Auricles Anomalies in Patients With a TCF12 Gene Mutation.

Craniostenosis is a morphological anomaly affecting about 0.5 of 1000 births and one third of the cases are of genetic origin. Among the syndromes responsible for craniostenosis, there is the Saethre-Chotzen syndrome due to a mutation of the TWIST 1 gene located on chromosome 7. This polymalformative syndrome classically includes a particular morphology of the auricles. The penetrance is variable and results in a phenotypic variability at the origin of "Saethre-Chotzen like" clinical pictures for which the TWIST 1 gene mutation is sometimes not found. Recently, the TCF 12 gene has been implicated in some of these cases. Among the multiple facial malformations, we have carefully examined the particular morphology of the auricle of these patients. The authors found several abnormalities in patients with a TCF 12 gene mutation, namely a thickened and hammered upper pole of the helix, a narrow concha without crux cymbae and a thickened lobe. These morphological features may guide the diagnosis and allow an earlier search for a TCF 12 gene mutation.

[Nipple-areola complex malformations]. / Les malformations du complexe aréolo-mamelonnaire.

THE NIPPLE-AREOLA COMPLEX, ALSO KNOWN AS THE NIPPLE-AREOLA PLATE, IS AN ESSENTIAL VISUAL FEATURE OF THE BREAST.THIS COMPLEX CAN BE AFFECTED BY VARIOUS MALFORMATIONS, BOTH CONGENITAL AND ACQUIRED. ALTHOUGH THESE ANOMALIES OFTEN HAVE A MODERATE IMPACT ON THE FUNCTIONALITY OF THIS COMPLEX, THE RESULTING PSYCHOLOGICAL CONSEQUENCES CAN BE SIGNIFICANT. THEIR TREATMENT IS MOST OFTEN SURGICAL AND MANY TECHNIQUES HAVE BEEN DESCRIBED OVER THE YEARS TO RECONSTRUCT AREOLA AND NIPPLE. REGARDLESS OF THE TECHNIQUE USED, THIS ONE AS TO BE SIMPLE, QUICK, IMITATE AS CLOSELY AS POSSIBLE A NATIVE AREOLA-NIPPLE COMPLEX AND BE RELATIVELY DURABLE, AVOIDING NUMEROUS SURGICAL PROCEDURES.: .

Benefits of cryopreserved human amniotic membranes in association with conventional treatments in the management of full-thickness burns.

The use of split-thickness skin autografts (STSA) with dermal substitutes is the gold standard treatment for third-degree burn patients. In this article, we tested whether cryopreserved amniotic membranes could be beneficial to the current treatments for full-thickness burns. Swines were subjected to standardised full-thickness burn injuries, and then were randomly assigned to treatments: (a) STSA alone; (b) STSA associated with the dermal substitute, Matriderm; (c) STSA plus human amniotic membrane (HAM); and (d) STSA associated with Matriderm plus HAM. Clinical and histological assessments were performed over time. We also reported the clinical use of HAM in one patient. The addition of HAM to classic treatments reduced scar contraction. In the presence of HAM, skin wound healing displayed high elasticity and histological examination showed a dense network of long elastic fibres. The presence of HAM increased dermal neovascularization, but no effect was observed on the recruitment of inflammatory cells to the wound. Moreover, the use of HAM with classical treatments in one human patient revealed a clear benefit in terms of elasticity. These results give initial evidence to consider the clinical application of HAM to avoid post-burn contractures and therefore facilitate functional recovery after deep burn injury.

Three-dimensional study of 31 cases of synostotic anterior plagiocephaly before and after surgical management the Lille protocol.

Synostotic anterior plagiocephaly is a rare pathological cranial malformation. Therapeutic options are rarely studied due to the rarity of the malformation and difficulties in diagnosis and care management. The objective of this study was to analyze the results obtained with the Lille protocol based on 62 CT-scans done before and after surgery in 31 patients. A specific analysis was designed for this work. Nine cephalometric measures enabled to evidence on each CT-Scan the corrections made on the fronto-orbital bandeau and the potential impact of surgery on the craniofacial structures. Results show that surgical symmetry of the fronto-orbital bandeau in the transversal plane, according to the symmetrical axis of the semicircular canals, allows a normalization of the skull's growth and morphogenesis for the surgically affected structures but also adjacent ones.

Blepharocheilodontic syndrome is a CDH1 pathway-related disorder due to mutations in CDH1 and CTNND1.

