Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones.

High-grade serous ovarian carcinoma (HGSOC) is genetically unstable and characterised by the presence of subclones with distinct genotypes. Intratumoural heterogeneity is linked to recurrence, chemotherapy resistance, and poor prognosis. Here, we use spatial transcriptomics to identify HGSOC subclones and study their association with infiltrating cell populations. Visium spatial transcriptomics reveals multiple tumour subclones with different copy number alterations present within individual tumour sections. These subclones differentially express various ligands and receptors and are predicted to differentially associate with different stromal and immune cell populations. In one sample, CosMx single molecule imaging reveals subclones differentially associating with immune cell populations, fibroblasts, and endothelial cells. Cell-to-cell communication analysis identifies subclone-specific signalling to stromal and immune cells and multiple subclone-specific autocrine loops. Our study highlights the high degree of subclonal heterogeneity in HGSOC and suggests that subclone-specific ligand and receptor expression patterns likely modulate how HGSOC cells interact with their local microenvironment.

The wearable activity technology and action-planning trial in cancer survivors: Physical activity maintenance post-intervention.

OBJECTIVES: The study objective was to assess whether moderate-to-vigorous intensity physical activity (MVPA) change in cancer survivors (n = 68, mean age = 64 years) was maintained 12-weeks following the Wearable Activity Technology and Action Planning (WATAAP) intervention. Secondary aims were to assess the effects of the intervention on blood pressure (BP) and body mass index (BMI), and to explore group differences between baseline and 24-weeks. DESIGN: Randomized controlled trial. METHODS: MVPA and sedentary behaviour were assessed using an accelerometer at baseline, the end of the intervention (12-weeks), and at 24-weeks. Generalised linear mixed models with random effects were used to examine between-group and within-group changes in MVPA, sedentary behaviour, BP and BMI. RESULTS: MVPA was significantly higher in the intervention group compared with the control group at 24-weeks following adjustment for known confounders (141.4 min/wk. (95% CI = 9.1 to 273.8), p = 0.036). At 24-weeks participants in the intervention group had maintained their increased levels of MVPA (change from 12-weeks = 8.8 min/wk.; 95% CI = -43 to 61; p = 0.74). The reduction in MVPA in the control group over the first 12-weeks was also maintained at 24-weeks (5.4 min/wk.; 95% CI = -3.6 to 4.6; p = 0.80). Secondary outcomes did not differ between groups at 24-weeks. CONCLUSIONS: Our results suggest distance-based interventions using wearable technology produce increases in MVPA that endure at least 12-weeks after the intervention is completed.

Lynch syndrome associated endometrial carcinomas in Western Australia: an analysis of universal screening by mismatch repair protein immunohistochemistry.

BACKGROUND: In 2016 universal screening with mismatch repair protein immunohistochemistry in all newly diagnosed endometrial carcinomas was introduced in Western Australia. OBJECTIVE: To compare the prevalence of Lynch syndrome associated endometrial carcinomas between 2016 and 2019 with a historical control (2015). Additionally, to compare the number of cases appropriately referred for genetic assessment. METHODS: A cross-sectional study of cases presented at the Western Australia gynecologic oncology tumor board was carried out. The primary outcome was the prevalence of Lynch syndrome associated endometrial carcinomas. A secondary outcome was the number of cases appropriately referred for genetic assessment. The following variables were extracted: date of birth; age at diagnosis; vital status; tumor mismatch repair protein expression status (retained or lost) and if lost, the specific mismatch repair protein deficiency; patients who were referred to a genetic clinic; and family history, if recorded. Data were collected from the clinical databases of the Familial Cancer Program at Genetic Services of Western Australia and WOMEN Center, to determine whether patients were appropriately referred for genetic evaluation and to ascertain the results of genetic testing. RESULTS: Between 2016 and 2019, there were 1040 new endometrial carcinomas. Tumors of 883 (85%) patients underwent mismatch repair protein immunohistochemistry compared with 117 of 199 patients (59%) in 2015 (χ2 73.14, p<0.001). Of 883 tumors tested, 242 (27%) showed loss of mismatch repair protein expression. In 2015, 30 (26%) tumors of 117 tested showed loss of mismatch repair protein expression. During the 4 years of universal screening, 13 (1.5%) of 883 patients screened were diagnosed with Lynch syndrome compared with 2 (1.7%) of 117 in 2015 (Fisher's exact test 0.04, p=0.69). In 2015, 11 (37%) of 30 patients with loss of mismatch repair protein expression were not referred for genetic assessment compared with 36 (17%) of 209 patients in the universal screening group (χ2 6.28, p=0.02). No cases of Lynch syndrome were diagnosed in patients aged over 70 years. CONCLUSIONS: Universal immunohistochemical screening did not increase the proportion of Lynch syndrome associated endometrial carcinomas identified, although the study was underpowered to detect small differences. There was an improvement in appropriate referrals for genetic assessment.

