Long-Term Health Consequences After Ovarian Removal at Benign Hysterectomy : A Nationwide Cohort Study.

BACKGROUND: More evidence is needed to substantiate current recommendations about removing ovaries during hysterectomy for benign conditions. OBJECTIVE: To compare long-term outcomes in women with and without bilateral salpingo-oophorectomy (BSO) during hysterectomy for benign conditions. DESIGN: Emulated target trial using data from a population-based cohort. SETTING: Women in Denmark aged 20 years or older during 1977 to 2017. PARTICIPANTS: 142 985 women with hysterectomy for a benign condition, 22 974 with BSO and 120 011 without. INTERVENTION: Benign hysterectomy with or without BSO. MEASUREMENTS: The primary outcomes were overall hospitalization for cardiovascular disease (CVD), overall cancer incidence, and all-cause mortality through December 2018. RESULTS: Compared with women without BSO, women with BSO who were younger than 45 years at surgery had a higher 10-year cumulative risk for hospitalization for CVD (risk difference [RD], 1.19 percentage points [95% CI, 0.09 to 2.43 percentage points]). Women with BSO had a higher 10-year cumulative risk for cancer for ages 45 to 54 years (RD, 0.73 percentage point [CI, 0.05 to 1.38 percentage points]), 55 to 64 years (RD, 1.92 percentage points [CI, 0.69 to 3.25 percentage points]), and 65 years or older (RD, 2.54 percentage points [CI, 0.91 to 4.25 percentage points]). Women with BSO had higher 10-year mortality in all age groups, although the differences were statistically significant only for ages 45 to 54 years (RD, 0.79 percentage point [CI, 0.27 to 1.30 percentage points]). The mortality at 20 years was inconsistent with that at 10 years in women aged 65 years or older. LIMITATION: Age was a proxy for menopausal status. CONCLUSION: The authors find that these results support current recommendations for conserving ovaries in premenopausal women without a high risk for ovarian cancer and suggest a cautious approach in postmenopausal women. PRIMARY FUNDING SOURCE: The Danish Cancer Society's Scientific Committee and the Mermaid Project.

An autologous blood-derived patch as a hemostatic agent: evidence from thromboelastography experiments and a porcine liver punch biopsy model.

Perioperative bleeding is a common complication in surgeries that increases morbidity, risk of mortality, and leads to increased socioeconomic costs. In this study we investigated a blood-derived autologous combined leukocyte, platelet, and fibrin patch as a new means of activating coagulation and maintaining hemostasis in a surgical setting. We evaluated the effects of an extract derived from the patch on the clotting of human blood in vitro, using thromboelastography (TEG). The autologous blood-derived patch activated hemostasis, seen as a reduced mean activation time compared to both non-activated controls, kaolin-activated samples, and fibrinogen/thrombin-patch-activated samples. The accelerated clotting was reproducible and did not compromise the quality or stability of the resulting blood clot. We also evaluated the patch in vivo in a porcine liver punch biopsy model. In this surgical model we saw 100% effective hemostasis and a significant reduction of the time-to-hemostasis, when compared to controls. These results were comparable to the hemostatic properties of a commercially available, xenogeneic fibrinogen/thrombin patch. Our findings suggest clinical potential for the autologous blood-derived patch as a hemostatic agent.

Ovarian removal and subsequent breast cancer prognosis: a nationwide cohort study.

PURPOSE: To evaluate whether previous ovarian removal concomitant with benign hysterectomy improves prognosis in a cohort of women with breast cancer. METHODS: In this nationwide register-based cohort study, risk of recurrence and mortality were examined in 4563 women with invasive breast cancer and previous bilateral salpingo-oophorectomy (BSO) concomitant with benign hysterectomy, during 1977-2018. Comparing with benign hysterectomy alone, hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated by Cox-proportional hazards regression models. Analyses were stratified on age at hysterectomy as a proxy for menopausal status (< 45, 45-54 and ≥ 55 years); tumor characteristics, estrogen receptor (ER)-status, and use of hormone therapy (HT) were included in multivariable models. RESULTS: Compared with hysterectomy alone, premenopausal (< 45 years) BSO at benign hysterectomy was associated with an age and calendar period adjusted HR of 1.48 (95% CI 0.83-2.65) for breast cancer recurrence within 10 years of follow-up, a HR of 1.07 (95% CI 0.66-1.72) for overall mortality after breast cancer, and a HR of 0.59 (95% CI 0.26-1.32) for breast cancer-specific mortality. The corresponding HRs for postmenopausal (≥ 55 years) BSO at benign hysterectomy were 1.51 (95% CI 0.73-3.12) for recurrences, 1.34 (95% CI 0.74-2.44) for overall mortality, and 1.78 (95% CI 0.74-4.30) for breast cancer mortality. Adjusting for tumor characteristics, ER-status and HT did not alter the results. CONCLUSION: Results from this cohort study did not indicate an improvement in breast cancer prognosis when removing the ovaries at benign hysterectomy prior to the cancer diagnosis.

