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Scurvy is a well-known clinical condition caused by vitamin C deficiency. Although considered a rare disease in high-income countries, it has been recently increasingly reported in children, especially in those with abnormal dietary habits, mental or physical disabilities. We performed an extensive review of the literature analyzing studies published in the last 20 years focusing on clinical features, differential diagnosis and diagnostic delay. Fifteen articles were selected, collectively reporting a total of 166 children. Because of the wide clinical spectrum (musculoskeletal complaints and/or mucocutaneous lesions or systemic symptoms), scurvy can mimic several conditions, including autoimmune diseases, infections, and neoplasia. In addition, frequent findings such as normal nutritional status, anemia or elevated inflammatory markers may guide clinicians towards the abovementioned misdiagnoses. Scurvy should be considered in patients presenting with musculoskeletal complaints, not only in those with risk factors but also in healthy children. A focused dietary history and a careful physical examination, assessing other signs of vitamin C deficiency, are mandatory in these patients. When suspected, the dosage of serum vitamin C is the diagnostic gold standard; furthermore, imaging studies, performed by an expert radiologist, can reveal the typical features of scurvy. Only early diagnosis can avoid unnecessary investigations and potentially fatal complications of the disease.

Background Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. Limited information is available in the current scientific literature on the concordance of genetic alterations between primary and metastatic CMM. In the present study, we performed next-generation sequencing (NGS) analysis of the main genes participating in melanoma pathogenesis and progression, among paired primary and metastatic lesions of CMM patients, with the aim to evaluate levels of discrepancies in mutational patterns. Methods Paraffin-embedded tumor tissues of the paired lesions were retrieved from the archives of the institutions participating in the study. NGS was performed using a specific multiple-gene panel constructed by the Italian Melanoma Intergroup (IMI) to explore the mutational status of selected regions (343 amplicons; amplicon range: 125–175 bp; coverage 100%) within the main 25 genes involved in CMM pathogenesis; sequencing was performed with the Ion Torrent PGM System. Results A discovery cohort encompassing 30 cases, and a validation cohort including eleven Sardinian patients with tissue availability from both the primary and metachronous metastatic lesions were identified; the global number of analyzed tissue specimens was 90. A total of 829 genetic non-synonymous variants were detected: 101 (12.2%) were pathogenic/likely pathogenic, 131 (15.8%) were benign/likely benign, and the remaining 597 (72%) were uncertain/unknown significance variants. Considering the global cohort, the consistency in pathogenic/pathogenic like mutations was 76%. Consistency for BRAF and NRAS mutations was 95.2% and 85.7% respectively, without statistically significant differences between the discovery and validation cohort. Conclusions Our study showed a high level of concordance in mutational patterns between primary and metastatic CMM, especially when pathogenic mutations in driver genes were considered.

Background The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)–positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. Methods In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan–Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients’ outcomes during the period from 5 to 20 years. Results Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1–3), and 34% with four to nine nodes involved (T1N4–9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1–3, and 41% with T2N4–9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively. Conclusions After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.)

BACKGROUND: Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. METHODS: We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). FINDINGS: Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4-8·6]; rate ratio 1·37 [95% CI 1·17-1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92-1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95-1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94-1·15]; p=0·45). INTERPRETATION: Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health. ispartof: LANCET ONCOLOGY vol:19 issue:1 pages:27-39 ispartof: location:England status: published

