Androgen receptors in Dupuytren's contracture.

Palmar fascia tissue and cultured cells from patients with Dupuytren's contracture and from normal subjects were characterized and analyzed for androgen receptor expression. Androgen receptors have never been studied in Dupuytren's myofibroblasts and may have a role in its high male predominance. Surgical samples were collected from eight patients undergoing surgery for Dupuytren's contracture and from four patients with carpal tunnel syndrome, used as control tissue. Immunohistochemical analysis was performed on tissue samples and on cell cultures with anti-androgen receptor, anti-alpha-smooth muscle actin, anti-fibronectin, and anti-type I and III collagen antibodies using the biotin avidin peroxidase method as revelatory system. Immunostaining for androgen receptors in tissue samples and cultured cells revealed nuclear reaction in many Dupuytren's myofibroblasts, but in few fibroblasts of the normal palmar fascia. In a double-labeling study, androgen receptors were seen to co-localize with alpha-actin in both cell cultures and tissue samples. We present the first evidence that the palmar fascia is a target tissue for androgen action and that the expression of androgen receptors in Dupuytren's contracture is considerably higher than in the normal palmar fascia. Further studies will need to evaluate whether the androgen-responsive state of the tissue is related to the high incidence of Dupuytren's contracture in the male sex.     

Is Dupuytren's disease caused by an imbalance between proliferation and cell death?

Dupuytren's contracture shares certain properties with malignant tumours, characterized by proliferation and lack of apoptosis, which may be induced by the c-myc oncogene. Because of these similarities, the relationship between the c-myc oncogene expression, bcl-2 oncogene (anti-apoptotic gene) and proliferation was investigated in Dupuytren's disease. Proliferation was assessed by immunohistochemical staining of the mib-1 antibody. Results were compared with those from fibrosarcoma specimens, representing a related malignant tumour. Non-diseased fascia from Dupuytren patients and flexor retinaculum from patients undergoing carpal tunnel release without Dupuytren's disease were used as controls. Expression of c-myc was elevated in primary Dupuytren's disease and fibrosarcoma specimens, whilst recurrent Dupuytren's disease, non-diseased Dupuytren fascia and flexor retinaculum exhibited significantly lower levels. Neither bcl-2 nor mib-1 were detected in Dupuytren's disease, non-diseased fascia or flexor retinaculum, in contrast to fibrosarcoma. The imbalance between proliferation and apoptosis, producing malignant growth was thus confirmed for fibrosarcoma, but not for Dupuytren's disease.     

The effect of 5-fluorouracil on Dupuytren fibroblast proliferation and differentiation

INTRODUCTION: Dupuytren's disease is a proliferative disease with contractile properties, prone to recur after surgery. Intra-operatively applied 5-fluorouracil has been used to avoid scar problems in the eye after glaucoma filtration surgery and was therefore investigated as a means to inhibit proliferation and myofibroblast differentiation in Dupuytren fibroblasts in vitro. METHOD: Primary cell lines were obtained by explants from Dupuytren's tissue (n = 6), non-diseased palmar fascia from patients with Dupuytren's disease (n = 3) and carpal ligament from patients undergoing carpal tunnel release (n = 3). The effect of 5-fluorouracil on proliferation was assessed by cell counting. Myofibroblast differentiation, an intergral part of Dupuytren's contracture, was investigated by staining for alpha smooth muscle actin, a marker for contractile cells, using immunohisto-chemical methods. RESULTS: A single exposure to 5-fluorouracil caused a sustained inhibition of proliferation in Dupuytren's and non-diseased fascia cultures, whilst the effect on carpal ligament cultures was transient. Untreated Dupuytren's fibroblasts exhibited the highest myofibroblast differentiation, whilst differentiation in non-diseased fascia cultures was shown to be proportional to cell density and virtually non-existent in carpal ligament cultures. After 5-fluorouracil exposure, the differentiation was significantly reduced in Dupuytren's fibroblasts cultures, reduced at high cell densities in non-diseased fascia and unchanged in carpal ligament cell cultures. DISCUSSION: 5-fluorouracil inhibits both proliferation and myofibroblast differentiation in Dupuytren's cell cultures and may have a potential use as an adjuvant treatment to Dupuytren surgery in order to reduce the rate of recurrence and contracture.     

An unusual cause of carpal tunnel syndrome. Case report.

