Three-year outcome of local injection of autologous stromal vascular fraction cells and microfat in refractory perianal fistulas of Crohn's disease.

Perianal fistulas in Crohn's disease are frequent and disabling, with a major impact on patients' quality of life. Cell-based therapy using mesenchymal stem cells represents new hope for these patients, but long-term efficacy remains challenging. In a pilot study, including patients with refractory complex perianal fistulas, autologous adipose-derived stromal vascular fraction (ADSVF) combined with microfat achieved combined remission in 60% of cases, with a good safety profile at 1 year. The purpose of this study is to assess whether these results were maintained at longer term. The safety and efficacy data of the ten patients were evaluated retrospectively 3 years after injection on the basis of clinical and radiological data. MRI were analysed according to the MAGNIFI-CD score. No adverse event was attributed to the experimental stem-cell treatment. Combined remission was achieved in 7 patients (70%) and associated with a significant improvement in the MAGNIFI-CD MRI score. In conclusion, the safety and efficacy of ADSVF and microfat injection in Crohn's disease fistulas were maintained at 3 years, demonstrating that this innovative strategy is effective in producing a long-lasting healing effect. The ongoing multicentre randomized placebo-controlled trial (NCT04010526) will be helpful to define the place for this approach in the current therapeutic arsenal.

Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis.

OBJECTIVE: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients. METHODS: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety. RESULTS: Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months' follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 [12.2] in the AD-SVF group vs -7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups. CONCLUSION: This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

Anatomical study of the clitoris and its implications on female genital mutilation and surgical repair.

BACKGROUND: Worldwide, 200 million girls and women have been subjected to female genital mutilation. To restore the clitoral function and vulvar anatomy, clitoral repair has been performed since the 2000s. Nevertheless, there is a lack of precise and comprehensive data on the clitoral anatomy during surgical repair. This study aimed to precisely describe the terminal anatomies of the dorsal nerve and artery of the clitoris, and the clitoral neurovascular flap advancement for reconstruction in patients with female genital mutilation. METHODS: This study was performed on seven fresh female cadavers. The site of origin, diameter, length, and trajectory of each nerve and artery were recorded. The clitoral neurovascular flap advancement was measured after a midline transection of the suspensory ligament was performed and after extensive liberation of the dorsal bundles at their emergence from the pubic rami. RESULTS: At the distal point of the clitoral body, the width of the dorsal nerve and artery was 1.9 ± 0.3 mm and 0.9 ± 0.2 mm, respectively. The total length of the dorsal bundles was 6.6 cm (± 0.4). The midpart of the suspensory ligament was sectioned, which allowed a mean anteroposterior mobility of 2.7 cm (± 0.2). Extensive dissection of the neurovascular bundles up to their point of emergence from the suspensory ligament allowed a mean mobility of 3.4 ± 0.2 cm. CONCLUSION: We described the anatomical characteristics of the dorsal nerve and artery of the clitoris and the mobility of the clitoral neurovascular flap for reconstruction post clitoridectomy. This was done to restore the anatomic position of the glans clitoris while preserving and potentially restoring clitoral function in patients with female genital mutilation.

ALGINATE versus NPWT in the Preparation of Surgical Excisions for an STSG: ATEC Trial.

A calcium alginate dressing (ALGINATE) and negative pressure wound therapy (NPWT) are frequently used to treat wounds which heal by secondary intention. This trial compared the healing efficacy and safety of these 2 treatments. METHODS: This randomized, non-inferiority trial enrolled patients who underwent skin excision (>30 cm2), which was left open to heal by secondary intention. They received ALGINATE or NPWT by a centralized randomization. Follow-up was performed weekly until optimal granulation tissue was obtained. The primary outcome was time to obtain optimal granulation tissue for a split thickness skin graft take (non-inferiority margin: 4 days). Secondary outcomes were occurrence of adverse events (AEs) and impact of the treatments on the patient's daily life. RESULTS: ALGINATE and NPWT were applied to 47 and 48 patients, respectively. The mean time to optimal granulation was 19.98 days (95% CI, 17.7-22.3) with ALGINATE and 20.54 (95% CI, 17.6-23.5) with NPWT. Between group difference was -0.56 days (95% CI -4.22 to 3.10). The non-inferiority of ALGINATE versus NPWT was demonstrated. No AE related to the treatment occurred with ALGINATE versus 14 AEs with NPWT. There was no difference in the impact of the treatments on the patient's daily life. CONCLUSION: This trial demonstrates that ALGINATE has a similar healing efficacy to that of NPWT and that is markedly better with regard to patient safety.