The Value of DICER1 Mutation Analysis in "Subtle" Diagnostically Challenging Embryonal Rhabdomyosarcomas of the Uterine Cervix.

Embryonal rhabdomyosarcoma of the uterine cervix is a rare neoplasm which is almost invariably associated with pathogenic somatic or germline DICER1 mutations; patients with germline mutations have DICER1 syndrome. We report 2 subtle cervical embryonal rhabdomyosarcoma, one occurring in a 21-yr-old woman with a known history of DICER1 syndrome and the other in a 19-yr-old woman with no history of DICER1 syndrome or DICER1-associated neoplasms. Both neoplasms focally involved otherwise benign endocervical polyps and were characterized histologically by subtle areas of increased stromal cellularity, nuclear atypia and mitotic activity; there was focal nuclear staining of these areas with the skeletal muscle markers myogenin and myoD1. In both cases, demonstration of a somatic DICER1 RNase IIIb mutation in the tumor was instrumental in establishing the diagnosis. We believe these neoplasms represent the earliest discernible phase of cervical embryonal rhabdomyosarcoma. Pathologists should have a high index of suspicion when atypical stromal elements are present in endocervical polyps and immunohistochemistry together with DICER1 sequencing will assist in diagnosis.

Excisional treatment comparison for in situ endocervical adenocarcinoma (EXCISE): A phase 2 pilot randomized controlled trial to compare histopathological margin status, specimen size and fragmentation after loop electrosurgical excision procedure and cold knife cone biopsy.

OBJECTIVE: Adenocarcinoma in situ (AIS) of the cervix is a precursor to cervical adenocarcinoma. When AIS is detected by cervical screening an excision biopsy is mandatory to exclude invasion. We aimed to compare margins status, specimen size and fragmentation after loop electrosurgical excision procedure (LEEP) and 'cold knife cone biopsy' (CKC). METHODS: The EXCISE Trial was an investigator-initiated, multicenter, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at seven hospitals in Australia and New Zealand. We randomly assigned women aged ≥18 to ≤45 years with screen detected AIS to LEEP or CKC. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat. RESULTS: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. Margin status was evaluable in 36 cases. The proportion of patients with involved margins did not differ between groups. 25 of 26 LEEP and all 14 CKC biopsies were excised as single specimens (p = 1·00). There were no differences in specimen dimensions. Patients in the CKC group had more post-operative complications (64.3% compared to 15.4% for LEEP p = ·00). There were no differences in grade three complications (p = ·65). CONCLUSIONS: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardized protocol. However, the study was not powered to establish non-inferiority of LEEP and a definitive phase 3 trial to compare margin status and rates of treatment failure after LEEP and CKC is warranted.

Exploring Attitudes to Conception in Partners and Young Women with Gynecologic Cancers Treated by Fertility Sparing Surgery.

BACKGROUND: Approximately 20% of women with gynecologic cancers are under age 40 and with delayed childbearing, women may be diagnosed before their first pregnancy. Although fertility preservation is a priority for many women, attitudes to conception have not previously been investigated in these patients or their partners. We explored attitudes to conception in partners and young women, following fertility preserving treatment for gynecologic cancers. METHODS: A total of 16 telephone interviews were conducted with a purposive sample of patients who had had an early stage gynecologic cancer or borderline ovarian tumor treated by fertility sparing surgery in Western Australia between January 1st, 2005 to December 31st, 2016. The interviews were audio recorded, transcribed and thematic analysis was conducted. RESULTS: Four main themes were identified: (i) Emotions at diagnosis and perception of information given; (ii) Discussions of fertility and factors affecting childbearing; (iii) Role of partners in decision making and relationship pressures; (iv) Decision for treatment and postoperative regrets. CONCLUSIONS: Regret and relationship breakdown were commonly reported. Women need appropriate support including inviting their partners to attend clinic appointments and may need several appointments before treatment. Regret was commonly reported by women who opted for completion surgery.
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Promoting physical activity in regional and remote cancer survivors (PPARCS) using wearables and health coaching: randomised controlled trial protocol.

