Surgery, Needle Fasciotomy, or Collagenase Injection for Dupuytren Contracture : A Randomized Controlled Trial.

BACKGROUND: Surgery, needle fasciotomy, and collagenase injection are used to treat Dupuytren contracture. The treatment decision requires balancing initial morbidity and costs of surgery against its potential long-term benefits over needle fasciotomy and collagenase. OBJECTIVE: To compare the effectiveness of surgery, needle fasciotomy, and collagenase injection at 3 months and 2 years (secondary time points of the trial). DESIGN: A multicenter, randomized, outcome assessor-blinded, superiority trial. (ClinicalTrials.gov: NCT03192020). SETTING: 6 public hospitals in Finland. PARTICIPANTS: 302 persons with treatment-naive Dupuytren contracture (contracture angle <135°). INTERVENTION: Surgery (n = 101), needle fasciotomy (n = 101), or collagenase (n = 100). MEASUREMENTS: The primary outcome was the success rate, defined as greater than 50% contracture release and patients reaching the patient acceptable symptom state. Secondary outcomes included hand function, pain, quality of life, patient satisfaction, residual contracture angle, finger flexion, risk for retreatment, and serious adverse events. RESULTS: A total of 292 (97%) and 284 (94%) participants completed the 3-month and 2-year follow-ups. Success rates were similar at 3 months: 71% (95% CI, 62% to 80%) for surgery, 73% (CI, 64% to 82%) for needle fasciotomy, and 73% (CI, 64% to 82%) for collagenase. At 2 years, surgery had superior success rates compared with both needle fasciotomy (78% vs. 50%; adjusted risk difference [aRD], 0.30 [CI, 0.17 to 0.43]) and collagenase (78% vs. 65%; aRD, 0.13 [CI, 0.01 to 0.26]). Secondary analyses paralleled with the primary analysis. LIMITATION: Participants were not blinded. CONCLUSION: Initial outcomes are similar between the treatments, but at 2 years success rates were maintained in the surgery group but were lower with both needle fasciotomy and collagenase despite retreatments. PRIMARY FUNDING SOURCE: Research Council of Finland.

Protective distal side-to-side neurorrhaphy in proximal nerve injury-an experimental study with rats.

BACKGROUND: Side-to-side neurorrhaphy may protect the denervated end organ and preserve the initial connection with proximal stump. We examined the effect of protective side-to-side anastomosis on nerve and end organ regeneration in proximal nerve injury model. METHODS: The left common peroneal nerve of 24 Sprague Dawley rats was proximally transected. In groups B and C, side-to-side neurorrhaphy was performed distally between the peroneal and tibial nerves without (group B) and with (group C) partial donor nerve axotomy inside the epineural window. Group A served as an unprotected control. After 26 weeks, the proximal transection was repaired with end-to-end neurorrhaphy on all animals. Regeneration was followed during 12 weeks with the walk track analysis. Morphometric studies and wet muscle mass calculations were conducted at the end of the follow-up period. RESULTS: The results of the walk track analysis were significantly better in groups B and C compared to group A. Groups B and C showed significantly higher wet mass ratios of the tibialis anterior and extensor digitorum longus muscle compared to group A. Group C showed significantly higher morphometric values compared to group A. Group B reached higher values of the fibre count, fibre density, and percentage of the fibre area compared to group A. CONCLUSIONS: Protective distal side-to-side neurorrhaphy reduced muscle atrophy and had an improving effect on the morphometric studies and walk track analysis. Distal side-to-side neurorrhaphy does not prevent the regenerating axons to grow from the proximal stump to achieve distal nerve stump.

Effect of Axonal Trauma on Nerve Regeneration in Side-to-side Neurorrhaphy: An Experimental Study.

BACKGROUND: Side-to-side (STS) neurorrhaphy can be performed distally to ensure timely end-organ innervation. It leaves the distal end of the injured nerve intact for further reconstruction. Despite encouraging clinical results, only few experimental studies have been published to enhance the regeneration results of the procedure. We examined the influence of different size epineural windows and degree of axonal injury of STS repair on nerve regeneration and donor nerve morbidity. METHODS: Three clinically relevant repair techniques of the transected common peroneal nerve (CPN) were compared. Group A: 10-mm long epineural STS windows; group B: 2-mm long windows and partial axotomy to the donor tibial nerve; and group C: 2-mm long windows with axotomies to both nerves. Regeneration was followed by the walk track analysis, nerve morphometry, histology, and wet muscle mass calculations. RESULTS: The results of the walk track analysis were significantly better in groups B and C compared with group A. The nerve fiber count, total fiber area, fiber density, and percentage of the fiber area values of CPN of the group C were significantly higher when compared with group A. The wet mass ratio of the CPN-innervated anterior tibial muscle was significantly higher in group C compared with group A. The wet mass ratio of the tibial nerve-innervated gastrocnemial muscle was higher in group A compared with the other groups. CONCLUSIONS: All three variations of the STS repair technique showed nerve regeneration. Deliberate donor nerve axotomy enhanced nerve regeneration. A larger epineural window did not compensate the effect of axonal trauma on nerve regeneration.

