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Objective: Nuanced distress screening tools can help cancer care services manage specific cancer groups' concerns more efficiently. This study examines the sensitivity and specificity of a tool specifically for women with gynaecological cancers (called the Gynaecological Cancer Distress Screen or DT‐Gyn). Methods: This paper presents cross‐sectional data from individuals recently treated for gynaecological cancer recruited through Australian cancer care services, partner organisations, and support/advocacy services. Receiver operating characteristics analyses were used to evaluate the diagnostic accuracy of the DT‐Gyn against criterion measures for anxiety (GAD‐7), depression (patient health questionnaire), and distress (IES‐R and K10). Results: Overall, 373 individuals aged 19–91 provided complete data for the study. Using the recognised distress thermometer (DT) cut‐off of 4, 47% of participants were classified as distressed, while a cut‐off of 5 suggested that 40% had clinically relevant distress. The DT‐Gyn showed good discriminant ability across all measures (IES‐R: area under the curve (AUC) = 0.86, 95% CI = 0.82–0.90; GAD‐7: AUC = 0.89, 95% CI = 0.85–0.93; K10: AUC = 0.88, 95% CI = 0.85–0.92; PHQ‐9: AUC = 0.85, 95% CI = 0.81–0.89) and the Youden Index suggested an optimum DT cut‐point of 5. Conclusions: This study established the psychometric properties of the DT‐Gyn, a tool designed to identify and manage the common sources of distress in women with gynaecological cancers. We suggest a DT cut point ≥5 is optimal in detecting 'clinically relevant' distress, anxiety, and depression in this population. [ABSTRACT FROM AUTHOR]

Aims: To assess the safety and feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreduction surgery (CRS) in advanced high‐grade serous ovarian, fallopian tube and peritoneal cancer within an Australian context. Methods: Data were collected from 25 consecutive patients undergoing CRS and HIPEC from December 2018 to July 2022 at the Peritoneal Malignancy Service at the Mater Hospital Brisbane, Australia. Data collected included demographics, clinical variables, surgical procedures and complications and intra‐operative and post‐operative indexes of morbidity. Results: Twenty‐five women who underwent CRS and HIPEC from December 2018 to July 2022 were included in analysis. Findings indicate that CRS with HIPEC is associated with low morbidity. Conclusion: While judicious patient selection is imperative, HIPEC during CRS was well tolerated by all patients and morbidity was comparable to results from the previously reported OVHIPEC‐1 trial. HIPEC appears to be a safe and feasible addition to CRS for the treatment of advanced ovarian cancer in Australian practice. [ABSTRACT FROM AUTHOR]

Indocyanine green (ICG) and near infra-red fluorescence imaging in minimally invasive surgery is an option to map sentinel lymph nodes (SLN). The aim of this study was to compare the outcomes of SLN mapping between laparoscopic and robotic surgery. One-hundred-and-forty women with histologically confirmed endometrial cancer, were treated with a minimally invasive hysterectomy, bilateral salpingo-oophorectomy and SLN mapping. After anaesthetic induction, ICG was superficially injected into cervical submucosa and deeply injected into the cervical stroma at the 3 and 9 o'clock positions (1.25 mg/site). Eleven cases were abandoned after ICG injection (laparoscopic surgery seven cases and robotic surgery four cases) because of obesity, technical difficulty and peritoneal disease. One-hundred-and-eleven patients were analysed. Seventy-six patients had a laparoscopic procedure and 33 patients had robotic surgery. The overall and bilateral detection rates were 97% and 83% for laparoscopic surgery and 88% and 73% for robotic surgery. Laparoscopic surgery was superior to robotic surgery in terms of overall detection (p-value.046). There was no significant difference in the intra-operative SLN identification time or SLN dissection time between laparoscopy and robotic surgery (p-value.247 and.145, respectively). Further research is required to compare laparoscopy and robotic surgery in terms of SLN detection. What is already known on this subject? Sentinel lymph node (SLN) mapping aims to avoid complications and provide useful staging information for endometrial cancer. ICG has been shown to improve the detection rate and NPV compared with other tracers (blue dye and technetium 99). No data exists comparing SLN mapping rates using ICG in laparoscopy and robotic surgery. What do the results of this study add? The overall and bilateral detection rates were 97% and 83% for laparoscopic surgery and 88% and 73% for robotic surgery. Laparoscopic surgery was superior to robotic surgery in terms of overall detection. There was no significant difference in the intra-operative SLN identification time or SLN dissection time between laparoscopy and robotic surgery. What are the implications of these findings for clinical practice and/or further research?: This study confirms that laparoscopy and robotic surgery are not different in terms of bilateral detection rate and SLN operating time; the study population is small. [ABSTRACT FROM AUTHOR]

