Feasibility of aponeurectomy in combination with perioperative 192Ir high dose rate brachytherapy for Dupuytren's disease.

PURPOSE: Partial aponeurectomy (PA) is a standard procedure for Dupuytren's contracture (DC). Here we report a novel approach using surgery combined with perioperative high dose rate (192Ir-HDR) brachytherapy. METHODS AND PATIENTS: From March 2018 until February 2020, thirteen rays of 6 patients with Dupyutren's contractures underwent PA followed by HDR brachytherapy. After removal of fibrous tissue and mobilization of the tendons, one to three catheters per patient were placed intraoperatively. Immediately after surgery, a planning computer tomography with 3D-planning was performed. Then 10-12 Gy were given to 0-2 mm from the catheters' surface and the catheters were removed 6-12 h after brachytherapy. RESULTS: No complications were observed. The mean contractures were reduced from 55.4° (standard error SE 19.6) to 15.4° (SE 6.7; p < 0.01). One patient showed progressive fibrosis of a nontreated ray during follow-up. CONCLUSIONS: HDR brachytherapy in combination with surgery is feasible and harbors the potential for combined modality therapy to reduce relapse rates of advanced or relapsing DC. Controlled studies are warranted to investigate the role of bimodal therapy compared with PA alone.

Radiation Therapy for Benign Disease: Arteriovenous Malformations, Desmoid Tumor, Dupuytren Contracture, Graves Ophthalmopathy, Gynecomastia, Heterotopic Ossification, Histiocytosis.

Although the use of ionizing radiation in malignant conditions has been well established, its application in benign conditions has not been fully accepted and has been inadequately recognized by health care providers outside of radiation therapy. Most frequently, radiation therapy in these benign conditions is used along with other treatment modalities, such as surgery, in instances where the condition causes significant disability or could even lead to death. Radiation therapy can be helpful for inflammatory/proliferative disorders. This article discusses the current use of radiation therapy in some of the more common benign conditions.

Blue light irradiation and its beneficial effect on Dupuytren's fibroblasts.

Dupuytren's contracture is a fibroproliferative disorder affecting the palmar fascia of the hand. Most affected are the ring fingers, and little fingers of middle-aged men. Symptomatic for this disease is the increased proliferation and differentiation of fibroblasts to myofibroblasts, which is accompanied by an elevated α-SMA expression. The present study evaluated the therapeutic benefit of blue light (λ = 453 nm, 38 mW/cm2, continuous radiance, spot size 10-12 cm2) as well as the molecular mechanism mediating this effect. It could be determined that blue light significantly diminished the induced α-SMA protein expression in both normal palmar fibroblasts and Duypuytren's fibroblasts. The beneficial effect mediated by this irradiance, radiant exposure and wavelength was associated with an elevated reactive oxygen species generation. Furthermore, the data underlines the potential usefulness of blue light irradiation as a promising therapy option for Dupuytren's disease, especially for relapse prevention, and may represent a useful strategy to treat further fibrotic diseases, such as keloids, hypertrophic scarring, and scleroderma.

T2 signal intensity as an imaging biomarker for patients with superficial Fibromatoses of the hands (Dupuytren's disease) and feet (Ledderhose disease) undergoing definitive electron beam irradiation.

OBJECTIVE: Electron beam therapy is a definitive radiation treatment option for superficial fibromatoses of the hands and feet. Because objective criteria for treatment response remain poorly defined, we sought to describe changes in electron beam treated lesions on MRI. MATERIALS AND METHODS: The study included 1 male and 9 female patients with a total of 37 superficial fibromatoses; average age was 60.7 years. Standard 6 MeV electron beam treatment included 3 Gy per fraction for 10 or 12 treatments using split-course with 3-month halfway break. Pre- and post-treatment MRIs were evaluated to determine lesion size (cm3), T2 signal intensity and contrast enhancement (5-point ordinal scales) by a fellowship trained musculoskeletal radiologist. MRI findings were correlated with clinical response using a composite 1-5 ordinal scale, Karnofsky Performance Scale and patient-reported 10-point visual analog scale for pain. RESULTS: Mean volume decreased from 1.5 to 1.2 cm3 (p = 0.01, paired t-test). Mean T2 hyperintensity score decreased from 3.0 to 2.1 (p < 0.0001, Wilcoxon signed-rank). Mean enhancement score available for 22 lesions decreased from 3.8 to 3.0 (p < 0.0001, Wilcoxon signed-rank). Performance scores improved from 78.9 ± 13.7 to 84.6 ± 6.9 (p = 0.007, paired t-test). Pain scores decreased from 3.0 ± 3.3 to 1.1 ± 2.0 (p = 0.0001, paired t-test). Post-treatment T2 signal correlated weakly with performance and pain (Spearman's ρ = -0.37 and 0.16, respectively). CONCLUSIONS: MRI is valuable for evaluating patients undergoing electron beam therapy for superficial fibromatoses: higher pretreatment T2 intensity may predict benefit from radiotherapy. T2 hypointensity may be a better marker than size for therapeutic effect.

