To Örebro University

BACKGROUND & AIM: Surgery causes development of insulin resistance. Women undergoing hysterectomy have different female sex hormonal status, ranging from premenopausal to postmenopausal. The aim of the study was to explore the relation between the female sex hormones and insulin resistance (IR%) after hysterectomy.

METHODS: A secondary analysis from a randomised controlled single-centre study at the Department of Obstetrics and Gynaecology, Örebro University Hospital, Sweden. Twenty women were randomised to robot-assisted laparoscopic or abdominal hysterectomy. Blood were drawn before and after surgery for measurement of oestrogens, progesterone, and gonadotropins alongside determination of insulin sensitivity using the hyperinsulinemic normolycaemic clamp.

RESULTS: Female sex hormonal status was not correlated to insulin sensitivity before operation. Premenopausal women developed more IR% than postmenopausal women (p = 0.012). Premenopausal women also showed a significant decrease in absolute levels of oestradiol (E2) (p = 0.016), and the relative decrease in E2 from preoperative to postoperative values (E2%) was significantly higher (p = 0.001). There was a significant positive correlation in the entire study population between E2% and IR% (r = 0.72, p = 0.001, r² 0.51) that remained when adjusted for age (p = 0.028), BMI (p = 0.001), and preoperative insulin sensitivity (p = 0.011) separately.

CONCLUSIONS: Premenopausal women developed a higher degree of postoperative insulin resistance that was associated with a parallel relative change in oestradiol levels compared with the postmenopausal women. It remains unclear whether these are independent phenomena in the overall stress response or whether a causal relationship exists.

BACKGROUND: This is the first updated Enhanced Recovery After Surgery (ERAS) Society guideline presenting a consensus for optimal perioperative care in gynecologic/oncology surgery.

METHODS: A database search of publications using Embase and PubMed was performed. Studies on each item within the ERAS gynecologic/oncology protocol were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.

RESULTS: All recommendations on ERAS protocol items are based on best available evidence. The level of evidence for each item is presented accordingly.

CONCLUSIONS: The updated evidence base and recommendation for items within the ERAS gynecologic/oncology perioperative care pathway are presented by the ERAS® Society in this consensus review.

BACKGROUND: The Enhanced Recovery After Surgery (ERAS) Society publishes guidelines on perioperative care, but these guidelines should be validated prospectively.

OBJECTIVES: To evaluate the association between compliance to ERAS Gynecologic/Oncology guideline elements and postoperative outcomes in an international cohort.

STUDY DESIGN: The study was comprised of 2,101 patients undergoing elective gynecologic/oncology surgery between January 2011 - November 2017 in 10 hospitals across Canada, the United States and Europe. Patient demographics, surgical/anesthesia details and ERAS protocol compliance elements (pre-, intra- and post-operative phases) were entered into the ERAS Interactive Audit System. Surgical complexity was stratified according to the Aletti scoring system (low versus medium/high). The following covariates were accounted for in the analysis: age, Body Mass Index, smoking status, presence of diabetes, American Society of Anesthesiologists class, International Federation of Gynecology and Obstetrics stage, preoperative chemotherapy, radiotherapy, operating time, surgical approach (open versus minimally invasive), intra-operative blood loss, hospital and ERAS implementation status. The primary end-points were primary hospital length of stay and complications. Negative binomial regression was used to model length of stay, and logistic regression to model complications, as a function of compliance score and covariates.

RESULTS: Patient demographics: median age 56 years, 35.5% obese,15% smokers, 26.7% American Society of Anesthesiologists Class III-IV. Final diagnosis was malignant in 49% of patients. Laparotomy was used in 75.9% of cases, and the remainder minimally invasive surgery. The majority of cases (86%) were of low complexity (Aletti score ≤ 3). In patients with ovarian cancer, 69.5% had a medium/high complexity surgery (Aletti score 4-11). Median length of stay was 2 days in the low- and 5 days in the medium/high-complexity group. Every unit increase in ERAS guideline score was associated with 8% (IRR: 0.92 (95% CI: 0.90 - 0.95; p<0.001)) decrease in days in hospital among low-complexity, and 12% (IRR: 0.88 (95% CI: 0.82 - 0.93; p<0.001) decrease among patients with medium/high complexity scores. For every unit increase in ERAS guideline score, the odds of total complications were estimated to be 12% lower (p<0.05) among low-complexity patients.

CONCLUSION: Audit of surgical practices demonstrates that improved compliance with ERAS Gynecologic/Oncology guidelines is associated with an improvement in clinical outcomes, including length of stay, highlighting the importance of ERAS implementation.

Background: Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival.

Primary Objective: To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy.

