Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy.

Angiogenesis is required in cancer, including gynecological cancers, for the growth of primary tumors and secondary metastases. Development of anti-angiogenesis therapy in gynecological cancers and improvement of its efficacy have been a major focus of fundamental and clinical research. However, survival benefits of current anti-angiogenic agents, such as bevacizumab, in patients with gynecological cancer, are modest. Therefore, a better understanding of angiogenesis and the tumor microenvironment in gynecological cancers is urgently needed to develop more effective anti-angiogenic therapies, either or not in combination with other therapeutic approaches. We describe the molecular aspects of (tumor) blood vessel formation and the tumor microenvironment and provide an extensive clinical overview of current anti-angiogenic therapies for gynecological cancers. We discuss the different phenotypes of angiogenic endothelial cells as potential therapeutic targets, strategies aimed at intervention in their metabolism, and approaches targeting their (inflammatory) tumor microenvironment

Effects of topical estrogen therapy on the vaginal microcirculation in women with vulvovaginal atrophy

Aims: This study aims to assess vaginal wall angioarchitecture and function in women with vulvovaginal atrophy (VVA) and determine the effect of topical estrogen on the vaginal microcirculation. Materials and Methods: In this prospective observational study, incident dark field imaging was used to assess the vaginal microcirculation. In patients with VVA, measurements were performed before and after treatment with topical estrogen and compared to measurements performed in women without VVA. Vaginal angioarchitecture was studied by assessing microcirculatory architecture and capillary tortuosity scores at four regions of the vaginal wall. In addition, the capillary density and microvascular flow index (MFI) were obtained. Results: Seventeen women were included in this study. Of these, eight women were diagnosed with VVA and nine women were considered healthy controls. Significant differences were observed between groups with regard to microcirculatory architecture scores. The architecture of the microvasculature in women with VVA was characterized by the appearance of a vascular network without capillary loops, whereas an array of capillary loops was predominantly seen in women without VVA. After estrogen treatment, no difference in architecture scores between patients and healthy controls was observed. Capillary tortuosity, capillary density, and MFI were similar in both groups before and after estrogen treatment. Conclusions: The architecture of vaginal microvasculature is altered in patients with VVA. In case of similar vascular architecture, capillary tortuosity and density seem to be comparable. Treatment with topical estrogen results in restoration of the angioarchitecture

The vaginal microcirculation after prolapse surgery

Aims: Oxygen plays a crucial role in wound healing after prolapse surgery. Trauma to the vaginal vasculature might limit the delivery of oxygen to the surgical wound, which may negatively affect wound healing and regeneration of connective tissue. This possibly increases the future risk of recurrence. We aimed to determine the effects of vaginal prolapse surger

Noninvasive, in vivo assessment of the cervical microcirculation using incident dark field imaging

Aim: This study evaluates the feasibility of handheld vital microscopy for noninvasive, objective assessment of the microcirculation of the human uterine cervix. We qualitatively and quantitatively describe the microcirculation in healthy subjects in order to provide a basis for its application in cervical pathology. Methods: Incident dark field imaging was used to image the microcirculation in four quadrants of the uterine ectocervix in ten healthy participants. If the squamocolumnar junction was visible, measurements were repeated on the endocervical columnar epithelium as well. Image acquisition time was recorded and participants scored the experienced level of discomfort. Angioarchitecture was classified according to Weber's classification. Quantitative parameters included capillary density (CD), total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV) and microvascular flow index (MFI). Results: Image acquisition was easy, fast and well tolerated. Angioarchitecture was characterized by two distinctive and organized patterns; capillary loops underneath the squamous epithelium of the ectocervix and vascular networks underneath the columnar epithelium. In the image sequences containing capillary loops, mean CD was 33.2 cpll/mm2 (95% CI 28.2–38.2 cpll/mm2). In the image sequences with vascular n

