Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE) : a randomised trial

Background: The two-stage Total Laparoscopic Hysterectomy (TLH) versus Total Abdominal Hysterectomy (TAH) for stage I endometrial cancer (LACE) randomised controlled trial was initiated in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved QoL up to 6 months after surgery compared to TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Results addressing the primary objective of stage 1 of the LACE trial are presented here. Methods: The first 361 LACE participants (TAH n= 142, TLH n=190) were enrolled in the QoL substudy at 19 centres across Australia, New Zealand and Hong Kong, and 332 completed the QoL analysis. Randomisation was performed centrally and independently from other study procedures via a computer generated, web-based system (providing concealment of the next assigned treatment) using stratified permuted blocks of 3 and 6, and assigned patients with histologically confirmed stage 1 endometrioid endometrial adenocarcinoma and ECOG performance status <2 to TLH or TAH stratified by histological grade and study centre. No blinding of patients or study personnel was attempted. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between the groups in QoL change from baseline at early and late time points (a 5% difference was considered clinically significant). Analysis was performed according to the intention-to-treat principle using generalized estimating equations on differences from baseline for the early and late QoL recovery. The LACE trial is registered with clinicaltrials.gov (NCT00096408) and the Australian New Zealand Clinical Trials Registry (CTRN12606000261516). Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. Findings: The proportion of missing values at the 5%, 10% 15% and 20% differences in the FACT-G scale was 6% (12/190) in the TLH and 14% (20/142) in the TAH group. There were 8/332 conversions (2.4%, 7 of which were from TLH to TAH). In the early phase of recovery, patients undergoing TLH reported significantly greater improvement of QoL from baseline compared to TAH in all subscales except the emotional and social well-being subscales. Improvements in QoL up to 6 months post-surgery continued to favour TLH except for the emotional and social well-being of the FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Length of operating time was significantly longer in the TLH group (138±43 mins), than in the TAH group at (109±34 mins; p=0.001). While the proportion of intraoperative adverse events was similar between the treatment groups (TAH 8/142, 5.6%; TLH 14/190, 7.4%; p=0.55), postoperatively, twice as many patients in the TAH group experienced adverse events of CTC grade 3+ than in the TLH group (33/142, 23.2% and 22/190, 11.6%, respectively; p=0.004). Postoperative serious adverse events occurred more frequently in patients who had a TAH (27/142, 19.0%) than a TLH (15/190, 7.9%) (p=0.002). Interpretation: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile significantly favour TLH compared to TAH for patients treated for Stage I endometrial cancer.

Epidural analgesia is associated with an increased incidence of postoperative complications in patients requiring an abdominal hysterectomy for early stage endometrial cancer

Objective Analgesia and early quality of recovery may be improved by epidural analgesia. We aimed to assess the effect of receiving epidural analgesia on surgical adverse events and quality of life after laparotomy for endometrial cancer. Methods Patients were enrolled in an international, multicentre, prospective randomised trial of outcomes for laparoscopic versus open surgical treatment for the management of apparent stage I endometrial cancer (LACE trial). The current analysis focussed on patients who received an open abdominal hysterectomy via vertical midline incision only (n = 257), examining outcomes in patients who did (n = 108) and did not (n = 149) receive epidural analgesia. Results Baseline characteristics were comparable between patients with or without epidural analgesia. More patients without epidural (34%) ceased opioid analgesia 3–5 days after surgery compared to patients who had an epidural (7%; p < 0.01). Postoperative complications (any grade) occurred in 86% of patients with and in 66% of patients without an epidural (p < 0.01) but there was no difference in serious adverse events (p = 0.19). Epidural analgesia was associated with increased length of stay (up to 48 days compared to up to 34 days in the non-epidural group). There was no difference in postoperative quality of life up to six months after surgery. Conclusions Epidural analgesia was associated with an increase in any, but not serious, postoperative complications and length of stay after abdominal hysterectomy. Randomised controlled trials are needed to examine the effect of epidural analgesia on surgical adverse events, especially as the present data do not support a quality of life benefit with epidural analgesia. Keywords Endometrial cancer; Hysterectomy; Epidural; Adverse events

The impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy on survival in patients with a history of breast cancer – a population-based data linkage study

