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OBJECTIVE: Abdominal Radical hysterectomy (ARH) with pelvic lymph node assessment is considered the standard treatment for early-stage cervical cancer. Accepted routes have previously included laparoscopic or robotic approaches (LRH). Laparoscopy-assisted vaginal or vaginal radical hysterectomy (LVRH) are performed in some centers. The objective of this study is to compare surgical and oncological outcomes of LVRH, to laparoscopic and abdominal approaches. DESIGN PATIENTS SETTING: A retrospective multicenter analysis of consecutive cervical cancer cases who underwent a radical hysterectomy between 2007 and 2017 in eleven regional cancer centers across Canada. MEASUREMENTS: A comparison of patients stratified by surgical technique was undertaken. T-test, Wilcoxon rank-sum and chi-square were used to compare patient characteristics. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across surgical groups. MAIN RESULTS: A total of 1071 patients with cervical cancer stage IA1 with lymphovascular invasion to stage IIIC (FIGO 2018) <4 cm were identified. Postoperative complication rate was lowest for women undergoing LVRH (9.1 %, vs 18.3 % and 22.1 % for minimally invasive and open respectively). During follow up, 114 women recurred, and 70 women died. 5-year recurrence-free survival was 85.4 % for LRH, 89.4 % for ARH and 92.2 % for LVRH. LVRH was not found to be associated with a higher risk of recurrence or death than ARH on multivariable analysis (aHR for recurrence 0.62, CI 0.21-1.77; aHR for death 0.63, CI 0.14-2.77) CONCLUSION: In this retrospective study, vaginal or laparoscopy-assisted vaginal radical hysterectomy for cervical cancer was associated with favorable perioperative and oncological outcomes.
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Importance: Neonates requiring surgery are often cared for in neonatal intensive care units (NICUs). Despite a breadth of surgical pathology, neonates share many perioperative priorities that allow for the development of unit-wide evidence-based Enhanced Recovery After Surgery (ERAS) recommendations. Observations: The guideline development committee included pediatric surgeons, anesthesiologists, neonatal nurses, and neonatologists in addition to ERAS content and methodology experts. The patient population was defined as neonates (first 28 days of life) undergoing a major noncardiac surgical intervention while admitted to a NICU. After the first round of a modified Delphi technique, 42 topics for potential inclusion were developed. There was consensus to develop a search strategy and working group for 21 topic areas. A total of 5763 abstracts were screened, of which 98 full-text articles, ranging from low to high quality, were included. A total of 16 recommendations in 11 topic areas were developed with a separate working group commissioned for analgesia-related recommendations. Topics included team communication, preoperative fasting, temperature regulation, antibiotic prophylaxis, surgical site skin preparation, perioperative ventilation, fluid management, perioperative glucose control, transfusion thresholds, enteral feeds, and parental care encouragement. Although clinically relevant, there were insufficient data to develop recommendations concerning the use of nasogastric tubes, Foley catheters, and central lines. Conclusions and Relevance: Despite varied pathology, neonatal perioperative care within NICUs allows for unit-based ERAS recommendations independent of the planned surgical procedure. The 16 recommendations within this ERAS guideline are intended to be implemented within NICUs to benefit all surgical neonates.
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OBJECTIVE: To investigate the prevalence and patterns of social media use among gynecologic oncologists for professional and academic purposes. METHODS: A prospective online survey between November and December 2022 targeted gynecologic oncology practitioners (gynecologic oncologists, surgical oncologists, medical oncologists, radiation/clinical oncologists, and onco-pathologists/pathologists). The survey, distributed via various social media platforms, included 40 questions to capture qualitative and quantitative data on social media use. RESULTS: Of 131 respondents from 32 countries, 106 (80.9%) were gynecologic oncologists and affiliated with academic institutions (84.7%). Facebook (n=110, 83.9%), Twitter (n= 108, 82.4%), and Instagram (n=100, 76.3%) were the most used platforms. Respondents used social media to stay updated (n=101, 77.1%), network (n=97, 74%), learn about conferences and webinars (n=97, 74%), and engage in academic discussions (n=84, 64.1%). Following the COVID-19 pandemic, 100/129 (77.5%) reported increased social media use. However, only 32 (24.4%) used it to connect with patients, and concerns were raised about privacy and the need for separate professional and personal accounts. A quarter of respondents hesitated to share their opinions on social media due to the fear of controversy, with 26 (20%) experiencing cyberbullying, yet 120/130 (92.3%) believed it enabled junior professionals to express their views. Concerns about differentiating valid content, information reliability, and the professional perception of sourcing knowledge from social media were noted. Gender, age, specialty, and income level influenced patterns of social media use, with variations in preferences for platforms, content engagement, and purposes, highlighting a complex landscape of social media interaction among gynecologic oncologists. CONCLUSION: While the use of social media among gynecologic oncologists is prevalent, particularly for academic and professional development, challenges such as cyberbullying, privacy concerns, and the need for formal training in social media navigation persist. Tailored training programs and guidelines could enhance social media's effective and ethical use in this field, promoting a safe environment for professional expression and engagement.
