Preservation of Ovarian Function in Young Women with Gynecologic Cancer Desiring Future Pregnancy: A Review

Objective: The aim of this paper is to present an overview of available published methods for preservation of ovarian function and fertility in young patients with gynecologic malignancies who desire to maintain their child-bearing capacity or ovarian function. Methods: A Medline search was conducted and published articles from American and European studies from 1984 to present were reviewed. The effect of cancer treatment on reproductive capacity and different methods of fertility preservation with their reproductive outcomes and ovarian function and long term side effects are presented.Results: The pregnancy rate in patients with gynecologic malignancies varies according to the type of the malignancy, stage of disease, treatment modalities, and other factors such as patient’s age and reproductive capacity, status of sexual partner, and potential for surrogacy. The highest success rates of pregnancy have been reported in patients who had fertility-sparing surgery and utilized assisted reproduction technology.Conclusion: Today, higher cure rates and longer survival are a result of early cancer detection and treatment. In conjunction with the advances in assisted reproduction and fertility , the preservation of ovarian function and fertility has become a major part of contemporary patient care and should be offered to any young patient with gynecologic cancer. These alternative options are appropriate only in highly selective patients with good prognoses. A multidisciplinary approach and collaboration between other related disciplines might optimize a successful outcome in these patients

Designing a Reverse Logistics Network for End-of-Life Vehicles Recovery

The environmental factors are receiving increasing attention in different life cycle stages of products. When a product reaches its End-Of-Life (EOL) stage, the management of its recovery process is affected by the environmental and also economical factors. Selecting efficient methods for the collection and recovery of EOL products has become an important issue. The European Union Directive 2000/53/EC extends the responsibility of the vehicle manufacturers to the postconsumer stage of the vehicle. In order to fulfill the requirements of this Directive and also efficient management of the whole recovery process, the conceptual framework of a reverse logistics network is presented. The distribution of new vehicles in an area and also collecting the End-of-Life Vehicles (ELVs) and their recovery are considered jointly. It is assumed that the new vehicles distributors are also responsible for collecting the ELVs. Then a mathematical model is developed which minimizes the costs of setting up the network and also the relevant transportation costs. Because of the complexity of the model, a solution methodology based on the genetic algorithm is designed which enables achieving good quality solutions in a reasonable algorithm run time

IDENTIFICATION OF OCCULT CEREBRAL MICROBLEEDS IN ADULTS WITH IMMUNE THROMBOCYTOPENIA

Management of symptoms and prevention of life-threatening hemorrhage in immune thrombocytopenia (ITP) must be balanced against adverse effects of therapies. Because current treatment guidelines based on platelet count are confounded by variable bleeding phenotypes, there is a need to identify new objective markers of disease severity for treatment stratification. In this cross-sectional prospective study of 49 patients with ITP and nadir platelet counts <30 × 109/L and 18 aged-matched healthy controls, we used susceptibility-weighted magnetic resonance imaging to detect cerebral microbleeds (CMBs) as a marker of occult hemorrhage. CMBs were detected using a semiautomated method and correlated with clinical metadata using multivariate regression analysis. No CMBs were detected in health controls. In contrast, lobar CMBs were identified in 43% (21 of 49) of patients with ITP; prevalence increased with decreasing nadir platelet count (0/4, ≥15 × 109/L; 2/9, 10-14 × 109/L; 4/11, 5-9 × 109/L; 15/25 <5 × 109/L) and was associated with longer disease duration (P = 7 × 10−6), lower nadir platelet count (P = .005), lower platelet count at time of neuroimaging (P = .029), and higher organ bleeding scores (P = .028). Mucosal and skin bleeding scores, number of previous treatments, age, and sex were not associated with CMBs. Occult cerebral microhemorrhage is common in patients with moderate to severe ITP. Strong associations with ITP duration may reflect CMB accrual over time or more refractory disease. Further longitudinal studies in children and adults will allow greater understanding of the natural history and clinical and prognostic significance of CMBs

Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of the HER inhibitors and cytotoxic drugs

Increased expression and activation of human epidermal growth factor receptor (EGFR) and HER-2 have been reported in numerous cancers. The aim of this study was to determine the sensitivity of a large panel of human ovarian cancer cell lines (OCCLs) to treatment with various forms of small molecule tyrosine kinase inhibitors (TKIs) and cytotoxic drugs. The aim was to see if there was any association between the protein expression of various biomarkers including three putative ovarian cancer stem cell (CSC) markers (CD24, CD44, CD117/c-Kit), P-glycoprotein (P-gp), and HER family members and response to treatment with these agents. The sensitivity of 10 ovarian tumour cell lines to the treatment with various forms of HER TKIs (gefitinib, erlotinib, lapatinib, sapitinib, afatinib, canertinib, neratinib), as well as other TKIs (dasatinib, imatinib, NVP-AEW541, crizotinib) and cytotoxic agents (paclitaxel, cisplatin and doxorubicin), as single agents or in combination, was determined by SRB assay. The effect on these agents on the cell cycle distribution, and downstream signaling molecules and tumour migration were determined using flow cytometry, western blotting, and the IncuCyte Clear View cell migration assay respectively. Of the HER inhibitors, the irreversible pan-TKIs (canertinib, neratinib and afatinib) were the most effective TKIs for inhibiting the growth of all ovarian cancer cells, and for blocking the phosphorylation of EGFR, HER-2, AKT and MAPK in SKOV3 cells. Interestingly, while the majority of cancer cells were highly sensitive to treatment with dasatinib, they were relatively resistant to treatment with imatinib (i.e., IC50 >10 µM). Of the cytotoxic agents, paclitaxel was the most effective for inhibiting the growth of OCCLs, and of various combinations of these drugs, only treatment with a combination of NVP-AEW541 and paclitaxel produced a synergistic or additive anti-proliferative effect in all three cell lines examined (i.e., SKOV3, Caov3, ES2). Finally, of the TKIs, only treatment with afatinib, neratinib and dasatinib were able to reduce the migration of HER-2 overexpressing SKOV3 cells. We did not find any significant association between the expression of putative ovarian CSC marker, HER family members, c-MET, ALK, and IGF-IR and the response to the irreversible HER TKIs. Our results support the need for further investigations of the therapeutic potential of these irreversible HER family blockers in ovarian cancer, and the therapeutic potential of dasatinib when used in combination with the inhibitors of the HER family members in ovarian cancer

Haemophilia and ageing

Advances in the development of effective and safe treatments for haemophilia over the last 50 years have resulted in a significant increase in the life expectancy of persons with haemophilia (PWH). The management of this new cohort of middle‐aged and elderly PWH is challenging because of the opposing risks of haemophilia and age‐related cardiovascular disease and malignancy. Furthermore, this cohort of ageing PWH has the additional comorbidities of human immunodeficiency virus/hepatitis C and chronic haemophilic arthropathy. This article reviews the prevalence, underlying mechanisms and treatment strategies for managing these comorbidities. International collaboration is essential for registry data and further prospective trials to inform optimal evidence‐based management for this rare disorder in the future