Prophylactic surgery including hysterectomy and bilateral salpingo-oophorectomy (BSO) is recommended in BRCA positive women, while in women from the general population, hysterectomy plus BSO may increase the risk of overall mortality. The effect of hysterectomy plus BSO on women previously diagnosed with breast cancer is unknown. We used data from a population-base data linkage study of all women diagnosed with primary breast cancer in Queensland, Australia between 1997 and 2008 (n=21,067). We fitted flexible parametric breast cancer specific and overall survival models with 95% confidence intervals (also known as Royston-Parmar models) to assess the impact of risk-reducing surgery (removal of uterus, one or both ovaries). We also stratified analyses by age 20-49 and 50-79 years, respectively. Overall, 1,426 women (7%) underwent risk-reducing surgery (13% of premenopausal women and 3% of postmenopausal women). No women who had risk-reducing surgery, compared to 171 who did not have risk-reducing surgery developed a gynaecological cancer. Overall, 3,165 (15%) women died, including 2,195 (10%) from breast cancer. Hysterectomy plus BSO was associated with significantly reduced risk of death overall (adjusted HR = 0.69, 95% CI 0.53-0.89; P =0.005). Risk reduction was greater among premenopausal women, whose risk of death halved (HR, 0.45; 95% CI, 0.25-0.79; P < 0.006). This was largely driven by reduction in breast cancer-specific mortality (HR, 0.43; 95% CI, 0.24-0.79; P < 0.006). This population-based study found that risk-reducing surgery halved the mortality risk for premenopausal breast cancer patients. Replication of our results in independent cohorts, and subsequently randomised trials are needed to confirm these findings.

The cost-effectiveness of total laparoscopic hysterectomy compared to total abdominal hysterectomy for the treatment of early stage endometrial cancer

Objective To summarise how costs and health benefits will change with the adoption of total laparoscopic hysterectomy compared to total abdominal hysterectomy for the treatment of early stage endometrial cancer. Design Cost-effectiveness modelling using the information from a randomised controlled trial. Participants Two hypothetical modelled cohorts of 1000 individuals undergoing total laparoscopic hysterectomy and total abdominal hysterectomy. Outcome measures Surgery costs; hospital bed days used; total healthcare costs; quality-adjusted life years; and net monetary benefits. Results For 1000 individuals receiving total laparoscopic hysterectomy surgery, the costs were $509 575 higher, 3548 hospital fewer bed days were used and total health services costs were reduced by $3 746 221. There were 39.13 more quality-adjusted life years for a 5 year period following surgery. Conclusions The adoption of total laparoscopic hysterectomy is almost certainly a good decision for health services policy makers. There is 100% probability that it will be cost saving to health services, a 86.8% probability that it will increase health benefits and a 99.5% chance that it returns net monetary benefits greater than zero.

Impact of hysterectomy or levonorgestrel-releasing intrauterine system on ovarian function, bone, and sexual functioning in menorrhagic patients

The `VuoKKo` trial consisted of 236 women referred and randomised due to menorrhagia in the five university hospitals of Finland between November 1994 and November 1997. Of these women, 117 were randomised to hysterectomy and 119 to use levonorgestrel-releasing intrauterine system (LNG-IUS) to treat this complaint. Their follow-up visits took place six and twelve months after the treatment and five years after the randomisation. The first aim in the primary trial was quality-of-life and monetary aspects, and secondly in the present study to compare ovarian function, bone mineral density (BMD) and sexual functioning after these two treatment options. Ovarian function seemed to decrease after hysterectomy, demonstrated by increased hot flashes and serum follicle-stimulating hormone concentrations twelve months after the operation. Such an increase was not seen among LNG-IUS users. The pulsatility index of intraovarian arteries measured by two-dimensional ultrasound decreased in the hysterectomy group, but not in the LNG-IUS group. The decrease in serum inhibin B concentrations was similar in both groups, while ovarian artery circulation remained unchanged. BMD of the women measured by dual x-ray absorptiometry (DXA) at the lumbar spine and femoral neck at baseline and at five years after treatment showed BMD decrease at the lumbar spine among hysterectomised women, but not among LNG-IUS users. In both groups, BMD at the femoral neck had decreased. Differences between the groups were not, however, significant. Sexual functioning assessed by McCoy s sexual scale showed that sexual satisfaction as well as intercourse frequency had increased and sexual problems decreased among hysterectomised women six months after treatment. Among LNG-IUS users, sexual satisfaction and sexual problems remained unchanged. Although, the two groups did not differ in terms of sexual satisfaction or sexual problems at one-year and five-year follow-ups, LNG-IUS users were less satisfied with their partners than hysterectomised women.