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Mesonephric-type (or -like) adenocarcinomas (MAs) of the ovary are an uncommon and aggressive histotype. They appear to arise through transdifferentiation from Müllerian lesions creating diagnostic challenges. Thus, we aimed to develop a histologic and immunohistochemical (IHC) approach to optimize the identification of MA over its histologic mimics, such as ovarian endometrioid carcinoma (EC). First, we screened 1,537 ovarian epithelial neoplasms with a four-marker IHC panel of GATA3, TTF1, ER, and PR followed by a morphological review of EC to identify MA in retrospective cohorts. Interobserver reproducibility for the distinction of MA versus EC was assessed in 66 cases initially without and subsequently with IHC information (four-marker panel). Expression of PAX2, CD10, and calretinin was evaluated separately, and survival analyses were performed. We identified 23 MAs from which 22 were among 385 cases initially reported as EC (5.7%) and 1 as clear cell carcinoma. The interobserver reproducibility increased from fair to substantial (κ = 0.376-0.727) with the integration of the four-marker IHC panel. PAX2 was the single most sensitive and specific marker to distinguish MA from EC and could be used as a first-line marker together with ER/PR and GATA3/TTF1. Patients with MA had significantly increased risk of earlier death from disease (hazard ratio = 3.08; 95% CI, 1.62-5.85; p < 0.0001) compared with patients with EC, when adjusted for age, stage, and p53 status. A diagnosis of MA has prognostic implications for stage I disease, and due to the subtlety of morphological features in some tumors, a low threshold for ancillary testing is recommended.
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Biomarcadores de Tumor , Neoplasias Ováricas , Factor de Transcripción PAX2 , Humanos , Femenino , Neoplasias Ováricas/patología , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/mortalidad , Factor de Transcripción PAX2/análisis , Factor de Transcripción PAX2/metabolismo , Biomarcadores de Tumor/análisis , Persona de Mediana Edad , Reproducibilidad de los Resultados , Anciano , Adulto , Estudios Retrospectivos , Prevalencia , Inmunohistoquímica , Adenocarcinoma/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Diagnóstico Diferencial , Variaciones Dependientes del Observador , Anciano de 80 o más Años , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/mortalidadRESUMEN
Objective: This study aims to investigate the relationship between body mass index (BMI) and molecular subtypes of endometrial carcinoma using an immunohistochemistry (IHC)-based classification approach. Methods: We analyzed a consecutive series of endometrial cancer cases undergoing surgical staging in southern Alberta (2019-2021). Molecular classification was determined through IHC-based molecular typing, incorporating p53 and mismatch repair (MMR), and further characterized with the addition of ER and PR. BMI associations with molecular classification were assessed using t-tests. Hormone receptor status was further examined in a separate cohort of MMRd endometrial cancer patients undergoing surgical staging at Foothills Medical Centre (Alberta, Canada). Results: Among 289 cases, comprising various histological subtypes, the pNSMP subtype exhibited the highest average BMI (33.93 kg/m2) compared to the p53 abnormal subtype (30.40 kg/m2, p = 0.02). The MMRd subtype had an average BMI of 33.22 kg/m2. While there were no significant BMI differences between FIGO grade 1 and grade 2/3 tumours in the pNSMP or MMRd, a trend toward higher BMI in grade 1 tumours versus grade 2/3 tumours in the MMRd was observed (p = 0.13). A separate cohort of 53 MMRd endometrial carcinomas revealed that FIGO grade 1 tumours were associated with higher BMI (p < 0.05) and more frequent ER/PR expression compared to grade 2/3 tumours (p < 0.05). Conclusions: This study suggests an association between obesity and NSMP endometrial carcinoma. The relationship between BMI and low-grade MMRd endometrial carcinomas with increased ER/PR expression warrants further exploration.