Supportive use of platelet-rich plasma and stromal vascular fraction for cell-assisted fat transfer of skin radiation-induced lesions in nude mice.

BACKGROUND: External radiotherapy has become indispensable in oncological therapies. Unfortunately, radiation is responsible for serious side effects, such as radiodermatitis. The skin is weakened and ulcerated. Our study aimed to evaluate the subcutaneous transfer of microfat (MF) alone and two mixes: MF+Platelet-rich plasma (PRP) and MF+stromal vascular fraction (SVF) to treat radiation-induced skin lesions. METHOD: We defined randomly five experimental groups of nine mice: 1 healthy control group and 4 irradiated (60 Grey) and treated groups. The skin lesions were treated 3 months after irradiation by MF, MF+PRP (50%-50%), MF+SVF (90%-10%) or Ringer-lactate subcutaneous injections. Wound healing was evaluated at 1, 2 and 3 months post-injection and histological wound analysis at 3 months, after euthanasia. RESULTS: All the irradiated mice presented with wounds. After sham-injection, the wound area increased by 91.1±71.1% versus a decrease of 15.9±23.1% after MF alone (NS), 27.3±23.8% after MF+SVF (NS) and 76.4±7.7% after MF+PRP (P=0.032). A significative reduction of skin thickness in wound periphery was measured for the three treated groups compared to sham-injection (P<0.05) but not in the healed wounds (NS). The most important subcutaneous neo-vessel density was shown after MF+SVF injection. CONCLUSION: The MF+PRP mix was the most efficient product to increase healing. The MF+SVF mix showed the highest rate of neo-angiogenesis but was disappointing in terms of healing. LEVEL OF EVIDENCE: Not gradable.

Feasibility of First Injection of Autologous Adipose Tissue-Derived Stromal Vascular Fraction in Human Scarred Vocal Folds: A Nonrandomized Controlled Trial.

Importance: Patients with scarred vocal folds, whether congenitally or after phonosurgery, often exhibit dysphonia that negatively affects daily life and is difficult to treat. The autologous adipose tissue-derived stromal vascular fraction (ADSVF) is a readily accessible source of cells with angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties. Objective: To evaluate the feasibility and tolerability of local injections of autologous ADSVF in patients with scarred vocal folds. Design, Setting, and Participants: CELLCORDES (Innovative Treatment for Scarred Vocal Cords by Local Injection of Autologous Stromal Vascular Fraction) is a prospective, open-label, single-arm, single-center, nonrandomized controlled trial with a 12-month follow-up and patient enrollment from April 1, 2016, to June 30, 2017. Eight patients with severe dysphonia attributable to vocal fold scarring associated with a congenital malformation or resulting from microsurgical sequelae (voice handicap index score >60 of 120) completed the study. Data analysis was performed from September 1, 2018, to January 1, 2019. Interventions: Injection of ADSVF into 1 or 2 vocal folds. Main Outcomes and Measures: The primary outcomes were feasibility and the number and severity of adverse events associated with ADSVF-based therapy. The secondary outcomes were changes in vocal assessment, videolaryngostroboscopy, self-evaluation of dysphonia, and quality of life at 1, 6, and 12 months after cell therapy. Results: Seven women and 1 man (mean [SD] age, 44.6 [10.4] years) were enrolled in this study. Adverse events associated with liposuction and ADSVF injection occurred; most of them resolved spontaneously. One patient received minor treatment to drain local bruising, and another experienced a minor contour defect at the liposuction site. At 12 months, the voice handicap index score was improved in all patients, with a mean (SD) improvement from baseline of 40.1 (21.5) points. Seven patients (88%) were considered to be responders, defined as improvement by 18 points or more in the voice handicap index score (the minimum clinically important difference). Conclusions and Relevance: The findings suggest that autologous ADSVF injection in scarred vocal folds is feasible and tolerable. The findings require confirmation in a randomized clinical trial with a larger population. Trial Registration: ClinicalTrials.gov Identifier: NCT02622464.

Two-stage free flap reconstruction of the scalp and calvaria for large neurosurgical resections.

