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Abstract Background Plant volatiles play an important role in both plant-pollinator and plant-herbivore interactions. Intraspecific polymorphisms in volatile production are ubiquitous, but studies that explore underlying differential gene expression are rare. Oenothera harringtonii populations are polymorphic in floral emission of the monoterpene (R)-(−)-linalool; some plants emit (R)-(−)-linalool (linalool+ plants) while others do not (linalool- plants). However, the genes associated with differential production of this floral volatile in Oenothera are unknown. We used RNA-Seq to broadly characterize differential gene expression involved in (R)-(−)-linalool biosynthesis. To identify genes that may be associated with the polymorphism for this trait, we used RNA-Seq to compare gene expression in six different Oenothera harringtonii tissues from each of three linalool+ and linalool- plants. Results Three clusters of differentially expressed genes were enriched for terpene synthase activity: two were characterized by tissue-specific upregulation and one by upregulation only in plants with flowers that produce (R)-(−)-linalool. A molecular phylogeny of all terpene synthases identified two putative (R)-(−)-linalool synthase transcripts in Oenothera harringtonii, a single allele of which is found exclusively in linalool+ plants. Conclusions By using a naturally occurring polymorphism and comparing different tissues, we were able to identify candidate genes putatively involved in the biosynthesis of (R)-(−)-linalool. Expression of these genes in linalool- plants, while low, suggests a regulatory polymorphism, rather than a population-specific loss-of-function allele. Additional terpene biosynthesis-related genes that are up-regulated in plants that emit (R)-(−)-linalool may be associated with herbivore defense, suggesting a potential economy of scale between plant reproduction and defense.

Here, we evaluate the mechanisms underlying the neurodevelopmental deficits in Drosophila and mouse models of lysosomal storage diseases (LSDs). We find that lysosomes promote the growth of neuromuscular junctions (NMJs) via Rag GTPases and mechanistic target of rapamycin complex 1 (MTORC1). However, rather than employing S6K/4E-BP1, MTORC1 stimulates NMJ growth via JNK, a determinant of axonal growth in Drosophila and mammals. This role of lysosomal function in regulating JNK phosphorylation is conserved in mammals. Despite requiring the amino-acid-responsive kinase MTORC1, NMJ development is insensitive to dietary protein. We attribute this paradox to anaplastic lymphoma kinase (ALK), which restricts neuronal amino acid uptake, and the administration of an ALK inhibitor couples NMJ development to dietary protein. Our findings provide an explanation for the neurodevelopmental deficits in LSDs and suggest an actionable target for treatment.

