Russell Land

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.

Nomograms to predict isolated loco-regional or distant recurrence among women with uterine cancer

OBJECTIVE While there is ample literature on prognostic factors for uterine cancer, currently there are nomeans to estimate an individuals risk for recurrence or to differentiate the risk of loco-regional recurrence from distant recurrence. We addressed this gap by developing nomograms to individualize the risk of recurrence. METHODS A total of 2097 consecutive patients who underwent primary surgery between 1997 and 2007 were included. Sixteen covariates were evaluated for their prognostic significance and modeled using multivariable competing risks regression to predict three-year outcomes as part of a nomogram. Each covariate in the nomogram is assigned a value, and a sum of these values form the overall risk score from which three-year incidence probabilities can be predicted for each individual. Predictive accuracy was assessed with concordance index and then corrected for optimism. RESULTS The median follow-up time (inter-quartile range, IQR) was 50.0 (28.3-77.5) months and 221 patients developed a recurrence (127 patients with isolated loco-regional recurrence, 94 patients with distant recurrence). The nomograms included the following covariates: age at diagnosis, FIGO stage (2009), grade, lymphovascular invasion, histological type, depth of myometrial invasion, and peritoneal cytology. Concordance indices for isolated loco-regional and distant recurrences were 0.73 and 0.86, respectively. CONCLUSIONS Our nomograms quantify an individual patients risk of isolated loco-regional and distant recurrence, using factors that are routinely collected. They may assist clinicians to assess an individuals prognosis, individualize treatment and also assist in the risk stratification in prospective randomized clinical trials evaluating the effectiveness of treatments for uterine cancer.

Pap smear screening history of women with squamous cell carcinoma and adenocarcinoma of the cervix

Background:  Since the introduction of the Pap smear screening, the incidence of squamous cell carcinoma (SCC) has decreased significantly, but the incidence of adenocarcinoma (AC) relative to SCC has increased.

Clinical audit in gynecological cancer surgery: development of a risk scoring system to predict adverse events.

BACKGROUND Advanced gynecological surgery undertaken in a specialized gynecologic oncology unit may be associated with significant perioperative morbidity. Validated risk prediction models are available for general surgical specialties but currently not for gynecological cancer surgery. OBJECTIVE The objective of this study was to evaluate risk factors for adverse events (AEs) of patients treated for suspected or proven gynecological cancer and to develop a clinical risk score (RS) to predict such AEs. METHODS AEs were prospectively recorded and matched with demographical, clinical and histopathological data on 369 patients who had an abdominal or laparoscopic procedure for proven or suspected gynecological cancer at a tertiary gynecological cancer center. Stepwise multiple logistic regression was used to determine the best predictors of AEs. For the risk score (RS), the coefficients from the model were scaled using a factor of 2 and rounded to the nearest integer to derive the risk points. Sum of all the risk points form the RS. RESULTS Ninety-five patients (25.8%) had at least one AE. Twenty-nine (7.9%) and 77 (20.9%) patients experienced intra- and postoperative AEs respectively with 11 patients (3.0%) experiencing both. The independent predictors for any AE were complexity of the surgical procedure, elevated SGOT (serum glutamic oxaloacetic transaminase, > or /=35 U/L), higher ASA scores and overweight. The risk score can vary from 0 to 14. The risk for developing any AE is described by the formula 100 / (1 + e((3.697 - (RS /2)))). CONCLUSION RS allows for quantification of the risk for AEs. Risk factors are generally not modifiable with the possible exception of obesity.

Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy on disease-free survival among women with stage I endometrial cancer. A randomized clinical trial

Importance Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. Objective To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. Design, Setting, and Participants The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Interventions Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). Main Outcomes and Measures The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Results Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, −5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, −3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, −3.0% to 4.2%]; P = .76). Conclusions and Relevance Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. Trial Registration clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516

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 patients who have surgery for apparent early stage endometrial cancer. METHODS We used data from 753 patients who were randomised 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 analysed 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 6weeks 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 Charlsons medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline Eastern Cooperative Oncology Group (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 minimise the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer.