INTRODUCTION: Physically active cancer survivors have substantially less cancer recurrence and improved survival compared with those who are inactive. However, the majority of survivors (70%-90%) are not meeting the physical activity (PA) guidelines. There are also significant geographic inequalities in cancer survival with poorer survival rates for the third of Australians who live in non-metropolitan areas compared with those living in major cities. The primary objective of the trial is to increase moderate-to-vigorous PA (MVPA) among cancer survivors living in regional and remote Western Australia. Secondary objectives are to reduce sedentary behaviour and in conjunction with increased PA, improve quality of life (QoL) in non-metropolitan survivors. Tertiary objectives are to assess the effectiveness of the health action process approach (HAPA) model variables, on which the intervention is based, to predict change in MVPA. METHODS AND ANALYSIS: Eighty-six cancer survivors will be randomised into either the intervention or control group. Intervention group participants will receive a Fitbit and up to six telephone health-coaching sessions. MVPA (using Actigraph), QoL and psychological variables (based on the HAPA model via questionnaire) will be assessed at baseline, 12 weeks (end of intervention) and 24 weeks (end of follow-up). A general linear mixed model will be used to assess the effectiveness of the intervention. ETHICS AND DISSEMINATION: Ethics approval has been obtained from St John of God Hospital Subiaco (HREC/#1201). We plan to submit a manuscript of the results to a peer-reviewed journal. Results will be presented at conferences, community and consumer forums and hospital research conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001743257; pre-results, U1111-1222-5698.

A randomized controlled trial of WATAAP to promote physical activity in colorectal and endometrial cancer survivors.

OBJECTIVE: The objective of this study was to ascertain whether wearable technology coupled with action planning was effective in increasing physical activity (PA) in colorectal and endometrial cancer survivors at cardiovascular risk. METHODS: Sixty-eight survivors who had cardiovascular risk factors and were insufficiently active were randomized to intervention and control arms. Intervention participants were given a wearable tracker for 12 weeks, two group sessions, and a support phone call. Participants in the control arm received print materials describing PA guidelines. Assessments at baseline and 12 weeks measured triaxial and uniaxial estimates of moderate-vigorous physical activity (MVPA), sedentary behaviour, blood pressure, and body mass index (BMI). RESULTS: The intervention group significantly increased MVPA by 45 min/wk compared with a reduction of 21 min/wk in the control group. Group by time interactions were significant for minutes of MVPA (F1,126  = 5.14, P = 0.025). For those with diastolic hypertension, there was a significant group by time interaction (F1,66  = 4.89, P = 0.031) with a net reduction of 9.89 mm Hg in the intervention group. CONCLUSIONS: Significant improvements in MVPA were observed following the intervention. The results display promise for the use of pragmatic, low-intensity interventions using wearable technology.

Wearable Activity Technology And Action-Planning (WATAAP) to promote physical activity in cancer survivors: Randomised controlled trial protocol.

Background/Objective: Colorectal and gynecologic cancer survivors are at cardiovascular risk due to comorbidities and sedentary behaviour, warranting a feasible intervention to increase physical activity. The Health Action Process Approach (HAPA) is a promising theoretical framework for health behaviour change, and wearable physical activity trackers offer a novel means of self-monitoring physical activity for cancer survivors. Method: Sixty-eight survivors of colorectal and gynecologic cancer will be randomised into 12-week intervention and control groups. Intervention group participants will receive: a Fitbit Alta™ to monitor physical activity, HAPA-based group sessions, booklet, and support phone-call. Participants in the control group will only receive the HAPA-based booklet. Physical activity (using accelerometers), blood pressure, BMI, and HAPA constructs will be assessed at baseline, 12-weeks (post-intervention) and 24-weeks (follow-up). Data analysis will use the Group x Time interaction from a General Linear Mixed Model analysis. Conclusions: Physical activity interventions that are acceptable and have robust theoretical underpinnings show promise for improving the health of cancer survivors.