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On February 6th, 2024, Gynecologic Oncology Reports and the Society of Gynecologic Oncology Education Committee co-hosted a webinar about ways to use social media for career enhancement and for dissemination of research. During the discussion, we reviewed:i.how to identify one's goals, target audience, and select a social media platform.ii.how to navigate the negatives of social media.iii.how to develop one's online academic brand.iv.how to use social media for academic promotion and career advancement.v.how to use social media as a research tool.vi.how to use visual tools to bring attention to one's research.The objective of this report is to review the literature on social media in oncology and review the webinar presentation.
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PURPOSE: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). EXPERIMENTAL DESIGN: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss. RESULTS: RB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. CONCLUSIONS: Co-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.
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Proteína BRCA1 , Proteína BRCA2 , Cistadenocarcinoma Seroso , Neoplasias Ováricas , Proteínas de Unión a Retinoblastoma , Humanos , Femenino , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Proteína BRCA2/genética , Proteína BRCA2/deficiencia , Proteína BRCA1/genética , Proteína BRCA1/deficiencia , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/inmunología , Proteínas de Unión a Retinoblastoma/genética , Pronóstico , Ubiquitina-Proteína Ligasas/genética , Clasificación del Tumor , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Persona de Mediana Edad , Mutación de Línea Germinal , Regulación Neoplásica de la Expresión Génica , Anciano , Biomarcadores de Tumor/genética , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismoRESUMEN
We examined associations between modifiable and non-modifiable cancer-related risk factors measured at endometrial cancer diagnosis and during early survivorship (~3 years post-diagnosis) with second primary cancer (SPC) risk among 533 endometrial cancer survivors in the Alberta Endometrial Cancer Cohort using Fine and Gray sub-distribution hazard models. During a median follow-up of 16.7 years (interquartile range (IQR)=12.2-17.9), 89 (17%) participants developed a SPC with breast (29%), colorectal (13%) and lung (12%) cancers being the most common. Dietary glycemic load before endometrial cancer diagnosis (≥90.4 vs. <90.4 g/day: sub-hazard ratios (sHR)=1.71, 95% confidence intervals (CI)=1.09-2.69) as well as older age (≥60 vs. <60: sHR=2.48, 95% CI=1.34-4.62) and alcohol intake (≥2 drink/week vs. none: sHR=3.81, 95% CI=1.55-9.31) during early survivorship were associated with increased SPC risk. Additionally, reductions in alcohol consumption from prediagnosis to early survivorship significantly reduced SPC risk (sHR=0.34, 95% CI=0.14-0.82). With one-in-six survivors developing a SPC, further investigation of SPC risk factors and targeted surveillance options for high-risk survivors could improve long-term health outcomes in this population. Reductions in dietary glycemic load and alcohol intake from prediagnosis to early survivorship showed promising risk reductions for SPCs and could be important modifiable risk factors to target among endometrial cancer survivors.
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Importance: A comprehensive review of the evidence exploring the outcomes of enhanced recovery after surgery (ERAS) guidelines has not been completed. Objective: To evaluate if ERAS guidelines are associated with improved hospital length of stay, hospital readmission, complications, and mortality compared with usual surgical care, and to understand differences in estimates based on study and patient factors. Data Sources: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central were searched from inception until June 2021. Study Selection: Titles, abstracts, and full-text articles were screened by 2 independent reviewers. Eligible studies were randomized clinical trials that examined ERAS-guided surgery compared with a control group and reported on at least 1 of the outcomes. Data Extraction and Synthesis: Data were abstracted in duplicate using a standardized data abstraction form. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Risk of bias was assessed in duplicate using the Cochrane Risk of Bias tool. Random-effects meta-analysis was used to pool estimates for each outcome, and meta-regression identified sources of heterogeneity within each outcome. Main Outcome and Measures: The primary outcomes were hospital length of stay, hospital readmission within 30 days of index discharge, 30-day postoperative complications, and 30-day postoperative mortality. Results: Of the 12â¯047 references identified, 1493 full texts were screened for eligibility, 495 were included in the systematic review, and 74 RCTs with 9076 participants were included in the meta-analysis. Included studies presented data from 21 countries and 9 ERAS-guided surgical procedures with 15 (20.3%) having a low risk of bias. The mean (SD) Reporting on ERAS Compliance, Outcomes, and Elements Research checklist score was 13.5 (2.3). Hospital length of stay decreased by 1.88 days (95% CI, 0.95-2.81 days; I2 = 86.5%; P < .001) and the risk of complications decreased (risk ratio, 0.71; 95% CI, 0.59-0.87; I2 = 78.6%; P < .001) in the ERAS group. Risk of readmission and mortality were not significant. Conclusions and Relevance: In this meta-analysis, ERAS guidelines were associated with decreased hospital length of stay and complications. Future studies should aim to improve implementation of ERAS and increase the reach of the guidelines.
