Outcome of patients with advanced ovarian cancer who do not undergo debulking surgery: A single institution retrospective review

OBJECTIVE: To assess the outcome of patients with advanced ovarian cancer (OC) who were treated without surgery, having received upfront chemotherapy and no interval debulking surgery (IDS). METHODS: Retrospective analysis of medical and chemotherapy records of consecutive patients with OC between 2005 and 2013 at UCL Hospitals London, UK who received neoadjuvant chemotherapy (NACT) was then found to be unsuitable for IDS following review by the multidisciplinary team. RESULTS: Eighty-three patients (18%) out of 467 receiving NACT did not undergo IDS. Median age was 70years (range 33-88); out of these 83 patients, 43 (51.8%) presented with stage IV disease. Forty-three of these 83 patients received carboplatin and paclitaxel (CP) (51.8%) and 37 received carboplatin alone (C) (44.6%); 3 patients (3.6%) received other platinum-based combinations. Reasons for not proceeding to surgery were: poor response to chemotherapy after 3-4 cycles of NACT (61/83, 73.5%); comorbidities (12/83, 14.5%); patient decision (4/83, 4.8%). Six patients (7.2%) received 2 lines of chemotherapy. In a univariate analysis CP, age <70years, and absence of comorbidities were factors influencing OS. In a multivariate analysis only having received CP remained independently associated with OS (HR 0.49, 95% CI 0.29-0.84). CONCLUSIONS: Chemotherapy alone can provide reasonable disease control in patients unsuitable for IDS and CP should be used if possible

Blinking statistics of a molecular beacon triggered by end-denaturation of DNA

We use a master equation approach based on the Poland-Scheraga free energy for DNA denaturation to investigate the (un)zipping dynamics of a denaturation wedge in a stretch of DNA, that is clamped at one end. In particular, we quantify the blinking dynamics of a fluorophore-quencher pair mounted within the denaturation wedge. We also study the behavioural changes in the presence of proteins, that selectively bind to single-stranded DNA. We show that such a setup could be well-suited as an easy-to-implement nanodevice for sensing environmental conditions in small volumes.Comment: 14 pages, 5 figures, LaTeX, IOP style. Accepted to J Phys Cond Mat special issue on diffusio

Quality of life in survivors after cervical artery dissection

Background and purpose : Little data exists about longterm outcome, quality of life (QOL) and its predictors after spontaneous cervical artery dissections (sCAD). Methods : Clinical and radiological data of 114 patients with sCAD were collected prospectively. Six patients died within 3 months, the remaining 108 were contacted after a mean of 1498 days (range: 379-3455), 99 survivors (92 %) replied. QOL, assessed with the stroke-specific QOL scale (SSQOL), and functional abilities, measured with modified Rankin Scale (mRS) were compared, and predictors of QOL were analyzed. Subgroup analyses were performed for patients with ischemic stroke, those with isolated local symptoms or transient ischemic symptoms and those without significant disabilities (mRS 0-1) at follow-up. Results : Seventy-one of 99 patients (72 %) had no significant disability, but only 53 (54 %) reported a good QOL (SS-QOL ≥ 4). Compared to the self-rated premorbid QOL of all patients, SS-QOL was impaired after sCAD (p 0.5). High National Institute of Health Stroke Scale score on admission and higher age were independent predictors of impaired QOL (p < 0.05). Conclusion : QOL is impaired in almost half of long-term survivors after sCAD, even in patients with local or transient symptoms or without functional disability. Impairment of QOL is a surprisingly frequent long-term sequela after sCAD and deserves attention as an outcome measure in these patient

Collagen-bound fibrin sealant (TachoSil®) for dural closure in cranial surgery: single-centre comparative cohort study and systematic review of the literature

Cerebrospinal fluid (CSF) leakage is a well-known complication of craniotomies and there are several dural closure techniques. One commonly used commercial product as adjunct for dural closure is the collagen-bound fibrin sealant TachoSil®. We analysed whether the addition of TachoSil has beneficial effects on postoperative complications and outcomes. Our prospective, institutional database was retrospectively queried, and 662 patients undergoing craniotomy were included. Three hundred fifty-two were treated with dural suture alone, and in 310, TachoSil was added after primary suture. Our primary endpoint was the rate of postoperative complications associated with CSF leakage. Secondary endpoints included functional, disability and neurological outcome. Systematic review according to PRISMA guidelines was performed to identify studies comparing primary dural closure with and without additional sealants. Postoperative complications associated with CSF leakage occurred in 24 (7.74%) and 28 (7.95%) procedures with or without TachoSil, respectively (p = 0.960). Multivariate analysis confirmed no significant differences in complication rate between the two groups (aOR 0.97, 95% CI 0.53-1.80, p = 0.930). There were no significant disparities in postoperative functional, disability or neurological scores. The systematic review identified 661 and included 8 studies in the qualitative synthesis. None showed a significant superiority of additional sealants over standard technique regarding complications, rates of revision surgery or outcome. According to our findings, we summarize that routinary use of TachoSil and similar products as adjuncts to primary dural sutures after intracranial surgical procedures is safe but without clear advantage in complication avoidance or outcome. Future studies should investigate whether their use is beneficial in high-risk settings