Antecedentes/Objetivo: Los sobrevivientes de cáncer tienen riesgo cardiovascular debido a la comorbilidad y al comportamiento sedentario, lo que justifica desarrollar una adecuada intervención para aumentar la práctica de actividad física. El Enfoque del Proceso de Acción de Salud (EPAS) constituye un marco teórico para el desarrollo de conductas saludables y los dispositivos electrónicos de actividad física son nuevas herramientas de automonitorización para los supervivientes de cáncer. Método: Sesenta y ocho sobrevivientes de cáncer colorrectal y ginecológico serán aleatorizados en grupos de intervención y control. Los participantes del grupo de intervención recibirán un Fitbit Alta™ para monitorizar la actividad física, sesiones grupales y aplicación de un folleto de EPAS, y una llamada telefónica de apoyo. Los participantes del grupo control únicamente recibirán un folleto basado en EPAS. Al inicio del estudio, a las 12 y 24 semanas, se evaluarán la actividad física (usando acelerómetros), la presión arterial, el Índice de Masa Corporal (IMC) y los constructos EPAS. El análisis de datos utilizará la interacción Grupo x Tiempo a partir de un análisis del Modelo Mixto Lineal General. Conclusiones: Las intervenciones de actividad física son factibles y tienen fundamentos teóricos que auguran mejorar la salud de los sobrevivientes de cáncer.

Wearable Activity Technology And Action-Planning (WATAAP) to promote physical activity in cancer survivors: Randomised controlled trial protocol / Pulseras inteligentes de actividad física y plan de acción (WATAAP) para promover la actividad física en sobrevivientes de cáncer: protocolo de un ensayo aleatorizado

BACKGROUND/OBJECTIVE: Colorectal and gynecologic cancer survivors are at cardiovascular risk due to comorbidities and sedentary behaviour, warranting a feasible intervention to increase physical activity. The Health Action Process Approach (HAPA) is a promising theoretical framework for health behaviour change, and wearable physical activity trackers offer a novel means of self-monitoring physical activity for cancer survivors. METHOD: Sixty-eight survivors of colorectal and gynecologic cancer will be randomised into 12-week intervention and control groups. Intervention group participants will receive: a Fitbit Alta™ to monitor physical activity, HAPA-based group sessions, booklet, and support phone-call. Participants in the control group will only receive the HAPA-based booklet. Physical activity (using accelerometers), blood pressure, BMI, and HAPA constructs will be assessed at baseline, 12-weeks (post-intervention) and 24-weeks (follow-up). Data analysis will use the Group X Time interaction from a General Linear Mixed Model analysis. CONCLUSIONS: Physical activity interventions that are acceptable and have robust theoretical underpinnings show promise for improving the health of cancer survivors

ANTECEDENTES/OBJETIVO: Los sobrevivientes de cáncer tienen riesgo cardiovascular debido a la comorbilidad y al comportamiento sedentario, lo que justifica desarrollar una adecuada intervención para aumentar la práctica de actividad física. El Enfoque del Proceso de Acción de Salud (EPAS) constituye un marco teórico para el desarrollo de conductas saludables y los dispositivos electrónicos de actividad física son nuevas herramientas de automonitorización para los supervivientes de cáncer. MÉTODO: Sesenta y ocho sobrevivientes de cáncer colorrectal y ginecológico serán aleatorizados en grupos de intervención y control. Los participantes del grupo de intervención recibirán un Fitbit Alta™ para monitorizar la actividad física, sesiones grupales y aplicación de un folleto de EPAS, y una llamada telefónica de apoyo. Los participantes del grupo control únicamente recibirán un folleto basado en EPAS. Al inicio del estudio, a las 12 y 24 semanas, se evaluarán la actividad física (usando acelerómetros), la presión arterial, el Índice de Masa Corporal (IMC) y los constructos EPAS. El análisis de datos utilizará la interacción Grupo X Tiempo a partir de un análisis del Modelo Mixto Lineal General. CONCLUSIONES: Las intervenciones de actividad física son factibles y tienen fundamentos teóricos que auguran mejorar la salud de los sobrevivientes de cáncer

Health-related quality of life and pelvic floor dysfunction in advanced-stage ovarian cancer survivors: associations with objective activity behaviors and physiological characteristics.

