Endogenously-Produced Hyaluronan and Its Potential to Regulate the Development of Peritoneal Adhesions

Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdominal surgery. It is primarily caused by activation of the mesothelial layer and underlying tissues in the peritoneal membrane resulting in the transition of mesothelial cells (MCs) and fibroblasts to a pro-fibrotic phenotype. Pro-fibrotic transition of MCs—mesothelial-to-mesenchymal transition (MMT), and fibroblasts activation to myofibroblasts are interconnected to changes in cellular metabolism and culminate in the deposition of extracellular matrix (ECM) in the form of fibrotic tissue between injured sides in the abdominal cavity. However, ECM is not only a mechanical scaffold of the newly synthetized tissue but reciprocally affects fibrosis development. Hyaluronan (HA), an important component of ECM, is a non-sulfated glycosaminoglycan consisting of N-acetyl-D-glucosamine (GlcNAc) and D-glucuronic acid (GlcUA) that can affect the majority of processes involved in PA formation. This review considers the role of endogenously produced HA in the context of different fibrosis-related pathologies and its overlap in the development of PA.

Regional Diversities in Fibrogenesis Weighed as a Key Determinant for Atrial Arrhythmogenesis

Atrial fibrosis plays a key role in atrial myopathy, resulting in the genesis of atrial fibrillation (AF). The abnormal distribution of fibrotic tissue, electrical coupling, paracrine interactions, and biomechanical–electrical interactions have all been suggested as causes of fibrosis-related arrhythmogenesis. Moreover, the regional difference in fibrogenesis, specifically the left atrium (LA) exhibiting a higher arrhythmogenesis and level of fibrosis than the right atrium (RA) in AF, is a key contributor to atrial arrhythmogenesis. LA fibroblasts have greater profibrotic cellular activities than RA fibroblasts, but knowledge about the regional diversity of atrial regional fibrogenesis remains limited. This article provides a comprehensive review of research findings on the association between fibrogenesis and arrhythmogenesis from laboratory to clinical evidence and updates the current understanding of the potential mechanism underlying the difference in fibrogenesis between the LA and RA.

Mesenchymal Stromal Cells Adapt to Chronic Tendon Disease Environment with an Initial Reduction in Matrix Remodeling

Tendon lesions are common sporting injuries in humans and horses alike. The healing process of acute tendon lesions frequently results in fibrosis and chronic disease. In horses, local mesenchymal stromal cell (MSC) injection is an accepted therapeutic strategy with positive influence on acute lesions. Concerning the use of MSCs in chronic tendon disease, data are scarce but suggest less therapeutic benefit. However, it has been shown that MSCs can have a positive effect on fibrotic tissue. Therefore, we aimed to elucidate the interplay of MSCs and healthy or chronically diseased tendon matrix. Equine MSCs were cultured either as cell aggregates or on scaffolds from healthy or diseased equine tendons. Higher expression of tendon-related matrix genes and tissue inhibitors of metalloproteinases (TIMPs) was found in aggregate cultures. However, the tenogenic transcription factor scleraxis was upregulated on healthy and diseased tendon scaffolds. Matrix metalloproteinase (MMPs) expression and activity were highest in healthy scaffold cultures but showed a strong transient decrease in diseased scaffold cultures. The release of glycosaminoglycan and collagen was also higher in scaffold cultures, even more so in those with tendon disease. This study points to an early suppression of MSC matrix remodeling activity by diseased tendon matrix, while tenogenic differentiation remained unaffected.