PURPOSE: Blepharocheilodontic (BCD) syndrome is a rare autosomal dominant condition characterized by eyelid malformations, cleft lip/palate, and ectodermal dysplasia. The molecular basis of BCD syndrome remains unknown. METHODS: We recruited 11 patients from 8 families and performed exome sequencing for 5 families with de novo BCD syndrome cases and targeted Sanger sequencing in the 3 remaining families. RESULTS: We identified five CDH1 heterozygous missense mutations and three CTNND1 heterozygous truncating mutations leading to loss-of-function or haploinsufficiency. Establishment of detailed genotype-phenotype correlations was not possible because of the size of the cohort; however, the phenotype seems to appear more severe in case of CDH1 mutations. Functional analysis of CDH1 mutations confirmed their deleterious impact and suggested accelerated E-cadherin degradation. CONCLUSION: Mutations in CDH1 encoding the E-cadherin were previously reported in hereditary diffuse gastric cancer as well as in nonsyndromic cleft lip/palate. Mutations in CTNND1 have never been reported before. The encoded protein, p120ctn, prevents E-cadherin endocytosis and stabilizes its localization at the cell surface. Conditional deletion of Cdh1 and Ctnnd1 in various animal models induces features reminiscent of BCD syndrome and underlines critical role of the E-cadherin-p120ctn interaction in eyelid, craniofacial, and tooth development. Our data assert BCD syndrome as a CDH1 pathway-related disorder due to mutations in CDH1 and CTNND1 and widen the phenotypic spectrum of E-cadherin anomalies.Genet Med advance online publication 09 March 2017.

Lengthening Temporalis Myoplasty: Virtual Animation-Assisted Technical Video.

Lengthening temporalis myoplasty is a well-established procedure for dynamic palliative reanimation of the lip in facial palsy sequelae. The particularity of this technique is that the entire temporal muscle is transferred from the coronoid process to the upper half of the lip without interposition of aponeurotic tissue. To date, no video describing the technique was available. This is the first video describing the entire procedure, from preoperative markings through postoperative rehabilitation. In the video presented herein, the authors craft virtual three-dimensional animations in addition to a live operation on a patient performed by Daniel Labbé, who first described this technique 20 years ago.

The Transverse Musculocutaneous Gracilis Free Flap: Virtual Animation-Assisted Dissection and Application in Breast Reconstruction.

The transverse musculocutaneous gracilis free flap is a valuable choice for autologous tissue, unilateral or bilateral breast reconstruction. This procedure is an excellent and customized option for immediate or delayed breast reconstruction in patients with small to moderate size breasts. Few descriptions of flap dissection and breast mound shaping are available. In this first educational video, the authors report the original dissection of the transverse musculocutaneous gracilis free flap used for breast reconstruction. Virtual animations insist on surgical key points and relevant details of the harvesting of the flap.

Patient-derived tumor xenograft strategies for informed management of patients with metastatic melanoma.

Metastatic melanoma has benefited from immunotherapy and targeted therapy advances. Faced with the inescapable onset of treatment resistance, the choice of a second-line treatment can be guided by a patient-derived tumor xenograft (PDTX). This new approach requires an excellent multidisciplinary collaboration where the surgeon has a key role to play. Each patient included (stage IIIC or IV) presented with subcutaneous melanoma metastasis that could be surgically resected. The surgeon performed orthotopic PDTX on CB17-SCID mice. To validate the model, tumor material was amplified over three successive generations of animals to obtain cohorts compatible with carrying out a study to compare treatment response by targeted therapy (vemurafenib versus controls). Tumors were characterized (histologically and genetically) at all stages of the generations' amplification. Functional imaging by fluorine-18 fluorodeoxyglucose PET scan was performed for the third generation PDTX. Seventeen patients with a mutated BRAF V600E subcutaneous metastasis were included, yielding 257 PDTX. Clinical, histological, and genetic characteristics of the grafted tumors were stable over the three mice generations. The treatment response to vemurafenib was observed for all PDTX. The fluorine-18 fluorodeoxyglucose PET scan evidenced a decreased in glucose uptake in the treated tumors. PDTX models are being widely used in fundamental research and are more compatible with clinical issues. If PDTX are simple and easily reproducible in metastatic melanoma, an organized multidisciplinary platform is essential to implement them. In our experience, surgeons have a key role to play in the cohesion of this new therapeutic approach.

Aplasia cutis congenita: review of 29 cases and proposal of a therapeutic strategy.

INTRODUCTION: Aplasia cutis congenita (ACC) is a rare congenital disorder, which most commonly involves the scalp, and can affect the galea, the pericranium, the bone, and the dura mater. ACC thus is at risk of infection and hemorrhage. There is no consensus over the ideal management and the role for plastic surgery. MATERIALS AND METHODS: We reviewed retrospectively our experience with 29 patients treated between 1976 and 2011. RESULTS: The patients were 17 male and 12 female, 25 being referred immediately at birth. The size of the defect ranged from 1 to 192 cm2. Thirteen patients had bone aplasia. Initial conservative treatment was decided in five cases; 15 patients underwent excision-sutures with or without local plasty, 8 underwent pedicled scalp flap, and 1 had skin graft followed by further reconstruction by a free flap. Four patients died in neonatal period because of infection or associated ailments. All others patients achieved complete healing. DISCUSSION: The mortality rate of ACC remains high and increases with the size of bone defect. We propose a therapeutic strategy based on the size of the skin defect and the nature of underlying exposed structures. Cranioplasty is exceptionally necessary because of good spontaneous bone regeneration within few months or years. Cosmetic appearance can be improved later by skin expansion. CONCLUSION: Aplasia cutis congenita is a rare malformation with sometimes a rapid fatal issue. A precise evaluation of surface and depth of the lesion is essential to decide if and how to operate, in order to provide rapid and efficient coverage.

