Treatment Of Dupuytren's Disease Research Articles

Genome-Wide Analysis Using Exon Arrays Demonstrates an Important Role for Expression of Extra-Cellular Matrix, Fibrotic Control and Tissue Remodelling Genes in Dupuytren's Disease

Dupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD. In this study we used primary cultures of fibroblasts derived from excisional biopsies of fibrotic tissue from DD patients to compare the gene expression profiles on a genome-wide basis with normal control fibroblasts. Our investigations have identified genes that may be involved with DD pathogenesis including some which are directly relevant to fibrosis. In particular, these include significantly reduced expression levels of three matrix metallopeptidases (MMP1, MMP3, MMP16), follistatin, and STAT1, and significantly increased expression levels of fibroblast growth factors (FGF9, FGF11), a number of collagen genes and other ECM genes in DD patient samples. Many of these gene products are known to be involved in fibrosis, tumour formation and in the normal processes of tissue remodelling. In addition, alternative splicing was identified in some DD associated genes. These highly sensitive genomic investigations provide new insight into the molecular mechanisms that may underpin the development and progression of DD.

Skin Graft Loss Resulting From Collagenase Clostridium Histolyticum Treatment of Dupuytren Contracture: Case Report and Review of the Literature

Treatment of Dupuytren disease with collagenase clostridium histolyticum is increasingly used among hand surgeons. Although it is generally safe and efficacious, complications related to enzymatic fasciotomy occur. Postapproval surveillance and communication among hand surgeons continues to refine the indications, contraindications, and complications recognized in the treatment of Dupuytren disease with enzymatic therapy. Major treatment-related adverse events previously reported include flexor tendon rupture and complex regional pain syndrome. We report a patient who experienced total loss of a well-established volar ring finger skin graft following collagenase injection and propose a potential mechanism of vulnerability. This case may illustrate the susceptibility of type I collagen, which is uniformly present in a healed skin graft bed, to degradation with collagenase. We propose a cautious approach when considering treatment of a Dupuytren cord with collagenase in the presence of an overlying skin graft, regardless of the age of the graft.

The consequences of different definitions for recurrence of Dupuytren's disease

Recurrence rates are important in the evaluation of the effectiveness of treatment for Dupuytren's disease (DD). In the literature, recurrence rates vary between 0% and 100%. The definition of recurrence of DD after treatment is inconsistently used. The aim of this study is to review all definitions of recurrence after treatment of DD and to evaluate the impact of using these definitions on a single cohort of patients treated for DD. A literature search was performed in PubMed and Embase to identify studies. Titles and abstracts were analysed to collect all articles that described recurrence rates or definitions of recurrence. Two independent reviewers selected relevant studies and extracted data. The different definitions of recurrence were applied on our data set of 66 patients. Of the 113 articles reporting recurrent rates of DD, 56 (49%) presented a definition of recurrence. We could categorise the definitions into three groups. By applying the different definition on our data set of a randomised controlled trial, the recurrence rates ranged from 2% to 86%. In the literature, different definitions of recurrence of DD are used and many authors failed to define recurrence. This study shows that the wide range of reported recurrence rates may largely be contributed by inconsistency in recurrence definitions. As a result, it is difficult or even impossible to compare recurrence rates between different treatments reported in the literature. The study indicates that consensus on a recurrence definition is needed.

Results of Surgery Treatment of Dupuytren's Contracture in 115 Patients

Dupuytren's disease (DD) is a progressive fibroproliferative disorder of the hand causing digital flexion contracture. Treatment goals include removing or releasing the fibrotic cord to allow extension of the affected finger(s) and restoration of hand function. In study period from 2001 through 2008, evaluation was performed in 115 patients. Limited or extensive fasciectomy was performed in all patients. Tubiana classification sheme to rate severity of DD was used. There were 106 male patients ( mean age 62.6 years) and 9 female patients (mean age 66.3 years). Before the operation, 38% of all patients were at Tubiana stage I, 32% were at stage II, 22% were at stage III and 8% were at stage IV. Of all patients, 43% were diagnosed with Dupuytren's in only one finger, 39% in two fingers and 18% in three fingers. In 23% of patients DD were diagnosed on both hands. Limited fasciectomy was peformed in 90.4% of patients and extensive fasciectomy in 9.6% of patients. The Tubiana stage achived after surgery was lower in 98% of patients. As a final result after surgery, 66% of patients didn't have contracture, stage I was reported in 28% and stage II in 3% of patients. There were no patients with Tubiana stage III or more after surgery. Postoperative complications were noted in 18% of patients. Wound healing problems were present 12% of patients. Haematoma was reported 5% of patients. Of all patients 22% had diabetes mellitus. DD is much more common in male than in female patients. Most of the patients are diagnosed at Tubiana stage I and II. Surgical correction has led to an improvement in most patients. Limited fasciectomy is still the gold-standard in DD treatment. Extensive fasciectomy or dermofasciectomy is preformed only in most severe cases.

