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.

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.

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.

Efeitos da Histerectomia Total Abdominal sobre o Fluxo Sangüíneo Ovariano

Objetivo: avaliar os efeitos da histerectomia total abdominal (HTA) sobre o fluxo sangüíneo ovariano, em mulheres no menacme, por meio da dopplervelocimetria e ultra-sonografia transvaginal. Métodos: estudo prospectivo no qual foram incluídas 61 mulheres, com idade igual ou inferior a 40 anos. As pacientes foram divididas em dois grupos: G1, com 31 pacientes submetidas à HTA, e G2, com 30 mulheres normais não submetidas à cirurgia. Somente foram incluídas pacientes eumenorréicas, ovulatórias, não-obesas ou fumantes, sem cirurgias ou doenças ovarianas prévias. Avaliou-se o fluxo sangüíneo das artérias ovarianas, inicialmente e aos 6 e 12 meses, pelo índice de pulsatilidade (IP) na dopplervelocimetria, e o volume ovariano pela ultra-sonografia transvaginal (US). Para análise estatística empregou-se teste t pareado, análise de perfil, teste de Friedman e teste de Mann-Whitney. Resultados: na comparação estatística inicial os grupos foram homogêneos quanto às características epidemiológicas e quanto aos demais parâmetros avaliados neste estudo. Nas pacientes submetidas à histerectomia, observaram-se aos 6 e 12 meses aumento do volume ovariano ao US e diminuição do IP avaliado pela dopplervelocimetria (p<0,05), quando confrontadas ao controle. Aos 12 meses, em 8 das 31 pacientes pós-HTA (25,5%) verificou-se ocorrência de cistos ovarianos de aspecto benigno. No grupo controle não houve alteração de nenhum desses parâmetros. Conclusão: a redução do IP na dopplervelocimetria das artérias ovarianas sugere aumento do fluxo sangüíneo ovariano pós-histerectomia total abdominal em mulheres no menacme.

Avaliação da função ovariana pós histerectomia total abdominal em mulheres no menacme

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

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

Total abdominal hysterektomi och sexualitet

SammanfattningSyftet med föreliggande systematiska litteraturstudie var att undersöka om ingreppet total abdominal hysterektomi (TAH) påverkade kvinnors sexualitet. Ett andra syfte var att granska huruvida kvinnors psykiska välmående förändrades efter operationen. För att klarlägga problemen insamlades artiklar via databaserna Blackwell Synergy, CINAHL, Elin och Pubmed. Sammanlagt 18 artiklar bedömdes med granskningsmodeller utarbetade efter bedömningsmallar av Forsberg och Wengström (2003) för artiklar med kvantitativ respektive kvalitativ ansats. Inalles 13 artiklar bedömdes såsom godkända (G) och 5 artiklar såsom väl godkända (VG). Av 18 studier rapporterades i 10 artiklar förbättrad sexualitet. Det betyder upplevelsen av bättre orgasm, ökad sexuell tillfredställelse eller lust. Beträffande psykiska symptom rapporterades ökat välbefinnande och bättre livskvalitet i 3 artiklar samt minskad ångest och depression i 5 av artiklarna. Resultaten diskuterades i termer av vikten av informerat samtycke i samråd med hälso- och sjukvårdspersonal vid fattandet av beslutet att avstå från livmodern.

Safe vaginal uterine morcellation following total laparoscopic hysterectomy.

The minimally invasive approach for hysterectomy with proven benefits and lower morbidity has become the gold standard, even in women with large uterine masses. Most women with a malignant condition present with abnormal vaginal bleeding and/or suspicious imaging such that few are diagnosed by final histopathology after surgery. However, if a malignancy is not diagnosed preoperatively, intraabdominal morcellation for uterus extraction has an increased risk for potential tumor spread and peritoneal metastases, especially in cases of unexpected leiomyosarcoma. We describe a simple method to wrap the uterus in a contained environment with a plastic bag through the posterior vaginal fornix prior to conventional coring morcellation for vaginal extraction in total laparoscopic hysterectomy. We further describe our experience with a risk stratification and treatment algorithm to implement this procedure in daily routine. A video and an illustrating sketch demonstrate the simplicity and safety of the procedure.