Background/aim: The COVID-19 pandemic brought unprecedented global changes, necessitating adjustments to address public health challenges. The impact on advanced epithelial ovarian cancer (EOC) surgery, marked by increased perioperative risks, and changes in management plans was explored in this study based on promptly published British Gynaecologic Cancer Society (BGCS) and European Society of Gynaecologic Oncology (ESGO) guidelines., Patients and Methods: Retrospective data from 332 patients with advanced EOC who underwent cytoreductive surgery at a UK tertiary center were analyzed, and the outcomes were compared between pre-COVID-19 (2018-2019) (n=189) and COVID-19 era (2020-2021) (n=143) cohorts, covering the same timeframe (March to December). Primary outcomes included residual disease (RD) and progression-free survival (PFS), while secondary outcomes were the ESGO quality indicators (QIs) for advanced EOC surgery. Kaplan-Meier curves were produced to illustrate PFS., Results: Complete cytoreduction rates remained comparable at 74.07% and 72.03% for pre-COVID-19 and COVID-19 groups, respectively. Differences were observed in ECOG performance status (p=0.015), Intensive Care Unit (ICU) admissions (p=0.039) with less interval debulking surgeries (p=0.03), lower surgical complexity scores (p=0.02), and longer operative times in the COVID-19 group (p=0.01) compared to the pre-COVID-19 group. The median PFS rates were 37 months and 34 months in the pre-COVID-19 and COVID-19 groups, respectively (p=0.08). The surgical QIs 1-3 remained uncompromised during the COVID-19 era., Conclusion: Management modifications prompted by the COVID-19 pandemic did not adversely impact cytoreduction rates or PFS., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Cytoreductive surgery is critical for optimal tumor clearance in advanced epithelial ovarian cancer (EOC). Despite best efforts, some patients may experience R2 (>1 cm) resection, while others may not undergo surgery at all. We aimed to compare outcomes between advanced EOC patients undergoing R2 resection and those who had no surgery., Methods: Retrospective data from 51 patients with R2 resection were compared to 122 patients with no surgery between January 2015 and December 2019 at a UK tertiary referral centre. Progression-free survival (PFS) and overall survival (OS) were the study endpoints. Principal Component Analysis and Term Frequency - Inverse Document Frequency scores were utilized for data discrimination and prediction of R>2 cm from computed tomography pre-operative reports, respectively., Results: No statistical significance was observed, except for age (73 vs 67 years in the no- surgery vs R2 group, P : .001). Principal Components explained 34% of data variances. Reasons for no surgery included age, co-morbidities, patient preference, refractory disease, patient deterioration or disease progression, and absence of measurable intra- abdominal disease). The median PFS and OS were 12 and 14 months for no-surgery, vs 14 and 26 months for R2 ( P : .138 and P : .001, respectively). Serous histology and performance status independently predicted PFS in both no-surgery and R2 cohorts. In the no-surgery cohort, serous histology independently predicted OS, while in the R2 cohorts, both serous histology and adjuvant chemotherapy were independent prognostic features for OS. The bi-grams "abdominopelvic ascites" and "solid omental" were amongst those best discriminating between R>2 cm and R1-2 cm., Conclusions: R2 resection and no-surgery cohorts displayed unfavourable prognosis with a notable degree of uniformity. When cytoreduction results in suboptimal results, the survival benefit may still be higher compared to those who underwent no surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There is no well-defined threshold for intra-operative blood transfusion (BT) in advanced epithelial ovarian cancer (EOC) surgery. To address this, we devised a Machine Learning (ML)-driven prediction algorithm aimed at prompting and elucidating a communication alert for BT based on anticipated peri-operative events independent of existing BT policies. We analyzed data from 403 EOC patients who underwent cytoreductive surgery between 2014 and 2019. The estimated blood volume (EBV), calculated using the formula EBV = weight × 80, served for setting a 10% EBV threshold for individual intervention. Based on known estimated blood loss (EBL), we identified two distinct groups. The Receiver operating characteristic (ROC) curves revealed satisfactory results for predicting events above the established threshold (AUC 0.823, 95% CI 0.76-0.88). Operative time (OT) was the most significant factor influencing predictions. Intra-operative blood loss exceeding 10% EBV was associated with OT > 250 min, primary surgery, serous histology, performance status 0, R2 resection and surgical complexity score > 4. Certain sub-procedures including large bowel resection, stoma formation, ileocecal resection/right hemicolectomy, mesenteric resection, bladder and upper abdominal peritonectomy demonstrated clear associations with an elevated interventional risk. Our findings emphasize the importance of obtaining a rough estimate of OT in advance for precise prediction of blood requirements.

Patients with ovarian cancer (OC) often experience anxiety, depression and fear of progression (FOP); however, it is unclear whether surgical complexity has a role to play. We investigated the prevalence of anxiety, depression and FOP at 12 months post-cytoreductive surgery and investigated associations with surgical complexity, patient (age, ethnicity, performance status, BMI) and tumour (stage, disease load) factors. One hundred and forty-one patients with FIGO Stage III-IV OC, who did not have disease progression at 12 months post-surgery, completed the Hospital Anxiety and Depression Scale and FOP short-form questionnaire. Patients underwent surgery with low (40.4%), intermediate (31.2%) and high (28.4%) surgical complexity scores. At 12 months post-surgery, 99 of 141 (70%) patients with advanced OC undergoing surgery experienced clinically significant anxiety, 21 of 141 (14.9%) patients experienced moderate to severe depression and 37 of 140 (26.4%) experienced dysfunctional FOP. No associations were identified between the three different surgical complexity groups with regards to anxiety, depression or FOP scores. Unsurprisingly, given the natural history of the disease, most patients with OC suffer from anxiety, depression and fear of progression after completion of first-line cancer treatment. Surgical complexity at the time of surgery is not associated with a deleterious impact on anxiety, depression or FOP for patients with OC. Patients with OC experience a profound mental health impact and should be offered mental health support throughout their cancer journey.