Radiotherapy in Dupuytren's disease: a systematic review of the evidence.

Radiotherapy has been advocated as an alternative treatment in early Dupuytren's disease. We have systematically reviewed the evidence on the use of radiotherapy in Dupuytren's disease. Only six articles met a minimum set standard, five of which were retrospective cohort studies and one a randomized controlled study. A total of 770 Dupuytren's hands, nearly all with Tubiana stage 0-1 disease, were irradiated with an average 30 Gy. Disease regression ranged from 0%-56%, stability from 14%-98% and progression from 2%-86%. Salvage surgery was successful in all cases of disease progression post-radiotherapy. There were no reports of adverse wound healing problems associated with such surgery or radiotherapy-associated malignancy. On balance, radiotherapy should be considered an unproven treatment for early Dupuytren's disease due to a scarce evidence base and unknown long-term adverse effects. Well-designed randomized controlled studies are required to confirm the benefits of radiotherapy treatment. LEVEL OF EVIDENCE: II.

To remember: Radiotherapy - a successful treatment for early Dupuytren's disease.

Dupuytren's disease (DD) is a common fibroproliferative condition of the hand which tends to cause progressive digital flexion contracture. Therapeutic strategies to treat the disease include radiotherapy, injections of collagenase clostridium histolyticum, needle fasciotomy and extended surgical intervention dependent on involvement and duration of the disease. We have reviewed the literature with the aim to assess the conditions and effects of radiotherapy in DD. In early stages of the disease, radiotherapy resulted in regression of symptoms/a lack of progression found on average in 40% (range 10-85%)/81% (range 50-100%) of the patients with recurrence rates of only 12-31% after long-term follow-up (>4 years). These results proved to be significantly better than in the untreated patients with natural course of the disease (about 50% progression after a follow-up of 5-6 years). Long-term side-effects (skin dryness) are observed on average in one quarter of the patients, but are well tolerated. Local occurrence of malignancies has not been reported yet. Due to severe functional impairment leading to individual suffering and the high economic burden, treatment of DD in early stages is necessary and radiation therapy represents an effective, safe and economic treatment option.

Radiotherapy with soft X-rays in Dupuytren's disease - successful, well-tolerated and satisfying.

BACKGROUND: Up to present no curative treatment is known for Dupuytren's disease (DD). Surgery remains the most common treatment but lack of long-term efficacy and complications limit this therapeutic option. OBJECTIVE: In a retrospective analysis, the results of radiotherapy with soft X-rays in the treatment of DD were evaluated. METHODS: A total of 206 patients (297 affected hands) with DD were included. Radiation therapy was carried out with soft X-rays. A structured questionnaire considering patient and disease characteristics and effects of radiotherapy was evaluated after a median follow-up time of 40 months. RESULTS: Ninety-three (45%) of the 206 treated patients were reported on a regression of symptoms after radiation. No further disease progression (including patients with regression) was present in 165 patients (80%). Satisfaction with the therapy was expressed with an average score of 7.9 points (visual analogue scale, 0 = not satisfied, 10 = extremely satisfied). Subjective therapeutic effects for 426 nodules and/or cords showed a reduction of 92 nodules and/or cords. CONCLUSION: In 206 DD patients further disease progression was stopped in most patients. Radiotherapy proved to be well-tolerated, successful and satisfying for the patients.

Recognition, diagnosis and referral of patients with Dupuytren's disease: a review of current concepts for general practitioners in Europe.

