Segmentation of Dilated Hemorrhoidal Veins in Hemorrhoidal Disease

Abstract

Vein segmentation is a vascular remodeling process mainly studied in experimental conditions and linked to hemodynamic factors, with clinical implications. The aim of this work is to assess the morphologic characteristics, associated findings, and mechanisms that participate in vein segmentation in humans. To this end, we examined 156 surgically obtained cases of hemorrhoidal disease. Segmentation occurred in 65 and was most prominent in 15, which were selected for serial sections, immunohistochemistry, and immunofluorescence procedures. The dilated veins showed differently sized spaces, separated by thin septa. Findings associated with vein segmentation were: (a) vascular channels formed from the vein intima endothelial cells (ECs) and located in the vein wall and/or intraluminal fibrin, (b) vascular loops formed by interconnected vascular channels (venous-venous connections), which encircled vein wall components or fibrin and formed folds/pillars/papillae (FPPs; the encircling ECs formed the FPP cover and the encircled components formed the core), and (c) FPP splitting, remodeling, alignment, and fusion, originating septa. Thrombosis was observed in some nonsegmented veins, while the segmented veins only occasionally contained thrombi. Dense microvasculature was also present in the interstitium and around veins. In conclusion, the findings suggest that hemorrhoidal vein segmentation is an adaptive process in which a piecemeal angiogenic mechanism participates, predominantly by intussusception, giving rise to intravascular FPPs, followed by linear rearrangement, remodeling and fusion of FPPs, and septa formation. Identification of other markers, as well as the molecular bases, hemodynamic relevance, and possible therapeutic implications of vein segmentation in dilated hemorrhoidal veins require further studies.

Intussusceptive Lymphangiogenesis in Lymphatic Malformations/Lymphangiomas

“…Likewise, segmentation of dilated hemorrhoidal veins and venous-venous loops have been described in hemorrhoidal disease (Díaz-Flores et al, 2018b). These processes are based on intussusception (Patan et al, 2001a, b;Díaz-Flores et al, 2018b). Our observations in serial sections reveal that segmented lymphatic vessels and lymphatic-lymphatic loops formed from dilated lymphatic spaces are equivalent to segmented veins and venousvenous loops described in dilated veins in the ovarian pedicle and in hemorrhoidal disease.…”

Participation of Intussusceptive Angiogenesis in the Morphogenesis of Lobular Capillary Hemangioma

“…www.nature.com/scientificreports www.nature.com/scientificreports/ This work and previous studies 14,16 show that LCH, sinusoidal hemangioma and IPEH present different morphologic patterns and share hallmarks of intussusception, in which vessel loops have an important morphogenic role. A similar participation of vessel loops has been demonstrated in the ovarian vein of the rat after ovariectomy and human tumour xenograft implantation 10,11 and in other human blood and lymphatic vessel diseases, such as hemorrhoidal disease, lymphangiomas/lymphatic malformations and vascular transformation of lymph node sinuses, as well as in some sinuses of developing human foetal lymph nodes 5,14,[27][28][29] . We use the term "piecemeal form of intussusceptive angiogenesis" to describe the mechanism of the formation and intravascular transport of pillars by vessel loops 5,[14][15][16]30 .…”

“…A similar participation of vessel loops has been demonstrated in the ovarian vein of the rat after ovariectomy and human tumour xenograft implantation 10,11 and in other human blood and lymphatic vessel diseases, such as hemorrhoidal disease, lymphangiomas/lymphatic malformations and vascular transformation of lymph node sinuses, as well as in some sinuses of developing human foetal lymph nodes 5,14,[27][28][29] . We use the term "piecemeal form of intussusceptive angiogenesis" to describe the mechanism of the formation and intravascular transport of pillars by vessel loops 5,[14][15][16]30 . The morphologic differences of sinusoidal hemangioma, IPEH and LCH depend on the number of interendothelial contacts between the opposite walls of the loops and intravascular pillars formed in/from vessel loops, as well as on the substrate in which vessel loops and pillars form and on the different arrangement of pillars (see Fig.…”

Tissue engineering strategies for the induction of angiogenesis using biomaterials

“…To stabilize the vessel structure, the attachment of Ang-1 to cognate receptor Tie-2 increases the integration of ECs with neighboring cells and surrounding peri-vascular pericytes thereby promoting vascular maturation and reducing migration activity of ECs. In addition to angiogenesis initiated by sprouting mechanism, other alternative remodeling mechanisms such as intussusception and bridging were also described as inverted angiogenesis in the context of vascular structure [8]. Intussusception is touted as trans-vascular tissue pillars formed inside vessels lumen extensively seen in developing vessels to form multi-vascular branches.…”