The Surgical Complexity Score (SCS) has been widely used to describe the surgical effort during advanced stage epithelial ovarian cancer (EOC) cytoreduction. Referring to a variety of multi-visceral resections, it best combines the numbers with the complexity of the sub-procedures. Nevertheless, not all potential surgical procedures are described by this score. Lately, the European Society for Gynaecological Oncology (ESGO) has established standard outcome quality indicators pertinent to achieving complete cytoreduction (CC0). There is a need to define what weight all these surgical sub-procedures comprising CC0 would be given. Prospectively collected data from 560 surgically cytoreduced advanced stage EOC patients were analysed at a UK tertiary referral centre.We adapted the structured ESGO ovarian cancer report template. We employed the eXtreme Gradient Boosting (XGBoost) algorithm to model a long list of surgical sub-procedures. We applied the Shapley Additive explanations (SHAP) framework to provide global (cohort) explainability. We used Cox regression for survival analysis and constructed Kaplan-Meier curves. The XGBoost model predicted CC0 with an acceptable accuracy (area under curve [AUC] = 0.70; 95% confidence interval [CI] = 0.63-0.76). Visual quantification of the feature importance for the prediction of CC0 identified upper abdominal peritonectomy (UAP) as the most important feature, followed by regional lymphadenectomies. The UAP best correlated with bladder peritonectomy and diaphragmatic stripping (Pearson's correlations > 0.5). Clear inflection points were shown by pelvic and para-aortic lymph node dissection and ileocecal resection/right hemicolectomy, which increased the probability for CC0. When UAP was solely added to a composite model comprising of engineered features, it substantially enhanced its predictive value (AUC = 0.80, CI = 0.75-0.84). The UAP was predictive of poorer progression-free survival (HR = 1.76, CI 1.14-2.70, P: 0.01) but not overall survival (HR = 1.06, CI 0.56-1.99, P: 0.86). The SCS did not have significant survival impact. Machine Learning allows for operational feature selection by weighting the relative importance of those surgical sub-procedures that appear to be more predictive of CC0. Our study identifies UAP as the most important procedural predictor of CC0 in surgically cytoreduced advanced-stage EOC women. The classification model presented here can potentially be trained with a larger number of samples to generate a robust digital surgical reference in high output tertiary centres. The upper abdominal quadrants should be thoroughly inspected to ensure that CC0 is achievable.

Background: No residual disease (CC 0) following cytoreductive surgery is pivotal for the prognosis of women with advanced stage epithelial ovarian cancer (EOC). Improving CC 0 resection rates without increasing morbidity and no delay in subsequent chemotherapy favors a better outcome in these women. Prerequisites to facilitate this surgical paradigm shift and subsequent ramifications need to be addressed. This quality improvement study assessed 559 women with advanced EOC who had cytoreductive surgery between January 2014 and December 2019 in our tertiary referral centre. Following implementation of the Enhanced Recovery After Surgery (ERAS) pathway and prehabilitation protocols, the surgical management paradigm in advanced EOC patients shifted towards maximal surgical effort cytoreduction in 2016. Surgical outcome parameters before, during, and after this paradigm shift were compared. The primary outcome measure was residual disease (RD). The secondary outcome parameters were postoperative morbidity, operative time (OT), length of stay (LOS) and progression-free-survival (PFS)., Results: R0 resection rate in patients with advanced EOC increased from 57.3% to 74.4% after the paradigm shift in surgical management whilst peri-operative morbidity and delays in adjuvant chemotherapy were unchanged. The mean OT increased from 133 + 55 min to 197 + 85 min, and postoperative high dependency/intensive care unit (HDU/ICU) admissions increased from 8.1% to 33.1%. The subsequent mean LOS increased from 7.0 + 2.6 to 8.4 + 4.9 days. The median PFS was 33 months. There was no difference for PFS in the three time frames but a trend towards improvement was observed., Conclusions: Improved CC 0 surgical cytoreduction rates without compromising morbidity in advanced EOC is achievable owing to the right conditions. Maximal effort cytoreductive surgery should solely be carried out in high output tertiary referral centres due to the associated substantial prerequisites and ramifications., (© 2023. The Author(s).)

Results of recent clinical trials using the immune check point inhibitors (ICI) pembrolizumab or dostarlimab with/without lenvatinib has led to their approval for specific molecular subgroups of advanced recurrent endometrial cancer (EC). Herein, we summarise the clinical data leading to this first tissue-agnostic approval. As this novel therapy is not yet available in the United Kingdom standard care setting, we explore the strengths, weaknesses, opportunities, and threats (SWOT) of ICI treatment in EC. Major databases were searched focusing on clinical trials using programmed cell death protein 1 (PD-1) and its ligand (PD-L1) ICI which ultimately contributed to anti-PD-1 approval in EC. We performed a data quality assessment, reviewing survival and safety analysis. We included 15 studies involving 1609 EC patients: 458 with mismatch repair deficiency (MMRd)/microsatellite instability-high (MSI-H) status and 1084 with mismatch repair proficiency/microsatellite stable (MMRp/MSS) status. Pembrolizumab/dostarlimab have been approved for MMRd ECs, with the addition of lenvatinib for MMRp cases in the recurrent setting. Future efforts will focus on the pathological assessment of biomarkers to determine molecular phenotypes that correlate with response or resistance to ICI in order to identify patients most likely to benefit from this treatment.