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Recuperación Mejorada Después de la Cirugía , Tiempo de Internación , Readmisión del Paciente , Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Tiempo de Internación/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/epidemiología , Recuperación Mejorada Después de la Cirugía/normas , Guías de Práctica Clínica como Asunto , Masculino , Femenino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate the clinical outcomes pre- and post-implementation of an evidence-informed surgical site infection prevention bundle (SSIPB) in gynecologic oncology patients within an Enhanced Recovery After Surgery (ERAS) care pathway. METHODS: Patients undergoing laparotomy for a gynecologic oncology surgery between January-June 2017 (pre-SSIPB) and between January 2018-December 2020 (post-SSIPB) were compared using t-tests and chi-square. Patient characteristics, surgical factors, and ERAS process measures and outcomes were abstracted from the ERAS® Interactive Audit System (EIAS). The primary outcomes were incidence of surgical site infections (SSI) during post-operative hospital admission and at 30-days post-surgery. Secondary outcomes included total postoperative infections, length of stay, and any surgical complications. Multivariate models were used to adjust for potential confounding factors. RESULTS: Patient and surgical characteristics were similar in the pre- and post-implementation periods. Evaluation of implementation suggested that preoperative and intraoperative components of the intervention were most consistently used. Infectious complications within 30 days of surgery decreased from 42.1% to 24.4% after implementation of the SSIPB (p < 0.001), including reductions in wound infections (17.0% to 10.8%, p = 0.02), urinary tract infections (UTI) (12.7% to 4.5%, p < 0.001), and intra-abdominal abscesses (5.4% to 2.5%, p = 0.05). These reductions were associated with a decrease in median length of stay from 3 to 2 days (p = 0.001). In multivariate analysis, these SSI reductions remained statistically significant after adjustment for potential confounders. CONCLUSION: Implementation of SSIPB was associated with a reduction in SSIs and infectious complications, as well as a shorter length of stay in gynecologic oncology patients.
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Recuperación Mejorada Después de la Cirugía , Neoplasias de los Genitales Femeninos , Paquetes de Atención al Paciente , Infección de la Herida Quirúrgica , Humanos , Femenino , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/epidemiología , Neoplasias de los Genitales Femeninos/cirugía , Persona de Mediana Edad , Recuperación Mejorada Después de la Cirugía/normas , Paquetes de Atención al Paciente/métodos , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Procedimientos Quirúrgicos Ginecológicos/métodos , Procedimientos Quirúrgicos Ginecológicos/normas , Anciano , Tiempo de Internación/estadística & datos numéricos , Adulto , Estudios RetrospectivosRESUMEN
OBJECTIVES: The objectives of our quality improvement (QI) initiative were (1) to increase the rate of same-day discharge (SDD) in eligible gynecologic oncology (GO) patients to 70% and (2) to evaluate the ease with which QI methods demonstrated in one study could be applied at another center. DESIGN: A pre-/postintervention design was used (50 patients/group). SETTING: SDD in patients undergoing minimally invasive GO surgery is a recent trend aligned with Enhanced Recovery After Surgery (ERAS) principles. SDD in GO is safe and feasible based on several recent studies, including a QI initiative in Edmonton, Alberta, which resulted in SDD rates >70%. PATIENTS: A baseline audit of GO patients at our center (Calgary, Alberta) found the SDD rate to be 14%. Given that Edmonton and our center are within the same province, they have similar patient populations and available resources-suggesting that interventions from the Edmonton QI initiative may be translatable. INTERVENTIONS: Four interventions were designed to address root causes for failed SDD identified after QI diagnostics: (1) SDD as the default discharge plan, including a "Day Surgery" surgical booking; (2 and 3) development and implementation of ERAS SDD preoperative and postoperative order sets; and (4) patient education SDD-specific documents. MEASUREMENTS AND MAIN RESULTS: Rate of SDD was measured together with patient demographics and surgical outcomes. Process and balancing measures were defined and tracked. SDD in GO increased from 14% (7 of 50) to 82% (41 of 50) after the implementation of the above-mentioned interventions (odds ratio [OR], 28; p <.001; 95% confidence interval [CI], 9.54-82.11). Improved SDD was achieved without negatively affecting postoperative rates of emergency department visits: 8% pre- and 4% postintervention within 7 days (OR, 0.48; p = .678; 95% CI, 0.09-2.74) and 12% pre- and 10% postintervention within 30 days (OR, 0.8148; p = 1.001; 95% CI, 0.2317-2.86). CONCLUSION: This ERAS QI initiative resulted in a substantial increase in SDD in GO, without a negative impact on balancing measures. We demonstrate that the "spread" of simple, clearly defined QI interventions across centers (where the patient population is similar) is feasible. This suggests that an ERAS SDD program for GO could be a realistic goal for other centers with similar characteristics.