Xanthogranulomatous Cholecystitis: Our Clinical Experience

Background: Xanthogranulomatous cholecystitis is a rarely encountered chronic inflammatory condition presenting with severely proliferated fibrotic tissue. It usually spreads the neighboring organs, imitates gallbladder cancer and may lead to difficulty in cholecystectomy. Objectives: The present study was directed towards reviewing the results of medical examinations and surgery for xan-thogranulomatous cholecystitis and providing proper surgical treatment for patients with xanthogranulomatous cholecystitis. Methods: This is an observational study in which clinical features of thirty six patients with diagnosis of cholecystitis who were operated in our institute between 2012 and 2019 and found as xanthogranulomatous cholecystitis on pathology were analyzed. Results: The rate of xanthogranulomatous cholecystitis in cholecystectomy patients was found to be 0.6 % (36/5999) in the hospital where this study was performed over 7 years. Xanthogranu-lomatous cholecystitis was not accompanied by gallbladder carcinoma in any of these cases. Xanthogranulomatous cholecystitis could not be diagnosed in any of the patients prior to surgery. Radiological imaging performed before surgery demonstrated cholelithiasis in 29 patients (80.6 %), thickening of the gallbladder wall in 28 patients (77.8%), and suspicious cancer in two patients (5.6%). However, none of the cases of xanthogranulomatous cholecystitis had concomitant gallbladder cancer. Nine (25%) patients underwent open cholecystectomy and Twenty seven patients (75 %) were scheduled to have laparoscopic cholecystectomy, but six of these patients (16,8%) were converted to open cholecystectomy. Conclusion: To conclude, it is still difficult to distinguish xanthogranulomatous cholecystitis from other gallbladder diseases both before and during surgery. The gallbladder commonly adheres to the neighboring organs and tissues and make surgical treatment difficult. A challenging laparoscopy is commonly converted to open surgery, which results in higher rates of complications as compared with standard open or laparoscopic cholecystectomy.

Closure of Oronasal Fistulae Post Palatoraphy with Tongue Flap in Bilateral Complete Cleft Lip Palate Patient: A Case Report

Oronasal fistulae are common complication following palatoraphy. There are several surgical procedures to repair oronasal fistulae. However, conventional oronasal fistulae closure technique is not always possible, especially when the surrounding tissue is replaced by fibrotic tissue due to previous palatoraphy. Tissue defects in oronasal fistulae should be replaced with tissues providing good vascularisation such as pedicle tongue flap. A case of pedicle tongue flap used to close oronasal fistulae was reported. Eleven-year-old girl, presented with oronasal fistulae and bilateral alveolar cleft after previous palatoraphy. The oronasal fistulae were closed with pedicled tongue flap. The healing was uneventful, and the division of the pedicle tongue flap was done three weeks later and closed primarily. There was no dehiscence of the wound and masticatory functions were recorded. Vascularised flap such as pedicle tongue flap is a preferred technique to close oronasal fistulae after palatoraphy.

Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions

Fibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different types of lesions. In the current study, we compared fibrotic scarring in human pathological tissue and corresponding mouse models of penetrating and non-penetrating spinal cord injury, traumatic brain injury, ischemic stroke, multiple sclerosis and glioblastoma. We show that the extent and distribution of stromal cells are specific to the type of lesion and, in most cases, similar between mice and humans. Employing in vivo lineage tracing, we report that in all mouse models that develop fibrotic tissue, the primary source of scar-forming fibroblasts is a discrete subset of perivascular cells, termed type A pericytes. Perivascular cells with a type A pericyte marker profile also exist in the human brain and spinal cord. We uncover type A pericyte-derived fibrosis as a conserved mechanism that may be explored as a therapeutic target to improve recovery after central nervous system lesions.