Postoperative analgesic requirements - total laparoscopic hysterectomy versus vaginal hysterectomy

Background: There is limited information available on the requirement for postoperative analgesic drugs in patients submitted to total laparoscopic hysterectomy (TLH) compared with patients undergoing vaginal hysterectomy (VH). Aim: To compare the postoperative analgesic requirements in patients who underwent a TLH with patients who had a VH. Methods: Chart review of 53 patients who had TLH and 47 who had VH and were seen postoperatively by an acute pain management service in order to assess postoperative analgesic requirements. Patient controlled analgesia (PCA) was part of the standard protocol for postoperative pain management. Analgesic requirement was recorded as the mean doses of morphine and number of days that patients used non-steroidal anti-inflammatory drugs (NSAIDs), oxycodone and tramadol. Results: The requirement for total morphine was approximately half the dose in patients who had a TLH (10.8 +/- 12.6 mg) compared with patients who had a VH (19.4 +/- 21.9 mg) (P 0.017). The length of use of NSAIDs was significantly reduced in patients who had undergone a TLH (2.0 +/- 0.95 days) as compared with patients who had a VH (2.85 +/- 1.1 days) (P < 0.0001). Conclusions: Patients submitted to TLH require less postoperative analgesic drugs when compared with patients who had VH. Prospective randomised trials are warranted to compare analgesic requirements between patients submitted to TLH and VH.

Risk factors to predict the incidence of surgical adverse events following open or laparoscopic surgery for apparent early stage endometrial cancer: results from a randomised controlled trial

Aims: To identify risk factors for major Adverse Events (AEs) and to develop a nomogram to predict the probability of such AEs in individual patients who have surgery for apparent early stage endometrial cancer. Methods: We used data from 753 patients who were randomized to either total laparoscopic hysterectomy or total abdominal hysterectomy in the LACE trial. Serious adverse events that prolonged hospital stay or postoperative adverse events (using common terminology criteria 3+, CTCAE V3) were considered major AEs. We analyzed pre-surgical characteristics that were associated with the risk of developing major AEs by multivariate logistic regression. We identified a parsimonious model by backward stepwise logistic regression. The six most significant or clinically important variables were included in the nomogram to predict the risk of major AEs within 6 weeks of surgery and the nomogram was internally validated. Results: Overall, 132 (17.5%) patients had at least one major AE. An open surgical approach (laparotomy), higher Charlson’s medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline ECOG score, higher body mass index and low haemoglobin levels were associated with AE and were used in the nomogram. The bootstrap corrected concordance index of the nomogram was 0.63 and it showed good calibration. Conclusions: Six pre-surgical factors independently predicted the risk of major AEs. This research might form the basis to develop risk reduction strategies to minimize the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer.

Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer : results from a randomised controlled trial

AIM: To compare Total Laparoscopic Hysterectomy (TLH) and Total Abdominal Hysterectomy (TAH) with regard to surgical safety. METHODS: Between October 2005 and June 2010, 760 patients with apparent early stage endometrial cancer were enroled in a multicentre, randomised clinical trial (LACE) comparing outcomes following TLH or TAH. The main study end points for this analysis were surgical adverse events (AE), hospital length of stay, conversion from laparoscopy to laparotomy, including 753 patients who completed at least 6 weeks of follow-up. Postoperative AEs were graded according to Common Toxicity Criteria (V3), and those immediately life-threatening, requiring inpatient hospitalisation or prolonged hospitalisation, or resulting in persistent or significant disability/incapacity were regarded as serious AEs. RESULTS: The incidence of intra-operative AEs was comparable in either group. The incidence of post-operative AE CTC grade 3+ (18.6% in TAH, 12.9% in TLH, p 0.03) and serious AE (14.3% in TAH, 8.2% in TLH, p 0.007) was significantly higher in the TAH group compared to the TLH group. Mean operating time was 132 and 107 min, and median length of hospital stay was 2 and 5 days in the TLH and TAH group, respectively (p<0.0001). The decline of haemoglobin from baseline to day 1 postoperatively was 2g/L less in the TLH group (p 0.006). CONCLUSIONS: Compared to TAH, TLH is associated with a significantly decreased risk of major surgical AEs. A laparoscopic surgical approach to early stage endometrial cancer is safe.

Differences in Epidural and Analgesic Use in Patients with Apparent Stage I Endometrial Cancer treated by open versus laparoscopic surgery: results from the randomised LACE trial