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Recuperación Mejorada Después de la Cirugía , Neoplasias de los Genitales Femeninos , Humanos , Femenino , Neoplasias de los Genitales Femeninos/cirugía , Alta del Paciente , Mejoramiento de la Calidad , Estudios Retrospectivos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Complicaciones Posoperatorias/epidemiologíaRESUMEN
BACKGROUND: Of all the care provided in health care systems, major surgical interventions are the costliest and can carry significant risks. Enhanced Recovery After Surgery (ERAS) is a bundle of interventions that help improve patient outcomes and experience along their surgical journey. However, given that patients can be overwhelmed by the multiple tasks that they are expected to follow, a digital application, the ERAS app, was developed to help improve the implementation of ERAS. OBJECTIVE: The objective of this work was to conduct a thorough assessment of patient and provider experiences using the ERAS app. METHODS: Patients undergoing colorectal or gynecological oncology surgery at 2 different hospitals in the province of Alberta, Canada, were invited to use the ERAS app and report on their experiences using it. Likewise, care providers were recruited to participate in this study to provide feedback on the performance of this app. Data were collected by an online survey and using qualitative interviews with participants. NVivo was used to analyze qualitative interview data, while quantitative data were analyzed using Excel and SPSS. RESULTS: Overall, patients found the app to be helpful in preparation for and recovery after surgery. Patients reported having access to reliable unbiased information regarding their surgery, and the app provided them with clarity of actions needed along their surgical journey and enhanced the self-management of their care. Clinicians found that the ERAS app was easy to navigate, was simple for older adults, and has the potential to decrease unnecessary visits and phone calls to care providers. Overall, this proof-of-concept study on the use of a digital health app to accompany patients during their health care journey has shown positive results. CONCLUSIONS: This is an important finding considering the massive investment and interest in promoting digital health in health care systems around the world.
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Background: Somatic loss of the tumour suppressor RB1 is a common event in tubo-ovarian high-grade serous carcinoma (HGSC), which frequently co-occurs with alterations in homologous recombination DNA repair genes including BRCA1 and BRCA2 (BRCA). We examined whether tumour expression of RB1 was associated with survival across ovarian cancer histotypes (HGSC, endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous carcinoma (LGSC)), and how co-occurrence of germline BRCA pathogenic variants and RB1 loss influences long-term survival in a large series of HGSC. Patients and methods: RB1 protein expression patterns were classified by immunohistochemistry in epithelial ovarian carcinomas of 7436 patients from 20 studies participating in the Ovarian Tumor Tissue Analysis consortium and assessed for associations with overall survival (OS), accounting for patient age at diagnosis and FIGO stage. We examined RB1 expression and germline BRCA status in a subset of 1134 HGSC, and related genotype to survival, tumour infiltrating CD8+ lymphocyte counts and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cell lines with and without BRCA1 mutations to model co-loss with treatment response. We also performed genomic analyses on 126 primary HGSC to explore the molecular characteristics of concurrent homologous recombination deficiency and RB1 loss. Results: RB1 protein loss was most frequent in HGSC (16.4%) and was highly correlated with RB1 mRNA expression. RB1 loss was associated with longer OS in HGSC (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.66-0.83, P = 6.8 ×10-7), but with poorer prognosis in ENOC (HR 2.17, 95% CI 1.17-4.03, P = 0.0140). Germline BRCA mutations and RB1 loss co-occurred in HGSC (P < 0.0001). Patients with both RB1 loss and germline BRCA mutations had a superior OS (HR 0.38, 95% CI 0.25-0.58, P = 5.2 ×10-6) compared to patients with either alteration alone, and their median OS was three times longer than non-carriers whose tumours retained RB1 expression (9.3 years vs. 3.1 years). Enhanced sensitivity to cisplatin (P < 0.01) and paclitaxel (P < 0.05) was seen in BRCA1 mutated cell lines with RB1 knockout. Among 126 patients with whole-genome and transcriptome sequence data, combined RB1 loss and genomic evidence of homologous recombination deficiency was correlated with transcriptional markers of enhanced interferon response, cell cycle deregulation, and reduced epithelial-mesenchymal transition in primary HGSC. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. Conclusions: Co-occurrence of RB1 loss and BRCA mutation was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.