Autologous Blood-Derived Patches Used as Anti-adhesives in a Rat Uterine Horn Damage Model.

BACKGROUND: Intra-abdominal adhesions are frequent side effects of surgery, associated with risks of serious complications such as abdominal pain, infertility, and small bowel obstruction. This study investigated a new autologous blood-based approach to adhesion prophylaxis. MATERIALS AND METHOD: Two autologous blood-derived patches (whole-blood-derived, n = 20, and plasma-derived, n = 20) were evaluated as anti-adhesives. The patches were tested in a rat uterine horn damage model. We simulated an intraabdominal surgery by cauterizing and suturing the uterine horns and created an opposing damage by denuding a part of the abdominal wall. Each rat served as its own control with one treated uterine horn and one untreated. After 14 d of post-surgical recovery, the adhesions were assessed and graded macroscopically and microscopically. Statistical analyses were performed with Wilcoxon signed rank and Mann-Whitney U tests. RESULTS: Both whole-blood and plasma-derived patches resulted in significantly less macroscopic adhesions than were found in untreated uterine horns (P = 0.001 and P = 0.002, respectively). Unpaired analysis found no significant differences between the whole-blood and plasma-derived patch outcomes in this study design. Histopathological evaluation of inflammation and fibrosis did not reveal significant differences between the patches and their matched controls. CONCLUSIONS: The autologous blood-derived patches reduced macroscopic adhesion formation significantly compared with no treatment. There were no adverse events and no histological differences between treatment and control, suggesting that the treatments were feasible and safe. In summary, this study confirms the potential of autologous anti-adhesives for the use in intraabdominal surgery.

Ovarian removal at or after benign hysterectomy and breast cancer: a nationwide cohort study.

PURPOSE: Large-scale population-based registry studies investigating the risk of breast cancer after removal of both ovaries at hysterectomy for benign conditions in women with no known genetic predisposition to cancer are needed. We aimed to perform such a study taking into account the age at surgery status and use of hormone replacement therapy (HRT). METHODS: Within the female population of Denmark born 1937-1996, we evaluated breast cancer incidence after unilateral or bilateral oophorectomy concomitant with or after benign hysterectomy in comparison with no surgery and with hysterectomy alone using health registry data during 1978-2016. In a subpopulation followed from 1996, the analyses were stratified according to use of HRT. RESULTS: We found a reduced risk of breast cancer among women aged < 45 years at bilateral oophorectomy compared with women with hysterectomy alone (HR = 0.78; 95% CI 0.66, 0.92), whereas slightly increased risks were seen in women above 50 years. In the subpopulation, non-users of HRT aged ≥ 50 years at oophorectomy had a HR of 0.74 (95% CI 0.56, 0.98) for breast cancer after bilateral oophorectomy compared with hysterectomy alone. CONCLUSIONS: Our large-scale study covering four decades provides evidence that bilateral oophorectomy performed at young age in women with benign indications for hysterectomy is associated with a reduction in breast cancer risk. The finding of a negative association at older ages in women not using HRT deserves further attention.

From prescription to guidance: a European framework for generic competencies.