Understanding Dupuytren's Disease Using Systems Biology: A Move Away from Reductionism

Dupuytren's disease (DD) resides within the poorly understood, yet important category of superficial quasi-neoplastic proliferative fibromatosis (McFarlane et al., 1990). This nodular palmar fibromatosis often causes permanent flexion contracture of the metacarpophalangeal (MCP) and proximal interphalangeal joints (PIPJ) of the digits (Rayan, 2007) leading to loss of function (Horner and Bralliar, 1971; Schroter, 1971; Tubiana, 1971; Rayan, 2007). DD may invade locally within the palmar aponeurosis of the hand (sparingly supplied with blood vessels). DD does not disseminate to other tissues (Seemayer et al., 1980), but, rather behaves as a benign neoplastic disorder: progressive and irreversible with a high rate of recurrence after surgical excision (current gold standard treatment for DD; Bayat and McGrouther, 2006). The increasing severity and aggressive recurrence may lead to amputation of the affected digit (Shaw et al., 2007). Phenotypically, DD is described by its two distinct fibrotic elements: the nodule and cord. Nodules are highly vascularized, soft-tissue masses containing mostly myofibroblasts, while the cords are relatively avascular with a thickened collagen-rich structure (Rayan, 2007; Rehman et al., 2008, 2011). Different schools of thought exist regarding the definition of DD progression; they debate whether the nodule develops into cord or the two fibrotic elements occur independently from a separate precursor cell. Processes associated with DD pathogenesis include cytokines, growth factors, adhesion molecules, and extracellular matrix components (Rehman et al., 2008; Shih et al., 2009). Free radicals and localized ischemia may trigger the proliferation of DD tissue (Murrell et al., 1987). Histology has confirmed the presence of collagens, myofibroblast, and myoglobin proteins in DD, but at widely varying abundances. Pathophysiology of DD is also thought to arise either from a defect in a wound repair process or from an abnormal response to wounding (Shih and Bayat, 2010). Some of these hypotheses are non-molecular or may associate the disease with effects, rather than with a single cause. No animal model exists for the study of DD fibromatosis, yet investigations in animal studies of possibly related diseases (Akai et al., 1997) may be informative (Tart and Dahners, 1989; Kandel et al., 1991; Akai et al., 1997; Hildebrand et al., 2004). Single gene changes have correlated poorly with DD, and DD is nowadays viewed as a complex disease. We propose that DD may be a network disease, such that a systems biology approach may help its understanding.

Microsurgical treatment of Dupuytren's disease: analysis of clinical ontcomes

掌腱膜挛缩症多表现为单侧或双侧掌指关节、指间关节掌腱膜进行性屈曲挛缩,局部可触及串珠状、条索状结节[1].2005至2010年,我院共收治15例掌腱膜挛缩症患者,分别采用传统手术方法及显微镜下手术切除,术后疗效满意. 1.一般资料:本组15例,均为男性;年龄42～82岁,平均60岁。

Update on the management of Dupuytren’s contracture

Dupuytren's disease (DD) is a pathological condition of the palmar fascia that is characterized by the formation of tight collagenous disease cords leading to permanent finger contractures. The disease is most prevalent in Caucasian men, and its incidence increases with age advancement. The most common complaint from patients having DD is the impairment of normal hand function. At present, the disease is incurable and the pathophysiology of DD is unknown. The most common treatment for DD is surgery; however, this treatment is associated with a high rate of recurrence. More recently, researchers have begun to explore the molecular basis of DD in the hopes of developing new, more effective treatment for DD. This review will summarize the history and clinical presentation of the disease, highlight current and emerging molecular treatments, and explore the implications of these advancements for future work.

Molecular mechanisms and treatment strategies for Dupuytren’s disease

Dupuytren's disease (DD) is a common disease of the hand and is characterized by thickening of the palmar fascia and formation of tight collagenous disease cords. At present, the disease is incurable and the molecular pathophysiology of DD is unknown. Surgery remains the most commonly used treatment for DD, but this requires extensive postoperative therapy and is associated with high rates of recurrence. Over the past decades, more indepth exploration of the molecular basis of DD has raised the hopes of developing new treatment modalities. This paper reviews the clinical presentation and molecular pathophysiology of this disease, as well as current and emerging treatment. It also explores the implications of new findings in the laboratory for future treatment.

Screening of potential prodrugs on cells derived from Dupuytren's disease patients

Dupuytren's disease (DD) is a fibroproliferative disorder, the cure for which is still limited to surgical excision of the affected fascia, often leading to high recurrence rates. Due to this fact, non-surgical treatments are being investigated, among them those targeting molecular processes of proliferation and differentiation in Dupuytren's cell cultures. Drugs with antiproliferative action may be valuable in DD treatment. Through characterization of changes on DD-specific cells, we, therefore, decided to test the therapeutic potential of new cytostatic drugs for DD treatment and/or for reduction of post-operative recurrence rates. The N-sulfonylpyrimidine derivative, amidino-substituted benzimidazo[1,2-a]quinoline, and amidino dihydrothienothienyl[2,3-c]quinolone hydrochloride, known to affect proliferation processes, were tested for their antiproliferative activity on primary fibroblasts/myofibroblasts cell cultures derived from the palmar fascia of patients with DD. Only amidino dihydrothienothienyl[2,3-c]quinolone hydrochloride acted in a highly specific manner on cells derived from diseased fascia of DD patients and exhibited a low cytotoxic effect. This result might be a consequence of its specific activity on cytoskeleton changes occurring in differentiating cells. A similar short-term differential antiproliferative effect was observed by the N-sulfonylpyrimidine derivative that was, however, completely lost after 6- and 14-day treatments. The amidino-substituted benzimidazo[1,2-a]quinoline exerted a strong non-specific, dose-related antiproliferative activity on cell types.

Treatment of Dupuytren's Disease: Experiences in Shin-Kong Wu-Ho-Su Memorial Hospital

Dupuytren's disease is a common disease in Caucasians. It occurs rarely in southern and southeastern Asians. Between 1993 and 1999, there were 9 cases of Dupuytren's disease treated in Shin Kong Wu-Ho-Su memorial hospital. All of these Patients were treated by multiple Y-to-V advancement skin flaps or multiple z-plasties, regional fasciectomy and postoperative rehabilitation. There was only one complication, the injury of ulnar digital nerve of ring finger, and the impairment of sensory was minimal after immediate nerve repair. All of our patients whose hands function were restored.