A 38 year old woman with carpal tunnel syndrome of the right hand was treated with operative decompression, initially successfully. Subsequently, she developed a compartment syndrome after an injury. On re-exploration, an accessory palmaris longus muscle was encasing the median nerve at the distal forearm and passing through the flexor sheath, underneath the flexor retinaculum, inserted into the deep palmar fascia.     

Investigation of segmental carpal tunnel pressure in patients with idiopathic carpal tunnel syndrome--is it necessary to release the distal aponeurotic portion of the flexor retinaculum in endoscopic carpal tunnel release surgery?

Segmental carpal tunnel pressure was measured in 12 hands of 11 idiopathic carpal tunnel syndrome patients before and after two-portal endoscopic carpal tunnel release. We aimed to determine at which part of the carpal tunnel the median nerve could be compressed, and to evaluate whether carpal tunnel pressure could be reduced sufficiently at all segments of the carpal tunnel after the surgery. Pressure measurements were performed using a pressure guide wire. The site with the highest pressure corresponded to the area around the hamate hook; the pressure in the area distal to the flexor retinaculum could be pathogenically high (more than 30 mmHg) before the surgery. The two-portal endoscopic carpal tunnel release achieved sufficient pressure reduction in all segments of the carpal tunnel when the flexor retinaculum and the fibrous structure between the flexor retinaculum and the palmar aponeurosis were completely released.     

Gene expression analysis of Dupuytren's disease: the role of TGF-beta2

Dupuytren's disease is characterised by nodular fibroblastic proliferation of the palmar fascia leading to contracture of the hand. Transforming growth factor beta (TGF-beta) is thought to play a role in its pathogenesis. We performed a cDNA microarray analysis of Dupuytren's diseased cord tissue with an emphasis on TGF-beta isoforms. Normal-appearing transverse ligament of the palmar fascia from adjacent to the diseased cord and palmar fascia from patients undergoing carpal tunnel release were used as controls. TGF-beta gene expression was confirmed by quantitative real-time polymerase chain reaction. Over 20 unique genes were found to be significantly up-regulated, including several previously reported genes. A dominant increase in TGF-beta2 expression was seen in the cord tissue, whereas TGF-beta1 and TGF-beta3 were found not to be significantly up-regulated. Quantitative real-time polymerase chain reaction confirmed these findings. This gene expression profile allows for further experiments that may eventually lead to gene therapy to block the development and progression of Dupuytren's disease clinically.     

The collagen changes of Dupuytren's contracture

In Dupuytren's contracture there is an increase in the ratio of type III to type I collagen. The objective of this study was to determine if fibroblasts from patients with Dupuytren's contracture have an intrinsic aberration in collagen production or whether local factors govern the collagen changes in Dupuytren's contracture. Using a new collagen micro-method, we found that fibroblasts cultured from palmar fascia affected by Dupuytren's contracture produced similar collagen to fibroblasts derived from the palmar fascia of age- and sex-matched patients with carpal tunnel syndrome. Furthermore, the collagen changes of Dupuytren's contracture could be reproduced in all cell lines by increasing fibroblast density. At high fibroblast density, type I collagen production was inhibited: a finding that could account for the increased types III/I collagen ratio in Dupuytren's contracture. These results suggest that a genetic defect in collagen production is unlikely and that the important phenomenon is an increase in fibroblast density.     

内窥镜下腕管松解术的应用解剖及临床应用

目的 从解剖及临床方面报告内窥境下腕管松解术的解剖人路及手术方法,旨在提高手术疗效、减少手术并发症。方法 以１８侧新鲜成人上肢标本及２６侧福尔马林液固定的成人上肢标本为对象,观察在内窥镜下碗管松解术入路的解剖结构,观察、测量及定周围相关组织结构。临床应用１９例２１侧,镜视下切断腕横韧带,手术在局麻、无止血带下进行。结果观测屈肌支持带、正中神经圾其分支和掌浅弓等结构。手术入口为腕横纹近端２～３ｃｍ、     

MRI evaluation of carpal tunnel morphology after carpal tunnel release by a retinaculum lengthening technique