Long-term results in scalp tissue expansion in children.

INTRODUCTION: Tissue expansion is frequently used in scalp repair in children. The short-term complications are well known and described in the literature. Impacts at a distance such as potential deformation of the skull or widening of the scar are not so often presented. The aim of this study is to analyze the results at a distance and the actual impact after scalp tissue expansion in young children. MATERIALS AND METHODS: We clinically reviewed 15 children operated on between May 2002 and April 2008 for scalp tissue expansion.Results Mean follow-up was 3 years and 5 months, and mean age of the patients at the first surgery was 20 months. In 11 cases, we observed a widening of the scar. Only two patients presented with a slight flattening of the skull. All parents were satisfied with the results. Children do not remind or keep no unpleasant memory of the surgical protocol. DISCUSSION: Only rare studies focused on very young children. Most of surgeons fear about the consequences of scalp tissue expansion on cranial bone and thus on cerebral growth in children under the age of 2. But it appears that cranial changes in young children are transient with a return to normal within 6 months after removing the implant. Another common problem is the scar enlargement. According to our results and the review of the literature, it seems essential to perform the suture in two layers associated to local reconstruction on the scar to provide the best cosmetic outcomes. CONCLUSION: Tissue expansion remains a good technique to repair large lesions of the scalp in children. The deformation of the skull spontaneously resolves and does not have any consequence on brain growth. The widening of the scar is a common problem in children but can be reduced by suture in two layers associated with local reconstruction. Moreover, young children do not keep any unpleasant memory of this period and are not susceptible to social pressure.

Radiotherapy alone for Merkel cell carcinoma: a comparative and retrospective study of 25 patients.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare skin cancer. Cumulative data from retrospective series support the notion that benefits are obtained by both wide excision and adjuvant radiation therapy. However, surgery may be difficult to perform with tumors located in the head and neck region and/or in elderly patients with comorbidities incompatible with general anesthesia. OBJECTIVE: We assessed the benefit of treating MCC exclusively with radiation when conventional treatment (surgery followed by radiotherapy) is not possible. METHODS: A total of 25 patients with primary MCC were treated at our institution exclusively with radiotherapy. Because there is no consensus about this specific approach, we compared the recurrence rate of the 25 patients receiving radiotherapy alone with that of 25 patients who received conventional treatment at our institution. RESULTS: The median follow-up periods were 3 years (range: 5 months-11 years) for the group receiving only radiotherapy (group 1) and 9 years (range: 12 months-16 years) for the conventional therapy group (group 2). No local relapses were observed, but two locoregional relapses were observed in group 1, and 4 in group 2. No statistical differences were found in overall and disease-free survival between the two groups of patients. LIMITATIONS: The limitation of this study is its retrospective nature. CONCLUSIONS: This study confirms the results of our previous research demonstrating that it is possible to treat inoperable MCC exclusively with radiotherapy to obtain an outcome similar to that which is achievable with conventional treatment.

Oral metronomic cyclophosphamide in elderly with metastatic melanoma.

INTRODUCTION: In Western countries, the number of frail elderly people with metastatic melanoma (MM) keeps increasing. Conventional chemotherapy frequently induces imbalance in frail physiological cases. We propose to treat these patients with oral metronomic cyclophosphamide. PATIENTS AND METHODS: This retrospective study analyses the data of patients with unresectable MM who received 50 to 100 mg of cyclophosphamide a day, 3 weeks out of 4. Main evaluation criterion was safety. Secondary evaluation criteria were objective response rate and overall survival. RESULTS: Thirteen patients were included (median age: 80, 5 AJCC stage III and 8 AJCC stage IV). Clinical and biological safety were good, leading to long home staying and rare treatment discontinuations. Main toxicity observed was lymphopenia; no opportunist infection occurred. The control rate was 46%: one partial response and five stable diseases (median: 10 months). Survival after beginning of treatment ranged from 4 to 37 months (median: 8 months). DISCUSSION: Literature about MM in frail elderly is limited. Still, specific treatment is necessary. Cyclophosphamide in metronomic schema was well tolerated. The response rate was difficult to assess (small population) but several patients presented with long lasting stabilisation. The mechanisms of action of this treatment are original, associating antiangiogenic action and immunomodulation. CONCLUSION: Cyclophosphamide in metronomic schema showed good safety results for this frail population. Oral treatment enabled patients to stay at home longer and limited hospitalisation time. A larger controlled study will be necessary to confirm these encouraging results in elderly with MM, a classical chemoresistant tumor.