Background: The Peritoneal Carcinomatosis Index (PCI) and the Intra-operative Mapping for Ovarian Cancer (IMO), to a lesser extent, have been universally validated in advanced-stage epithelial ovarian cancer (EOC) to describe the extent of peritoneal dissemination and are proven to be powerful predictors of the surgical outcome with an added sensitivity of assessment at laparotomy of around 70%. This leaves room for improvement because the two-dimensional anatomic scoring model fails to reflect the patient's real anatomy, as seen by a surgeon. We hypothesized that tumor dissemination in specific anatomic locations can be more predictive of complete cytoreduction (CC0) and survival than PCI and IMO tools in EOC patients. (2) Methods: We analyzed prospectively data collected from 508 patients with FIGO-stage IIIB-IVB EOC who underwent cytoreductive surgery between January 2014 and December 2019 at a UK tertiary center. We adapted the structured ESGO ovarian cancer report to provide detailed information on the patterns of tumor dissemination (cancer anatomic fingerprints). We employed the extreme gradient boost (XGBoost) to model only the variables referring to the EOC disseminated patterns, to create an intra-operative score and judge the predictive power of the score alone for complete cytoreduction (CC0). Receiver operating characteristic (ROC) curves were then used for performance comparison between the new score and the existing PCI and IMO tools. We applied the Shapley additive explanations (SHAP) framework to support the feature selection of the narrated cancer fingerprints and provide global and local explainability. Survival analysis was performed using Kaplan-Meier curves and Cox regression. (3) Results: An intra-operative disease score was developed based on specific weights assigned to the cancer anatomic fingerprints. The scores range from 0 to 24. The XGBoost predicted CC0 resection (area under curve (AUC) = 0.88 CI = 0.854-0.913) with high accuracy. Organ-specific dissemination on the small bowel mesentery, large bowel serosa, and diaphragmatic peritoneum were the most crucial features globally. When added to the composite model, the novel score slightly enhanced its predictive value (AUC = 0.91, CI = 0.849-0.963). We identified a "turning point", ≤5, that increased the probability of CC0. Using conventional logistic regression, the new score was superior to the PCI and IMO scores for the prediction of CC0 (AUC = 0.81 vs. 0.73 and 0.67, respectively). In multivariate Cox analysis, a 1-point increase in the new intra-operative score was associated with poorer progression-free (HR: 1.06; 95% CI: 1.03-1.09, p < 0.005) and overall survival (HR: 1.04; 95% CI: 1.01-1.07), by 4% and 6%, respectively. (4) Conclusions: The presence of cancer disseminated in specific anatomical sites, including small bowel mesentery, large bowel serosa, and diaphragmatic peritoneum, can be more predictive of CC0 and survival than the entire PCI and IMO scores. Early intra-operative assessment of these areas only may reveal whether CC0 is achievable. In contrast to the PCI and IMO scores, the novel score remains predictive of adverse survival outcomes.

(1) Background: Length of stay (LOS) has been suggested as a marker of the effectiveness of short-term care. Artificial Intelligence (AI) technologies could help monitor hospital stays. We developed an AI-based novel predictive LOS score for advanced-stage high-grade serous ovarian cancer (HGSOC) patients following cytoreductive surgery and refined factors significantly affecting LOS. (2) Methods: Machine learning and deep learning methods using artificial neural networks (ANN) were used together with conventional logistic regression to predict continuous and binary LOS outcomes for HGSOC patients. The models were evaluated in a post-hoc internal validation set and a Graphical User Interface (GUI) was developed to demonstrate the clinical feasibility of sophisticated LOS predictions. (3) Results: For binary LOS predictions at differential time points, the accuracy ranged between 70-98%. Feature selection identified surgical complexity, pre-surgery albumin, blood loss, operative time, bowel resection with stoma formation, and severe postoperative complications (CD3-5) as independent LOS predictors. For the GUI numerical LOS score, the ANN model was a good estimator for the standard deviation of the LOS distribution by ± two days. (4) Conclusions: We demonstrated the development and application of both quantitative and qualitative AI models to predict LOS in advanced-stage EOC patients following their cytoreduction. Accurate identification of potentially modifiable factors delaying hospital discharge can further inform services performing root cause analysis of LOS.