Squamous Cell Carcinoma (SCC) includes several subtypes and these can be classified according to their clinical behaviours from the least invasive to the most aggressive. Moreover, it is appropriate to analyse their clinicalpathological patterns 1. In light of its wide histopathological variability, we encountered a rare malignant cutaneous lesion: a SCC of a proliferating trichilemmal tumour (PTT) nature.We describe the clinical and pathologic findings of an 82-year-old woman, who developed a SCC with areas of trichilemmal differentiation. It has a surprising thickness of 25 mm, which passes through the dermis, infiltrates the hypodermis and evolves quickly.Considering its exophytic growth and the negative results of the post operative tests (ultrasounds confirmed absence of metastasis), the tumour was eradicated thanks to the surgical approach (a 1 cm border wide excision, including the periosteum in the central part of the lesion, followed by its reconstruction using a full-thickness skin graft) and the prompt intervention, without need for further complimentary treatments. The overall aesthetic results were pleasing.Adnexal tumour, PPT, SCC, Surgery.Il carcinoma sqaumocellulare annovera diversi sottotipi classificabili in base alle loro aggressività. In virtù di questa grande variabilità istopatologica riportiamo il caso clinico di un’ottantaduenne caucasica affetta da una rara forma di carcinoma a cellule squamose, con aree di differenziazione trichilemmale/pilare. Tale paziente giunge alla nosta osservazione con una lesione ulcerata, esofitica, nodulare, di 4 cm x 4 cm, localizzata in regione frontale, già precedentemente sottoposta a biopsia incisionale presso altra struttura e con diagnosi di “adenocarcinoma moderatamente differenziato con immunofenotipo compatibile con istogenesi annessiale cutanea”. Considerate l’età della paziente, le comorbidità nonchè la sua storia clinica, effettuate le dovute indagini preoperatorie, si procede all’intervento chirurgico: ampia escissione en bloc della lesione con un margine radiale di 1 cm e approfondimento fino al periostio, incluso nella porzione centrale della lesione. Chiusura della perdita di sostanza post-chirurgica a mezzo di innesto a tutto spessore prelevato dalla regione anteriore del braccio destro. L’intervento chirurgico è privo di complicanze. Il referto anatomo-patologico diagnostica, con valutazione definitiva, “un carcinoma a cellule squamose, moderatamente differenziato, con aree di differenziazione trichilemmale/ pilare, infiltrante l’ipoderma con uno spessore di 25mm. Margini chirurgici indenni”. Sebbene sia noto un comportamento non invasivo di questo tipo di lesione, la letteratura evidenzia molteplici casi di aggressività locoregionale e presenza di potenziale metastatico, strettamente legati all’infiltrazione dei tessuti adiacenti la neoplasia. Si rendono quindi opportuni follow-up e consulenza oncologica. Alla rivalutazione della paziente, non vi è evidenza di recidiva locale clinicamente nonchè a mezzo di indagine ecografica negativa si per recidia locale che per presenza di metastasi locoregionali. Ecco che nonstante lo spessore, l’invasività della lesione e la rapidità della sua evoluzione, dato anche il suo atteggiamento esofitico, la negatività delle indagini diagnostiche e la prontezza dell’approccio terapeutico, è stato possibile eradicare il tumore grazie al solo approccio chirurgico, scongiurando la necessità di terapie complementari. L’esito estetico è stato soddisfacente.

BACKGROUND: Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection.METHODS: We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status.FINDINGS: 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2pINTERPRETATION: After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council.

Background In microvascular transfer of fibular osteocutaneous flap for mandible reconstruction after cancer ablation, good bone union is necessary to allow timely radiation therapy after surgery. As the area of bone contact between fibula and the original mandible at the edge of the mandibular defect is small, a periosteal excess at both ends of the fibula covering the bone junction can be used to increase the chance of bone union. The purpose of this study is to investigate whether a periosteal excess surrounding both ends of the fibula flap can provide better blood supply and, therefore, ensure bone union and wound healing at 6 weeks after surgery and before radiation therapy initiation. Patients and methods The transfer of fibular osteocutaneous flap with periosteal excess was only applied to reconstruct segmental mandibular defects. As a consequence, only cases in which osteotomy of fibula was not performed were included in this study. A total of 34 fibular flaps without osteotomies were performed between 2000 and 2008; 17 with and 17 without the periosteal excess. The bone union was evaluated in terms of osseous callus formation using X-rays and CT three-dimensional images at 6 weeks after surgery, and results were assessed by three independent radiologists. Results There was a significant difference between reconstructions with and without the periosteal excess in terms of bone union (P = 0.022). With reference to postoperative complications, the group reconstructed without periosteal excess presented a higher number of complications, mainly consisting of partial and total flap necrosis, respectively six (35.29%) and two (11.76%) cases. In the group reconstructed with periosteal excess, no loss of the skin island has occurred. A significant difference was observed in terms of partial flap necrosis (P = 0.024), while the other complications did not reveal a statistically significant difference (P > 0.05). Conclusions The use of a periosteal excess at both ends of the fibula flap provides better blood supply and is, therefore, able to ensure good bone healing and skin paddle survival regardless of the radiotherapy. © 2013 Wiley Periodicals, Inc.

