Evaluation of the Suprafascial Thin ALT Flap in Foot and Ankle Reconstruction.

BACKGROUND: Distal lower extremity reconstruction can be challenging in terms of flap design. Bulky flaps result in limited mobility accompanied with the need of customized footwear. Raising the ALT-flap in a superficial fascial plane (thin ALT-flap) can be beneficial. This study evaluates thin ALT-flaps for lower distal extremity reconstruction. METHODS: In a retrospective study, patients that underwent microvascular extremity reconstruction at the level of the ankle and dorsal foot at the University of Freiburg from 2008-2018 were reviewed. RESULTS: 95 patients could be included in the study (35 perforator flaps, 8 fascia flaps and 54 muscle flaps).Among the perforator flaps, 21 ALT-flaps were elevated conventionally and 14 in the superficial fascial plane (thin ALT-flap). Among the conventional ALT-flaps, there was one flap loss (5%) and one successful revision (5%). 5(24%) flaps received secondary thinning. 57%(n = 12) were able to wear conventional footwear. There were 2(15%) successful revisions of thin ALT-flaps. 100% of thin ALT-flaps survived and 85%(n = 11) of the patients wore ordinary footwear after defect coverage.Among fascial flaps, 50%(n = 4) had to be revised with 2(25%) complete and 1 (13%) partial flap loss. All patients achieved mobility in ordinary shoes (n = 8).In muscle flaps, there were 7(13%) revisions and 5(9%) flap losses. 5(9%) flaps received secondary thinning. Only 33%(n = 18) were mobile in ordinary footwear. CONCLUSION: The thin ALT-flap is a save one-stage evolution for lower distal extremity reconstruction with a favorable flap survival rate. Compared with conventional ALT-flaps it might be beneficial in reducing the need for expensive custom fitted shoes and secondary thinning procedures.

Symptoms associated with malignancy of peripheral nerve sheath tumours: a retrospective study of 69 patients with neurofibromatosis 1.

BACKGROUND: Neurofibromatosis 1 (NF1) is a common genetic disorder with variable clinical manifestations and an unpredictable course. Plexiform neurofibromas are common complications of NF1. Their malignant transformation is the main cause of mortality in adult patients with NF1. OBJECTIVES: To identify clinical factors associated with malignant transformation of plexiform neurofibromas. METHODS: Using the database of our neurofibromatosis clinic we included in a retrospective study all patients with NF1 having at least one peripheral nerve sheath tumour for which they underwent surgery or surgical biopsy. Predictive values for malignant transformation of three clinical symptoms, i.e. pain, enlargement of mass and neurological symptoms, were evaluated in association with histological parameters. RESULTS: Of 69 patients studied, 48 had at least one plexiform neurofibroma and 21 had a malignant peripheral nerve sheath tumour. Only enlargement of the tumour had high negative and positive predictive values for malignant transformation: 0.92 and 0.95, respectively. In multivariate analysis, tumour enlargement was independently associated with malignant transformation (odds ratio 167.8, 95% confidence interval 14.0-2012.1). CONCLUSIONS: From a practical point of view, pain, neurological deficit and enlargement of a pre-existing peripheral nerve sheath tumour in NF1 must lead to deep surgical biopsy to rule out malignant transformation.

Association between benign and malignant peripheral nerve sheath tumors in NF1.