Study Hypothesis: Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes.

Trial Design: Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden.

Major Inclusion/Exclusion Criteria: Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years.

Primary Endpoint: Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer.

Sample Size: The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (alpha) of 5% and a power (1-beta) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients.

Estimated Dates for Completing Accrual and Presenting Results: Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter.

BACKGROUND & AIMS: Surgery causes inflammatory and metabolic responses in the body. The aim of the study was to investigate whether robotic-assisted total laparoscopic hysterectomy induces less insulin resistance than abdominal hysterectomy, and to compare inflammatory response and clinical recovery between the two techniques.

METHODS: A randomised controlled study at the Department of Obstetrics and Gynaecology, Örebro University Hospital, Sweden. Twenty women scheduled for a planned total hysterectomy with or without salpingo-oophorectomy between October 2014 and May 2015, were randomly allocated to robotic-assisted total laparoscopic hysterectomy or abdominal hysterectomy. Insulin resistance after surgery was measured by the hyperinsulinemic normoglycaemic clamp method, inflammatory response measured in blood samples, and clinical recovery outcomes registered.

RESULTS: There were no differences in development of insulin resistance between the robotic group and the abdominal group (mean ± SD: 39% ± 22 vs. 40% ± 19; p = 0.948). The robotic group had a significantly shorter hospital stay (median 1 vs. 2 days; p = 0.005). Inflammatory reaction differed; in comparison to the robotic group, the abdominal group showed significantly higher increases in serum interleukin 6 levels, white blood cell count and cortisol from preoperative values to postoperative peak values.

CONCLUSIONS: Robotic laparoscopic surgery reduced inflammatory responses and recovery time, but these changes were not accompanied by decreased insulin resistance.

CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov Identifier no NCT02291406.

Objectives: To study recovery after hysterectomy under Enhanced Recovery After Surgery (ERAS) care, and in relation to different operation techniques.

Materials and Methods: An observational study was conducted comparing 85 patients undergoing hysterectomy with ERAS care to 120 patients immediately before establishing ERAS. In a prospective cohort study of 121 consecutive patients undergoing hysterectomy, the outcome was compared for patients with malignant versus benign indications. The main outcome measure was length of stay (LOS). A randomised controlled trial (RCT) of 20 women scheduled for hysterectomy compared robot-assisted laparoscopic with abdominal hysterectomy in terms of the development of insulin resistance, inflammatory reactions, and clinical recovery, and examined the relation to hormonal status. All studies were conducted in 2011--2015, at the Department of Obstetrics and Gynaecology, Örebro University Hospital, Sweden.

Results: Implementation of a structured ERAS protocol significantly reduced LOS compared to non-ERAS care. The effect was similar between patients with malignant and benign indications for surgery. No difference in complications was found. There was no difference in development of insulin resistance between robotic and abdominal technique, but clinical outcomes and inflammatory responses significantly favoured robot-assisted hysterectomy. Female sex hormone status was associated with the development of insulin resistance.

Conclusions: Recovery after hysterectomy can be influenced. ERAS care seems to be effective and safe. Clinical outcome can also be influenced by operational technique. Hysterectomy triggers a stress reaction in both the metabolic and the inflammatory system. It remains unclear why the reduced inflammatory reaction and favourable clinical outcome in robotic surgery were not mirrored by less insulin resistance. This could not be explained by female sex hormone status.

Background: The enhanced recovery after surgery (ERAS) protocol combines unimodal evidence-based interventions aiming to enhance recovery after surgery and reduce length of stay (LOS). We introduced an ERAS protocol in gynecological surgery and compared outcomes after hysterectomies performed for malignant vs. benign indications.

Methods: This prospective cohort study was conducted at the Department of Obstetrics and Gynecology, Örebro University Hospital, Sweden, among 121 consecutive patients undergoing abdominal hysterectomy and salpingo-oophorectomy for malignant (n = 40) or benign (n = 81) indications between 2012 and 2014. Clinical data were prospectively collected and extracted from the patient records and from a specific database. The primary outcomes were LOS and proportion of patients achieving target LOS (2 days).

Results: Patients operated for malignant vs. benign disease did not differ significantly in terms of LOS (2 (1-5) vs. 2 (1-11) days; p = 0.505), proportion discharged at target LOS (62 vs. 69%; p = 0.465; OR 0.74, 95% CI 0.3-1.6), complications (2 vs. 7% in primary stay, 8 vs. 11% within 30 days after discharge), re operations (0 vs. 2%), or readmissions (2 vs. 1%).

Conclusion: The ERAS protocol may be equally applicable to patients undergoing hysterectomy either for a malignant or for a benign disease.