Objective Interval cytoreduction following neoadjuvant chemotherapy is a well-recognized treatment alternative to primary debulking surgery in the treatment of advanced epithelial ovarian cancer where patient and/or disease factors prevent complete macroscopic disease resection to be achieved. More recently, the strain of the global COVID-19 pandemic on hospital resources has forced many units to alter the timing of interval surgery and extend the number of neoadjuvant chemotherapy cycles. In order to support this paradigm shift and provide more accurate counseling during these unprecedented times, we investigated the survival outcomes in advanced epithelial ovarian cancer patients with the intent of maximal cytoreduction following neoadjuvant chemotherapy with respect to timing of surgery and degree of cytoreduction. Methods A retrospective review of all patients aged 18 years and above with FIGO (2014) stage III/IV epithelial ovarian cancer treated with neoadjuvant chemotherapy and the intention of interval cytoreduction surgery between January 2008 and December 2017 was conducted. Overall and progression-free survival outcomes were analyzed and compared with patients who only received chemotherapy. Outcome measures were correlated with the number of neoadjuvant chemotherapy cycles and amount of residual disease following surgery. Results Six hundred and seventy-one patients (median age 67 (range 20--91) years) were included in the study with 572 patients treated with neoadjuvant chemotherapy and surgery and 99 patients with chemotherapy only. There was no difference in the proportion of patients in whom complete cytoreduction was achieved based on number of cycles of neoadjuvant chemotherapy (2--4 cycles: 67.7%, n=337/498); ≥5 cycles: 62.2%, n=46/74). Patients undergoing cytoreduction surgery after neoadjuvant chemotherapy had a median 5-year progression-free and overall survival of 24 and 38 months, respectively. No significant difference in overall survival between surgical groups was observed (interval cytoreduction: 41 months vs delayed cytoreduction: 43 months, p=0.52). Those who achieved complete cytoreduction to R0 (no macroscopic disease) had a significant median overall survival advantage compared with those with any macroscopic residual disease (R0: 49--51 months vs R<1: 22--39 months, p<0.001 vs R≥1: 23--26 months, p<0.001). Conclusions Survival outcomes do not appear to be worse for patients treated with neoadjuvant chemotherapy if cytoreduction surgery is delayed beyond three cycles. In advanced epithelial ovarian cancer patients the imperative to achieve complete surgical cytoreduction remains gold standard, irrespective of surgical timing, for best survival benefit. [ABSTRACT FROM AUTHOR]

Exosomes are small nanovesicles that carry bioactive molecules which can be delivered to neighbouring cells to modify their biological functions. Studies have showed that exosomes from ovarian cancer (OVCA) cells can alter the cell migration and proliferation of cells within the tumour microenvironment, an effect modulated by the invasiveness capacity of their originating cells. Using an OVCA cell line xenograph mouse model, we showed that exosomes derived from a high invasiveness capacity cell line (exo-SKOV-3) promoted metastasis in vivo compared with exosomes from a low invasiveness capacity cell line (exo-OVCAR-3). Analysis from anin vivo imaging system (IVIS) revealed that exo-SKOV-3 formed metastatic niches, whereas exo-OVCAR-3 formed colonies of clustered cells close to the site of injection. Interestingly, kinetic parameters showed that the half-maximal stimulatory time (ST50) of tumour growth with exo-OVCAR-3 (4.0 +- 0.31 weeks) was significantly lower compared with the ST50 in mice injected with exo-SKOV-3 (4.5 +- 0.32 weeks). However, the number of metastic nodes in mice injected with exo-SKOV-3 was higher compared with exo-OVCAR-3. Using a quantitative mass spectrometry approach (SWATH MS/MS) followed by bioinformatics analysis using the Ingenuity Pathway Analysis (IPA), we identified a total of 771 proteins. Furthermore, 40 of these proteins were differentially expressed in tumour tissues from mice injected with exo-SKOV-3 compared with exo-OVCAR-3, and associated with Wnt canonical pathway (ß-catenin). Finally, we identified a set of proteins which had elevated expression in the circulating exosomes in association with tumour metastasis. These observations suggest that exosomal signalling plays an important role in OVCA metastasis. [ABSTRACT FROM AUTHOR]

