologic diagnosis, greater estimated blood loss, longer operating time, the presence of residual disease, and lower preoperative albumin and hemoglobin. Perioperative packed red blood cell transfusion was not associated with an increased risk for recurrence or death, in an analysis adjusting for other risk factors in a multivariable model or in an analysis using propensity score matching or stratification to control for differences between the patients with and without PRBCT. Conclusions Perioperative packed red blood cell transfusion does not seem to be directly associated with recurrence and death in EOC. However, lower preoperative hemoglobin was associated with a higher risk for recurrence. The need for PRBCT seems to be a stronger prognostic indicator than the receipt of PRBCT.

Burch Retropubic Urethropexy Compared With Midurethral Sling With Concurrent Sacrocolpopexy: A Randomized Controlled Trial.

OBJECTIVE: To compare efficacy and safety of retropubic Burch urethropexy and a midurethral sling in women with stress urinary incontinence (SUI) undergoing concomitant pelvic floor repair with sacrocolpopexy. METHODS: Women were randomly assigned to Burch retropubic urethropexy (n=56) or retropubic midurethral sling (n=57) through dynamic allocation balancing age, body mass index, history of prior incontinence surgery, intrinsic sphincter deficiency, preoperative incontinence diagnosis, and prolapse stage. Overall and stress-specific continence primary outcomes were ascertained with validated questionnaires and a blinded cough stress test. RESULTS: Enrollment was June 1, 2009, through August 31, 2013. At 6 months, no difference was found in overall (29 midurethral sling [51%] compared with 23 Burch [41%]; P=.30) (odds ratio [OR] 1.49, 95% confidence interval [CI] 0.71–3.13) or stress-specific continence rates (42 midurethral sling [74%] compared with 32 Burch [57%]; P=.06) (OR 2.10, 95% CI 0.95–4.64) between groups. However, the midurethral sling group reported greater satisfaction (78% compared with 57%; P=.04) and were more likely to report successful surgery for SUI (71% compared with 50%; P=.04) and to resolve pre-existing urgency incontinence (72% compared with 41%; P=.03). No difference was found in patient global impression of severity or symptom improvement, complication rates, or mesh exposures. CONCLUSION: There was no difference in overall or stress-specific continence rates between midurethral sling and Burch urethropexy groups at 6 months. However, the midurethral sling group reported better patient-centered secondary outcomes.

FIRSTT Study: Randomized Controlled Trial of Uterine Artery Embolization Versus Focused Ultrasound

Background: Uterine leiomyomas (fibroid tumors) cause considerable symptoms in 30–50% of women and are the leading cause of hysterectomy in the United States. Women with uterine fibroid tumors often seek uterine‐preserving treatments, but comparative effectiveness trials are lacking. Objective: The purpose of this study was to report treatment effectiveness and ovarian function after uterine artery embolization vs magnetic resonance imaging‐guided focused ultrasound surgery from the Fibroid Interventions: Reducing Symptoms Today and Tomorrow study. Study Design: The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study, which is a randomized controlled trial of uterine artery embolization vs magnetic resonance imaging‐guided focused ultrasound surgery, enrolled premenopausal women with symptomatic uterine fibroid tumors; women who declined randomization were enrolled in a parallel observational cohort. A comprehensive cohort design was used for outcomes analysis. Our target enrollment was 220 women, of which we achieved 41% (n=91) in the randomized and parallel arms of the trial. Primary outcome was reintervention for uterine fibroid tumors within 36 months. Secondary outcomes were change in serum anti‐Müllerian hormone levels and standardized measures of fibroid symptoms, quality of life, pain, and sexual function. Results: From 2010–2014, 83 women (mean age, 44.4 years) were treated in the comprehensive cohort design (43 for magnetic resonance imaging‐guided focused ultrasound surgery [27 randomized]; 40 for uterine artery embolization [22 randomized]); baseline clinical and uterine characteristics were similar between treatment arms, except for higher fibroid load in the uterine artery embolization arm. The risk of reintervention was higher with magnetic resonance imaging‐guided focused ultrasound surgery than uterine artery embolization (hazard ratio, 2.81; 95% confidence interval, 1.01–7.79). Uterine artery embolization showed a significantly greater absolute decrease in anti‐Müllerian hormone levels at 24 months compared with magnetic resonance imaging‐guided focused ultrasound surgery. Quality of life and pain scores improved in both arms but to a greater extent in the uterine artery embolization arm. Higher pretreatment anti‐Müllerian hormone level and younger age at treatment increased the overall risk of reintervention. Conclusion: Our study demonstrates a lower reintervention rate and greater improvement in symptoms after uterine artery embolization, although some of the effectiveness may come through impairment of ovarian reserve. Both pretreatment anti‐Müllerian hormone level and age are associated with risk of reintervention. Clinical Trial Registration Number: NCT00995878, clinicaltrials.gov

Medical therapy versus radiofrequency endometrial ablation in the initial treatment of heavy menstrual bleeding (iTOM Trial): A clinical and economic analysis

Background Radiofrequency endometrial ablation (REA) is currently a second line treatment in women with heavy menstrual bleeding (MHB) if medical therapy (MTP) is contraindicated or unsatisfactory. Our objective is to compare the effectiveness and cost burden of MTP and REA in the initial treatment of HMB. Methods We performed a randomized trial at Mayo Clinic Rochester, Minnesota. The planned sample size was 60 patients per arm. A total of 67 women with HMB were randomly allocated to receive oral contraceptive pills (Nordette ®) or Naproxen (Naprosyn®) (n = 33) or REA (n = 34). Primary 12-month outcome measures included menstrual blood loss using pictorial blood loss assessment chart (PBLAC), patients’ satisfaction, and Menorrhagia Multi-Attribute Scale (MMAS). Secondary outcomes were total costs including direct medical and indirect costs associated with healthcare use, patient out-of-pocket costs, and lost work days and activity limitations over 12 months. Results Compared to MTP arm, women who received REA had a significantly lower PBLAC score (median [Interquartile range, IQR]: 0 [0–4] vs. 15 [0–131], p = 0.003), higher satisfaction rates (96.8%vs.63.2%, p = 0.003) and higher MMAS (median [IQR]: 100 [100–100] vs. 100 [87–100], p = 0.12) at 12 months. Direct medical costs were higher for REA (

Fibroid interventions: reducing symptoms today and tomorrow: extending generalizability by using a comprehensive cohort design with a randomized controlled trial.

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Fetoscopic Therapy for Severe Pulmonary Hypoplasia in Congenital Diaphragmatic Hernia: A First in Prenatal Regenerative Medicine at Mayo Clinic

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