We investigated URS and impact on survival in whole patient cohorts with AOC treated within gynaecological cancer centres that participated in the previously presented SOCQER 2 study. National cancer registry datasets were used to identify FIGO Stage 3,4 and unknown stage patients from 11 cancer centres that had previously participated in the SOCQER2 study. Patient outcomes’ association with surgical ethos were evaluated using logistic regression and Cox proportional hazards. Centres were classified into three groups based on their surgical complexity scores (SCS); those practicing mainly low complexity, (5/11 centres with >70% low SCS procedures, 759 patients), mainly intermediate (3/11, 35−50% low SCS, 356 patients), or mainly high complexity surgery (3/11, >35% high SCS, 356 patients). Surgery rates were 43.2% vs. 58.4% vs. 60.9%. across mainly low, intermediate and high SCS centres, respectively, p < 0.001. Combined surgery and chemotherapy rates were 39.2% vs. 51.8% vs. 38.3% p < 0.000 across mainly low, intermediate and high complexity groups, respectively. Median survival was 23.1 (95% CI 19.0 to 27.2) vs. 22.0 (95% CI 17.6 to 26.3) vs. 17.9 months (95% CI 15.7 to 20.1), p = 0.043 in mainly high SCS, intermediate, and low SCS centres, respectively. In an age and deprivation adjusted model, compared to patients in the high SCS centres, patients in the low SCS group had an HR of 1.21 (95% CI 1.03 to 1.40) for death. Mainly high/intermediate SCS centres have significantly higher surgery rates and better survival at a population level. Centres that practice mainly low complexity surgery should change practice. This study provides support for the utilization of URS for patients with advanced OC.

(1) Background: Surgical cytoreduction for epithelial ovarian cancer (EOC) is a complex procedure. Encompassed within the performance skills to achieve surgical precision, intra-operative surgical decision-making remains a core feature. The use of eXplainable Artificial Intelligence (XAI) could potentially interpret the influence of human factors on the surgical effort for the cytoreductive outcome in question; (2) Methods: The retrospective cohort study evaluated 560 consecutive EOC patients who underwent cytoreductive surgery between January 2014 and December 2019 in a single public institution. The eXtreme Gradient Boosting (XGBoost) and Deep Neural Network (DNN) algorithms were employed to develop the predictive model, including patient- and operation-specific features, and novel features reflecting human factors in surgical heuristics. The precision, recall, F1 score, and area under curve (AUC) were compared between both training algorithms. The SHapley Additive exPlanations (SHAP) framework was used to provide global and local explainability for the predictive model; (3) Results: A surgical complexity score (SCS) cut-off value of five was calculated using a Receiver Operator Characteristic (ROC) curve, above which the probability of incomplete cytoreduction was more likely (area under the curve [AUC] = 0.644; 95% confidence interval [CI] = 0.598−0.69; sensitivity and specificity 34.1%, 86.5%, respectively; p = 0.000). The XGBoost outperformed the DNN assessment for the prediction of the above threshold surgical effort outcome (AUC = 0.77; 95% [CI] 0.69−0.85; p < 0.05 vs. AUC 0.739; 95% [CI] 0.655−0.823; p < 0.95). We identified “turning points” that demonstrated a clear preference towards above the given cut-off level of surgical effort; in consultant surgeons with <12 years of experience, age <53 years old, who, when attempting primary cytoreductive surgery, recorded the presence of ascites, an Intraoperative Mapping of Ovarian Cancer score >4, and a Peritoneal Carcinomatosis Index >7, in a surgical environment with the optimization of infrastructural support. (4) Conclusions: Using XAI, we explain how intra-operative decisions may consider human factors during EOC cytoreduction alongside factual knowledge, to maximize the magnitude of the selected trade-off in effort. XAI techniques are critical for a better understanding of Artificial Intelligence frameworks, and to enhance their incorporation in medical applications.