Expression of p53, Ki-67, and CD31 in the vaginal margins of radical hysterectomy in patients with stage IB carcinoma of the cervix

Objectives. This study was undertaken to evaluate the expression of p53, Ki-67, and CD31 both in the tumor and in the vaginal margins of radical hysterectomy in patients with stage IB squamous cell carcinoma of the cervix, as an attempt to use these proteins as possible markers for residual tumor in cervical cancer.Methods. Thirty patients with stage IB squamous cell carcinoma of the cervix were submitted to radical hysterectomy (study group), and thirty patients with uterine myoma were submitted to vaginal hysterectomy (control group) and were prospectively studied from November 2001 to September 2002. Tissue samples were taken from the tumor or cervix, anterior vaginal margin (AVM), and posterior vaginal margin (PVM) and were immunohistochemically evaluated by monoclonal antibodies for p53, Ki-67, and CD31. Vaginal samples in which the histological examination showed tumor involvement were excluded from the study.Results. Patient's mean age was 48.7 +/- 10.4 years (27-73 years). The clinical stage was IB1 in 22 patients (73.3%) and IB2 in eight patients (26.7%). The expressions of p53, Ki-67, and CD31 were significantly higher in the tumor than in the benign cervix (P < 0.001). Higher expressions of these markers were noted in the vaginal margins of radical hysterectomy in patients with cervical carcinoma compared to the vaginal margins of control patients. This association was demonstrated for p53 in the AVM proximal (P = 0.045), for Ki-67 in AVM proximal (P < 0.001), AVM distal (P < 0.001), PVM proximal (P = 0.009), and PVM distal (P < 0.001), and for CD31 in AVM proximal (P = 0.003) and AVM distal (P = 0.018). There was no difference in p53, Ki-67, and CD31 expression between the proximal and distal regions of the vaginal margins in patients with carcinoma of the cervix.Conclusion. The expressions of p53, Ki-67, and CD31 were significantly higher in both the histologically positive (cervical tumor) and negative (vaginal margins) tissues of patients who had undergone radical hysterectomy for cervical cancer compared to the benign control tissues. (C) 2004 Elsevier B.V. All rights reserved.

Effect of total abdominal hysterectomy on ovarian blood supply in women of reproductive age

Objective. The purpose of this study was to evaluate the effect of total abdominal hysterectomy on ovarian blood supply using transvaginal color Doppler ultrasonography in women of reproductive age. Methods. This prospective study included 61 women aged 40 years or younger who were divided into 2 groups: group 1, comprising 31 patients who underwent total abdominal hysterectomy (TAH), and group 2, comprising 30 women with no abnormalities. Inclusion criteria included normal ovarian function at baseline, with basal follicle-stimulating hormone levels of less than 15 mUI/mL, normal body weight, no tobacco use, and no history of laparotomy or ovarian disease. Ovarian arterial blood supply by determination of the pulsatility index (PI) on Doppler analysis and ovarian volume on transvaginal ultrasonography were assessed at baseline and at 6 and 12 postoperative months. The Student t test, profile analysis, and Friedman and Mann-Whitney tests were used in the statistical analysis of data. Results. Statistical analysis of baseline data revealed that both groups were homogeneous. At months 6 and 12, greater ovarian volumes and lower PI values were observed in patients who underwent TAH (P < .05). By the end of the study, in 8 of the 31 patients who underwent TAH (25.5%), benign ovarian cysts were observed. in the control group, all the parameters studied remained unchanged. Conclusions. The reduced PI values observed on Doppler ultrasonography suggested a decrease in the resistance flow in the ovarian arteries in women of reproductive age who underwent TAH.