In literature an elevated number of isolated cases of endometriosis in post-laparoscopic scar or laparoscopic trocar tract are described. Actually no theory can completely account for endometriosis, and it is most likely that a combination of events is responsible for it. The case of a 37-year-old woman with a nodular mass in the right hypochondrium is reported. The nodule appeared after a laparoscopic cholecystectomy. Surgical excision was performed and microscopic analysis showed skeletal muscle and fibrous connective tissues with a typical glandular proliferation as in endometriosis. Endometrioma etiology is far to be cleared; the most practical and popular explanation is direct implantation. Our case may be explained according to this theory but it is difficult to achieve definitive conclusions due to the rarity of endometrioma and to the lack of information.

The authors briefly describe the commonest forms of mitochondrial myopathies particularly those associated with disorders of ocular motility. They report their series of four patients suffering from ptosis of the eyelid caused by mitochondrial myopathies. The ptosis was corrected surgically in all cases by means of Müller's muscle adaptation technique. The authors discuss their results and the indication for this technique.

We have devised a low cost system to quickly infiltrate tumescent solution: we call it the "Tedde's system". This low-cost system offers an improvement in quality and quantity of the infiltration because all the procedure depends on the operators, reducing also the time of the infiltration and consequently of the whole surgical procedure. Moreover, this system can be applied to other surgical procedure that requires large infiltration volumes.

Lobular and ductal carcinomas in situ of the breast (LCIS and DCIS) origin from the ductal-lobular unit of mammary gland, but they are characterized for different morphologic patterns and evolution. In 1980 they represent 1.4% of diagnosis in breast biopsy, less of 5% of carcinomas of the breast. Actually in 7.5% of breast biopsy an in situ carcinoma is recognized (approximating 40% of breast cancers). Our purpose is to evaluate the different available strategies in the clinic management of DCIS and LCIS and, in case of surgical treatment, which reconstructive approach obtains satisfactory breast conformation.The study enclose 125 patients: 40 of them presented LCIS (32%) and 85 DCIS (68%). In 40 patients (32%) underposed to mastectomy was performed a reconstruction in cooperation with aesthetic surgeons. 35 of 40 women with LCIS are included in a follow-up programme, 5 of them had a bilateral mastectomy and reconstruction.No recurrences were observed in patients affected by LCIS. Six patients underposed to wide excision for DCIS developed local recurrence, treated by mastectomy. No recurrences were observed in patients treated initially with mastectomy. Some complications correlated to reconstruction were detected.One of most controversial sights in breast pathology is the understanding of biological meaning of CLIS: in facts CDIS can be considered a pre-invasive cancer, CLIS is reasonably considerable only a risk indicator for developing breast cancer but it isn't a pre-neoplastic lesion. Very important is the reconstruction of the breast to improve the quality life of patients.

Surgery for breast cancer has changed in the last few decades in favor of more conservative approaches, without compromising loco‐regional control and survival. Common immediate complications fol ‐lowing breast surgery are hematoma, seroma, and wound infection.1Traditionally, surgeons have implemented the use of closed‐suction drains in this setting with the aim of preventing these complications, which can cause discomfort, morbidity, increased follow‐up visits,and possible delay in the beginning of adjuvant therapies.2 On the other hand, potential benefits of performing breast procedures without using a drain have been increasingly considered.3 There is lack of modern and official guidelines on use of drains in breast sur ‐gery, with no consensus regarding their management and the appro‐priate use of antibiotics in this setting. Almost all reports agree withthe use of drains after breast procedures, especially if they are asso‐ciated with reconstruction or axillar lymph node dissection (ALND), but an extreme variability is reported regarding practice patterns.4A national survey regarding the management of drains afterbreast cancer surgery was sent by email on January 2018 to all Breast Centers (BC) registered with Senonetwork Italia. Data col ‐lected by the administrative office of Senonetwork were de‐iden‐tified and exported for statistical analysis. A Steering Committeecomposed of general surgeons and plastic surgeons was appointedto coordinate the survey, which consisted of 22 multiple choicequestions, designed to inquire about surgeons' demographics, use of drains after breast procedures with and without reconstructionand/or ALND, antibiotic use and to characterize drain managementin their clinical practice.