OBJECTIVE: People with neurofibromatosis type 1 (NF1) have a 10% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST). MPNSTs are often metastatic and are a frequent cause of death among people with NF1. Clinical evidence suggests that most MPNSTs in people with NF1 develop from preexisting plexiform neurofibromas. However, it is not known whether an individual's risk of developing an MPNST is associated with the burden of benign neurofibromas. The authors conducted a study to determine whether people with NF1 who have benign neurofibromas of various kinds are at greater risk of developing MPNSTs than patients with NF1 who lack these benign tumors. METHODS: Clinical information on 476 NF1 probands in the Henri Mondor Database was analyzed by logistic regression to examine associations between MPNSTs and internal plexiform, superficial plexiform, subcutaneous, and cutaneous neurofibromas. RESULTS: Individuals with subcutaneous neurofibromas were approximately three times more likely to have internal plexiform neurofibromas or MPNSTs than individuals without subcutaneous neurofibromas. Individuals with internal plexiform neurofibromas were 20 times more likely to have MPNSTs than individuals without internal plexiform neurofibromas. When this analysis was done with both subcutaneous and internal plexiform neurofibromas as explanatory variables, only the association of MPNSTs with internal plexiform neurofibromas remained significant. CONCLUSIONS: The observation that malignant peripheral nerve sheath tumors are strongly associated with internal plexiform neurofibromas suggests that patients with neurofibromatosis type 1 with these benign tumors warrant increased surveillance for malignancy.

[The French version of Skindex (Skindex-France). Adaptation and assessment of psychometric properties]. / Version française du Skindex (Skindex-France). Adaptation et évaluation des propriétes psychométriques.

INTRODUCTION: The Skindex is an American tool designed to measure the impact of skin diseases on quality of life. The aim of our study was to adapt and validate this questionnaire in French in a population of patients with neurofibromatosis 1. MATERIAL AND METHODS: Translation and cultural adaptation: Translations were performed independently by two bilingual persons, then discussed. A preliminary version was obtained and confronted with 5 persons with low level of education and 6 patients with neurofibromatosis 1, before assessment in 24 neurofibromatosis 1 patients. The final version was named Skindex-France. Validation study: a test-retest study (1 month interval) was performed on 129 subjects with neurofibromatosis 1 to assess reliability and validity. RESULTS: Acceptability was good with a low rate of missing data (less than 5 p. 100). Ceiling and floor effects were less than 20 p. 100. The scores are sufficiently reliable (Cronbach alpha coefficient: emotions: 0.95, symptoms: 0.86, functioning: 0.94, and test-retest Spearman r: emotions: 0.92, symptoms: 0.84, functioning: 0.90). CONCLUSION: Skindex-France can be used to measure with precision the impact of skin diseases.

Usefulness of systematic ophthalmologic investigations in neurofibromatosis 1: a cross-sectional study of 211 patients.

PURPOSE: To evaluate the usefulness of ophthalmologic examination for diagnosis and for detection of complications in adult patients with neurofibromatosis 1. METHODS: PATIENTS with at least one criterion of neurofibromatosis 1 (excluding ophthalmologic criteria) seen at a referral centre had a systematic ophthalmologic examination including best-corrected visual acuity, slit-lamp examination and dilated funduscopy. The ophthalmologist was unaware of all other anamnestic data. PATIENTS: 211 patients with NF1 were included (mean age: 32 +/- 14 yr.). Ophthalmologic examination in neurofibromatosis 1 patients: Lisch nodules (n = 185) (87.7%); choroidal hamartomas (n = 61) (29%); enlarged corneal nerves (n = 1); 3 plexiform neurofibromas (n = 3); symptomatic optic pathway gliomas (n = 5). Diagnostic contribution of presence of Lisch nodules: 6 (3%) of 211 patients. Detection of complications: none. CONCLUSIONS: In adult patients with neurofibromatosis 1, the contribution of ophthalmologic examination to diagnosis and to the detection of complications is low. Ophthalmologic examination should be performed in patients for whom questioning and clinical examination failed to give evidence of NF1 or to determine the NF subtypes.

[Blue-red macules and pseudoatrophic macules in neurofibromatosis 1]. / Taches violines ou macules pseudo-atrophiques neurofibromateuses au cours de la neurofibromatose 1.