296 Case Report: Pacemaker Lead-Induced Fibrosis Resulting in Right Atrial and Tricuspid Stenosis Managed with An Open Surgical Approach

Pacemaker leads can result in localised inflammation and, over time, fibrosis. Rarely, this can significantly alter the anatomy of the heart and impair cardiac function. In this case, a fifty-year-old female had undergone pacemaker placement in her teens having experienced symptomatic bradycardia. Due to pacemaker pocket erosion, she had undergone a lead extraction where lead fragments had been left in-situ. Years after a new generator and leads were placed, she presented with symptoms of proximal venous congestion and superior vena cava (SVC) syndrome. A venogram demonstrated completely occluded brachiocephalic and innominate veins with significant adjacent venous collateralization. Computed tomography showed partial obstruction of the SVC and tricuspid stenosis. Initially, a decision was made not to intervene. After developing abdominal distension, she was diagnosed with hepatic congestion and cirrhosis secondary to elevated right sided pressures and right atrial congestion due to tricuspid stenosis. It was concluded that the patient’s symptoms were the result of occluded proximal veins, SVC syndrome, and functional tricuspid stenosis, all of which were likely the result of fibrotic tissue secondary to pacemaker lead-induced inflammation. Due to the severity of her symptoms, the patient accepted the risks associated with surgical management. Intra-operatively, electrocautery was used to debride the fibrotic tissue inhibiting the leaflets of the tricuspid valve. This worked to great effect and additional valve repair/replacement was not necessary. Whilst the patient has been left with SVC syndrome, her tricuspid stenosis symptoms are greatly improved. To our knowledge, such a case has not been previously described.

Scrotal bridge flap reconstructive surgery for extensive penile paraffinoma: steps and outcomes from a single center: a case series

Background To describe our scrotal bridge flap technique in reconstructive surgery for extensive penile paraffinoma, a debilitating late complication of penile subcutaneous foreign material injection intended to achieve penile augmentation. Case presentation We reviewed the medical records of 10 patients who underwent reconstructive surgery with the scrotal bridge flap technique for penile paraffinoma at our center between 2016 and 2019. Complete excision of fibrotic tissue and the overlying skin was performed, and penile resurfacing was achieved by mobilizing the scrotal skin superiorly to wrap around the penile shaft, leaving a skin bridge at the median raphe. All 10 patients successfully underwent scrotal bridge flap penile reconstruction with satisfying results. The mean operation duration was 286.1 min (range 213–363 min). No immediate major complications were observed in any of the patients, and no patients required revision surgery. Conclusion The scrotal bridge flap technique is a reliable method for reconstructive surgery after the excision of penile paraffinoma.

Small intestinal submucosa extracellular matrix envelopes secure cardiovascular implantable devices and promote healthy tissue remodeling

Introduction: Cardiac implantable electronic devices (CIEDs) induce a foreign body reaction and persistent inflammatory response that produces a fibrotic capsule around the implanted material. The study’s aim was to investigate the ability of small intestinal submucosa (SIS) extracellular matrix (ECM) envelopes to mitigate fibrotic tissue formation and secure devices within healthy, vascularized tissue. Methods: Clinically relevant pacemakers without leads were subcutaneously implanted in a pre-clinical rabbit model. Eleven CIEDs were placed in CanGaroo ECM Envelopes, while ten devices were implanted without envelopes and analyzed at 13 and 26 weeks. The subcutaneous pocket and newly formed connective tissue adjacent to the CIED were evaluated by an independent, blinded pathologist for the local tissue response and constructive remodeling. CIED movement in the pocket was also documented as implant sites were prone to abrasion due to normal rabbit behavior. Results: CanGaroo Envelopes surrounding the CIEDs remodeled into native tissue with normally organized collagen. The tissue had a lower average thickness at 13 and 26 weeks compared to tissue encapsulating CIEDs without envelopes. The tissue also scored significantly higher in neovascularization versus capsule tissue surrounding CIEDs without envelopes at 26 weeks. Use of the ECM envelope reduced the incidence of device flipping within the pocket by 40% compared to CIEDs without envelopes, showing the ability of CanGaroo Envelopes to secure CIEDs in place. Conclusions: CanGaroo ECM Envelopes remodeled into native, vascularized tissue surrounding clinically applicable CIEDs. This thinner, healthy tissue pocket secured CIEDs and significantly improved stabilization versus devices without envelopes over 26 weeks.