Inhibin B and ovarian function after total abdominal hysterectomy in women of reproductive age

The aim of this prospective study was to assess ovarian function using clinical and endocrine parameters in women of reproductive age who underwent total abdominal hysterectomy. Sixty-one women, aged ≤ 40 years, were allocated into two groups: group 1, consisting of 31 patients who had hysterectomy, and group 2, consisting of 30 normal women. Inclusion criteria were normal ovarian function at baseline, normal body weight, no hormonal diseases and basal follicle stimulating hormone (FSH) level of < 15 mIU/ml. FSH, luteinizing hormone (LH), estradiol and inhibin B levels as well as maturation value (MV) were measured by vaginal cytology on three occasions: baseline, and 6 and 12 months after hysterectomy. Analysis of variance, the Friedman test, Mann-Whitney test and t-test statistics were employed to compare the two groups. At baseline the groups were homogeneous. At months 6 and 12, hysterectomized women showed decreased median values of inhibin B, increased median values of estradiol (p < 0.05), unchanged median values of FSH and LH, and decreased median values of MV (p < 0.05). In the hysterectomy group, 12.9% (4/31) of the patients had FSH levels of > 40 mIU/ml, estradiol of < 20 pg/ml and inhibin B of < 5 ng/ml, compatible with ovarian failure. In the control group, all the parameters studied remained unchanged. These results suggest that total abdominal hysterectomy accelerates the decline in ovarian function in women of reproductive age.

Telomerase activity in the vaginal margins of radical hysterectomy in patients with carcinoma of the cervix: Correlation with histology and human papillomavirus

This study was undertaken to evaluate the telomerase activity both in the tumor and in the vaginal margins of radical hysterectomy in patients with squamous cell carcinoma (SCC) of the cervix. Thirty-three patients with SCC of the cervix (study group) and 13 patients with uterine myoma (control group) were prospectively studied. Tissue samples were taken from the tumor or cervix, anterior vaginal margin (AVM), and posterior vaginal margin (PVM). The specimens were analyzed by histopathology, by a telomerase PCR-TRAP-ELISA kit, and by polymerase chain reaction using human papillomavirus (HPV) DNA. The telomerase activity was significantly higher in the tumor than in the benign cervix (P < 0.001). There was no difference in telomerase activity in the AVM and PVM in patients with cervical carcinoma compared to the control group. Telomerase activity was associated with the presence of histologic malignancy in the PVM of patients submitted to radical hysterectomy (P = 0.03). This association was not observed with the presence of HPV in AVM or PVM in the study group. Telomerase activity is a marker of histologic malignancy in patients with SCC of the cervix. There was no association between the telomerase activity and the presence of HPV in vaginal margins of patients submitted to radical hysterectomy. © 2006, Copyright the Authors.

Usefulness of vaginal cytology tests in women with previous hysterectomy for benign diseases: assessment of 53,891 tests

Objective. To assess the value of vaginal screening cytology after hysterectomy for benign disease.Methods. This cross-sectional study used cytology audit data from 2,512,039 screening tests in the metropolitan region of Campinas from 2000 to 2012; the object was to compare the prevalence of abnormal tests in women who had undergone a hysterectomy for benign diseases (n = 53,891) to that of women who had had no hysterectomy. Prevalence ratios (95% confidence intervals, 95% Cl) were determined, and chi-square analysis, modified by the Cochrane-Armitage test for trend, was used to investigate the effects of age.Results. The prevalence of atypical squamous cells (ASC), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion or squamous-cell carcinoma (HSIL/SCC) was 0.13%, 0.04% and 0.03%, respectively, in women who had undergone hysterectomy, and 0.93%, 0.51% and 0.26% in women who had not undergone hysterectomy. The prevalence ratios for ASC, LSIL and HSIL/SCC were 0.14(0.11-0.17), 0.08 (0.06-0.13) and 0.13 (0.08-020), respectively, in women with a hysterectomy versus those without. For HSIL/SCC, the prevalence ratios were 0.09 and 029, respectively, for women <50 or >= 50 years. The prevalence rates in women with a previous hysterectomy showed no significant variation with age.Conclusion. The prevalence rates of ASC, LSIL and HSIL/SCC were significantly lower in women with a previous hysterectomy for benign disease compared with those observed in women with an intact uterine cervix. This study reinforces the view that there is no evidence that cytological screening is beneficial for women who have had a hysterectomy for benign disease. (C) 2015 Elsevier Inc. All rights reserved.