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INTRODUCTION: Iron-deficiency anaemia is common in gynaecological oncology patients. Blood transfusions are immunosuppressive and carry immediate and long-term risks. Oral iron replacement remains the standard of care but requires prolonged treatment courses associated with gastrointestinal side effects, poor compliance and variable absorption in cancer patients. Intravenous iron has been shown to decrease the need for allogeneic blood transfusion in gynaecological oncology patients undergoing chemotherapy, but the efficacy of this treatment in the preoperative period is unknown. The goal of this pilot study is to determine the effect of intravenous ferric derisomaltose on preoperative haemoglobin in patients undergoing surgery for gynaecological malignancy. METHODS AND ANALYSIS: We will conduct a pilot single-centre, parallel-arm randomised controlled trial of intravenous ferric derisomaltose versus placebo among consenting patients with iron-deficiency anaemia having elective major surgery on the gynaecological oncology service. Patients, clinicians and outcome assessors will be blinded. The intervention consists of a single infusion of 500-1000 mg of intravenous ferric derisomaltose administered a minimum of 21 days prior to the planned operation. The primary outcome is mean preoperative haemoglobin concentration measured 0-3 days prior to surgery in patients receiving intravenous ferric derisomaltose compared with those receiving placebo. Secondary outcomes include the following: change in haemoglobin concentration, postoperative haemoglobin concentration, perioperative blood transfusion rates, patient-reported quality of life scores (Quality of Recovery 15, Modified Short Form 36 v1, EuroQol 5-dimension 5-level and Functional Assessment of Cancer Therapy - Anaemia), surgical site infection, complication rates, length of hospital stay and readmission rate. Analyses will follow intention-to-treat principles for all randomised participants. All patients will be followed up to 60 days following surgery. ETHICS AND DISSEMINATION: Ethical approval has been granted by Health Research Ethics Board of Alberta (Project ID: HREBA.CC-22-0187) and Health Canada (HC6-024-c264013). Results will be disseminated through presentation at scientific conferences, peer-reviewed publication and social and traditional media. TRIAL REGISTRATION NUMBER: NCT05407987.
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Anemia Ferropénica , Recuperación Mejorada Después de la Cirugía , Neoplasias de los Genitales Femeninos , Humanos , Femenino , Anemia Ferropénica/tratamiento farmacológico , Proyectos Piloto , Neoplasias de los Genitales Femeninos/complicaciones , Neoplasias de los Genitales Femeninos/cirugía , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Estudios de Factibilidad , Calidad de Vida , Cuidados Preoperatorios/métodos , Hierro/uso terapéutico , Hemoglobinas , Alberta , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Enhanced recovery after surgery (ERAS) has established benefits in open gynecologic oncology surgery. However, the benefits for gynecologic oncology patients undergoing minimally invasive surgery (MIS) are less well defined. We conducted a review of this topic after a comprehensive search of the peer-reviewed literature using MEDLINE and PubMed databases. Our search yielded 25 articles, 14 of which were original research articles, in 10 distinct patient cohorts describing ERAS in minimally invasive gynecologic oncology surgery. Major benefits of ERAS in MIS included: decreased length of stay and increased rates of same-day discharge, cost-savings, decreased opioid use, and increased patient satisfaction. ERAS in minimally invasive gynecologic oncology surgery is an area of great promise for both patients and the healthcare system.
