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

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

Supplementary Material for: The microcirculation of vaginal tissue in women with obstetric vesicovaginal fistula and short-term effects of surgical repair on microvascular parameters

Objectives: To better understand the extent of the ischemic trauma and the effects of surgical repair on the vaginal microcirculation in patients with obstetric vesicovaginal fistula (VVF). Design: In this observational study, we evaluated the vaginal microvasculature surrounding VVF using handheld vital microscopy (HVM) before, during and two weeks after surgical VVF repair. Participants: Seventeen women undergoing VVF repair were included in this study. Setting: The study was conducted in the Fistula Care Centre in Lilongwe, Malawi. Methods: We used HVM with incident dark-field (IDF) imaging to non-invasively visualize the microvasculature of the vaginal tissue surrounding fistulas. The primary outcome was the presence of microvascular flow. Secondary outcomes included angioarchitecture, fistula closure (postoperative dye test) and urinary continence (pad weight test). Results: Microvascular flow was present before, during and after surgical repair in respectively 83.8%, 83.9% and 93.4% of obtained image sequences. The angioarchitecture was normal in 75.8% of the image sequences before surgery, 69.4% at fistula closure and 89.1% two weeks after VVF repair. Fourteen (82.4%) patients had a closed fistula after surgical repair. Limitations: The study was limited by the lack of a control group and the relatively small sample size. Conclusion: Although the vaginal microcirculation in women with VVF is compromised, extensive ischemic damage is not observed in the tissue surrounding fistulas. This suggests significant regenerative capacity of the vaginal vasculature in young women, or less extensive ischemic damage than presumed. Following surgical repair, we observed improvement of microcirculatory flow and angioarchitecture, suggesting that surgery is a good option for patients with obstetric VVF

Supplementary Material for: The microcirculation of vaginal tissue in women with obstetric vesicovaginal fistula and short-term effects of surgical repair on microvascular parameters

Objectives: To better understand the extent of the ischemic trauma and the effects of surgical repair on the vaginal microcirculation in patients with obstetric vesicovaginal fistula (VVF). Design: In this observational study, we evaluated the vaginal microvasculature surrounding VVF using handheld vital microscopy (HVM) before, during and two weeks after surgical VVF repair. Participants: Seventeen women undergoing VVF repair were included in this study. Setting: The study was conducted in the Fistula Care Centre in Lilongwe, Malawi. Methods: We used HVM with incident dark-field (IDF) imaging to non-invasively visualize the microvasculature of the vaginal tissue surrounding fistulas. The primary outcome was the presence of microvascular flow. Secondary outcomes included angioarchitecture, fistula closure (postoperative dye test) and urinary continence (pad weight test). Results: Microvascular flow was present before, during and after surgical repair in respectively 83.8%, 83.9% and 93.4% of obtained image sequences. The angioarchitecture was normal in 75.8% of the image sequences before surgery, 69.4% at fistula closure and 89.1% two weeks after VVF repair. Fourteen (82.4%) patients had a closed fistula after surgical repair. Limitations: The study was limited by the lack of a control group and the relatively small sample size. Conclusion: Although the vaginal microcirculation in women with VVF is compromised, extensive ischemic damage is not observed in the tissue surrounding fistulas. This suggests significant regenerative capacity of the vaginal vasculature in young women, or less extensive ischemic damage than presumed. Following surgical repair, we observed improvement of microcirculatory flow and angioarchitecture, suggesting that surgery is a good option for patients with obstetric VVF