BACKGROUND: The DyeVert™ system (Osprey Medical Inc., Minnesota, MN) may reduce contrast media (CM) volume during coronary procedures while maintaining fluoroscopic image quality. Here, we assessed whether the use of the DyeVert system reduces acute kidney injury (AKI) rate in patients with acute coronary syndrome (ACS) undergoing invasive coronary procedures. METHODS: ACS patients scheduled for coronary procedure from January 2017 to December 2019 were included. Two groups were identified: (a) Control group (n= 339), including patients in which a conventional manual injection syringe was used; and (b) DyeVert group (n= 112), in which CM injection was handled by the DyeVert™ system. A propensity score matching was performed to reduce the effect of treatment selection bias and potential confounders. In all cases, a low-osmolar, nonionic CM was administered. The primary objective was the rate of AKI, defined as a serum creatinine increase ≥0.3mg/dl within 72 hr after CM exposure. RESULTS: CM volume was higher in the Control group than in the DyeVert group (130 [120–188] ml vs. 99 [69–136] ml; p&nbsp

Background: Safety of reconstructive microsurgery in elderly patients is still a topic of debate, because no conclusive evidence exists that provides indications and risk evaluation in elderly patients. The purpose of this study, which the Italian Society for Plastic, Reconstructive, and Aesthetic Surgery (SICPRE) has promoted, is to evaluate the safety and the complication risk of elective reconstructive microsurgery in elderly patients as well as to identify patient- or procedure-related risk factors. The secondary aim is to evaluate the predictive role for complications of the Geriatric 8 score (G8). Methods: A total of 194 consecutive patients from 18 centers, aged 65 or older, who received an elective microsurgical flap between April 2018 and April 2019 were prospectively evaluated. Patient-related, treatment-related, and outcomes data were recorded and statistically analyzed through multiple-adjusted logistic regression models. Results: Our study showed an increased risk of complications and a longer hospitalization in patients aged ≥75 years with the American Society of Anesthesiologists (ASA) score ≥3 (or G8 score ≤11) as compared to patients >65 years of age and

What is the optimal antithrombotic therapy in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains one of the most doubtful and demanding topics in cardiology. As of today, there are no trial powered to prove the efficacy of double versus triple antithrombotic therapy in terms of ischemic coronary events prevention after PCI. Until further evidence on this topic becomes available, we recommend a personalized strategy, with a careful individual assessment of the patient ischemic and bleeding risk.

Background: Limited clinical data exist describing the use of direct oral anticoagulants (DOACs) in patient with extreme body weight. Thus, the International Society of Thrombosis and Haemostasis (ISTH) recommends avoiding DOACs in patients with weight >120Kg, and on the contrary, no restrictions exist for underweight patients. Objective: To evaluate the effects of extreme body weight on DOAC activity and to compare the clinical outcomes of patients with an extreme body weight versus patients with a normal weight (61-119Kg) treated with DOACs. Methods: Single tertiary care Italian centre multidisciplinary registry including nonvalvular atrial fibrillation (NVAF) patients treated with DOACs. Based on weight, three subcohorts were defined: (i) underweight patients (≤60Kg); (ii) patients with a normal weight (61-119Kg, as control group); and (iii) overweight patients (≥120Kg). Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox-Mantel test. Results: 812 NVAF patients were included, 108 patients weighed ≤60Kg (13%, underweight), 688 weighed between 61 and 119Kg (85%, normal weight), and 16 weighed ≥120Kg (2%, overweight). In particular, among underweight patients, dabigatran was prescribed in 26% patients, apixaban in 27%, rivaroxaban in 28% and edoxaban in 22% ones. Instead, among overweight patients, 44% were treated with dabigatran, 25% with apixaban, 25% with rivaroxaban and 4% with edoxaban. Underweight patients were older, more frequently women, with lower creatinine clearance and a history of previous strokes, resulting in higher CHA2DS2-VASc score than in both remaining groups. Up to 2years, no statistically significant difference was observed between the three groups of weight for thromboembolic events (P=.765) and for overall bleeding (P=.125), but a trend towards decreased overall bleeding rates was noticed as weight increased (24.1% vs 16.7% vs 12.5%, respectively). Conclusion: In this tertiary care centre registry, 15% of patients treated with DOACs presented an extreme weight. Compared to patients with a normal weight, no significant rates of thromboembolic events were observed for underweight or overweight patients. A trend towards decreased overall bleeding frequency as weight increased was highlighted up to 2years. The present results should be considered as preliminary and hypothesis generating.