Comparison of Peripheral Nerve Regeneration with Side-to-side, End-to-side, and End-to-end Repairs: An Experimental Study.

BACKGROUND: The present study was conducted to find out a tool to enable improved functional recovery with proximal nerve injury. In this experimental study, nerve regeneration was compared between side-to-side (STS), end-to-side (ETS), and end-to-end repairs. METHODS: The walk track analysis was used as an outcome of functional recovery. Nerve regeneration was studied with morphometry and histology 6 or 26 weeks postoperatively. RESULTS: All 3 repair techniques showed regeneration of the nerve. From 12 weeks onward, the functional results of the 3 intervention groups were significantly better compared with the unrepaired control group. End-to-end repair was significantly better when compared with the STS and ETS groups. At 26 weeks, the functional and morphometric results and histologic findings did not differ between the STS and ETS groups. The functional results correlated with the morphometric findings in all groups. CONCLUSIONS: STS neurorrhaphy showed nerve regeneration, and the end results did not differ from clinically widely used ETS repair. Further studies are warranted to optimize the neurorrhaphy technique and examine possible applications of STS repair in peripheral nerve surgery.

Cytokine responses during chronic denervation.

BACKGROUND: The aim of the present study was to examine inflammatory responses during Wallerian degeneration in rat peripheral nerve when the regrowth of axons was prevented by suturing. METHODS: Transected rat sciatic nerve was sutured and ligated to prevent reinnervation. The samples were collected from the left sciatic nerve distally and proximally from the point of transection. The endoneurium was separated from the surrounding epi- and perineurium to examine the expression of cytokines in both of these compartments. Macrophage invasion into endoneurium was investigated and Schwann cell proliferation was followed as well as the expression of cytokines IL-1beta, IL-10, IFN-gamma and TNF-alpha mRNA. The samples were collected from 1 day up to 5 weeks after the primary operation. RESULTS: At days 1 to 3 after injury in the epi-/perineurium of the proximal and distal stump, a marked expression of the pro-inflammatory cytokines TNF-alpha and IL-1beta and of the anti-inflammatory cytokine IL-10 was observed. Concurrently, numerous macrophages started to gather into the epineurium of both proximal and distal stumps. At day 7 the number of macrophages decreased in the perineurium and increased markedly in the endoneurium of both stumps. At this time point marked expression of TNF-alpha and IFN-gamma mRNA was observed in the endo- and epi-/perineurium of the proximal stump. At day 14 a marked increase in the expression of IL-1beta could be noted in the proximal stump epi-/perineurium and in the distal stump endoneurium. At that time point many macrophages were observed in the longitudinally sectioned epineurium of the proximal 2 area as well as in the cross-section slides from the distal stump. At day 35 TNF-alpha, IL-1beta and IL-10 mRNA appeared abundantly in the proximal epi-/perineurium together with macrophages. CONCLUSION: The present studies show that even during chronic denervation there is a cyclic expression pattern for the studied cytokines. Contrary to the previous findings on reinnervating nerves the studied cytokines show increased expression up to 35 days. The high expressions of pro-inflammatory and anti-inflammatory cytokines in the proximal epi-/perineurial area at day 35 may be involved in the formation of fibrosis due to irreversible nerve injury and thus may have relevance to the formation of traumatic neuroma.

Contralateral non-operated nerve to transected rat sciatic nerve shows increased expression of IL-1beta, TGF-beta1, TNF-alpha, and IL-10.

Recent reports indicate that after a peripheral nerve injury, the uninjured contralateral nerve is also affected. Because cytokines play an important role in the peripheral nerve injury, we studied the expression of five different mRNAs (interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor-beta1 (TGF-beta1) and interleukin-4 (IL-4)) in the contralateral, non-operated, left sciatic nerve when the right rat sciatic nerve was transected. This study extended up to 42 days after the transection. No IL-4 expression was noted. During the first 3 days, high expression of the other studied cytokines was noted in the endoneurium. At day 7, the expression diminished to the control levels. After this, a cyclic expression pattern appeared, which was most pronounced in the endoneurium at 35 days. We also show that the expression pattern in the endoneurium is different from that in the surrounding epi- and perineurium. Also, our present study shows clearly that contralateral nerves are poor controls after injury.