In postgraduate medical education, required competencies are described in detail in existing competency frameworks. This study proposes an alternative strategy for competency-based medical education design, which is supported by change management theories. We demonstrate the value of allowing room for re-invention and creative adaptation of innovations. This new strategy was explored for the development of a new generic competency framework for a harmonised European curriculum in Obstetrics and Gynaecology. The generic competency framework was developed through action research. Data were collected by four European stakeholder groups (patients, nurses, midwives and hospital boards), using a variety of methods. Subsequently, the data were analysed further in consensus discussions with European specialists and trainees in Obstetrics and Gynaecology. These discussions ensured that the framework provides guidance, is specialty-specific, and that implementation in all European countries could be feasible. The presented generic competency framework identifies four domains: 'Patient-centred care', 'Teamwork', 'System-based practice' and 'Personal and professional development'. For each of these four domains, guiding competencies were defined. The new generic competency framework is supported by European specialists and trainees in Obstetrics and Gynaecology, as well as by their European stakeholders. According to change management theories, it seems vital to allow room for re-invention and creative adaptation of the competency framework by medical professionals. Therefore, the generic competency framework offers guidance rather than prescription. The presented strategy for competency framework development offers leads for implementation of competency-based medical education as well as for development of innovations in postgraduate medical education in general.

Reduced Complications Following Implementation of Laparoscopic Hysterectomy: A Danish Population-based Cohort Study of Minimally Invasive Benign Gynecologic Surgery between 2004 and 2018.

STUDY OBJECTIVE: To monitor and report nationwide changes in the rates of and complications after different methods for benign hysterectomy, operative hysteroscopy, myomectomy, and embolization in Denmark. To report the national mortality after benign hysterectomy DESIGN: National prospective, observational cohort study. SETTING: The Danish Hysterectomy and Hysteroscopy Database. PATIENTS: Women undergoing surgery for benign gynecologic diseases: 64 818 hysterectomies, 84 175 hysteroscopies, 4016 myomectomies, and 1209 embolizations in Denmark between 2004 and 2018. INTERVENTIONS: National meetings with representatives from all departments, annual working reports of institutional complication rates, workshops, and national guideline initiative to improve minimally invasive surgical methods. MEASUREMENTS AND MAIN RESULTS: Rates of the different methods and complications after each method with follow-up to 5 years as recorded by the database directly in the National Patient Registry. Nationwide, a decline in the use of hysterectomy, myomectomy, embolizations, and endometrial ablation. The total short-term complications were 9.8%, 7.5%, 8.9%, and 2.7% respectively, however, with a persistent risk of approximately 20% for recurrent operations within 5 years after endometrial ablation. Initially, we urged for increased use of vaginal hysterectomy, but only reached 36%. From 2010, we urged for reducing abdominal hysterectomies by implementing laparoscopic hysterectomy and reached 72% laparoscopic and robotic procedures. Since 2015, we used coring or contained morcellation for removal of large uterus at laparoscopic hysterectomy. The major and minor complication rates (modified Clavien-Dindo classification) were reduced significantly from 8.1% to 4.1% and 9.9% to 5.7% respectively. Mortality after benign hysterectomy was 0.27‰. The odds ratio for major complications after abdominal hysterectomy was 1.66 (1.52-1.81) compared to minimally invasive hysterectomy independent of the length of stay, high-volume departments, indications, comorbidity, age, and calendar year. CONCLUSION: Fifteen years with a national database has resulted in a marked quality improvement. Denmark has 85% minimally invasive hysterectomies and has reduced the number of major complications by 50%.

Risk of adhesive bowel obstruction after abdominal surgery. A national cohort study of 665,423 Danish women.

BACKGROUND: Adhesive bowel obstruction is associated with considerable morbidity and mortality, but the magnitude of the risk is debated. METHOD: In a national cohort of all Danish women with an abdominal operation (N = 665,423) between 1977 and 2013, the risk of adhesive bowel obstruction was assessed by Cox multiple regression. Covariates were the number of abdominal operations, the surgical methods, the anatomical site involved, and the calendar year. RESULTS: In the cohort, 1.4% experienced an episode of adhesive bowel obstruction. The risk increased 33-43% during the study period, was lower after gynecological and obstetrical procedures compared to gastrointestinal (HR 0.36 [0.34-0.38]), lower after laparoscopic compared to laparotomic surgery (HR 0.51 [0.48-0.54]) and increased proportionally after each additional operation. CONCLUSIONS: The risk of adhesive bowel obstruction after abdominal operations depends on the site of earlier operations, the method of access and the number of earlier operations.

Systematic review of the limited evidence for different surgical techniques at benign hysterectomy: A clinical guideline initiated by the Danish Health Authority.

