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'openFrame' is a modular, low‐cost, open‐hardware microscopy platform that can be configured or adapted to most light microscopy techniques and is easily upgradeable or expandable to multiple modalities. The ability to freely mix and interchange both open‐source and proprietary hardware components or software enables low‐cost, yet research‐grade instruments to be assembled and maintained. It also enables rapid prototyping of advanced or novel microscope systems. For long‐term time‐lapse image data acquisition, slide‐scanning or high content analysis, we have developed a novel optical autofocus incorporating orthogonal cylindrical optics to provide robust single‐shot closed‐loop focus lock, which we have demonstrated to accommodate defocus up to ±37 μm with <200 nm accuracy, and a two‐step autofocus mode which we have shown can operate with defocus up to ±68 μm. We have used this to implement automated single molecule localisation microscopy (SMLM) in a relatively low‐cost openFrame‐based instrument using multimode diode lasers for excitation and cooled CMOS cameras. LAY DESCRIPTION: We present a modular, low‐cost, microscopy platform called 'openFrame' that can be configured or adapted to most light microscopy techniques and is easily upgradeable. openFrame‐based microscopes are designed to be used with open‐source software tools and low‐cost/self‐built hardware components, such that cost‐effective instruments can be assembled and maintained locally by skilled users instead of requiring visits from service engineers. The core openFrame hardware components can be fabricated using freely shared CAD files or they can be purchased by users to implement a wide range of instruments, which can utilise a mixture of open and proprietary hardware components as desired. We intend this platform to widen access to basic and advanced microscopy techniques, including in lower‐resource settings. We also expect it to be useful to researchers prototyping new microscopes, since it allows a core instrument to be rapidly assembled and then easily modified with minimal constraints, for example, from proprietary software or legacy design choices. The flexibility to reconfigure openFrame‐based microscopes and interchange/recycle components between different instruments reduces obsolescence. The openFrame‐based microscope presented here includes a novel open‐source optical autofocus unit (openAF) that may be useful for long‐term time‐lapse imaging, and in slide‐scanning or automated multiwell plate microscopes. We demonstrate the use of an openFrame‐based instrument for super‐resolved microscopy using single molecule localisation microscopy (SMLM) utilising low‐cost cooled CMOS cameras and multimode diode lasers for high power excitation. [ABSTRACT FROM AUTHOR]

This article discusses a study that aimed to identify factors that influence the success rate and time-to-result of testing for tumour homologous recombination deficiency (HRD) in patients with advanced high-grade epithelial ovarian cancer. The study found that samples taken during surgery had a higher test success rate compared to those obtained using ultrasound-guided biopsy. Additionally, diagnostic biopsies taken with a larger needle gauge resulted in greater rates of test success. The article concludes that by optimizing HRD testing, treatment can be optimized at the earliest possible timepoint. [Extracted from the article]

Objective: To determine the rates of germline BRCA1 and BRCA2 mutations in Scottish patients with ovarian cancer, before and after a change in testing policy.Design: Retrospective cohort study.Setting: Four cancer/genetics centres in Scotland.Population: Patients with ovarian cancer undergoing germline BRCA1 and BRCA2 (gBRCA1/2) sequencing before 2013 (under the 'old criteria', with selection based solely on family history), after 2013 (under the 'new criteria', with sequencing offered to newly presenting patients with non-mucinous ovarian cancer), and in the 'prevalent population' (who presented before 2013, but were not eligible for sequencing under the old criteria but were sequenced under the new criteria).Methods: Clinicopathological and sequence data were collected before and for 18 months after this change in selection criteria.Main Outcome Measures: Frequency of germline BRCA1, BRCA2, RAD51C, and RAD51D mutations.Results: Of 599 patients sequenced, 205, 236, and 158 were in the 'old criteria', 'new criteria', and 'prevalent' populations, respectively. The frequency of gBRCA1/2 mutations was 30.7, 13.1, and 12.7%, respectively. The annual rate of gBRCA1/2 mutation detection was 4.2 before and 20.7 after the policy change. A total of 48% (15/31) 'new criteria' patients with gBRCA1/2 mutations had a Manchester score of <15 and would not have been offered sequencing based on family history criteria. In addition, 20 patients with gBRCA1/2 were identified in the prevalent population. The prevalence of gBRCA1/2 mutations in patients aged >70 years was 8.2%.Conclusions: Sequencing all patients with non-mucinous ovarian cancer gives a much higher annual gBRCA1/2 mutation detection rate, with the frequency of positive tests still exceeding the 10% threshold upon which many family history-based models operate.Tweetable Abstract: BRCA sequencing all non-mucinous cancer patients increases mutation detection five fold. [ABSTRACT FROM AUTHOR]