BACKGROUND: Dupuytren's disease (DD) is a fairly prevalent yet under-recognised disorder of the palmar fascia, resulting in fixed-flexion contractures of joints in the hand. Numerous population-based studies have been conducted in countries around the world, and published prevalence estimates vary widely. Nevertheless, most studies have shown that the prevalence of DD increases with age. Because the global population is aging, the prevalence of DD will also continue to increase. SCOPE: Patients with DD typically present to a variety of physicians, generalists and specialists alike. Thus, it is critical that providers have clear guidance on the early recognition of signs and symptoms, comprehensive evaluation of potential risk factors, differential diagnosis and when to refer a patient for treatment. Treatment options range from minimally invasive injections with collagenase to surgery. FINDINGS: Results from a large-scale study of the surgical management of DD in Europe indicate that most DD diagnoses and referrals are made by general practitioners, but there is much inter-country variation. Different patient- and physician-based factors affect diagnosis rates and referral pathways. Different healthcare systems and regulations are also influential. A simple management algorithm is provided herein and explained. CONCLUSION: It is important for generalists to understand the natural history of DD and the potential benefits of early referral and treatment. General practitioners should diagnose and/or refer patients with DD to a specialist as early as possible to optimise disease management and treatment outcomes.

[Squamous cell carcinoma in Dupuytren's disease--a case report]. / Höherdifferenziertes verhornendes Plattenepithelkarzinom in einer Palmarfibromatose (M. Dupuytren)--Fallbericht.

Squamous cell carcinoma in the palm is an extremely rare entity. In the following case report we describe the occurrence of a squamous cell carcinoma in the presence of Dupuytren's disease. A 49-year-old man was operated on the right hand for ulcerating Dupuytren's disease. A squamous cell carcinoma was diagnosed by performing obtaining a fast section intraoperatively. The patient had an invasive, highly differentiated keratinizing squamous cell carcinoma. The lesion was resected together with the Dupuytren lesion and the defect covered with a full-thickness graft. Postoperatively the patient was irradiated. He is free of recurrence for three years now. To our knowledge, this is the first published report of a squamous cell carcinoma in the presence of Dupuytren's disease.

Radiotherapy in early-stage Dupuytren's contracture. Long-term results after 13 years.

BACKGROUND AND PURPOSE: In early-stage Dupuytren's contracture, radiotherapy is applied to prevent disease progression. Long-term outcome and late toxicity of the treatment were evaluated in a retrospective analysis. PATIENTS AND METHODS: Between 12/1982 and 02/2006, 135 patients (208 hands) were irradiated with orthovoltage (120 kV; 20 mA; 4-mm Al filter), in two courses with five daily fractions of 3.0 Gy to a total dose of 30 Gy; separated by a 6- to 8-week interval. The extent of disease was described according to a modified classification of Tubiana et al. Long-term outcome was analyzed at last follow-up between 02/2008 and 05/2008 with a median follow-up of 13 years (range, 2-25 years). Late treatment toxicity and objective reduction of symptoms as change in stage and numbers of nodules and cords were evaluated and used as evidence to assess treatment response. RESULTS: According to the individual stages, 123 cases (59%) remained stable, 20 (10%) improved, and 65 (31%) progressed. In stage N 87% and in stage N/I 70% remained stable or even regressed. In more advanced stages, the rate of disease progression increased to 62% (stage I) or 86% (stage II). 66% of the patients showed a long-term relief of symptoms (i.e., burning sensations, itching and scratching, pressure and tension). Radiotherapy did not increase the complication rate after surgery in case of disease progression and only minor late toxicity (skin atrophy, dry desquamation) could be observed in 32% of the patients. There was no evidence for a second malignancy induced by radiotherapy. CONCLUSION: After a mean follow-up of 13 years radiotherapy is effective in prevention of disease progression and improves patients' symptoms in early-stage Dupuytren's contracture (stage N, N/I). In case of disease progression after radiotherapy, a "salvage" operation is still feasible.

Radiation therapy for early stages of morbus Ledderhose.

