Robot-assisted approach to cervical cancer (RACC): an international multi-center, open-label randomized controlled trial.

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 (α) of 5% and a power (1-ß) 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. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT03719547).

International validation of Enhanced Recovery After Surgery Society guidelines on enhanced recovery for gynecologic surgery.

BACKGROUND: Enhanced Recovery After Surgery Society publishes guidelines on perioperative care, but these guidelines should be validated prospectively. OBJECTIVE: To evaluate the association between compliance with Enhanced Recovery After Surgery Gynecologic/Oncology guideline elements and postoperative outcomes in an international cohort. STUDY DESIGN: The study comprised 2101 patients undergoing elective gynecologic/oncology surgery between January 2011 and November 2017 in 10 hospitals across Canada, the United States, and Europe. Patient demographics, surgical/anesthesia details, and Enhanced Recovery After Surgery protocol compliance elements (pre-, intra-, and postoperative phases) were entered into the Enhanced Recovery After Surgery Interactive Audit System. Surgical complexity was stratified according to the Aletti scoring system (low vs 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 vs minimally invasive), intraoperative blood loss, hospital, and Enhanced Recovery After Surgery 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 included a median age 56 years, 35.5% obese, 15% smokers, and 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 Enhanced Recovery After Surgery guideline score was associated with 8% (IRR, 0.92; 95% confidence interval, 0.90-0.95; P<.001) decrease in days in hospital among low-complexity, and 12% (IRR, 0.88; 95% confidence interval, 0.82-0.93; P<.001) decrease among patients with medium/high-complexity scores. For every unit increase in Enhanced Recovery After Surgery guideline score, the odds of total complications were estimated to be 12% lower (P<.05) among low-complexity patients. CONCLUSION: Audit of surgical practices demonstrates that improved compliance with Enhanced Recovery After Surgery Gynecologic/Oncology guidelines is associated with an improvement in clinical outcomes, including length of stay, highlighting the importance of Enhanced Recovery After Surgery implementation.

Guidelines for perioperative care in gynecologic/oncology: Enhanced Recovery After Surgery (ERAS) Society recommendations-2019 update.

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.

Female sex hormones in relation to insulin resistance after hysterectomy: A pilot study.

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.

Guidelines for perioperative care in gynecologic/oncology: Enhanced Recovery After Surgery (ERAS) Society recommendations - 2019 update

Enhanced Recovery After Surgery (ERAS) is now firmly established as a global surgical quality improvement initiative that results in both clinical improvements1 and cost benefits to the healthcare system.2 ERAS guidelines are based on the highest quality evidence available and as such require updating on a regular basis.3 The ERAS Gynecologic/Oncology guidelines4 5 were first published in February 2016. This article represents the joint efforts of the ERAS® Society (www.erassociety.org) and authors from the international ERAS Gynecology chapters to present an updated consensus review of perioperative care for gynecologic/oncology surgery based on best current evidence.

Metabolic and inflammatory responses and subsequent recovery in robotic versus abdominal hysterectomy: A randomised controlled study.

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.

Enhanced Recovery after Surgery Protocol in Abdominal Hysterectomies for Malignant versus Benign Disease.

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), reoperations (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.

Implementing a structured Enhanced Recovery After Surgery (ERAS) protocol reduces length of stay after abdominal hysterectomy.

OBJECTIVE: To study the effects of introducing an Enhanced Recovery After Surgery (ERAS) protocol, modified for gynecological surgery, on length of stay and complications following abdominal hysterectomy. DESIGN: Observational study. SETTING: Department of Obstetrics and Gynecology, Örebro University Hospital, Sweden. POPULATION: Eighty-five patients undergoing abdominal hysterectomy for benign or malignant indications between January and December 2012, with or without salpingo-oophorectomy. Outcomes were compared with all consecutive patients who had undergone the same surgery from January to December 2011, immediately before establishing the ERAS protocol (n = 120). METHODS: The ERAS protocol was initiated in January 2012 as part of a targeted implementation program. Data were extracted from patient records and from a specific database. MAIN OUTCOME MEASURES: Length of stay and the proportion of patients achieving target length of stay (2 days). RESULTS: Length of stay was significantly reduced in the study population after introducing the ERAS protocol from a mean of 2.6 (SD 1.1) days to a mean of 2.3 (SD 1.2) days (p = 0.011). The proportion of patients discharged at 2 days was significantly increased from 56% pre-ERAS to 73% after ERAS (p = 0.012). No differences were found in complications (5% vs. 3.5% in primary stay, 12% vs. 15% within 30 days after discharge), reoperations (2% vs. 1%) or readmission (4% vs. 4%). CONCLUSIONS: Introducing the ERAS protocol for abdominal hysterectomy reduced length of stay without increasing complications or readmissions.

Changes in dentofacial morphology after adeno-/tonsillectomy in young children with obstructive sleep apnoea--a 5-year follow-up study.

The aim of this study was to compare a number of dentofacial variables and airway space in children suffering from obstructive sleep apnoea (OSA) syndrome with the corresponding variables in control children exhibiting a normal breathing pattern, to study the development of these variables prospectively over a 5-year-period following treatment for OSA, and to compare the recorded changes with the corresponding changes occurring in the controls. The subjects were 17 children (10 boys and 7 girls, mean age 5.6 years) diagnosed with OSA syndrome. The treatment for the OSA was adeno-/tonsillectomy. The control group comprised 17 age- and gender-matched children (mean age 5.8 years) without breathing problems. Lateral cephalograms were taken of the OSA children at baseline and then at 1, 3, and 5 years post-treatment. The control records comprised registrations at baseline and then after 1 and 5 years. In comparison with the controls, the OSA children exhibited a more posteriorly inclined mandible (P < 0.05), a more anteriorly inclined maxilla (P < 0.001), a greater lower anterior face height (P < 0.01), a shorter anterior cranial base (P < 0.01), retroclined upper and lower incisors (P < 0.05 and P < 0.01, respectively), reduced airway space (P < 0.05 and P < 0.01), and a less pronounced nose (P < 0.05). At 5 years post-treatment, there were no statistically significant differences between the groups except for the lengths of the anterior cranial base and the nose which were still shorter (P < 0.05) in the patient group. OSA in young children has an unfavourable effect on the development of several dental and facial components. However, if OSA is diagnosed and treated at an early age, an almost complete normalization of dentofacial morphology may be achieved.