PURPOSE: Little is known about the relationship between health-related quality of life (HRQoL), pelvic floor dysfunction (PFD), and modifiable lifestyle and physiological factors for ovarian cancer survivors (OCS). The primary aim of the study was to compare post-treatment advanced-stage OCS with age-matched controls on measures of HRQoL and PFD. The secondary aim was to examine associations between HRQoL, PFD, objective activity behaviors, physical function, and body composition in OCS. METHODS: Twenty advanced-stage OCS and 20 controls completed questionnaires assessing HRQoL (SF-36) and PFD (Australian Pelvic Floor Questionnaire), and underwent objective assessments of activity behavior (7-day accelerometry), physical function (400-m walk, repeated chair rise, 6-m usual-pace walk, one-repetition maximum chest press, and single-leg extension), and body composition (dual-energy x-ray absorptiometry). RESULTS: Compared to controls, OCS had worse physical HRQoL (- 4.3 median difference, p = 0.013), but equivalent self-reported PFD, indicated by combined bladder, bowel, and pelvic organ prolapse symptoms (0.89 mean difference, p = 0.277). In OCS, physical HRQoL was significantly negatively associated with PFD (r = 0.468, p = 0.043). Decreased physical HRQoL and increased PFD were significantly associated with less moderate-to-vigorous physical activity in ≥ 10-min bouts (ρ = 0.627, p = 0.003; ρ = - 0.457, p = 0.049), more sedentary time (r = - 0.449, p = 0.047; r = 0.479, p = 0.038), and slower 400-m walk time (ρ = - 0.565, p = 0.022; ρ = 0.504, p = 0.028). CONCLUSIONS: Post-treatment advanced-stage OCS have decreased physical HRQoL, which is associated with modifiable factors such as worse PFD, less moderate-to-vigorous physical activity, more sedentary time, and decreased objective physical function. This highlights the need for ongoing supportive care and multidisciplinary interventions after first-line ovarian cancer treatment.

Activity Behaviors and Physiological Characteristics of Women With Advanced-Stage Ovarian Cancer: A Preliminary Cross-sectional Investigation.

OBJECTIVES: Ovarian cancer (OC) survivors experience many disease and treatment adverse effects. However, the impact of OC and its treatment on objective activity behaviors and physiological status have not been examined. The purpose of this study was to compare objectively measured activity behaviors and physiological characteristics of advanced-stage OC survivors to age-matched controls. METHODS: Twenty stage III-IV OC survivors and 20 controls completed assessments of activity behaviors (7-day accelerometry), physical function (400-meter walk as indicator of cardiorespiratory fitness, repeated chair rise, 6-meter walking tests), muscle strength (1-repetition maximum and handgrip), body composition (dual-energy x-ray absorptiometry), and musculoskeletal morphology (peripheral quantitative computed tomography). RESULTS: Compared with controls, OC survivors spent more time/day in prolonged sedentary bouts (P = 0.039, r = 0.32), had lower cardiorespiratory fitness (P = 0.041, r = 0.33) and upper body strength (P = 0.023, r = 0.37), had higher areal bone mineral content (P = 0.047, r = 0.33) and volumetric trabecular density (P = 0.048, r = 0.31), but were not different in other measures of body composition nor in muscle morphology (P > 0.050). Only 20% (n = 4) of OC survivors accrued 150 minutes/week or greater moderate and vigorous physical activity (MVPA) time in 10-minute bouts or greater. Moderate and vigorous physical activity time/day in 10-minute bouts or greater was strongly associated with cardiorespiratory fitness (P = 0.001, ρ = -0.702) and lower extremity function (P = 0.019, ρ = -0.519) and moderately associated with muscle cross-sectional area (P = 0.035, ρ = 0.473). CONCLUSIONS: Posttreatment OC survivors spent more time in prolonged sedentary bouts and had lower cardiorespiratory fitness and upper body strength compared with controls. Moderate and vigorous physical activity was associated with physical function and muscle cross-sectional area. Future studies should test the efficacy of exercise interventions to increase MVPA, reduce sedentary behavior, and increase cardiorespiratory fitness and muscle strength in OC survivors.

Do Groin Drains Reduce Postoperative Morbidity in Women Undergoing Inguinofemoral Lymphadenectomy for Vulvar Cancer?