Chemoresistance is one of the major obstacles in the treatment of cancer patients. It poses a fundamental challenge to the effectiveness of chemotherapy and is often linked to relapse in patients. Chemoresistant cells can be identified in different types of cancers; however, ovarian cancer has one of the highest rates of chemoresistance-related relapse (50% of patients within 5 years). Resistance in cells can either develop through prolonged cycles of treatment or through intrinsic pathways. Mechanistically, the problem of drug resistance is complex mainly because numerous factors are involved, such as overexpression of drug efflux pumps, drug inactivation, DNA repair mechanisms and alterations to and/or mutations in the drug target. Additionally, there is strong evidence that circulating miRNAs participate in the development of chemoresistance. Recently, miRNAs have been identified in exosomes, where they are encapsulated and hence protected from degradation. These miRNAs within exosomes (exo-miRNAs) can regulate the gene expression of target cells both locally and systemically. Exo-miRNAs play an important role in disease progression and can potentially facilitate chemoresistance in cancer cells. In addition, and from a diagnostic perspective, exo-miRNAs profiles may contribute to the development of predictive models to identify responder and non-responder chemotherapy. Such model may also be used for monitoring treatment response and disease progression. Exo-miRNAs may ultimately serve as both a predictive biomarker for cancer response to therapy and as a prognostic marker for the development of chemotherapy resistance. Therefore, this review examines the potential role of exo-miRNAs in chemotherapy in ovarian cancer. [ABSTRACT FROM AUTHOR]

Summary LINE-1 (L1) retrotransposons are a source of insertional mutagenesis in tumor cells. However, the clinical significance of L1 mobilization during tumorigenesis remains unclear. Here, we applied retrotransposon capture sequencing (RC-seq) to multiple single-cell clones isolated from five ovarian cancer cell lines and HeLa cells and detected endogenous L1 retrotransposition in vitro . We then applied RC-seq to ovarian tumor and matched blood samples from 19 patients and identified 88 tumor-specific L1 insertions. In one tumor, an intronic de novo L1 insertion supplied a novel cis -enhancer to the putative chemoresistance gene STC1 . Notably, the tumor subclone carrying the STC1 L1 mutation increased in prevalence after chemotherapy, further increasing STC1 expression. We also identified hypomethylated donor L1s responsible for new L1 insertions in tumors and cultivated cancer cells. These congruent in vitro and in vivo results highlight L1 insertional mutagenesis as a common component of ovarian tumorigenesis and cancer genome heterogeneity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Abnormally invasive placenta is a major cause of maternal morbidity and mortality. The aim of this study was to assess the effectiveness of a standardized operative approach performed by gynecological oncologists in the surgical management of abnormally invasive placenta.Materials and Methods: We performed a retrospective analysis of all cases of morbid placental adherence managed at the Mater Mothers' Hospitals, Brisbane, Australia between January 2000 and June 2013. A standard operative approach involving extensive retro-peritoneal and bladder dissection before delivery of the fetus, was undertaken when a gynecological oncologist was present at the start of the procedure. Main outcome measures were estimated blood loss, transfusion requirements, and maternal and neonatal morbidity.Results: The study includes 98 cases of histologically confirmed abnormally invasive placenta. Median estimated blood loss for the entire cohort was 2150 mL (range 300-11 500 mL). Women were divided into three groups, (1) those who had a gynecological oncologist present at the start of the procedure (group 1; n = 43), (2) those who had a gynecological oncologist called in during the procedure (group 2; n = 23), and (3) those who had no gynecological oncologist involved (group 3; n = 32). Group 2 had a significantly higher blood loss than the other groups (p = 0.001) (median 4400 mL). Transfusion requirements were higher in groups 2 and 3 compared with group 1 (p = 0.004). Other maternal and neonatal morbidity was similar across all three groups.Conclusion: This study supports the early presence of a gynecological oncologist at delivery when abnormally invasive placenta is suspected and demonstrates that a "call if needed" approach is not acceptable for these complex cases. [ABSTRACT FROM AUTHOR]