AIM: The benefits of maintaining the pulley function of the flexor retinaculum in carpal tunnel release by lengthening or reconstructing it have been described. Quantitative MR imaging was used to investigate the morphological changes after open carpal tunnel release by such a retinaculum lengthening technique. METHOD: Ten patients had bilateral carpal tunnel MRI pre- and postoperatively. The MRI examinations were performed with a 1.5 Tesla imaging system and wrist coils. Carpal tunnel volume, carpal arch width, median nerve position and flexor tendon position in relation to the hamate-trapezial axis were recorded . RESULTS: Like other methods of carpal tunnel release with complete division of the flexor retinaculum, the retinaculum lengthening technique showed a significant postoperative increase of carpal tunnel volume. Carpal arch width increased only slightly. There was a significant palmar displacement of the median nerve but not of the flexor tendons. CONCLUSION: The findings support the hypothesis that maintenance of the pulley function of the retinaculum may lead to an early postoperative recovery of grip strength. In spite of some difficulties in application quantitative MR imaging may be a useful tool in evaluating the carpal tunnel morphology.     

Failed endoscopic carpal tunnel release. Operative findings and results of open revision surgery.

From 1994 to 1997, 22 patients (24 wrists) underwent open revision carpal tunnel release for persistent carpal tunnel syndrome after a primary endoscopic release. The age range was from 21 to 77 years. At the time of revision surgery, 22 wrists had an incomplete release of the flexor retinaculum and two patients had median nerve transection (one partial and one complete). One patient had release of Guyon's canal and not the carpal tunnel. After the open revision carpal tunnel release, 20 patients returned to work with five patients returning to jobs of lighter duty. In addition, these 20 patients had significant improvement in symptoms. The remaining two patients had sustained a median nerve injury and did not return to work. One of these patients developed a painful neuroma in continuity of the median nerve which required vein wrapping with a saphenous vein graft. This study indicates that endoscopic release of the flexor retinaculum holds the same risks and complications as open release. Based on our study we believe that patients with persistent carpal tunnel syndrome after failed endoscopic flexor retinaculum release can be successfully treated with open release.     

Anatomical study of the pre-retinacular fat pad of the wrist: application to a new surgical approach to the carpal tunnel

INTRODUCTION: Decompression of the median nerve in the carpal tunnel by section of the flexor retinaculum is the generally accepted treatment for carpal tunnel syndrome and is usually effective in relieving the symptoms. Following postoperative observations we proposed the hypothesis that incisional pain following open carpal tunnel release could be partly explained by injury to the fat pad situated between the palmar carpal ligament and the flexor retinaculum. METHOD: We performed an anatomical study on 20 fresh adult latex injected upper limbs. RESULTS: The sus-retinacularis fat pad is a real anatomical structure, clearly delineated and located inside a defined fibrous space with its own innervation from the ulnar nerve. It lies in the path of the normal carpal tunnel approach. DISCUSSION: Although most postoperative scar tenderness is attributed to neuroma formation because of injury to transverse branches of the palmar cutaneous nerves, we nevertheless consider that injury to the preretinacular fat pad also plays a part. We propose a modified approach to the carpal tunnel. This is a safe and simple method which respects the integrity of the sus-retinacularis fat pad so as to minimise the extent of scar tenderness.     

Palmar uniportal extrabursal endoscopic carpal tunnel release

A new technique of endoscopic carpal tunnel release using a 1.5-cm longitudinal palmar incision was used in 280 cases. The incision allows identification of the superficial palmar arch as well as the median nerve and its branches. A new knife/sleeve device that attaches to a standard 4-mm endoscope was created to simplify the procedure. The flexor retinaculum is endoscopically divided proximally into the distal forearm; the “interthenar fascia” (fascia superficial to transverse carpal ligament) can be preserved. Early postoperative results include a mean overall return to work and full activity of 14 days. Postoperative pinch and grip strengths were near or at the preoperative level by weeks after surgery. One third of patients required no postoperative analgesics with minimal scar, ulnar pillar, and radial pillar tenderness.     

Carpal tunnel syndrome - is high-frequency ultrasound a useful diagnostic tool?