Objective: To investigate quality of life (QoL) and association with surgical complexity and disease burden after surgical resection for advanced ovarian cancer in centres with variation in surgical approach., Design: Prospective multicentre observational study., Setting: Gynaecological cancer surgery centres in the UK, Kolkata, India, and Melbourne, Australia., Sample: Patients undergoing surgical resection (with low, intermediate or high surgical complexity score, SCS) for late-stage ovarian cancer., Main Outcome Measures: Primary: change in global score on the European Organisation for Research and Treatment of Cancer (EORTC) core quality-of-life questionnaire (QLQ-C30). Secondary: EORTC ovarian cancer module (OV28), progression-free survival., Results: Patients' preoperative disease burden and SCS varied between centres, confirming differences in surgical ethos. QoL response rates were 90% up to 18 months. Mean change from the pre-surgical baseline in the EORTC QLQ-C30 was 3.4 (SD 1.8, n = 88) in the low, 4.0 (SD 2.1, n = 55) in the intermediate and 4.3 (SD 2.1, n = 52) in the high-SCS group after 6 weeks (p = 0.048), and 4.3 (SD 2.1, n = 51), 5.1 (SD 2.2, n = 41) and 5.1 (SD 2.2, n = 35), respectively, after 12 months (p = 0.133). In a repeated-measures model, there were no clinically or statistically meaningful differences in EORTC QLQ-C30 global scores between the three SCS groups (p = 0.840), but there was a small statistically significant improvement in all groups over time (p < 0.001). The high-SCS group experienced small to moderate decreases in physical (p = 0.004), role (p = 0.016) and emotional (p = 0.001) function at 6 weeks post-surgery, which resolved by 6-12 months., Conclusions: The global QoL of patients undergoing low-, intermediate- and high-SCS surgery improved at 12 months after surgery and was no worse in patients undergoing extensive surgery., Tweetable Abstract: Compared with surgery of lower complexity, extensive surgery does not result in poorer quality of life in patients with advanced ovarian cancer., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Achieving complete surgical cytoreduction in advanced stage high grade serous ovarian cancer (HGSOC) patients warrants an availability of Critical Care Unit (CCU) beds. Machine Learning (ML) could be helpful in monitoring CCU admissions to improve standards of care. We aimed to improve the accuracy of predicting CCU admission in HGSOC patients by ML algorithms and developed an ML-based predictive score. A cohort of 291 advanced stage HGSOC patients with fully curated data was selected. Several linear and non-linear distances, and quadratic discriminant ML methods, were employed to derive prediction information for CCU admission. When all the variables were included in the model, the prediction accuracies were higher for linear discriminant (0.90) and quadratic discriminant (0.93) methods compared with conventional logistic regression (0.84). Feature selection identified pre-treatment albumin, surgical complexity score, estimated blood loss, operative time, and bowel resection with stoma as the most significant prediction features. The real-time prediction accuracy of the Graphical User Interface CCU calculator reached 95%. Limited, potentially modifiable, mostly intra-operative factors contributing to CCU admission were identified and suggest areas for targeted interventions. The accurate quantification of CCU admission patterns is critical information when counseling patients about peri-operative risks related to their cytoreductive surgery.

Introduction: Accurate prediction of patient prognosis can be especially useful for the selection of best treatment protocols. Machine Learning can serve this purpose by making predictions based upon generalizable clinical patterns embedded within learning datasets. We designed a study to support the feature selection for the 2-year prognostic period and compared the performance of several Machine Learning prediction algorithms for accurate 2-year prognosis estimation in advanced-stage high grade serous ovarian cancer (HGSOC) patients., Methods: The prognosis estimation was formulated as a binary classification problem. Dataset was split into training and test cohorts with repeated random sampling until there was no significant difference (p = 0.20) between the two cohorts. A ten-fold cross-validation was applied. Various state-of-the-art supervised classifiers were used. For feature selection, in addition to the exhaustive search for the best combination of features, we used the-chi square test of independence and the MRMR method., Results: Two hundred nine patients were identified. The model's mean prediction accuracy reached 73%. We demonstrated that Support-Vector-Machine and Ensemble Subspace Discriminant algorithms outperformed Logistic Regression in accuracy indices. The probability of achieving a cancer-free state was maximised with a combination of primary cytoreduction, good performance status and maximal surgical effort (AUC 0.63). Standard chemotherapy, performance status, tumour load and residual disease were consistently predictive of the mid-term overall survival (AUC 0.63-0.66). The model recall and precision were greater than 80%., Conclusion: Machine Learning appears to be promising for accurate prognosis estimation. Appropriate feature selection is required when building an HGSOC model for 2-year prognosis prediction. We provide evidence as to what combination of prognosticators leads to the largest impact on the HGSOC 2-year prognosis.

