Dupuytren's Disease: Anatomy and Surgical Treatment

The principal aim of this written account is to describe the evolution of a surgical approach to the treatment of Dupuytren's Disease based on current knowledge of pathogenesis and precise description of the anatomy. The historical record of the life and works of Baron Guillaume Dupuytren, together with those of his contemporaries, pupils and critics have been reviewed to clarify the understanding of the condition at that time and to uncover wisdom which has been forgotten. The disease process is considered by analysis of studies of incidence, aetiological factors, pathology and related fibromatous lesions. Series of dissections of the palm and digits in fresh and preserved cadaveric hands have been performed to establish a new perspective on the micro-anatomy of the normal ligamentous components of the hand. The lesions of Dupuytren's Disease - palmar nodules, pits and cords, distortion of palmar creases and knuckle changes - have been examined by observations of clinical signs and operative dissections. New clinical signs -the "blanching" sign in the palm, and knuckle changes -have been described. A new classification of operative interventions is described according to the approach to a) the skin, b) the fascia and c) the joints. The operative experience and long term results, using an evolution of techniques, have been reviewed in a series of 100 patients. Dupuytren's Disease is viewed as a process akin to wound healing which involves not only the palmar fascia, as described by Dupuytren, but many of the connective tissues of the hand including the dermis of the skin. The distribution of the pathological tissue is not random, but dictated by lines of tension or stress concentrations transmitted through certain anatomical pathways. Movement of the hand may be the stimulus to the propagation of the contracture once it has commenced. Treatment has been found to be generally not curative, but affording only temporary release. A less extensive and more precise operative approach has been developed. The values of minimal surgery and maximal rehabilitation are stressed

Identification of novel keloid biomarkers through Profiling of Tissue Biopsies versus Cell Cultures in Keloid Margin specimens Compared to adjacent Normal Skin

Objective: Keloid disease (KD) is a benign fibroproliferative skin tumor that results from abnormal wound healing and has no single definitive treatment. This study aims to identify KD biomarkers, which are cellular mediators that can serve as indicators of normal, pathological, and therapeutic processes. Methods: Bioinformatics analytic approaches, including comprehensive literature searches and DAVID Bioinformatics Resources 2008, were performed on the established KD linkage and previously reported microarray data to identify potential candidate genes for the study. Keloid margins and unaffected skin were obtained from KD patients (n = 4). RNA was extracted from the biopsies and second-passage culture equivalents. Reverse-transcriptase quantitative polymerase chain reactions were used to determine the gene expression levels. Student t tests were used to analyze the statistical significance in differential gene expressions. Results: Nineteen candidate genes were initially selected by bioinformatics analysis. Of the 19 genes, 10 were significantly (P < .05) upregulated in keloid margin biopsy specimens. The top-5 fold changes range from 10-fold to 175-fold, including aggrecan; asporin; inhibin, beta A; tumor necrosis factor-α inducible protein 6; and chromosome 5 open reading frame 13. There was no significant differential gene expression between the fibroblasts established using keloid margin or internal control sites. Conclusions: The transcriptomic data generated from cultures did not consistently correlate to the biopsy equivalents. This study has demonstrated 10 genes that are significantly upregulated in biopsy samples of keloid margin, 5 of which have a fold change higher than 10-fold. Importantly these genes may serve as a potential biomarker for KD

Grayson Ligament:A Revised Description of its Anatomy and Function

PURPOSE: Grayson ligament has been described as a common pathway for digital contracture in Dupuytren disease. Its anatomical descriptions in the literature are, however, inconsistent. METHODS: We have performed a microsurgical dissection study in 20 fresh-frozen and thawed digits to revisit the anatomy of Grayson ligaments. We also performed dissections in Thiel-preserved hands to be able to study the changes in tension of the ligaments during flexion and extension of the finger. RESULTS: We found the ligaments originally described by Grayson to be the best developed part of a trabecular network of fibers, originating in continuity with the outer adventitial layer of the flexor tendon sheath and running toward their insertions into the skin in multiple planes, all volar to the neurovascular bundle. The most dorsal fibers, which cover the neurovascular bundles, form a chevron shape with its midline apex pointing distally in an extended finger. During flexion, the fibers become more transversely oriented. CONCLUSIONS: We found Grayson ligament comprises a trabecular network of fibers, instead of a ligament, with a dynamic fiber orientation on the volar side of the finger. The main function of this network of fibers seems to be the stabilization of the skin and fat pad in digit extension while the relaxation in flexion allows the skin and volar fat pad to adapt optimally to the form of the object that is held. CLINICAL RELEVANCE: The new insights in the anatomy of Grayson trabecular network of fibers may be of importance in the understanding of the pathological anatomy of Dupuytren disease