This study assessed the clinical use of three ultrasound measurements; median nerve cross-sectional area, median nerve flattening ratio and palmar displacement of the flexor retinaculum, for the diagnosis of carpal tunnel syndrome. The measurements were made in 20 carpal tunnel sufferers and 20 controls. The sensitivity, specificity and predictive values of each were calculated in various clinical settings. Values for each of the three variables were significantly different in the patient and control populations. The differences we recorded were smaller than those found in previous studies. The tests had a sensitivity of 72% and a specificity of 90%. Alterations in the morphology of the carpal tunnel in patients with carpal tunnel syndrome can be measured in the district general hospital setting. The measurements described maybe a useful non-invasive confirmatory test in patients in whom there is a strong clinical suspicion of carpal tunnel syndrome. However, they would be of no benefit in epidemiological surveys of populations with a low incidence of carpal tunnel syndrome.     

Two cases of endoscopic management of carpal tunnel syndrome in macrodactyly patients.

Some cases of carpal tunnel syndrome in macrodactyly patients have been reported. We performed endoscopic carpal canal release on two unilateral macrodactyly patients suffering from bilateral carpal tunnel syndrome. We measured carpal canal pressure before performing endoscopic surgery using the Universal Subcutaneous Endoscope system to confirm median nerve compression. We diagnosed median nerve compression in each patient due to the high preoperative carpal canal pressure. Carpal canal pressure immediately decreased to within normal range following release of both the flexor retinaculum and the distal holdfast fibres of the flexor retinaculum. One patient recovered to within normal in terms of sensory disturbances and abductor pollicis brevis muscle strength. The other patient showed improvement in terms of sensory disturbance, however, muscle power did not recover because this patient had suffered from carpal tunnel syndrome for ten years. Endoscopic carpal canal release and decompression surgery was effective for carpal tunnel syndrome in both macrodactyly patients.     

Safety of carpal tunnel release with a short incision. A cadaver study

The standard long incision technique for carpal tunnel release causes inevitable damage to skin sensation, the inter-thenar plexus and especially the distal branches of the palmar cutaneous branch of the median nerve (PCM), and may cause long-term disabling pain and scar tenderness. There are many variations in the distal branches of the median nerve at the wrist. Anatomic studies of this region also have important clinical implications to prevent injury to important anatomic structures. The purpose of this study was to evaluate the short-incision carpal tunnel release in cadavers. Several important anatomic structures, with possible anatomic variations, pass through the carpal tunnel, and blind percutaneous transection of the transverse ligament seems to be a high risk procedure. Sixty hands from 40 fresh cadavers were evaluated. Both the transverse ligament and the distal third of the deep forearm fascia were released using a Smillie knife. At the end of each procedure, the hand was explored for injury to tendinous and neurovascular structures of the wrist. In all cases the release of the carpal tunnel and the distal third of the forearm fascia was found to be complete. The superficial palmar arterial arch, flexor tendons, ulnar nerve and vessels, digital nerves, median nerve and its recurrent accessory branches, the flexor tendons, and even the subcutaneous tissue over the transverse ligament were damaged in no instance. Guyon's canal was entered in 6 (10%) hands without damage to its components. The distal branches from the ulnar side of the palmar cutaneous branch of the median nerve (PCM) were injured in 8 (13.6%) hands, an injury that is almost unavoidable with the classic open technique.     

Carpal tunnel decompression. Is lengthening of the flexor retinaculum better than simple division?

This prospective randomized double-blind control trial compared lengthening and simple division of the flexor retinaculum in carpal tunnel decompression. Twenty-six patients with bilateral carpal tunnel syndrome were randomly allocated to have the flexor retinaculum divided on one side and lengthened on the other. All 52 hands were reviewed at regular intervals up to 25 weeks. The patients, therapists and the final reviewer were unaware of treatment allocation. The Levine symptom and function scores were used to assess the severity of the carpal tunnel syndrome and showed that the two treatments were comparable for relief of carpal tunnel symptoms. The two treatments were also similar for function measured with the Jebsen-Taylor test. There is no identifiable benefit in lengthening the flexor retinaculum when decompressing the carpal tunnel. Moderate or severe pillar and scar pain is common, occurring in 13 of 52 hands after surgery, but only in four by the 12th week and two by the 25th week.     

Endoscopic carpal tunnel release in selected rheumatoid patients

Twenty endoscopic carpal tunnel releases were performed in 15 patients with quiescent seropositive rheumatoid arthritis using the Agee technique. Patients were not considered for endoscopic carpal tunnel release if there was florid synovitis with crepitus or loss of active finger flexion, if there was evidence of flexor tendon rupture or if they had previously undergone surgery in the region. Access to the tunnel was significantly easier than normal and visualization of the flexor retinaculum was satisfactory in all cases. There were no complications. We conclude that endoscopic carpal tunnel release can be safely performed in selected patients with rheumatoid arthritis. The absence of a palmar scar can be a great advantage to these disabled patients.     