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.To compare the 1988 FIGO vulval carcinoma staging system with that of 2009 with regard to stage migration and prognostication.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.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.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. [ABSTRACT FROM AUTHOR]

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.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.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.Depth of myometrial invasion predicts nodal involvement independently when compared with TFD. [ABSTRACT FROM AUTHOR]

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. Aim: To compare the Pap smear history of patients with AC and SCC of the cervix. Methods: Patients for the study were identified from the database of Queensland Centre for Gynaecological Cancer. Patients with AC and SCC were matched for age at diagnosis and International Federation of Gynecology and Obstetrics stage. The final population included 188 matched pairs, being 376 patients in total. Data were collected upon the histological type of cancer, result of the most recent Pap smear, date and result of the Pap smear prior to the most recent Pap smear and symptoms. Chi-squared tests and Fisher's exact test were used to compare the two patient groups for several variables. Results: Patients with AC had significantly more false-negative results on their most recent Pap smear ( P < 0.0001) than patients with SCC. The incidence of symptoms such as bleeding and/or vaginal discharge was comparable in patients with AC and SCC. The time between the most recent Pap smear and the diagnosis of cervical cancer was significantly shorter for patients with AC ( P = 0.01). Conclusions: Patients with AC had Pap smears more regularly than those with SCC, and their most recent Pap smear was significantly more likely to be normal. Thus, Pap smear prior to a diagnosis of AC is more likely than SCC false-negative and therefore not indicative of cervical cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer is one of the most lethal cancers affecting women worldwide. Its high mortality rate is often attributed to the non-specific nature of early symptoms of the disease. Developing a better understanding of the disease progression and identifying clinically useful biomarkers that aid in clinical management are requisite to reducing the mortality rate of ovarian cancer. Reduced oxygen tension (i.e., hypoxia) is not only a characteristic of solid tumors but may also enhance the metastatic capacity of tumors by inducing the release of tumor growth promoting factors. Recently, it has been proposed that small tumor-derived extracellular vesicles (sEVs) facilitate cancer progression. In this study, we established that sEVs produced under low oxygen tension induce a metabolic switch in ovarian cancer cells associated with changes in glycolytic pathway proteins that promote resistance to carboplatin. Significantly, we identified a suite of sEV-associated glycolysis pathway proteins that are present in patients with ovarian cancer that can predict disease recurrence with over 90% accuracy. Hypoxia is a key regulator of cancer progression and chemoresistance. Ambiguity remains about how cancer cells adapt to hypoxic microenvironments and transfer oncogenic factors to surrounding cells. In this study, we determined the effects of hypoxia on the bioactivity of sEVs in a panel of ovarian cancer (OvCar) cell lines. The data obtained demonstrate a varying degree of platinum resistance induced in OvCar cells when exposed to low oxygen tension (1% oxygen). Using quantitative mass spectrometry (Sequential Window Acquisition of All Theoretical Fragment Ion Mass Spectra, SWATH) and targeted multiple reaction monitoring (MRM), we identified a suite of proteins associated with glycolysis that change under hypoxic conditions in cells and sEVs. Interestingly, we identified a differential response to hypoxia in the OvCar cell lines and their secreted sEVs, highlighting the cells' heterogeneity. Proteins are involved in metabolic reprogramming such as glycolysis, including putative hexokinase (HK), UDP-glucuronosyltransferase 1–6 (UD16), and 6-phosphogluconolactonase (6 PGL), and their presence correlates with the induction of platinum resistance. Furthermore, when normoxic cells were exposed to sEVs from hypoxic cells, platinum-resistance increased significantly (p < 0.05). Altered chemoresistance was associated with changes in glycolysis and fatty acid synthesis. Finally, sEVs isolated from a clinical cohort (n = 31) were also found to be enriched in glycolysis-pathway proteins, especially in patients with recurrent disease. These data support the hypothesis that hypoxia induces changes in sEVs composition and bioactivity that confers carboplatin resistance on target cells. Furthermore, we propose that the expression of sEV-associated glycolysis-pathway proteins is predictive of ovarian cancer recurrence and is of clinical utility in disease management. [ABSTRACT FROM AUTHOR]

Presents a case study of endometrial carcinoma presenting with neurological signs due to a thoracic vertebral metastasis in a 63-year-old woman. Medical history of the patient; Symptoms and manifestations of the disease; Diagnosis and treatment.