Validation of the FIGO 2009 Staging System for Carcinoma of the Vulva

Background The previous (1988) International Federation of Gynecology and Obstetrics (FIGO) vulval cancer staging system failed in 3 important areas: (1) stage 1 and 2 disease showed similar survival; (2) stage 3 represented a most heterogeneous group of patients with a wide survival range; and (3) the number and morphology of positive nodes were not taken into account. Objective To compare the 1988 FIGO vulval carcinoma staging system with that of 2009 with regard to stage migration and prognostication. Methods Information on all patients treated for vulval cancer at the Queensland Centre for Gynecological Cancers, Australia, between 1988 to the present was obtained. Data included patients’ characteristics as well as details on histopathology, treatments, and follow-up. We recorded the original 1988 FIGO stage, reviewed all patients’ histopathology information, and restaged all patients to the 2009 FIGO staging system. Data were analyzed using the Kaplan-Meier method to compare relapse-free survival and overall survival. Results Data from 394 patients with primary vulval carcinoma were eligible for analysis. Patients with stage IA disease remained unchanged. Tumors formerly classified as stage II are now classified as stage IB. Therefore, FIGO 2009 stage II has become rare, with only 6 of 394 patients allocated to stage II. Stage III has been broken down into 3 substages, thus creating distinct differences in relapse-free survival and overall survival. Prognosis of patients with stage IIIC disease is remarkably poor. Conclusion The FIGO 2009 staging system for vulval carcinoma successfully addresses some concerns of the 1988 system. Especially, it identifies high-risk patients within the heterogeneous group of lymph node–positive patients.

Evaluation of tumor-free distance and depth of myometrial invasion as prognostic factors for lymph node metastases in endometrial cancer.

Introduction: Concurrent uterine lesions or an irregular endomyometrial junction can make accurate assessment of depth of myometrial invasion (DOI) and percentage of myometrial invasion (%MI) difficult, leading to patients being staged and or treated suboptimally. An alternative measurement, known as the tumor-free distance (TFD), which measures the distance between maximal myometrial invasion and the uterine serosa, has been proposed. Previous studies comparing the predictive abilities of DOI and TFD were underpowered and inconclusive. Our objective was to compare TFD, DOI, and %MI as predictors for lymph node involvement in surgically staged endometrial cancer patients. Methods: Patients with endometrioid adenocarcinoma of the endometrium treated between January 1997 and December 2007 were included. Tumor-free distance, DOI, and %MI were evaluated along with other pathological variables to determine their predictive ability for nodal involvement. Depth of myometrial invasion was measured between the endomyometrial junction and the maximal myometrial invasion. Tumor-free distance was calculated by subtracting the DOI from myometrial thickness (MT). Percentage MI was derived by dividing DOI by MT and expressed as a percentage of MT invaded. These 3 variables were transformed to z scores, and their ability to predict nodal involvement was compared. Results: A total of 338 patients were eligible for analysis. Mean (SD) MT was 18.7 (5.9) mm. Median DOI was 6 mm, and median TFD was 10.3 mm. On univariate analysis, all 3 variables showed significant associations with nodal involvement. On multivariate analysis, after adjusting for lymphovascular space invasion, cervical involvement, serosal/adnexal involvement, grade, %MI, and TFD, DOI retained its statistical significance along with lymphovascular space invasion and cervical involvement. Conclusions: Depth of myometrial invasion predicts nodal involvement independently when compared with TFD.

Gynaecology meets neurology: Paraneoplastic cerebellar degeneration

Paraneoplastic syndromes (PNS) are defined as a constellation of symptoms involving non-metastatic systemic effects which accompany malignant disease. Gynaecological tumours can manifest a variety of paraneoplastic sequelae including neurologic, haematopoietic, vascular, rheumatologic, dermal and endocrine disorders. Neurologic paraneoplastic phenomena occur in less then 1:20 0000 of the population per year. Cerebellar degeneration is a rare and frequently devastating paraneoplastic syndrome which can be associated with gynaecological malignancies amongst others. Despite this rarity, over 50% of those patients over the age of 50 with subacute cerebellar degeneration will be associated with a paraneoplastic phenomena. Overall 90% of all paraneoplastic cerebellar degeneration (PCD) is associated with either lymphoma, lung, breast, or ovarian cancers. The two cases reported here demonstrate the marked variation in clinical outcomes, salient points in workup and treatment for patients with this difficult clinical scenario.

Hospital costs associated with adverse events in gynecological oncology

BACKGROUND AND OBJECTIVE Treatment for gynecological malignancies is complex and may cause unintended or accidental adverse events (AE). We evaluated the costs of hospitalization associated with those AEs among patients who had an abdominal or laparoscopic procedure for proven or suspected gynecological cancer at a tertiary gynecological cancer center in Australia. METHODS Data on AEs were prospectively collected and matched with cost data (AU