Background: The value of the magnetic resonance imaging (MRI) in the assessment of women with endometrial hyperplasia and its role in diagnosis of myometrial invasion or coexistence of cancer is not known. This study aimed to evaluate the accuracy and usefulness of MRI in the management of patients diagnosed on endometrial biopsy with complex endometrial hyperplasia with atypia (CEHA)., Methods: A retrospective study of 86 cases diagnosed with endometrial hyperplasia with atypia on the initial endometrial biopsy in a tertiary university teaching hospital between 2010 and 2015 was carried out. The MRI accuracy in predicting malignant changes and influence the clinical management was compared among women who had either pelvic MRI, transvaginal ultrasound (TVUS), or no additional imagistic studies., Results: MRI was performed in 24 (28%) and TVUS in 11 (13%)cases, while 51 (59%) women had no additional imagistic studies. In the group of women with no imaging studies, 26/51 (51%) were surgically treated and 8/26 (31%) were diagnosed with endometrial cancer (EEC) stage 1a. In the group of women who had TVUS, 5/11 (45%) were surgically treated and none was diagnosed with EEC. In the group of women who underwent an MRI examination, 20/24 (83%) were surgically treated. Among these, 11/20 (55%) were diagnosed with EEC, 7 had EEC stage 1a, and 4 had EEC stage 1b. Although MRI was able to identify malignant changes with a good sensitivity (91.7%), it had a low specificity in characterisation of malignant transformation (8%). MRI correctly identified 31% of the stage 1a and 33% of the stage 1b endometrial cancer., Conclusion: In this study, we found a potential diagnostic value of MRI for identifying malignant transformation in patients with CEHA. However, pelvic MRI has a rather weak predictive value of myometrial invasion in women with CEHA and concurrent EEC. The diagnostic and therapeutic benefits of MRI assessment in patients with CEHA need further validation.

Eicosanoids comprise a diverse group of bioactive lipids which orchestrate inflammation, immunity, and tissue homeostasis, and whose dysregulation has been implicated in carcinogenesis. Among the various eicosanoid metabolic pathways, studies of their role in endometrial cancer (EC) have very much been confined to the COX-2 pathway. This study aimed to determine changes in epithelial eicosanoid metabolic gene expression in endometrial carcinogenesis; to integrate these with eicosanoid profiles in matched clinical specimens; and, finally, to investigate the prognostic value of candidate eicosanoid metabolic enzymes. Eicosanoids and related mediators were profiled using liquid chromatography-tandem mass spectrometry in fresh frozen normal, hyperplastic, and cancerous (types I and II) endometrial specimens (n = 192). Sample-matched epithelia were isolated by laser capture microdissection and whole genome expression analysis was performed using microarrays. Integration of eicosanoid and gene expression data showed that the accepted paradigm of increased COX-2-mediated prostaglandin production does not apply in EC carcinogenesis. Instead, there was evidence for decreased PGE 2 /PGF 2α inactivation via 15-hydroxyprostaglandin dehydrogenase (HPGD) in type II ECs. Increased expression of 5-lipoxygenase (ALOX5) mRNA was also identified in type II ECs, together with proportional increases in its product, 5-hydroxyeicosatetraenoic acid (5-HETE). Decreased HPGD and elevated ALOX5 mRNA expression were associated with adverse outcome, which was confirmed by immunohistochemical tissue microarray analysis of an independent series of EC specimens (n = 419). While neither COX-1 nor COX-2 protein expression had prognostic value, low HPGD combined with high ALOX5 expression was associated with the worst overall and progression-free survival. These findings highlight HPGD and ALOX5 as potential therapeutic targets in aggressive EC subtypes. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Purpose: To assess the significance of CA-125 regression as a prognostic indicator and predictor of optimal cytoreduction at interval debulking surgery (IDS) in women with ovarian or primary peritoneal carcinoma receiving neoadjuvant chemotherapy (NAC)., Methods: 63 women treated between 2004 and 2007 with neoadjuvant platinum-based chemotherapy followed by IDS were studied retrospectively. Pre-operative CA-125 values were used to calculate a regression coefficient (CA-125r) using exponential regression analysis. Outcome endpoints were overall survival (OS), time to CA-125 progression (TTC) by Rustin criteria and time to second-line treatment (TTS)., Results: Women with a CA-125 half-life greater than 18 days had a significantly worse OS compared to those with a half-life less than 12 days on univariate testing (HR 3.34, 95% CI 1.25-8.94, p = 0.017). On multivariable analysis, CA-125r was an independent predictor of OS [HR 1.18 (per 0.01 increase in CA-125r), 95% CI 1.01-1.40, p = 0.043]. CA-125r was independently predictive of TTC and TTS (HR 1.17, p ≈ 0.03 for each). CA-125r was also predictive of achieving optimal cytoreduction at IDS (AUC 0.756, p < 0.001)., Conclusions: CA-125 regression rate during pre-operative NAC is of independent prognostic value. CA-125 regression rate strongly predicts for optimal cytoreduction.