Fermi surface renormalization in Hubbard ladders

We derive the one-loop renormalization equations for the shift in the Fermi-wavevectors for one-dimensional interacting models with four Fermi-points (two left and two right movers) and two Fermi velocities v_1 and v_2. We find the shift to be proportional to (v_1-v_2)U^2, where U is the Hubbard-U. Our results apply to the Hubbard ladder and to the t_1-t_2 Hubbard model. The Fermi-sea with fewer particles tends to empty. The stability of a saddle point due to shifts of the Fermi-energy and the shift of the Fermi-wavevector at the Mott-Hubbard transition are discussed.Comment: 5 pages, 4 Postscript figure

Rhizobium determinants of rhizosphere persistence and root colonization

Bacterial persistence in the rhizosphere and colonization of root niches are critical for the establishment of many beneficial plant–bacteria interactions including those between Rhizobium leguminosarum and its host legumes. Despite this, most studies on R. leguminosarum have focused on its symbiotic lifestyle as an endosymbiont in root nodules. Here, we use random barcode transposon sequencing to assay gene contributions of R. leguminosarum during competitive growth in the rhizosphere and colonization of various plant species. This facilitated the identification of 189 genes commonly required for growth in diverse plant rhizospheres, mutation of 111 of which also affected subsequent root colonization (rhizosphere progressive), and a further 119 genes necessary for colonization. Common determinants reveal a need to synthesize essential compounds (amino acids, ribonucleotides, and cofactors), adapt metabolic function, respond to external stimuli, and withstand various stresses (such as changes in osmolarity). Additionally, chemotaxis and flagella-mediated motility are prerequisites for root colonization. Many genes showed plant-specific dependencies highlighting significant adaptation to different plant species. This work provides a greater understanding of factors promoting rhizosphere fitness and root colonization in plant-beneficial bacteria, facilitating their exploitation for agricultural benefit

Switching from standard to dose-dense chemotherapy in front-line treatment of advanced ovarian cancer: a retrospective study of feasibility and efficacy

BACKGROUND: Current standard neoadjuvant treatment for advanced ovarian cancer is 3-weekly platinum-based chemotherapy (CP3w). Patients unable to have interval debulking surgery (IDS) or with significant residual disease have a poor outcome to CP3w treatment. We investigated the outcome in patients who were switched to dose-dense chemotherapy. METHODS: We retrospectively analysed 30 patients treated at UCLH in 2009–2013, who switched to dose-dense chemotherapy after neoadjuvant CP3w, having achieved a poor response/progressed and unable to proceed to IDS (n=21), or had >1 cm residual disease after IDS (n=9). Treatment was 3-weekly carboplatin and weekly paclitaxel (n=23), or both drugs weekly (n=7). For comparison, we included 30 matched patients treated with CP3w followed by IDS (n=24, without or ≤1 cm residual disease; n=6, with >1 cm residual disease). Time to progression (TTP) and overall survival (OS) were measured from the date of diagnosis until progression (CT scan or CA-125) and death from any cause, respectively. RESULTS: Baseline characteristics were similar in both groups. The response rate to dose-dense chemotherapy was 70% (Gynecological Cancer Intergroup criteria). In the dose-dense group, 24 patients had tumour progression and 16 died; the corresponding numbers in the control group were 24 and 11. Median TTP was 15.8 months with dose-dense therapy, higher than expected for this patient group, and the same as in the control group (15.7 months) undergoing IDS, p=0.27. Median TTP in patients with residual disease postsurgery was 16.5 months (dose-dense) and 10.8 months (controls), p=0.02. TTP in dose-dense patients who did not have surgery was 10.4 months. Median OS was 31.3 (dose-dense) and 59.6 months (controls), p=0.06. Dose-dense chemotherapy was well tolerated: only three patients interrupted treatment due to toxicity. CONCLUSION: Switching to dose-dense chemotherapy in patients who failed to respond to CT3w neoadjuvant chemotherapy appears to be an effective strategy and requires further investigation

ESMO management and treatment adapted recommendations in the COVID-19 era: gynaecological malignancies

The rapid spread of severe acute respiratory syndrome coronavirus 2 infection and its related disease (COVID-19) has required an immediate and coordinate healthcare response to face the worldwide emergency and define strategies to maintain the continuum of care for the non-COVID-19 diseases while protecting patients and healthcare providers. The dimension of the COVID-19 pandemic poses an unprecedented risk especially for the more vulnerable populations. To manage patients with cancer adequately, maintaining the highest quality of care, a definition of value-based priorities is necessary to define which interventions can be safely postponed without affecting patients' outcome. The European Society for Medical Oncology (ESMO) has endorsed a tiered approach across three different levels of priority (high, medium, low) incorporating information on the value-based prioritisation and clinical cogency of the interventions that can be applied for different disease sites. Patients with gynaecological cancer are at particular risk of COVID-19 complications because of their age and prevalence of comorbidities. The definition of priority level should be based on tumour stage and histology, cancer-related symptoms or complications, aim (curative vs palliative) and magnitude of benefit of the oncological intervention, patients' general condition and preferences. The decision-making process always needs to consider the disease-specific national and international guidelines and the local healthcare system and social resources, and a changing situation in relation to COVID-19 infection. These recommendations aim to provide guidance for the definition of deferrable and undeferrable interventions during the COVID-19 pandemic for ovarian, endometrial and cervical cancers within the context of the ESMO Clinical Practice Guidelines