Objective To establish the optimal management strategy for women with suspected stage 1 ovarian cancer. Design We created a flowchart to illustrate each of six hypothetical management strategies. These considered two surgical approaches (systematic lymphadenectomy versus no lymph node dissection at all) in combination with three different policies for giving adjuvant chemotherapy. Setting Gynaecological cancer centre, London, UK. Data sources Patient data and published papers. Methods We developed a deterministic model that uses information from multiple sources to estimate patient flow through each level of a hypothesised decision tree. Results We estimated that for every 100 cases of suspected early-stage ovarian cancer, there would be 37 cases with ‘apparent’ stage 1 disease and that of these, two (6%) would be denied potentially life-saving adjuvant treatment if systematic lymphadenectomy was not performed. The number of women given chemotherapy would not, according to our estimates, differ greatly between the two surgical approaches, the 7% increase with systematic lymphadenectomy being because of cases identified as having nodal metastases. Conclusions We present a model of the intraoperative decision-making process that determines the extent of the staging procedure to be performed within our department when early-stage ovarian cancer is suspected. Unless adjuvant chemotherapy is prescribed for all, systematic pelvic and para-aortic node dissection is required to optimise survival. However, in our department, this would result in 32% of women with suspected early-stage ovarian cancer undergoing systematic node dissection. This flexible focused model may facilitate multidisciplinary team discussion when this part of the surgical staging procedure is considered within the context of the population presenting to the team, the morbidity of the procedure within the department and the predictive values of frozen section within that department. As the model is not disease-specific, it may be useful for decision making in other medical disciplines. [ABSTRACT FROM AUTHOR]

The authors examines whether disease management protocols in Great Britain are restricting innovations in the treatment of cancer, highlighting a legislative bill introduced by Lord Maurice Saatchi. The legislative bill is discussed which aims to promote responsible innovation in case the available treatment options are limited or are projected to fail. Other topics include the bill's section that prevents quackery, its possible impact on clinical trials, and stratification of medicine.

The article discusses considerations and feasibility on surgery of advanced ovarian cancer as a means to improve ovarian cancer patient survival. It cites several meta-analysis studies on the pre surgery treatment and viability of ovarian cancer surgery and the challenges surgeons may meet during operations like knowing the extent of the disease. It states that studies have evidenced that the best practice for ovarian cancer treatment is surgery.

A response by C. Pomel, I. McNeish, D. Barton, and J. Shepherd to a letter to the editor about their article regarding the issue for primary debulking surgery in ovarian cancer in the 2008 issue is presented.

A response by D. Barton, J. Shepherd, I. McNeish, and C. Pomel to a letter to the editor about their article "A statement for extensive primary cytoreductive surgery in advanced ovarian cancer" in the 2008 issue is presented.