Hysterectomy for benign gynecological conditions is a common operation that has developed extensively through the last 20 years. Methods and surgical techniques vary throughout the regions in Denmark as well as internationally. Consequently, the Danish Health Authority initiated a national clinical guideline on the subject based on a systematic review of the literature. A guideline panel of seven gynecologists formulated the clinical questions for the guideline. A search specialist performed the comprehensive literature search. The guideline panel reviewed the literature and rated the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Finally, the panel weighted the evidence and formulated the clinical recommendations. Based on the limited available literature and the corresponding quality of evidence according to GRADE, the guideline panel gave the following recommendations: ↓ Subtotal hysterectomy should only be preferred over total hysterectomy after careful consideration because there are documented disadvantages such as persistent cyclic vaginal bleeding (⊕ΟΟΟ). ↑ Consider vaginal hysterectomy rather than conventional laparoscopic hysterectomy for non-prolapsed uteri when feasible (⊕ΟΟΟ). ↓ Robot-assisted laparoscopic hysterectomy should only be preferred over conventional laparoscopic hysterectomy after careful consideration because the beneficial effect is uncertain and because of the longer operating time (⊕⊕ΟΟ). ↑ Consider concomitant bilateral salpingectomy at the time of hysterectomy if the procedure is not considered to increase the risk of complications significantly (⊕ΟΟΟ). ↑ Consider vaginal vault suspension to the cardinal and the uterosacral ligaments when performing hysterectomy for non-prolapsed uteri (⊕ΟΟΟ). Though supporting evidence is missing, the guideline panel emphasizes that it is good practice not to morcellate uteri with presumed fibroids inside the peritoneal cavity (√). The recommendations serve as professional advice in specific clinical situations. The implementation of the guideline in Denmark will be monitored through the national Danish Hysterectomy and Hysteroscopy Database.

A systematic review and meta-analysis of the effect of prophylactic tranexamic acid treatment in major benign uterine surgery.

BACKGROUND: The value of tranexamic acid (TA) treatment as bleeding prophylaxis in major uterine surgery is unclear. OBJECTIVES: To evaluate the antihemorrhagic effect of prophylactic TA treatment in major benign uterine surgery. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, and Web of Science were searched from 1980 to 2015 without language restriction using search terms related to major uterine surgery combined with TA. SELECTION CRITERIA: Randomized controlled trials comparing prophylactic TA with placebo or no intervention in women undergoing elective major benign uterine surgery. DATA COLLECTION AND ANALYSIS: Basic information and outcomes were collected and meta-analyses performed. MAIN RESULTS: Sixteen trials were included, with five trials considered to have an overall low risk of bias. In cesarean delivery, TA significantly reduced intraoperative bleeding (mean -136 mL, 95% confidence interval [CI] -189 to -83), blood loss of more than 1000 mL (relative risk 0.38, 95% CI 0.18-0.81), and blood transfusion (relative risk 0.32, 95% CI 0.17-0.59). In abdominal myomectomy, TA also significantly reduced intraoperative bleeding (mean -251 mL, 95% CI -391 to -110). CONCLUSIONS: Prophylactic TA treatment significantly reduced operative bleeding in women undergoing elective cesarean delivery or abdominal myomectomy. Additional randomized trials with low risk of bias are needed.

The Danish Hysterectomy and Hysteroscopy Database.

AIM OF THE DATABASE: The steering committee of the Danish Hysterectomy and Hysteroscopy Database (DHHD) has defined the objective of the database: the aim is firstly to reduce complications, readmissions, reoperations; secondly to specify the need for hospitalization after hysterectomy; thirdly to secure quality assessment of hysterectomy and hysteroscopy by setting standards and national guidelines; and finally to intensify the monitoring of laparoscopic surgery and explore long-term side effects after hysterectomy. STUDY POPULATION: We include all women in Denmark who have had elective benign uterine surgery since 2003. The surgery includes hysterectomy and operative hysteroscopy. In the latter, we include resection of the endometrium and submucosal leiomyomas and ablations of the endometrium. MAIN VARIABLES: Detailed information about the hysterectomy and hysteroscopy operation techniques, cooperations, and indications is registered directly in the National Patient Register (NPR), as well as relevant lifestyle factors and confounders. It is mandatory to register information about complications and readmissions in the NPR. Data included in DHHD are directly extracted from the NPR. DESCRIPTIVE DATA: Annually approximately 4,300 hysterectomies and 3,200 operative hysteroscopies are performed in Denmark. Since the establishment of the database in 2003, 50,000 hysterectomies have been registered. DHHD's nationwide cooperation and research have led to national guidelines and regimes. Annual national meetings and nationwide workshops have been organized. CONCLUSION: The use of vaginal and laparoscopic hysterectomy methods has increased during the past decade and the overall complication rate and hospital stay have declined. The regional variation in operation methods has also decreased.