The cellular biology of tendon grafting and graft integration

Background: Prolonged recovery after tendon injury has given rise to the need for innovative therapy including tendon engineering and cell based therapies. The role of cells in grafted or engineered tendon is poorly understood. Clarifying the persistence of grafted tissue is fundamentally important to ensure that tissue engineering strategies are fit for clinical application. We have devised a murine model for tendon grafting that allows for cell tracking and the assessment of tendon integration and engineered construct integration. Materials and methods: We studied the macroscopic and microscopic architecture of the mouse Achilles tendon to investigate its properties as a study model. Using microsurgical techniques, transgenic tendon grafting procedures were then carried out between C57B/L6 wild type and GFP (Green Fluorescent Protein) mice Achilles tendon. The temporal and spatial fate of the cells in the graft was assessed using quantitative serial histology and immunohistochemistry with Three Dimensional reconstruction. Markers for proliferation, collagen synthesis, cell death and inflammatory infiltrate were used. The Achilles tendon model was also applied to test its applicability to investigate tissue engineered tendon constructs developed in vitro. Results: GFP positive graft cells were seen at Day 3 and Day 21 but disappeared by Day 90. At Day 21both graft cells and the cells of the recipient tendon showed intense collagen synthetic activity. At the same time both graft and host tendon cells began to show signs of apoptosis which continued till Day 90. Subcutaneous tissue and paratenon maintained a much higher level of cellularity, cell proliferation, collagen synthesis and apoptosis at all time. The interplay between cell activity and cell death appear to play central role in the integration of the tendon graft. The persistence of tissue engineered tendon constructs was far less than syngenic or autografts. The Achilles tendon model proved to be a robust and economically viable model for testing of biomaterials particularly at the early stage of their development. Conclusion: The cells of tendon grafts persist only for a finite time before being repopulated by host cells. Tissue engineered cell-based constructs do not provide sufficient persistence to substitute in place of syngenic or autologous graft options. Future designs of engineered tendon should facilitate tendon integration and aim to persist for longer periods of time in order to participate in the healing process.EThOS - Electronic Theses Online ServiceThe Royal College of Surgeons of England (RCSEng)British Society for Surgery of the Hands (BSSH)GBUnited Kingdo

Tendon Is Covered by a Basement Membrane Epithelium That Is Required for Cell Retention and the Prevention of Adhesion Formation

The ability of tendons to glide smoothly during muscle contraction is impaired after injury by fibrous adhesions that form between the damaged tendon surface and surrounding tissues. To understand how adhesions form we incubated excised tendons in fibrin gels (to mimic the homeostatic environment at the injury site) and assessed cell migration. We noticed cells exiting the tendon from only the cut ends. Furthermore, treatment of the tendon with trypsin resulted in cell extravagation from the shaft of the tendons. Electron microscopy and immunolocalisation studies showed that the tendons are covered by a novel cell layer in which a collagen type IV/laminin basement membrane (BM) overlies a keratinised epithelium. PCR and western blot analyses confirmed the expression of laminin β1 in surface cells, only. To evaluate the cell retentive properties of the BM in vivo we examined the tendons of the Col4a1+/Svc mouse that is heterozygous for a G-to-A transition in the Col4a1 gene that produces a G1064D substitution in the α1(IV) chain of collagen IV. The flexor tendons had a discontinuous BM, developed fibrous adhesions with overlying tissues, and were acellular at sites of adhesion formation. In further experiments, tenotomy of wild-type mice resulted in expression of laminin throughout the adhesion. In conclusion, we show the existence of a novel tendon BM-epithelium that is required to prevent adhesion formation. The Col4a1+/Svc mouse is an effective animal model for studying adhesion formation because of the presence of a structurally-defective collagen type IV-containing BM