INTRODUCTION: Blue-red macules are exception during neurofibromatosis 1. Between October 1988 and March 2000 in our cohort of patients, we systematically looked for these lesions. PATIENTS AND METHODS: Presence and number of blue-red macules were evaluated. Biopsies and photographs were proposed to patients. RESULTS: Forty-four patients out of 583 (39 y; range: 20-66 y) (7.5 p. 100; CI 95 p. 100: 5.5-9.8 p. 100) had blue-red macules mainly on the trunk. Histologically, blue-red macules corresponded to neurofibromatous tissue infiltrating capillary blood vessels and venules. CONCLUSION: Blue-red macules are a peculiar type of neurofibroma and can therefore be considered as a criterion for the diagnosis of neurofibromatosis 1.

[Neurofibromatosis 1: recommendations for management]. / Neurofibromatose 1: recommandations de prise en charge.

Twenty experts, members of a French medical network devoted to neurofibromatosis 1 have elaborated recommendations for the management of the disease. Bibliography was obtained through a Medline of articles from 1966 to 1999 for the terms neurofibromatosis, NF1, neurofibroma and from textbooks. A consensual document was written taking into account extracted data. An annual careful clinical examination is recommended except in cases with complications. Screening investigations are not recommended due to the rarity of complications, generally symptomatic and easily detected during the clinical follow-up. The only controversial exception might be magnetic resonance imaging for early detection of optic pathway gliomas in young children. A co-ordinated follow-up in specialised multidisciplinary centres, providing patients with a rational management, is recommended.

Quality-of-life impairment in neurofibromatosis type 1: a cross-sectional study of 128 cases.

BACKGROUND: Neurofibromatosis type 1 affects quality of life (QoL) through association with severe complications, impact on cosmetic features, and uncertainty of the effects of the disorder. OBJECTIVE: To evaluate the impact of the severity and visibility of neurofibromatosis type 1 on QoL. DESIGN: Monocenter, cross-sectional study. SETTING: One French academic dermatological and neurofibromatoses clinic. PATIENTS: A total of 128 adult patients with neurofibromatosis type 1. MAIN OUTCOME MEASURES: Evaluation of severity and visibility using, respectively, the Riccardi and Ablon scales. Evaluation of skin disease-specific and general QoL using, respectively, Skindex-France and SF-36 (Short Form 36 health survey) profiles controlled for sex, age, severity, and visibility. RESULTS: In a multiple regression model controlling for sex, age, and visibility, visibility remained independently associated with the alteration of 3 aspects of the skin disease-specific QoL (Skindex-France): emotions, physical symptoms, and functioning (P =.03, P =.009, and P =.002, respectively). Patients with more severe neurofibromatosis reported more effects on the following domains of their general health QoL (SF-36): physical function, bodily pain, general health perception, and vitality (P =.006, P =.03, P =.01, and P =.04, respectively). CONCLUSIONS: Neurofibromatosis type 1 has a significant impact on QoL through alteration of health and appearance. The consequences of visibility and severity from the viewpoint of patients can be evaluated using Skindex and the SF-36, respectively.

Malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1: a clinicopathologic and molecular study of 17 patients.

OBJECTIVE: To identify potential prognostic factors and criteria for early detection of malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1 (NF1). DESIGN: Retrospective study of malignant peripheral nerve sheath tumors in a cohort of 395 patients with NF1 followed up between October 1, 1988, and January 1, 1999; review of the clinical and histological characteristics of treatment and course; and analysis of p53 mutations and overexpression in tumors. SETTING: Teaching hospital referral neurofibromatosis center for adults. PATIENTS: Seventeen patients with NF1 (9 males and 8 females). Mean +/- SD patient age at diagnosis was 32 +/- 14 years. MAIN OUTCOME MEASURES: (1) Clinical symptoms, (2) comparison of p53 mutations and overexpression in benign vs malignant tumors; and (3) median survival. RESULTS: Twelve patients had high-grade tumors. All tumors except 1 developed on preexisting nodular or plexiform neurofibromas. Pain and enlarging mass were the first and predominant signs. None of the benign tumors displayed significant p53 staining or p53 mutations. Six of 12 malignant tumors significantly overexpressed p53, and 4 of 6 harbored p53 missense mutations. Median survival was 18 months overall, 53 months in peripheral locations, and 21 months in axial locations. CONCLUSIONS: Malignant peripheral nerve sheath tumors are highly aggressive in NF1. They mostly arise from plexiform or nodular neurofibromas. Investigations and deep biopsy of painful and enlarging nodular or plexiform neurofibromas should be considered in patients with NF1. Late appearance of p53 mutations and overexpression precludes their use as predictive markers of malignant transformation.