Anti-hemorrhagic effect of prophylactic tranexamic acid in benign hysterectomy-a double-blinded randomized placebo-controlled trial.

BACKGROUND: Hysterectomy is one of the most frequently performed major gynecological surgical procedures. Even when the indication for the procedure is benign, relatively high complication rates have been reported. Perioperative bleeding seems to represent the most common cause of complications and in 2004, 8% of all women in Denmark undergoing benign hysterectomy experienced a bleeding complication. Tranexamic acid is an antifibrinolytic agent that has shown to effectively reduce bleeding complications within other surgical and medical areas. However, knowledge about the drug's effect in relation to benign hysterectomy is still missing. OBJECTIVE: To investigate the antihemorrhagic effect of prophylactic tranexamic acid in elective benign hysterectomy. STUDY DESIGN: A double-blinded randomized placebo-controlled trial was conducted at 4 gynecological departments in Denmark from April 2013 to October 2014. A total of 332 women undergoing benign abdominal, laparoscopic, or vaginal hysterectomy were included in the trial, randomized to either 1 g of intravenous tranexamic acid or placebo at start of surgery. Chi-square test and Student t test statistical analyses were applied. RESULTS: The primary outcome of intraoperative total blood loss was reduced in the group treated with tranexamic acid compared to the placebo group when estimated both subjectively by the surgeon and objectively by weight (98.4 mL vs 134.8 mL, P = .006 and 100.0 mL vs 166.0 mL, P = .004). The incidence of blood loss ≥500 mL was also significantly reduced (6 vs 21, P = .003), as well as the use of open-label tranexamic acid (7 vs 18, P = .024). Furthermore, the risk of reoperations owing to postoperative hemorrhage was significantly reduced in the tranexamic acid group compared to the placebo group (2 vs 9, P = .034). This corresponds to an absolute risk reduction of 4.2% and number needed to treat of 24. No incidence of thromboembolic events or death was observed in any of the groups. CONCLUSION: The results support the hypothesis that prophylactic treatment with tranexamic acid reduces the overall total blood loss, the incidence of substantial blood loss, and the need for reoperations owing to postoperative hemorrhage in relation to benign hysterectomy. No incidences of serious adverse events occurred. Thus, tranexamic acid should be considered as a prophylactic treatment prior to elective benign hysterectomy.

[Spontaneous bilateral tubal pregnancy following caesarean section]. / Spontan bilateral ekstrauterin graviditet efter kejsersnit

We describe a rare case of bilateral tubal pregnancy following natural conception in a woman with no other known risk factor than two former caesarean sections. Intraabdominal adhesions following the caesarean sections complicated the salpingectomy thus diminishing certainty of a healthy contralateral tube. The woman was readmitted three weeks later and had an additional salpingectomy on behalf of an unrecognized tubal pregnancy. Considering the rising caesarean section rates clinicians need to be certain of no additional ectopic pregnancy while performing the primary operation.

Use of vaginal hysterectomy in Denmark: rates, indications and patient characteristics.