The development of a capsule around an implant is part of the physiological response to a foreign body. Capsular contracture is the most specific and frustrating complication of augmentation mammaplasty, and a lot of studies have been devoted to it. The aim of the current study is to examine the fine architecture of the contracted capsule around textured implants in humans. Eight capsules from augmented and contracted breasts with gel-filled, textured-surface silicone implants were studied after standard preparation for light and scanning electron microscopy, and after partial digestion in sodium hydroxide. Two capsules from contracted breasts around smooth implants and two noncontracted capsules around textured implants were prepared and studied in the same fashion as controls. A multilayer structure of the contracted capsule was seen, and the architecture of the various layers is described. The inner surface presents irregular craterlike depressions. The arrangement of collagen fibers varies in capsule layers. The effect of a textured-surface implant on the mechanism of capsule contraction based on the observed capsular architecture is that only part of the capsule is effective mechanically in producing a contracting force. A thin vascular layer was identified near the inner surface in contracted capsules around textured implants, and the authors' think that this layer is probably the key structure in the histological development and growth of the capsule.

Purpose The prevalence of BRAF, NRAS, and p16CDKN2A mutations during melanoma progression remains inconclusive. We investigated the prevalence and distribution of mutations in these genes in different melanoma tissues. Patients and Methods In all, 291 tumor tissues from 132 patients with melanoma were screened. Paired samples of primary melanomas (n = 102) and synchronous or asynchronous metastases from the same patients (n = 165) were included. Tissue samples underwent mutation analysis (automated DNA sequencing). Secondary lesions included lymph nodes (n = 84), and skin (n = 36), visceral (n = 25), and brain (n = 44) sites. Results BRAF/NRAS mutations were identified in 58% of primary melanomas (43% BRAF; 15% NRAS); 62% in lymph nodes, 61% subcutaneous, 56% visceral, and 70% in brain sites. Mutations were observed in 63% of metastases (48% BRAF; 15% NRAS), a nonsignificant increase in mutation frequency after progression from primary melanoma. Of the paired samples, lymph nodes (93% consistency) and visceral metastases (96% consistency) presented a highly similar distribution of BRAF/NRAS mutations versus primary melanomas, with a significantly less consistent pattern in brain (80%) and skin metastases (75%). This suggests that independent subclones are generated in some patients. p16CDKN2A mutations were identified in 7% and 14% of primary melanomas and metastases, with a low consistency (31%) between secondary and primary tumor samples. Conclusion In the era of targeted therapies, assessment of the spectrum and distribution of alterations in molecular targets among patients with melanoma is needed. Our findings about the prevalence of BRAF/NRAS/p16CDKN2A mutations in paired tumor lesions from patients with melanoma may be useful in the management of this disease.

To reconstruct the airways in the case of serious nasoseptal deviation it is preferable to remove the cartilaginous septum, reshape it, and put it back. This may be done through an open rhinoplasty approach with a transcolumellar scar resulting in wide visual access to the septal structures. As the transcolumellar scar may give problems in some cases, it might be helpful to use an extended paramarginal incision. A traditional open rhinoplasty approach was used in eight patients and the extended paramarginal incision technique in 19 patients. Two of the eight patients who had the open rhinoplasty technique developed unsatisfactory transcolumellar scars. Of the 19 patients who had paramarginal incisions no patient developed late problems. The paramarginal approach was superior to the traditional open rhinoplasty approach despite the slightly better visualisation with open rhinoplasty.

The authors describe their experience in rigid fixation of maxillo-facial fractures with resorbable plates made from poly-L-lactic acid. Seven cases are presented, with a one-year follow-up or longer. Plate resorption was evaluated by means of echographic examination, repeated every three months. All fractures healed well, with no complications. Finally, advantages and limits of the material are considered, as well as its future prospects and margins of improvement.