Mitochondrial metabolism and the generation of reactive oxygen species (ROS) contribute to the acquisition of DNA mutations and genomic instability in cancer. How genomic instability influences the metabolic capacity of cancer cells is nevertheless poorly understood. Here, we show that homologous recombination-defective (HRD) cancers rely on oxidative metabolism to supply NAD + and ATP for poly(ADP-ribose) polymerase (PARP)-dependent DNA repair mechanisms. Studies in breast and ovarian cancer HRD models depict a metabolic shift that includes enhanced expression of the oxidative phosphorylation (OXPHOS) pathway and its key components and a decline in the glycolytic Warburg phenotype. Hence, HRD cells are more sensitive to metformin and NAD + concentration changes. On the other hand, shifting from an OXPHOS to a highly glycolytic metabolism interferes with the sensitivity to PARP inhibitors (PARPi) in these HRD cells. This feature is associated with a weak response to PARP inhibition in patient-derived xenografts, emerging as a new mechanism to determine PARPi sensitivity. This study shows a mechanistic link between two major cancer hallmarks, which in turn suggests novel possibilities for specifically treating HRD cancers with OXPHOS inhibitors., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Objective: To determine the rates of germline BRCA1 and BRCA2 mutations in Scottish patients with ovarian cancer, before and after a change in testing policy., Design: Retrospective cohort study., Setting: Four cancer/genetics centres in Scotland., Population: Patients with ovarian cancer undergoing germline BRCA1 and BRCA2 (gBRCA1/2) sequencing before 2013 (under the 'old criteria', with selection based solely on family history), after 2013 (under the 'new criteria', with sequencing offered to newly presenting patients with non-mucinous ovarian cancer), and in the 'prevalent population' (who presented before 2013, but were not eligible for sequencing under the old criteria but were sequenced under the new criteria)., Methods: Clinicopathological and sequence data were collected before and for 18 months after this change in selection criteria., Main Outcome Measures: Frequency of germline BRCA1, BRCA2, RAD51C, and RAD51D mutations., Results: Of 599 patients sequenced, 205, 236, and 158 were in the 'old criteria', 'new criteria', and 'prevalent' populations, respectively. The frequency of gBRCA1/2 mutations was 30.7, 13.1, and 12.7%, respectively. The annual rate of gBRCA1/2 mutation detection was 4.2 before and 20.7 after the policy change. A total of 48% (15/31) 'new criteria' patients with gBRCA1/2 mutations had a Manchester score of <15 and would not have been offered sequencing based on family history criteria. In addition, 20 patients with gBRCA1/2 were identified in the prevalent population. The prevalence of gBRCA1/2 mutations in patients aged >70 years was 8.2%., Conclusions: Sequencing all patients with non-mucinous ovarian cancer gives a much higher annual gBRCA1/2 mutation detection rate, with the frequency of positive tests still exceeding the 10% threshold upon which many family history-based models operate., Tweetable Abstract: BRCA sequencing all non-mucinous cancer patients increases mutation detection five fold., (© 2018 Royal College of Obstetricians and Gynaecologists.)

Objective: To establish the optimal management strategy for women with suspected stage 1 ovarian cancer., Design: We created a flowchart to illustrate each of six hypothetical management strategies. These considered two surgical approaches (systematic lymphadenectomy versus no lymph node dissection at all) in combination with three different policies for giving adjuvant chemotherapy., Setting: Gynaecological cancer centre, London, UK., Data Sources: Patient data and published papers., Methods: We developed a deterministic model that uses information from multiple sources to estimate patient flow through each level of a hypothesised decision tree., Results: We estimated that for every 100 cases of suspected early-stage ovarian cancer, there would be 37 cases with 'apparent' stage 1 disease and that of these, two (6%) would be denied potentially life-saving adjuvant treatment if systematic lymphadenectomy was not performed. The number of women given chemotherapy would not, according to our estimates, differ greatly between the two surgical approaches, the 7% increase with systematic lymphadenectomy being because of cases identified as having nodal metastases., Conclusions: We present a model of the intraoperative decision-making process that determines the extent of the staging procedure to be performed within our department when early-stage ovarian cancer is suspected. Unless adjuvant chemotherapy is prescribed for all, systematic pelvic and para-aortic node dissection is required to optimise survival. However, in our department, this would result in 32% of women with suspected early-stage ovarian cancer undergoing systematic node dissection. This flexible focused model may facilitate multidisciplinary team discussion when this part of the surgical staging procedure is considered within the context of the population presenting to the team, the morbidity of the procedure within the department and the predictive values of frozen section within that department. As the model is not disease-specific, it may be useful for decision making in other medical disciplines.