OBJECTIVE: Sentinel lymph node biopsy has been widely adopted in the surgical management of women with early-stage vulvar cancer, but many patients require inguinofemoral lymphadenectomy (IFL). Following IFL, many surgeons drain the groin to prevent lymphocyst formation despite a lack of evidence to support this practice. Our objective was to investigate whether groin drains after IFL are associated with reduced postoperative morbidity in women undergoing surgery for vulvar cancer. METHODS: A retrospective cohort study of women diagnosed as having primary vulvar cancer who underwent vulvectomy/radical local excision and unilateral or bilateral IFL was conducted. Cases were ascertained from the weekly outcome reports of a statewide tertiary gynecologic oncology tumor board. Data including postoperative outcomes were abstracted from medical records. Patients were stratified into 1 of 2 groups according to whether a groin drain had been used. RESULTS: Seventy-one patients were included. Inguinal drains were used in 48 patients (67.6%) and 23 patients (32.4%) did not have their groin wound(s) drained. The most common postoperative complications recorded were wound infection (59.2%), groin lymphocyst (32.4%), and cellulitis (25.4%). The mean length of hospital admission was 11.5 days (2-40 days). Compared with patients in whom inguinal drains were placed, those in the "no drain" group had a significantly lower incidence of postoperative groin cellulitis (8.7% vs 25.4% P = 0.039). No significant differences were observed between patients in the "drain" and "no drain" groups in lymphocyst formation, wound infection, return to the operating room, duration of hospital stay, readmission post-discharge, and lower-limb lymphedema. CONCLUSIONS: In this study of patients undergoing inguinofemoral dissection for primary vulvar cancer, postoperative cellulitis occurred less frequently in patients without an inguinal drain. The incidence of other postoperative complications was no different whether or not a groin drain was used. Prospective studies may be warranted.

Advanced Training of Gynecologic Surgeons and Incidence of Intraoperative Complications after Total Laparoscopic Hysterectomy: A Retrospective Study of More Than 2000 Cases at a Single Institution.

STUDY OBJECTIVE: To investigate whether surgeon factors including level of training undertaken in laparoscopic surgery, time in specialist practice, and case volume were associated with surgical morbidity for total laparoscopic hysterectomy (TLH). DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: A tertiary care setting in Western Australia. PATIENTS: Two thousand thirteen patients who underwent TLH for benign or malignant indications. INTERVENTIONS: Women undergoing TLH were allocated to 1 of 3 groups of surgeons: general gynecologists, gynecologic endoscopists, and subspecialists. MEASUREMENTS AND MAIN RESULTS: All patients undergoing elective TLH at St John of God Subiaco Hospital, Subiaco, Perth, Western Australia, between January 1, 2011, and December 31, 2016, were included for analysis. Variables recorded included cystotomy, ureteric injury, enterotomy/colostomy, bowel serosa injury, vascular injury, conversion to laparotomy, return to the operating room, hemorrhage, blood transfusion, operating time, length of stay, and postoperative complications to 42 days. The primary outcome was any major intraoperative complication. The incidence of any major intraoperative complication was 1.8% (36/2013 cases). Forty-five patients (2.2%) had a postoperative complication, and 74 (3.7%) patients were readmitted to the hospital after discharge. The incidence of any major intraoperative complication was significantly higher among general gynecologists compared with subspecialists (3.3% vs 1.1%, p = .002). No association was found between time in specialist practice and the incidence of major intraoperative complications (p = .629). A significant association for major intraoperative complications was observed for surgeons who had performed <100 laparoscopic hysterectomies during the study period (p = .032). CONCLUSION: In this study, despite a higher level of surgical acuity and the performance of additional and more complex procedures, surgical morbidity was lower in patients undergoing TLH by gynecologic surgeons with a higher level of subspecialist training.

Outcomes in women undergoing robotic-assisted laparoscopic hysterectomy compared to conventional laparoscopic hysterectomy at a tertiary hospital in Western Australia.

BACKGROUND: Robotic-assisted laparoscopic hysterectomy (RALH) is associated with improved outcomes compared to open surgery in patients with endometrial cancer but data are conflicting when comparing RALH to conventional total laparoscopic hysterectomy (TLH). In October 2014, a RALH program was established in Perth, Western Australia. AIM: To compare outcomes in patients undergoing RALH with a matched cohort undergoing TLH. MATERIALS AND METHODS: A retrospective matched cohort study compared outcomes in 45 patients who underwent RALH with 45 controls who were patients treated with TLH. RESULTS: Mean operating time was longer in the RALH group compared to controls (75.42 min vs 53.18 min, mean difference 22.24 min, P < 0.001, 95% Cl, 11.07-33.42). No differences were observed in mean pain scores (RALH 1.47 vs TLH 1.84 P = 0.31), mean parenteral and oral opioid use (RALH 14.3 mg and 42.4 mg vs TLH 17.5 mg and 52.57 mg, P = 0.42 and 0.42, respectively), and mean length of stay (RALH 1.51 vs TLH 1.67 days, P = 0.49). Two patients in the RALH group and one patient in the TLH group sustained iatrogenic bladder injuries (P = 0.62). CONCLUSION: The establishment of the RALH program at our institution appeared to be associated with equivalent morbidity, post-operative pain, opioid use and length of stay compared to conventional laparoscopy. A surgical learning curve for RALH was observed. Well-designed prospective studies are needed to further evaluate short- and long-term patient function, morbidity, quality of life and oncologic outcomes.