BACKGROUND: Free tissue transfer is occasionally necessary during reconstruction of large scalp and calvarial bone resections. A single-stage procedure is usually performed but if a flap becomes necrotic it exposes brain tissue or the meninges. Performing a two-stage procedure, the surgeon must preserve flap vitality and manage flap complications before resecting a tumor, and therefore before exposing the brain or meninges. We report here the first series of two-stage free-flap reconstruction during major neurosurgical resection. METHODS: From 2012 to 2018, nine free-flaps were performed to eight patients (61 years-old, on average). Average skull resection was 10.1 cm × 15 cm (range 6-18 cm × 9-24 cm). It was performed in all cases due to large malignant tumors. Resection/reconstruction was performed in all case in a two-step procedure: during the first step, the free-flap was harvested and anastomosed to the cranial site; during the second step, resection was performed and the flap was positioned into the defect to assure coverage. RESULTS: Average flap size was 11.3 cm × 17.7 cm (range: 7-20 cm × 11-30 cm). Two flap complications occurred after the first stage and one flap did not survive. One patient died before the second stage. Seven patients had the second procedure; no flap complication occurred. All procedures ended in complete wound healing. Follow-up period was 41.5 months on average (range: 10-83 months). Final outcome was total remission for two patients, recurrence for four patients, and two patients died. CONCLUSIONS: Our data suggest that the two-stage free-flap reconstruction may be employed for major scalp and calvaria resection.

Fat Grafting for Treatment of Facial Scleroderma.

Reparative, angiogenic, and immunomodulatory properties have been attributed to the cells in the adipose tissue-derived stromal vascular fraction. Because of these characteristics, in the last decade, fat grafting for treatment of autoimmune diseases has grown. This article focuses on systemic sclerosis, a rare autoimmune disease characterized by skin fibrosis and microvascular damage. Lesions of the face are almost always present; however, current therapy is insufficient and patients have considerable disability and social discomfort. This article presents our approach to using fat grafting in the face as an innovative and promising therapy for patients with systemic sclerosis.

Reconstruction of columellar defects: Which surgical technique to choose? A retrospective study of 18 patients.

The reconstruction of the columella is challenging and poorly evaluated in the literature. Our study aimed to evaluate retrospectively the different techniques used in our center and to propose an algorithm of reconstruction adapted to each patient. We report a retrospective cohort study included 18 patients (9 men and 9 women; 53 years-old in average) with columellar reconstruction treated from 1999 through 2014. Six different techniques were used: chondrocutaneous graft, nasolabial flap, paramedian forehead flap and scalping flap according to the Converse technique or the Raulo technique. Four independent plastic surgeons evaluated the aesthetic result on a 10 cm visual analogue scale comparing the patients' photographs before and after the reconstruction. Furthermore, we asked the patients to perform the same evaluation, and to evaluate their level of satisfaction. The mean follow-up was 4 years. Three chondrocutaneous grafts were performed to reconstruct partial defects (Surgical Evaluation (SE): 7.9, Patient Evaluation (PE): 8.3).Three bilateral nasolabial flaps (SE: 6.1, PE: 6.7), 5 paramedian forehead flap (SE: 6.9, PE: 7.3) 6 Converse scalping flap (SE: 4.9, PE: 5.4) and 1 Raulo scalping flap (SE: 6,1, PE: 6,3) were performed to reconstruct total defects exceeding the columella. The use of composite graft was the most satisfactory procedure for partial defects. Paramedian forehead flaps and Raulo scalping flap were the most satisfactory procedures for extended defects. Nasolabial flap was the most adapted procedure for patients with general anesthesia contraindication or for defects extended to the lip.

Free antero-lateral thigh flap for total knee prosthesis coverage after infection complicating malignant tumour resection.

BACKGROUND: Infection is a common complication of major lower limb-sparing surgery with massive total knee prosthesis (MTKP) reconstruction after extensive tumour resection. When free tissue transfer is required to cover the prosthesis, musculo-cutaneous flaps are usually preferred based on proven efficacy when used in both one-stage and two-stage procedures. The use of a free fascio-cutaneous antero-lateral thigh (FC-ALT) flap in 3 patients with infected knee reconstructions is reported here. MATERIAL AND METHOD: A retrospective study was performed of 3 patients in whom a free FC-ALT flap was used during a two-stage procedure to treat MTKP infection after femoral sarcoma resection. RESULTS: Free FC-ALT flap transfer and exchange arthroplasty were successful in all 3 patients. Two years after the procedure, no patient had required amputation or experienced recurrent infection. CONCLUSION: A free FC-ALT flap can provide adequate coverage of infected MTKP and deserves to be viewed as a valid alternative to free muscle flaps.

Gastrocnemius Myocutaneous Flaps for Knee Joint Coverage.

