PurposeWhile hemorrhoidal disease is common, its etiology remains unclear. It has been postulated that disturbances in collagen lead to reduced connective tissue stability, and in turn to the development of hemorrhoidal disease. We aimed to compare the quality and quantity of collagen in patients with hemorrhoidal disease versus normal controls.MethodsSpecimens from 57 patients with grade III or IV internal hemorrhoids undergoing hemorrhoidectomy between 2006 and 2011 were evaluated. Samples from 20 human cadavers without hemorrhoidal disease served as controls. Quality of collagen was analyzed by collagen I/III ratio, and quantity of collagen was determined by collagen/protein ratio. The study group was subdivided into gender and age subgroups.ResultsThe male:female ratios in the study and control groups were 30:27 and 10:10, respectively. Median age was significantly less in the study group [46.9 years (range 20–69)] compared to the control group [76 years (range 46–90)] with P < 0.05. Tissues from patients in the study group had significantly lower collagen I/III ratio as compared to the control group (4.4 ± 1.1 vs. 5.5 ± 0.6; P < 0.0001). Nevertheless, despite a trend toward lower collagen/protein ratio in the study group, it did not reach statistical significance (57 ± 42.4 vs. 73 ± 32.5 g/mg; P = 0.167). There was no difference in collagen I/III or collagen/protein ratios among different age groups and genders.ConclusionsHemorrhoidal tissues from patients with hemorrhoidal disease appear to have reduced mechanical stability as compared to normal controls.

Matrix metalloproteinase-2 (MMP-2) is a key regulator in wound healing that orchestrates tissue remodeling. In the present study the spatial and temporal distribution of MMP-2 gene transcription, protein synthesis, and enzymatic activity were analyzed following polymeric mesh (polyglactin, polypropylene) implantation in transgenic reporter mice harboring MMP-2 regulatory sequences -1686/+423 or -1241/+423. Polymers induced MMP-2 promoter activity in macrophages within the foreign body granuloma via sequences -1686/+423 with concomitantly up-regulated protein synthesis and enzymatic activity. Macrophages distant from mesh filaments exhibited low MMP-2 expression levels. Fibroblasts surrounding mesh material displayed strong MMP-2 gene transcription independent of the included promoter sequences, whereas fibroblasts without close contact to mesh material had low MMP-2 synthesis rates due to silencing activity of sequences -1686/-1241. In vitro studies support a cellular crosstalk concept, as macrophages trans-repressed MMP-2 gene transcription in fibroblasts. The zonal and cell-specific regulation of MMP-2 gene transcription illuminates an intimate cellular crosstalk in foreign body reaction that may provide a new approach for mesh modification.

The absence of circulating aldosterone attenuates inflammatory intensity around suture material. Foreign body granuloma seems to be an appropriate model to study chronic inflammatory process.

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