Objectives: We compared post-operative analgesic requirements between women with early stage endometrial cancer treated by total abdominal hysterectomy (TAH) or total laparoscopic hysterectomy (TLH). Methods: 760 patients with apparent stage I endometrial cancer were treated in the international, multicentre, prospective randomised trial (LACE) by TAH (n=353) or TLH (n=407) (2005-2010). Epidural, opioid and non-opioid analgesic requirements were collected until ten months after surgery. Results: Baseline demographics and analgesic use were comparable between treatment arms. TAH patients were more likely to receive epidural analgesia than TLH patients (33% vs 0.5%, p<0.001) during the early postoperative phase. Although opioid use was comparable in the TAH vs TLH groups during postoperative 0-2 days (99.7% vs 98.5%, p 0.09), a significantly higher proportion of TAH patients required opioids 3-5 days (70% vs 22%, p<0.0001), 6-14 days (35% vs 15%, p<0.0001), and 15-60 days (15% vs 9%, p 0.02) post-surgery. Mean pain scores were significantly higher in the TAH versus TLH group one (2.48 vs 1.62, p<0.0001) and four weeks (0.89 vs 0.63, p 0.01) following surgery. Conclusion: Treatment of early stage endometrial cancer with TLH is associated with less frequent use of epidural, lower post-operative opioid requirements and better pain scores than TAH.

Tratamento Clínico e Seguimento das Hiperplasias de Endométrio

Objetivos: avaliar a eficácia do acetato de medroxiprogesterona e do acetato de megestrol nas hiperplasias de endométrio. Métodos: foram incluídas, retrospectivamente 47 pacientes com sangramento uterino anormal, submetidas a curetagem uterina diagnóstica e/ou biópsia de endométrio, cujo achado histopatológico foi de hiperplasia de endométrio. Nas pacientes com hiperplasia sem atipia foi iniciado a terapêutica com acetato de medroxiprogesterona por via oral, na dose de 10 mg/dia durante 10-12 dias por mês. Nas com atipia, era utilizado o acetato de megestrol por via oral, dose de 160 mg/dia, uso contínuo. O período de tratamento variou de 3 a 18 meses. Biópsia de endométrio e/ou curetagem uterina de controle foram realizadas entre três e seis meses do início do tratamento e periodicamente para avaliar a resposta terapêutica. Resultados: foram analisadas 42 pacientes com hiperplasia endometrial sem atipia e cinco com atipia. A média de idade das pacientes foi de 49,5 ± 10,6 anos, sendo 70,2% com idade superior a 45 anos. O acetato de medroxiprogesterona foi eficaz em fazer regredir as hiperplasias sem atipias em 83,2% (35/42) e o acetato de megestrol em 80% (4/5) das hiperplasias com atipia. em 16,8% (7 casos) das hiperplasias sem atipia e em 20% (1 caso) das com atipia, ocorreu persistência das lesões, apesar do tratamento. em nenhum caso ocorreu progressão para câncer de endométrio, durante o período de seguimento que foi de 3 meses a 9 anos. No acompanhamento dessas pacientes, verificamos que 18 (38,3%) apresentaram amenorréia, em 12 (25,5%) ocorreu regularização do ciclo menstrual e 17 (36,2%) permaneceram com sangramento uterino anormal, sendo submetidas a histerectomia total abdominal. O exame anatomopatológico mostrou a persistência da lesão hiperplásica em oito casos, leiomioma em quatro, adenomiose em três, mio-hipertrofia uterina difusa em um caso e útero normal em outro, tendo havido regressão das lesões hiperplásicas nesses últimos nove casos. Conclusões: o tratamento das hiperplasias de endométrio com acetato de medroxiprogesterona e/ou acetato de megestrol, representa uma alternativa satisfatória para mulheres que desejam preservar o útero ou que tenham risco cirúrgico elevado. Entretanto, é necessário monitorização cuidadosa do endométrio, o que deve ser realizado pela avaliação dos sintomas, ultra-sonografia transvaginal e biópsia periódica.

AN EXTREMELY LARGE, CAULIFLOWER-TYPE, CUTANEOUS METASTASIS OF OVARIAN-CANCER ASSOCIATED WITH GOOD PROGNOSIS

We report an unusual case of a 37-year-old woman who presented in 1980 with a serous papillary cystadenocarcinoma of the ovary. The patient refused any treatment and the patient was lost to follow-up for 6 years. After this period of time she returned with an extremely large, cutaneous, cauliflower-type of metastasis located in the lower abdominal wall and measuring 20 x 20 cm. She received two courses of chemotherapy treatment consisting of intraperitoneal cisplatin (100 mg/m2) and intravenous epirubicin (50 mg/m2) every 3 weeks. After the second course of chemotherapy she received cobalt radiotherapy (5000 cGy). Subsequently, she received four more courses of chemotherapy with dramatic remission of the cutaneous metastasis. Shortly after chemotherapy, the patient underwent a laparotomy consisting of the resection of the abdominal wall including the cutaneous metastasis completed by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The patient is well after the surgery and without any evidence of residual disease after 6 years of follow up. This description illustrates a rare example of ovarian cancer with skin metastases and favorable outcome. (C) 1994 Academic Press, Inc.