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Recuperación Mejorada Después de la Cirugía , Neoplasias de los Genitales Femeninos , Humanos , Femenino , Neoplasias de los Genitales Femeninos/cirugía , Alta del Paciente , Satisfacción del Paciente , Procedimientos Quirúrgicos Mínimamente InvasivosRESUMEN
OBJECTIVE: Inhibition of the MAPK pathway by MEK inhibitors (MEKi) is currently a therapeutic standard in several cancer types, including ovarian low-grade serous carcinoma (LGSC). A common MAPK pathway alteration in tubo-ovarian high-grade serous carcinoma (HGSC) is the genomic inactivation of neurofibromin 1 (NF1). The primary objectives of our study were to survey the prevalence of NF1 inactivation in the principal ovarian carcinoma histotype as well as to evaluate its associations with clinico-pathological parameters and key biomarkers including BRCA1/2 status in HGSC. METHODS: A recently commercialized NF1 antibody (clone NFC) was orthogonally validated on an automated immunohistochemistry (IHC) platform and IHC was performed on tissue microarrays containing 2140 ovarian carcinoma cases. Expression was interpreted as loss/inactivated (complete or subclonal) versus normal/retained. RESULTS: Loss of NF1 expression was detected in 250/1429 (17.4%) HGSC including 11% with subclonal loss. Survival of NF1-inactivated HGSC patients was intermediate between favorable BRCA1/2 mutated HGSC and unfavorable CCNE1 high-level amplified HGSC. NF1 inactivation was mutually exclusive with CCNE1 high-level amplifications, co-occurred with RB1 loss and occurred at similar frequencies in BRCA1/2 mutated versus wild-type HGSC. NF1 loss was found in 21/286 (7.3%) endometrioid carcinomas with a favorable prognostic association (p = 0.048), and in 4/64 (5.9%) LGSC, mutually exclusive with other driver events. CONCLUSIONS: NF1 inactivation occurs in a significant subset of BRCA1/2 wild-type HGSC and a subset of LGSC. While the functional effects of NF1 inactivation need to be further characterized, this signifies a potential therapeutic opportunity to explore targeting NF1 inactivation in these tumors.
Asunto(s)
Carcinoma Endometrioide , Cistadenocarcinoma Seroso , Neoplasias Ováricas , Femenino , Humanos , Proteína BRCA1 , Neurofibromina 1/genética , Inmunohistoquímica , Proteína BRCA2 , Neoplasias Ováricas/patología , Carcinoma Endometrioide/patología , Cistadenocarcinoma Seroso/patología , Carcinoma Epitelial de OvarioRESUMEN
OBJECTIVES: To characterize the effect of transversus abdominis plane (TAP) blocks on post-operative outcomes in patients undergoing laparotomy for gynecologic malignancy. METHODS: This retrospective cohort study assessed patients undergoing laparotomy in 2016-2017 and 2020 in Alberta, Canada. The primary outcome was opioid consumption in oral morphine milligram equivalent (MME). Secondary outcomes included maximum pain scores, length of stay, and patient-controlled analgesia (PCA) use. Outcomes were compared using t-test with subgroup analysis by NSAID use. Multivariate regression modelling was performed for potential confounders. RESULTS: Data was collected on 956 patients; 828 received a TAP block, 128 did not. Opioid use in the first 24 h was lower in the TAP block group (35.9 mg MME vs 44.5 mg MME, p = 0.0294), without any increase in pain scores, this did not remain significant after regression analysis. Patients with TAP blocks had significant reduced mean length of stay (3.2 days vs. 5.0 days, p < 0.0001), and PCA use (19.9% vs. 56.25%, p < 0.0001). On subgroup analysis of patients that did not receive NSAIDs (n = 160), mean opioid use was decreased in those patients with TAP blocks compared to those without TAP blocks in the first 24 h (36.1 mg vs. 61.2 mg, p = 0.0017), and at 24 to 48 h (16.3 mg vs. 51.0 mg, p < 0.0001). CONCLUSIONS: Surgeon-administered TAP blocks were associated with decreased length of stay and post-operative opioid use in patients not receiving scheduled NSAIDs. This decrease in opioid use was not associated with any increase in average or maximum pain scores.