Background: Parenteral nutrition (PN) in patients with disseminated ovarian cancer remains controversial. The role of PN in providing nutrition and improving quality of life is unclear. The present study aimed to determine the pattern of prescribing in a large teaching hospital, and to identify subgroups where the use of PN was justified., Methods: Sixty-five patients with advanced ovarian carcinoma received PN between January 2002 and May 2008. A retrospective case note review was undertaken to retrieve data on PN prescribing and outcomes in terms of duration of PN provision, complications, and survival., Results: Three subgroups were identified. Group I consisted of 18 (28%) patients who received PN for a median [interquartile range (IQR)] of 5 (2-11) days. The majority of these 18 patients (n = 13, 72%) had disease-related terminal bowel obstruction. Out of 18 of these patients, 17 (95%) had poor performance status. The median (IQR) survival was 12 (6-28) days. Group II consisted of 40 (61%) patients who were re-established on enteral nutrition. The median (IQR) duration of PN administration was 10 (6-17) days. The most common indication of PN was protracted ileus (n = 25, 63%). Out of 40 of these patients, 35 (88%) patients had good performance status. The median (IQR) survival was 264 (96-564) days. The third group of patients required home PN (n = 7, 11%). Four (58%) patients had short bowel syndrome and three (42%) had terminal intestinal obstruction. All of the patients had good performance status. The median (IQR) duration of PN administration and survival was 241 (90-305) days., Conclusions: Administration of PN appears to be justified in those patients with a good performance status (i.e. patients capable of self-care), which constituted three-quarters of this cohort. In the remaining patients with poor performance status, and particularly those with terminal intestinal obstruction, PN administration was difficult to justify. PN should not be denied based purely on the pathology, although cautious judgment is required to select those who are most likely to benefit., (© 2010 The Authors. Journal compilation © 2010 The British Dietetic Association Ltd.)

Objective: To assess the safety and targeting ability of the engineered human antibody (hCTMO1) in women with ovarian carcinoma., Design: The monoclonal antibody labelled with Indium-111 was administered to women with suspected primary or recurrent ovarian carcinoma six days pre-operatively. The first group of women was given a dose of 0.1 mg per kg body weight of radiolabelled antibody. A second group of women received 1 mg per kg body weight and finally a third group was given 1 mg per kg body weight of unlabelled antibody followed one hour later by 0.1 mg per kg body weight of radiolabelled antibody. All the women were then imaged using a gamma camera one hour and up to 96 hours after injection., Participants: Fourty-four women in whom there was a high suspicion of primary ovarian carcinoma on the basis of ultrasound or CT imaging and serum CA125 and those in whom there was a suspicion of recurrent ovarian carcinoma after being treated for histologically confirmed carcinoma., Setting: The Queen's Medical Centre, Nottingham and University Hospital Vrije Universiteit, Amsterdam, The Netherlands., Results: At the low dose of antibody the sensitivity for detection of ovarian carcinoma was 70%. After increasing the dose of antibody and also after pre-dosing with unlabelled antibody the sensitivity increased to 100%, but there was a large number of false positive results at the higher dose, and therefore the specificity was low. The liver and bone marrow were the organs with the highest activities., Conclusion: The genetically engineered antibody hCTMO1 is safe for use in women. This antibody effectively targets ovarian carcinoma and has greater potential as a vector for therapeutic use than as a diagnostic agent.

Fourteen non-insulin-dependent diabetics (9 female, 5 male), aged 46 to 64 years, uncontrolled by diet (fasting plasma glucose greater than or equal to 8 mmol/l), were treated with metformin, 1-3 g daily, and followed prospectively at 1 week, then at 2-weekly intervals for 6 months. The fasting plasma glucose fell significantly (p less than 0.01) after 1 week of therapy and HbA1 showed a significant reduction, 13.4 +/- 2.5% (mean +/- SD) to 10.7 +/- 1.8% (normal range 5.1-9.3%) at 8 weeks (p less than 0.001). There was no significant change in body weight, plasma insulin, serum cholesterol or triglycerides, blood lactate, pyruvate, glycerol, alanine, 3-hydroxybutyrate or acetoacetate concentration. Systolic, diastolic, and mean arterial blood pressures, along with resting heart rate remained unchanged. This study shows that metformin effectively lowers plasma glucose without hyperinsulinism or significant rise in fasting blood lactate and other gluconeogenic precursors.