Leptomeningeal carcinomatosis as the primary presentation of relapse in breast cancer

Leptomeningeal metastasis (LM) is an uncommon presentation of relapse in breast cancer, which is associated with poor clinical outcomes and poor prognosis. Notably, LM most commonly occurs in breast cancer. The aim of the present review was to investigate the occurrence of LM as the primary presentation of relapse following remission in breast cancer patients and to determine whether specific histological subtypes are predisposed to meningeal metastases. In addition, the present review evaluated whether patients presenting with LM as the primary site of relapse exhibit differences in survival when compared with patients exhibiting metastasis to other sites. Cross-sectional studies have demonstrated that LM is commonly associated with other sites of distant metastasis including lung, liver and bone metastases. The histological breast cancer subtype most commonly associated with LM was invasive lobular carcinoma, while triple-negative breast cancer patients appear to be predisposed to the development of LM when considering the overall prevalence of histological breast cancer subtypes. At present, data regarding LM as the primary site of relapse are limited due to its rarity as the first site of metastasis in breast cancer. Case-controlled studies are required to investigate the incidence of LM as the primary site of recurrence in breast cancer patients as this would enable treatment standardization and identification of prognostic factors for improved survival

Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions

Tumours require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. Since one or more of the VEGF ligand family is overexpressed in most solid cancers, there was great optimism that inhibition of the VEGF pathway would represent an effective anti-angiogenic therapy for most tumour types. Encouragingly, VEGF pathway targeted drugs such as bevacizumab, sunitinib and aflibercept have shown activity in certain settings. However, inhibition of VEGF signalling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumours. Here we present a succinct review of the progress with VEGF-targeted therapy and the unresolved questions that exist in the field: including its use in different disease stages (metastatic, adjuvant, neoadjuvant), interactions with chemotherapy, duration and scheduling of therapy, potential predictive biomarkers and proposed mechanisms of resistance, including paradoxical effects such as enhanced tumour aggressiveness. In terms of future directions, we discuss the need to delineate further the complexities of tumour vascularisation if we are to develop more effective and personalised anti-angiogenic therapies. © 2014 The Author(s)

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution

Cryoglobulinemia due to Hepatitis C with Pulmonary Renal Syndrome

Cryoglobulinemia is an uncommon condition typically due to hepatitis C infection. Its clinical presentation is varied and often reflects deposition of immune complex and complement deposition. Renal compromise is observed in approximately one third of patients with mixed cryoglobulinemia and reports of concomitant pulmonary involvement are quite rare. We report a case of a patient who presented with pulmonary and renal manifestations of cryoglobulinemia with a serum rheumatoid factor over one hundred times the upper limit of normal and benefited from high-dose steroids and plasmapheresis in the acute setting

Exploring indirect impacts of COVID-19 on local health systems from the perspectives of health workers and higher education stakeholders in the Philippines using a phenomenological approach

Background Our study aimed to explore the experiences of stakeholders from local government units, health facilities and higher education institutions on the delivery of non-COVID-19 health services after the initial wave of the pandemic. Methods Twenty-nine public health workers, thirteen university staff, and four hospital administrators in the Philip- pines participated. Using a descriptive phenomenological approach, we analysed transcripts from six focus group discussions conducted online between March and June 2021. Findings The COVID-19 pandemic made the routine health programs inaccessible due to hesitancy among patients to visit health facilities, a shift in public health priorities, and lack of students to augment the existing workforce. Public health workers reported stress and mental health exhaustion. Apart from fear of infection during service pro- vision, public health workers and university staff experienced work overload, pressure to learn new technology, and webinar fatigue. Mental health problems have surfaced as health workers and young people have become more affected while support services remain insufficient. Public health workers have reported actions to maintain service delivery in the new normal such as use of telehealth and social media. However, issues on workforce wellbeing and digital equity posed adaptation challenges. Participants sug- gested partnership with higher education institutions as pivotal to position local health systems towards recovery. Interpretation The rapid change in the service landscape highlights the importance of sustainable partnerships, effective workforce management, equitable digital innovations, and promoting mental wellbeing to preserve com- munity, school, and occupational health and rebuild resilient local health systems in low-resourced areas. Funding This research is proudly supported by the Australia-ASEAN Council, Australian Government Department of Foreign Affairs and Trade