The microcirculation in gynaecological disease

The microcirculation consists of the smallest blood vessels in the human body. These small blood vessels are essential for proper organ functioning and in processes such as wound healing and the development of cancer. The microcirculation can be visualized with handheld vital microscopes, allowing assessment of microcirculatory function and whether certain diseases or therapies affect this function. This thesis describes literature reviews and translational studies of different aspects of the microcirculation in patients with benign and malignant gynaecological diseases. We demonstrated that incident dark field (IDF) imaging is a suitable method to assess the microcirculation in these patients. The first part consists of four chapters that focus on the vaginal microcirculation, in the context of pelvic organ prolapse and vaginal surgery, vulvovaginal atrophy and estrogen therapy. The second part of this thesis consists of three chapters that focus on the peritoneal microcirculation and its role in peritoneal carcinomatosis of epithelial ovarian cancer. We showed that in addition to the more common sublingual microcirculatory assessment, IDF imaging of the microcirculation can also be used for a myriad of purposes in gynaecology: assessment of vascular damage after vaginal surgery, assessment of angioarchitecture to measure the effect of estrogens, focal depth to measure epithelial thickness and to improve understanding of metastatic disease

Application of amniotic membranes in reconstructive surgery of internal organs-A systematic review and meta-analysis

Amniotic membrane (AM) has great potential as a scaffold for tissue regeneration in reconstructive surgery. To date, no systematic review of the literature has been performed for the applications of AM in wound closure of internal organs. Therefore, in this systematic review and meta-analysis, we summarize the literature on the safety and efficacy of AM for the closure of internal organs. A systematic search was performed in MEDLINE-PubMed database and OVID Embase to retrieve human and controlled animal studies on wound closure of internal organs. The Cochrane Risk of Bias tool for randomized clinical trials and the SYRCLE risk of bias tool for animal studies were used. Meta-analyses (MAs) were conducted for controlled animal studies to assess efficacy of closure, mortality and complications in subjects who underwent surgical wound closure in internal organs with the application of AM. Sixty references containing 26 human experiments and 36 animal experiments were included. The MAs of the controlled animal studies showed comparable results with regard to closure, mortality and complications, and suggested improved mechanical strength and lower inflammation scores after AM application when compared to standard surgical closure techniques. This systematic review and MAs demonstrate that the application of AM to promote wound healing of internal organs appears to be safe, efficacious, and feasible

[The practice guideline 'Diagnosis and treatment of familial hypercholesterolaemia' of the Dutch Health Care Insurance Board]

Until 2010, the Dutch ministry of Health, Welfare and Sport will fund a nationwide project to identify the approximately 40,000 patients with familial hypercholesterolaemia (FH) in the Netherlands. The Health Care Insurance Board will coordinate the project and safeguard its quality, while the 'Stichting Opsporing Erfelijke Hypercholesterolemie' [Foundation for the Detection of Hereditary Hypercholesterolaemia], with its national network of genetic fieldworkers, will search systematically within families with assessed FH-mutations. The referral of the first suspected case of FH in a family for DNA diagnosis remains a task for GPs, internists and other clinical professionals; these will also be expected to take the responsibility for treatment. The list of diagnostic criteria of the 'Dutch Lipid Clinic Network' has recently been validated and is recommended as a decision-tool for initiating DNA diagnosis. After confirmation of the DNA diagnosis, the plasma level of LDL-cholesterol remains the main criterion for pharmacotherapy; treatment with hypocholesterolaemic agents is recommended at levels above 2.5 mmol/l

[The practice guideline 'Diagnosis and treatment of familial hypercholesterolaemia' of the Dutch Health Care Insurance Board],Richtlijn 'diagnostiek en behandeling van familiaire hypercholesterolemie' van het College voor zorgverzekeringen.

Item does not contain fulltextUntil 2010, the Dutch ministry of Health, Welfare and Sport will fund a nationwide project to identify the approximately 40,000 patients with familial hypercholesterolaemia (FH) in the Netherlands. The Health Care Insurance Board will coordinate the project and safeguard its quality, while the 'Stichting Opsporing Erfelijke Hypercholesterolemie' [Foundation for the Detection of Hereditary Hypercholesterolaemia], with its national network of genetic fieldworkers, will search systematically within families with assessed FH-mutations. The referral of the first suspected case of FH in a family for DNA diagnosis remains a task for GPs, internists and other clinical professionals; these will also be expected to take the responsibility for treatment. The list of diagnostic criteria of the 'Dutch Lipid Clinic Network' has recently been validated and is recommended as a decision-tool for initiating DNA diagnosis. After confirmation of the DNA diagnosis, the plasma level of LDL-cholesterol remains the main criterion for pharmacotherapy; treatment with hypocholesterolaemic agents is recommended at levels above 2.5 mmol/l