PURPOSE: To evaluate the efficacy of radiation therapy (RT) in the treatment of early stages of benign plantar fibromatosis (Morbus Ledderhose [ML]). PATIENTS AND METHODS: From 2003 to 2008, 24 patients (33 sites) with a mean age of 52 years received RT for symptomatic ML. Prior to RT, 19 patients complained of pain and 15 had walking difficulties. 21 patients (28 sites) were irradiated with orthovoltage X-rays and three (five sites) received electron-beam irradiation. The RT protocol consisted of five weekly fractions of 3.0 Gy (15 Gy), repeated after 6 weeks to a total dose of 30 Gy in 20 patients (28 sites). In four patients (five sites), two single fractions of 4.0 Gy were applied, repeated at intervals of 4 weeks to total doses of 24-32 Gy. Primary study endpoints were the prevention of disease progression and the avoidance of a surgical intervention. Secondary endpoints were pain relief, improvement of gait, and patients' subjective satisfaction measured with a linear analog scale (LAS). RESULTS: After a median follow-up of 22.5 months, none of the patients experienced a progression of number and size of the lesions or the clinical symptoms. In eleven sites (33.3%) complete remission of cords or nodules occurred, in 18 (54.5%) a reduced number or size was noted, and four sites (12.1%) were unchanged. Pain relief was achieved in 13/19 patients (68.4%), and an improvement of gait abnormalities was noted in 11/15 patients (73.3%). The patients' subjective satisfaction measured by means of the LAS revealed a median improvement of 3.5 points in 22/24 patients (91.6%). Skin or soft tissues toxicities RTOG grade > 2 were not noted. CONCLUSION: RT is effective for treatment of the early stages of ML and may obviate the need for a surgical intervention. Long-term follow-up studies including a larger number of patients are required to define the role of RT in the management of this disorder.

[Treatment of Dupuytren's contracture; an overview of options]. / Behandeling van de ziekte van Dupuytren: Een overzicht van de mogelijkheden.

In this article we systematically review treatment options for Dupuytren's contracture. There is little evidence on the effectiveness of many treatment modalities for Dupuytren's disease other than expert's opinions (level 4). Most hand surgeons perform selective fasciectomy for Dupuytren's disease. Because of its lower recurrence rate, dermofasciectomy is increasingly being performed to treat recurrences. Percutaneous needle fasciotomy is a minimally invasive treatment with good short-term results in patients with mild to moderate contractures, but it has a high recurrence rate. Radiotherapy and the use of collagenase are promising, but their role in treating Dupuytren's disease is still unclear.

[Optimization of radiotherapy in Dupuytren's disease. Initial results of a controlled trial]. / Optimierung der Radiotherapie bei Morbus Dupuytren. Erste Ergebnisse einer kontrollierten Studie.

PURPOSE: Radiotherapy prevents progression of Dupuytren's contracture. Herein, 1-year results of a prospective randomized trial comparing 2 different dose concepts are presented. PATIENTS AND METHODS: 129 patients (67 males, 62 females) were included in the study with a minimum 1-year follow-up: 69 had bilateral and 60 unilateral involvement of Dupyutren's disease accounting for 198 irradiated hands. According to Tubiana, 73 hands had Stage N, 61 Stage N/I (< or = 10 degrees flexion deformity), 59 Stage I (11 to 45 degrees) and 5 Stage II disease (46 to 90 degrees). Radiotherapy was randomly delivered: group A (63 patients/95 hands) received 10 times 3 Gy (total: 30 Gy) in 2 series (each 5 times 3 Gy) separated by 8 weeks; group B (66 patients/103 hands) received 7 times 3 Gy (total: 21 Gy) within 2 weeks. Orthovoltage radiotherapy (120 kV) with 40 cm standard cones and individual shielding was applied. Patient and disease parameters were equally distributed in both groups. Evaluation (toxicity, efficacy) was performed at 3 and 12 months with regard to subjective (patient's opinion) and objective parameters (palpation, measurements, comparative photographs--physician). RESULTS: Acute toxicity was minimal: 76 (38%) hands had skin reactions CTC Grade 1, 12 (6%) CTC Grade 2. Chronic side effects (dryness, skin atrophy, change of sensation, LENT Grade 1) occurred in 9 (5%) hands without differences between treatment groups. At 3 and 12 months follow-up, subjective symptoms and objective signs, nodules and cords, were reduced in both groups (p < 0.01) with no differences between groups: a total of 110 (55%) hands (group A: 55, group B: 55) regressed, 74 (37%) hands (group A: 35; group B: 39) were stable. Overall and mean number of nodules, cords and skin changes decreased at 3 and 12 months. 16 of 198 (8%) hands (group A: 7; group B: 9) progressed at 12 months follow-up ("treatment failure"); at 1 year, 7 of 60 patients with unilateral Dupyutren's disease required prophylactic radiotherapy for the contralateral hand due to disease progression. CONCLUSIONS: Prophylactic radiotherapy reduces symptoms and prevents disease progression in early-stage Dupyutren's disease. Both treatment concepts are well-tolerated and equally effective. Acute toxicity is slightly increased with treatment concept B (7 times 3 Gy), while chronic sequelae are low in both treatment groups. Long-term evaluation with follow-up of more than 5 years has to be awaited to recommend one or the other dose concept.