INTRODUCTION: The gastrocnemius muscular flap has already proven its efficiency for soft tissue coverage in cases of knee joint exposure. However, it may be too small to cover large defects and has not the same aesthetic and mechanical properties as normal skin. Perforator fasciocutaneous flaps have recently been described in knee joint coverage with good results as they replace skin by skin, but they can be hard to harvest. Gastrocnemius flaps can be easily harvested with a planned skin paddle designed over the chosen muscle. This simple technique combines the advantages of muscular and fasciocutaneous flaps for knee joint area coverage. Perforator fasciocutaneous flap take a growing place in coverage of this localization in recent literature, but very few articles report the results of gastrocnemius myocutaneous flaps (MCFs). METHODS: All patients who underwent knee joint coverage with the use of a lateral or medial gastrocnemius MCFs between January 2012 and February 2017 in our university institution were included in this retrospective study. RESULTS: Sixteen gastrocnemius MCFs (10 medial and 6 lateral) were performed. The indication was posttraumatic in 5 cases, posttumoral in 5 cases, and after total knee prosthesis exposure in 6 cases. Skin paddles up to 15 cm in width and 18 cm in length were harvested. Complete healing was achieved in 15 days in all cases without suffering or nonunion. Three flaps were secondarily raised to allow total knee prosthesis reimplantation or arthrodesis, and 4 patients were treated with postoperative radiotherapy without complication. CONCLUSIONS: In addition to its reliability and very easy harvesting, the gastrocnemius MCF allows a robust joint coverage and good skin resurfacing that makes eventual revision easier and allows early radiotherapy. Furthermore, skin paddle also increases the effective area of the flap. This technique should always be considered with the other classic alternatives.

First clinical case report of local microinjection of autologous fat and adipose-derived stromal vascular fraction for perianal fistula in Crohn's disease.

Mesenchymal stem cell therapy is a promising treatment for perianal Crohn's fistulas refractory to conventional therapy, which are an extremely morbid complication and a true therapeutic challenge. Autologous adipose-derived stromal vascular fraction (ADSVF) is an easily accessible source of cells with angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties. Here, we describe a case involving a patient with severe perianal Crohn's fistulas refractory to the best medical and surgical practices who received local treatment with ADSVF and microfat. This patient was first examined under anesthesia with drainage via seton placement; 1 week later, on a single day, he underwent adipose tissue extraction, ADSVF and microfat preparation, and the local injection of 14 ml of microfat and approximately 20 million viable ADSVF cells into the soft tissue around the fistulas. No serious adverse events were observed. At the first endpoint at 12 weeks, the fistula had clinically healed with complete re-epithelialization of all external openings; no fistula tract was detected on magnetic resonance imaging, confirming this finding. This good clinical outcome was sustained at 48 weeks and was associated with a reduction in the severity of perianal disease and an improvement in quality of life. The current case highlights the therapeutic potential of a new cellular treatment for Crohn's patients with refractory perianal fistulas based on the innovative hypothesis that the combined action of ADSVF in association with the trophic characteristics of a microfat graft could be beneficial for this condition. TRIAL REGISTRATION: EudraCT number 201325, NCT02520843 . Registered on 5 August 2015.

Soft Tissue Coverage in Distal Lower Extremity Open Fractures: Comparison of Free Anterolateral Thigh and Free Latissimus Dorsi Flaps.

BACKGROUND: When microsurgical transfers are required in posttraumatic lower limb reconstruction, surgeons must choose among many types of free flaps. Historically, surgeons have advocated muscular flaps for coverage of open lower extremity wounds, but fasciocutaneous free flaps are now often used with good results. This study aimed to compare the functional and aesthetic outcome of reconstruction by free muscular latissimus dorsi (LD) flap and free fasciocutaneous anterolateral thigh (ALT) flap used for soft tissue coverage of distal lower extremity open fractures. METHODS: We performed a single-center, retrospective study of subjects with distal lower limb open fractures treated with LD flaps or ALT flaps between 2008 and 2014. Patients with limited follow-up or incomplete data were excluded from the analysis. Donor and recipient sites, early complications and long-term outcomes (functional and aesthetic) were studied and compared according to the type of flap. RESULTS: A total of 47 patients were included: 27 patients in the LD flap group and 20 patients in the ALT flap group. No significant difference was found regarding early and late complications and long-term functional outcomes (bone healing, infectious bone complications, flap healing). As for aesthetic outcome and donor-site morbidity, reconstruction using the ALT free flap had significantly better results (p < 0.05). CONCLUSIONS: In posttraumatic lower limb injury, either LD or ALT free flaps can be used for wound coverage with comparable long-term functional outcomes. The ALT flap provides better cosmetic results than LD.