Differential Gene Expression Analysis of Subcutaneous Fat, Fascia, and Skin Overlying a Dupuytren’s Disease Nodule in Comparison to Control Tissue

Dupuytren’s disease (DD) is a benign fibroproliferative tumor with an unknown etiology and high recurrence postsurgery. Several observations suggest the possible involvement of skin overlying nodule (SON) and the subcutaneous fat in the pathogenesis of DD. This study aims to (1) compare the gene expression levels of SON and subcutaneous fat in DD and normal subjects and (2) to compare transverse palmar fascia (Skoog’s fibers) from DD patients as internal control tissue, with palmar fascia (transverse carpal ligament) from patients undergoing carpal tunnel release as external control. Skin, fat, and fascia were obtained from five DD patients of Caucasian origin (age = 66 ± 14) and from five control subjects (age = 57 ± 19) undergoing carpal tunnel release. Total ribonucleic acids was extracted from each sample and used for complementary deoxyribonucleic acid synthesis. Real-time quantitative polymerase chain reaction was used to assess the gene expression levels of six candidate genes: A disintegrin and metalloproteinase domain (ADAM12), aldehyde dehydrogenase 1 family member A1 (ALDH1A1), iroquois homeoboxprotein 6 (IRX6), periostin, osteoblast specific factor, proteoglycan 4, and tenascin C. Using independent t test, ADAM12, ALDH1A1, and IRX6 expression levels in DD fats were significantly (p < 0.05) higher than those in the controls. There is no significant difference in the gene expression levels of all six genes when comparing disease and control fascia and skin. Interestingly, ADAM12 up-regulation has also been observed in several other fibrotic and proliferative disorders. In conclusion, this study demonstrates potential roles for subcutaneous fat in DD pathogenesis as well as supports the use of transverse palmar fascia as appropriate control tissues in DD research.     

The different characteristics of Dupuytren's disease fibroblasts derived from either nodule or cord: expression of alpha-smooth muscle actin and the response to stimulation by TGF-beta1

Mechanisms behind the onset and progression of Dupuytren's disease are poorly understood. Both myofibroblasts and transforming growth factor beta 1 (TGF-beta(1)) have been implicated. We studied fibroblast cultures derived from nodules or cords of Dupuytren's contracture tissue to determine the proportion of myofibroblasts present in comparison with flexor retinaculum fibroblast cultures. We identified myofibroblasts by immunohistochemical staining for alpha-SMA. We then investigated the effects of TGF-beta(1) stimulation on these fibroblasts. Basal myofibroblast/fibroblast proportions were 9.7% in nodule cell cultures, 2.7% in cord cell cultures and only 1.3% in flexor retinaculum cell cultures. Nodule and cord myofibroblast proportions increased to 25.4% and 24.2%, respectively, in response to TGF-beta(1) treatment. Flexor retinaculum cell cultures showed no response to TGF-beta(1) stimulation. Fibroblasts cultured from specific regions of Dupuytren's tissue retain myofibroblast features in culture. TGF-beta(1) stimulation causes an increased myofibroblast phenotype to similar levels in both nodule and cord, suggesting that previously quiescent cord fibroblasts can be reactivated to become myofibroblasts by TGF-beta(1). This could be an underlying reason for high recurrence rates seen after surgery or progression following injury.     

Enzymes of glucose metabolism in palmar fascia and Dupuytren's contracture.

Several enzymes participating in glucose metabolism and some of the acid hydrolases were assayed in palmar fascia and Dupuytren's contracture with fluorometric microanalytical methods. The enzyme activities of glucose metabolism were lower in normal palmar fascia than in dermis. The fascia of Dupuytren's contracture exhibited a general increase in the enzyme activities of glucose catabolism. Little alteration was found in alanine aminotransferase and UDP-glucose dehydrogenase activity in the lesion. Lysosomal hydrolytic enzyme activities were increased five to ten times in Dupuytren's tissue. The dermis overlying Dupuytren's contracture exhibited an increase in the enzyme activities of glucose catabolism, but to a lesser degree than did the fascia of the lesion. The epidermis of involved palmar skin displayed normal enzyme activities.