Radiotherapy optimization in early-stage Dupuytren's contracture: first results of a randomized clinical study.

PURPOSE: Radiotherapy (RT) can prevent progression of Dupuytren's contracture (DC). It is unknown whether there is a dose response and which dose is sufficient. Herein, the 1-year results of a prospective randomized trial are presented which compared two different RT dose concepts with each other. METHODS: 129 patients (67 males; 62 females) were entered in this study: 69 had bilateral and 60 uni-lateral involvement of DC accounting for 198 irradiated hands. According to Tubiana's classification, 73 hands had Stage N (nodules/cords, no extension deficit = flexion deformity), 61 had Stage N/I (< or = 10 degrees deficit), 59 had Stage I (11-45 degrees deficit), and 5 had Stage II (46-90 degrees deficit) DC. Prophylactic RT was randomly delivered; in Group A, 63 patients (95 hands) received 10 x 3 Gy (total dose, 30 Gy) in 2 series (5 x 3Gy) separated by 8 weeks; in Group B, 66 patients (103 hands) received 7 x 3 Gy (total dose, 21 Gy) in 1 series within 2 weeks. Orthovoltage RT (120 kV) was applied using standard cones and individual shielding of uninvolved areas of the palm. Relevant patient and disease parameters were equally distributed in both groups. Evaluation (toxicity, efficacy) was performed at 3 and 12 months after RT. Subjective (patient's opinion) and objective parameters (palpation, measurements, and comparative photographs) were applied to assess treatment response. Minimum follow-up (FU) was 1 year. RESULTS: Acute toxicity was minimal, but slightly more pronounced in Group B. Seventy-six (38%) hands developed skin reactions CTC 1 degrees (A, 30; B, 46); and 12 (6%) had skin reactions CTC 2 degrees (A, 4; B, 8). Chronic side effects were limited to dryness, desquamation, skin atrophy, and change of sensation (LENT 1 degrees ) in 9 (5%) sites without differences between the two groups. At 3 and 12 months after RT, subjective and objective reduction of symptoms, nodules, and cords occurred in both groups (p < 0.01) with no differences between the groups: in Group A, 55 (56%) sites regressed, 35 (37%) remained stable, and 7 (7%) progressed, whereas in Group B, 55 (53%) regressed, 39 (38%) remained stable, and 9 (9%) progressed at 12 months FU (NS). Overall and mean number of nodules, cords, and skin changes decreased at 3 and 12 months. The "treatment failure" rate at 1 year was 16 of 198 (8%), but only 4 (2%) sites required hand surgery for disease progression. Seven of 60 patients with unilateral DC received prophylactic RT for the initially uninvolved, contralateral hand due to progression of DC. CONCLUSION: Both prophylactic RT concepts have been well accepted and tolerated by patients. Within the first year, they were equally effective to prevent further disease progression of DC and obtain considerable symptomatic improvement. Although 1-year results suggest similar response rates for both treatment groups, long-term FU of > 5 years has to be awaited for final assessment and recommendation of an optimized RT treatment schedule.

[Radiotherapy of early stage Dupuytren disease. Long-term results after a median follow-up period of 10 years]. / Die Radiotherapie des Morbus Dupuytren im Frühstadium. Langzeitresultate nach einer medianen Nachbeobachtungszeit von 10 Jahren.