Prognostic Role of Histological Tumor Regression in Patients Receiving Neoadjuvant Chemotherapy for High-Grade Serous Tubo-ovarian Carcinoma.

OBJECTIVE: Our objective was to validate the prognostic role of the chemotherapy response score (CRS), which has been proposed for measuring tumor response to neoadjuvant chemotherapy in patients with high-grade serous tubo-ovarian carcinoma, in predicting progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective cohort study was conducted of patients with advanced high-grade serous tubo-ovarian carcinoma diagnosed between January 1, 2010, and December 31, 2014, and treated with neoadjuvant chemotherapy. Treatment-related tumor regression was determined according to the 3-tier CRS, and results were compared with standard clinicopathological variables. Survival analysis was performed using Cox proportional hazards models and the log-rank test. RESULTS: Seventy-one patients were eligible for analysis. Median OS was 25.5 months. Fifty-eight patients (82%) had disease recurrence and 32 (45%) had died at study census. Of the 71 patients, 19, 29, and 23 patients had a CRS of 1, 2, and 3, respectively. On univariate analysis, the CRS significantly predicted PFS (hazard ratio [HR], 3.77; 95% confidence interval [CI], 1.83-7.78; P = 0.000) and OS (HR, 2.81; 95% CI, 1.16-6.79; P = 0.022). In a multivariate model, the CRS was significantly associated with PFS (HR, 2.81; 95% CI, 1.16-6.79; P = 0.022) but not with OS (HR, 2.39; 95% CI, 0.47-3.08; P = 0.079). Patients with CRS of 1 and 2 combined were twice as likely to progress during the study period compared with patients with a CRS of 3 (HR, 2.0; 95% CI, 1.06-3.78; P = 0.032; median PFS, 16 vs 26 months). No significant association was observed for OS (CRS 1/2 vs 3; HR, 1.57; 95% CI, 0.68-3.65; P = 0.291). CONCLUSIONS: In this study, the CRS showed independent prognostic significance for PFS but not for OS.

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 of persistent or recurrent neoplasia in conservatively treated women with cervical adenocarcinoma in situ with negative histological margins.

INTRODUCTION: Conservative treatments including cold knife cone biopsy (CKC) or loop electrosurgical excision procedure (LEEP) are fertility-preserving alternatives to hysterectomy. The risks of persistent cervical neoplasia in women with negative surgical margins following conservative treatment of adenocarcinoma-in-situ (AIS) are uncertain. This study aims to investigate the risk of persistent or recurrent cervical neoplasia [AIS, adenocarcinoma and/or high-grade cervical squamous intraepithelial neoplasia (CIN)] and compliance with follow-up recommendations in conservatively treated women with AIS and negative histopathological margins. MATERIAL AND METHODS: A retrospective, population-based study of Western Australian women treated by CKC or LEEP for AIS between 2001 and 2012. Histopathology reports were reviewed for demographic information, treatment procedures and clinicopathological factors. Primary outcomes were the diagnosis of cervical neoplasia during follow-up (defined as <12 months) and surveillance (≥12 months) periods. RESULTS: The cohort comprised 360 women, with 175 (48.6%) initially treated by CKC and 185 (51.4%) treated by LEEP. The median patient age at time of excisional treatment was 30.0 years (range 18-64 years) and the median follow-up time was 3.9 years (range six months to 12.2 years). During the follow-up and surveillance periods, seven (1.9%) women were diagnosed with CIN 2/3, 10 (2.8%) with AIS, and one (0.3%) with cervical adenocarcinoma, despite their initial excision specimens having negative histological margins. CONCLUSION: In this study, there was a low but significant risk of persistent or recurrent cervical neoplasia in women who had initial conservative management of AIS with negative histopathological margins.