[Large hairy pigmented spots in neurofibromatosis type 1: an atypical form of neurofibromas]. / Grandes taches pigmentées pileuses au cours de la neurofibromatose de type 1: une forme atypique de neurofibromes.

INTRODUCTION: Large hairy pigmented spots have been observed in patients with neurofibromatosis type 1. In this study we tried to determine the nature and the frequency of these hairy pigmented spots in neurofibromatosis type 1. PATIENTS AND METHODS: In patients with neurofibromatosis type 1, hairy pigmented spots with a diameter more than 3 cm were systematically notified. Realisation of the biopsy of the spot was proposed to the patient. RESULTS: Among 614 patients with neurofibromatosis type 1, seven (1.1 p. 100) had a large hairy pigmented spot. Biopsy was realized in six cases. In five cases, diagnosis was superficial and plexiform neurofibroma, the 6(th) case was a Becker's nevus. CONCLUSION: Large hairy pigmented spot is a rare aspect of superficial and plexiform neurofibroma during neurofibromatosis type 1. A biopsy may be useful if it is necessary for the disorder diagnosis.

NF1 gene analysis focused on CpG-rich exons in a cohort of 93 patients with neurofibromatosis type 1.

We studied the NF1 gene in 93 unrelated patients with neurofibromatosis type1, focusing the analysis on four exons that contain the highest number of possible mutations occurring at CpG sites. We used denaturing gradient gel electrophoresis to analyse exons 16, 28, 29 and 49, which contain 45 (25%) of the 183 possible mutations that could occur at the 120 CpG dinucleotides of the coding sequence. Six different mutations were identified, five of which are novel: two truncating mutations, W1810X and 5448insG, located in exon29; two splice defects leading to exon29 skipping, 5206-2A>G and 5546G>A; and one missense mutation, L844F, located in exon16. The already described R1748X mutation located in exon29 was found in two unrelated patients. The 5546G>A and R1748X mutations are located at CpG sites, whereas the W1810X involves a CpNpG site. Four novel polymorphisms, which may be helpful for family studies, were also identified. Overall, all but one mutations were found in exon29, a result which suggests that all the CpG sites of the NF1 coding sequence do not have the same mutability, and that exon29, the most CpG-rich exon, contains mutational hotspots associated with NF1.

Cost evaluation of the medical management of neurofibromatosis 1: a prospective study on 201 patients.

Neurofibromatosis 1 (NF1) is associated with many internal complications as well as skin manifestations, and patients may require a variety of medical and surgical interventions. We aimed to assess the medical needs of NF1 patients, and to evaluate the financial cost of the resources used for them in relation to the severity of the disease. We conducted a prospective analysis on a cohort of 201 patients in our referral centre for adults. Severity of the disease was assessed. Therapeutic management was considered as multidisciplinary if it required more than three different specialists. Plastic and dermatological surgery procedures performed were recorded. Hospital costs were computed over a 3-year period and included all hospitalization days, clinic visits and procedures performed in all departments where the patients were admitted. One hundred and thirty-seven patients had at least one out-patient procedure or one hospitalization during the follow-up period. The mean cost per patient per year was pound810 (median 240; range 0-13, 860). Multidisciplinary procedures were more frequent in moderately and severely affected NF1 patients than in milder cases (P < 0. 0001); hence, the costs for moderate and severe cases were higher than for less severe groups (P = 0.005). Plastic and/or dermatological surgery was performed with the same frequency in the different severity groups (71%). Regardless of the presence of serious intractable complications, the patients' priority is for treatment of the disfigurement due to the disease. The management of these patients can be considered relatively inexpensive from the viewpoint of the healthcare system.