PURPOSE: In early stage Dupuytren's contracture radiotherapy was applied to prevent disease progression. Long-term results and late toxicity of this treatment were evaluated in a retrospective analysis. PATIENTS AND METHODS: Between 1982 and 1994, 99 patients (176 hands) received orthovoltage radiotherapy, which consisted of two courses with 5 x 3 Gy (total dose: 30 Gy, daily fractionated; 120 kV, 4 mm Al), separated by a 6 to 8-week pause. The Dupuytren's contracture was staged according to the classification of Tubiana et al. The long-term outcome was analyzed at last follow-up between July and November 1999. The median follow-up was 10 years (range 7-18 years). Late toxicity was assessed using the LENT-SOMA criteria. RESULTS: In Stage N 84% and Stage N/I 67% of cases remained stable. 65% of the cases in Stage I and 83% in Stage II showed progressive nodules and cords. In case of progression we saw no complications after a second radiotherapy or salvage operation. CONCLUSION: Radiotherapy effectively prevents disease progression for early stage Dupuytren's contracture (Stage N, N/I). Moreover, in case of disease progression despite radiotherapy salvage surgery is still feasible.

[Radiotherapy of non-malignant diseases: principles and recommendations]. / Strahlenbehandlung von nicht-malignen Erkrankungen: Grundsätze und Empfehlungen.

The plenty options and high quality of radiation therapy for non-malignant disorders is not well known outside the field of radiology. It is necessary to transfer this information to cooperating general practitioners, surgeons, orthopedics and other specialists. To warrant quality assurance and quality control and to allow a uniform performance of radiotherapy of non-malignant conditions, general guidelines and recommendations according to the German Working Group of Scientific Medical Societies are useful. This paper summarizes the essential aspects of radiotherapy for non-malignant diseases: indication of, informed consent for, documentation and conduct of radiation therapy for non-malignant diseases using orthovoltage equipment and specific recommendations for follow up examinations. Radiotherapy concepts for non-malignant diseases are summarized.

[Radiotherapy in the early stage of Dupuytren's disease. The indications, technic and long-term results]. / Radiotherapie im frühen Stadium des Morbus Dupuytren. Indikation, Technik und Langzeitergebnisse.

AIM: Radiotherapy was applied in our clinic to prevent the disease progression in early stage Dupuytren's contracture. Initial response, long-term outcome, acute and late toxicity of the treatment were evaluated in a retrospective analysis. PATIENTS AND METHOD: Between 1982 and 1993, 96 patients (142 hands) received orthovoltage radiotherapy, which consisted of 2 radiotherapy courses with daily fractionation of 5 x 3 Gy (total dose: 30 Gy) separated by a 6 weeks interval. The Dupuytren's contracture was staged according to the classification of Tubiana et al. [38]. The initial evaluation was performed 3 months after completion of radiotherapy, while long-term outcome was analysed at last follow-up between February and April 1994. The mean follow-up was 6 +/- 2 (range 1 to 12) years. Fifty-seven patients with a follow-up of > or = 5 (median 7,5; mean 9,5 to 12) years were separately evaluated for long-term outcome, i.e. prevention of disease progression. Acute and late treatment toxicity was assessed using the RTOG/EORTC criteria. RESULTS: According to stage, 130 (92%) cases remained stable at 3 months follow-up, 10(7%) improved and 2 (1%) progressed. An objective reduction of symptomatic cords and nodules was achieved in 107 (75%) cases at 3 months follow-up. Moreover, 87% of the patients reported a subjective relief of symptoms. In long-term follow-up, only 16 of 142 (11%) cases had progressed according to stage. In the group with a minimum follow-up of 5 years (n = 57), 44 (77%) patients experienced no progression, while 13 (23%) progressed inside (8 cases) or outside (5 cases) of the radiotherapy field. Many "failures" could have been avoided with appropriate choice of larger safety margins included in the treated portals, however, most failures were successfully managed by a second radiotherapy or hand surgery. CONCLUSION: Radiotherapy prevents disease progression for early stage Dupuytren's contracture. Thus, an otherwise necessary surgical procedure in advanced stages of Dupuytren's contracture can be avoided. Moreover, in case of disease progression despite radiotherapy a second radiotherapy or salvage operation is still feasible.