OBJECTIVE: To describe the use of vaginal, abdominal and laparoscopic hysterectomy in Denmark from 1999 to 2008, the influence of national guidelines and the patient and procedure-related characteristics associated with the choice of vaginal hysterectomy. Design. Nationwide register-based cohort study. SETTING: Danish Hysterectomy Database and Danish National Patient Registry. POPULATION: All women with a hysterectomy for benign indications in Denmark from 1999 to 2008. METHODS: The incidence rate/100,000 women was used to describe the route of surgery in hysterectomies of 50,755 women. A multiple logistic regression analysis was done to examine the association between patient- and procedure-related characteristics and choice of surgical procedure including 20,486 women. MAIN OUTCOME MEASURES: Trends in surgical approach from 1999 to 2008. Patient- and surgery-related characteristics associated with vaginal hysterectomy from 2004 to 2008. RESULTS: There was an overall increase in the use of vaginal hysterectomies from 12 to 34%, a decrease in the use of abdominal hysterectomies and a consistent number of laparoscopic hysterectomies. The number of vaginal hysterectomies varied between regions, ranging from 2 to 86%. The use of vaginal hysterectomy was not dependent on the total number of hysterectomies performed at the hospital. The characteristics associated with vaginal hysterectomy were higher age, smaller uterus size, indications for surgery (genital prolapse and severe uterine bleeding), less smoking and moderate alcohol intake. CONCLUSIONS: Vaginal hysterectomy has replaced abdominal hysterectomy increasingly but cannot be directly correlated to the implementation of national guidelines as there was large national variation. Several characteristics are significantly associated with vaginal hysterectomy.

[Successful training course in academic research in gynaecology and obstetrics]. / Velfungerende forskningstræning i gynækologi og obstetrik.

In 2003 The National Board of Health, Denmark, enforced a compulsory training course in academic research as part of the specialist training for doctors. The trainees must learn to search and evaluate relevant literature and be able to implement the results in clinical practice. The structure of the 20 days of academic training in gynaecology and obstetrics is described. In 2008, 17 doctors participated in these sessions. We performed a questionnaire survey to explore the implementation. The academic training was well rated by the participants with respect to content, form and outcome.

Hysterectomy, oophorectomy and risk of dementia: a nationwide historical cohort study.

BACKGROUND: This study aimed to determine whether there is an association between hysterectomy and dementia. METHODS: All female Danish residents born before 1966, alive on their 40th birthday and without a dementia diagnosis prior to 1977 (n = 2,313,388) were followed from January 1, 1977, or the age of 40, whichever came later, until dementia diagnosis, death, emigration or December 31, 2006, whichever came first. The relative risks (RR) for developing dementia in women with hysterectomy/oophorectomy compared to referent women were calculated. RESULTS: Overall, hysterectomy did not increase the risk of dementia. When stratified by age at dementia diagnosis, hysterectomy was associated with an increased risk for early-onset dementia before the age of 50: hysterectomy alone (RR = 1.38, 95% confidence interval (CI) = 1.07-1.78), with unilateral oophorectomy (RR = 2.10, 95% CI = 1.28-3.45), with bilateral oophorectomy (RR = 2.33, 95% CI = 1.44-3.77). The younger the age at hysterectomy/oophorectomy, the greater was the risk. CONCLUSIONS: Although statistically significant, the association between premenopausal hysterectomy and early-onset dementia is uncertain due to study limitations. Premenopausal bilateral oophorectomy is associated with a higher risk, suggesting a dose effect of premature estrogen deficiency on dementia. The age-dependent effect suggests that the younger brain is probably more vulnerable to estrogen deficiency.

Hypertension is associated with an increased risk for hysterectomy: a Danish cohort study.

OBJECTIVE: To assess whether hypertension is a risk factor for hysterectomy, endometrial resection, and myomectomy. STUDY DESIGN: Self-report questionnaires were collected from 81% of 1959 Danish women aged 30 or 40 years selected at random in 1976-1991, in four different cohort studies. Baseline data included standardized information about cardiovascular diseases, hypertension, use of medicine, gynecologic history, social background, and life style factors. Weight, height and blood pressure were measured. The women were followed via central registers to assess the incidence of hysterectomy, endometrial resection, and myomectomy performed for benign diagnoses. Cox regression analyses were used to control for confounding. RESULTS: The average time to follow-up was 15 years, and 135 operations performed for benign diagnoses were identified. Women with a history of hypertension had a double risk of having an operation compared to women without hypertension, independent of confounders. CONCLUSION: Hypertension seems to be a risk factor for hysterectomy performed for benign diagnoses, and thus contributes to women undergoing hysterectomy having an increased risk of cardiovascular diseases. It might be relevant to pay increased attention to the blood pressure in candidates for hysterectomy, as optimal antihypertensive treatment could decrease their otherwise increased risk of cardiovascular disease years after hysterectomy.