Whole-exome sequencing in osteosarcoma reveals important heterogeneity of genetic alterations.

BACKGROUND: Whole-genome sequencing studies have recently shown that osteosarcomas (OSs) display high rates of structural variation, i.e. they contain many somatic mutations and copy number alterations. TP53 and RB1 show recurrent somatic alterations in concordant studies, suggesting that they could be key players in bone oncogenesis. PATIENTS AND METHODS: we carried out whole-genome sequencing of DNA from seven high-grade OS samples matched with normal tissue from the same patients. RESULTS: We confirmed the presence of genetic alterations of the TP53 (including novel unreported mutations) and RB1 genes. Most interestingly, we identified a total of 84 point mutations and 4 deletions related to 82 different genes in OS samples, of which only 15 have been previously reported. Interestingly, the number of mutated genes (ranging from 4 to 8) was lower in TP53mut cases compared with TP53wt cases (ranging from 14 to 45). This was also true for the mutated RB1 case. We also observed that a dedifferentiated OS harboring MDM2 amplification did not carry any other mutations. CONCLUSION: This study suggests that bone oncogenesis driven by TP53 or RB1 mutations occurs on a background of relative genetic stability and that the dedifferentiated OS subtype represents a clinico-pathological entity with distinct oncogenic mechanisms and thus requires different therapeutic management.

CXCR7-mediated progression of osteosarcoma in the lungs.

BACKGROUND: Osteosarcoma (OS) is the most frequent primary malignant bone tumour in children and adolescents with a high propensity for lung metastasis. Chemokines and chemokine receptors have been described to have an important role in many malignancies including OS. The aim of this study was to investigate the expression of CXCR7 receptor in OS tissues and its role in the progression of the disease in the lungs. METHODS: Immunohistochemistry was used to study CXCR7 expression in primary tumours and metastatic tissues from patients with OS. Its contribution to tumour expansion in the lungs has been also assessed using animal models and synthetic-specific CXCR7 ligands. RESULTS: CXCR7 was expressed on human primary bone tumours and on lung metastases. Its expression was predominantly located on tumour-associated blood vessels. Mice challenged with OS cells and systematically treated with synthetic CXCR7 ligands presented a significant reduction of lung nodules compared with untreated mice. CONCLUSION: This study shows that CXCR7 has a critical role in OS progression in the lungs, where are expressed CXCR7 ligands, especially CXCL12. Moreover, we highlight that synthetic CXCR7 ligands could represent a powerful therapeutic tool to impede lung OS progression.

Osteosarcomas of the mandible: multidisciplinary management of a rare tumor of the young adult a cooperative study of the GSF-GETO, Rare Cancer Network, GETTEC/REFCOR and SFCE.

BACKGROUND: Mandibular osteosarcomas (MOS) mostly affect young adults. Their treatment is extrapolated from that of extragnathic osteosarcomas. MATERIAL AND METHODS: A retrospective multicooperative group study was conducted to determine the impact of chemotherapy, adjuvant radiation therapy and surgery on outcomes and to identify prognostic factors. This ethical committee-approved study included a centralized review of histology slides and operative reports. RESULTS: Of 111 patients, 58.6% were male, median age 35 years (13%, ≤18 years). Histology was osteoblastic, chondroblastic, fibroblastic, conventional not otherwise specified and others in 39.6%, 30.6%, 8.1%, 12.6% and 8.0%, respectively. Pathological World Health Organisation grades were low, intermediate and high grade in 6.4%, 11.8% and 81.8%, respectively. Surgery was carried out for 94.5% of patients. Neoadjuvant chemotherapy (mixed protocols) was carried out in 93.1% of patients. Postoperative chemotherapy and radiotherapy were carried out in 54.7% and 23.8%, respectively. Median follow-up was 59.6 months (range). Five-year local control, metastasis-free, disease-free and overall survival rates were 64.6%, 68.9%, 53.2% and 69.2%, respectively. Survival was significantly associated with age, tumor size and surgery. Wide surgery with clear margins and free flap reconstruction was the strongest prognostic factor. Neoadjuvant chemotherapy improved disease-free and metastatic-free survival and increased clear margins rates from 50% to 68%. Intermediate grades behaved like high grades in terms of metastatic-free and disease-free survival. CONCLUSION: This homogeneous series is the largest to date and emphasizes the major impact of clear margins and multidisciplinary management. Neoadjuvant chemotherapy improves disease-free survival and should be recommended for both high and intermediate grade MOS.

Can we rely on histopathological results for the diagnosis of prosthetic joint infection?

BACKGROUND: Histopathology is one of the diagnostic criteria for prosthetic joint infection (PJI) proposed by all academic societies. The aim of this study was to compare histopathological and microbiological results from samples taken intraoperatively at the same site in patients with suspected or proven PJI. PATIENTS AND METHODS: We conducted a monocenter retrospective study including all patients having undergone surgery from 2007 to 2015 with suspected or proven PJI. During surgery, both histopathological and microbiological samples were taken. Patients with a history of antimicrobial treatment 2 weeks prior to surgery were excluded. We considered as major criteria and gold standard for PJI diagnosis the presence of a sinus tract communication and/or the same microorganism in at least two cultures. RESULTS: Finally, 181 patients who underwent 309 surgeries were included. The median number of samples per surgery was 4 (interquartile range (IQR) = 3-5) for histopathology and 5 (IQR = 4-6) for microbiology. Major criteria were observed in 177 patients (57.3%), while positive histology in at least one intraoperative sample was present in 119 (38.5%). The concordance was 74%. The sensitivity and specificity of histopathology were 61% and 92% respectively. Available "histopathology-culture" sample pairs numbered 1247. Among them, positive histopathology was found in 292 samples (23%) and culture in 563 (45%). Concordance was 64%. The highest correlation was observed for very early infection (<1 month) (OR: 9.1, 95% CI: 3.6-23) and for virulent microorganisms, such as Staphylococcus aureus (OR: 7.8, 95% CI: 5.2-11.8), Streptococci (OR:7.8; 95% CI: 4-15.2) or Enterobacterales (OR: 7.4; 95% CI: 4.2-13.1). CONCLUSION: Histopathologic examination is a valuable criterion for PJI diagnosis, but it may lack sensitivity for chronic infections or due to low-virulence pathogens.

Osteosarcoma of the jaws: An overview of the pathophysiological mechanisms.

Osteosarcoma (OS) is the most common cancer of bone. Jaw osteosarcoma (JOS) is rare and it differs from long-bone OS (LBOS) in terms of the time of onset (two decades later), lower metastatic spread, and better survival. OS is characterized by the proliferation of osteoblastic precursor cells and the production of osteoid or immature bone. OS arises from a combination of genetic aberrations and a favourable microenvironment. This local microenvironment includes bone cells, blood vessels, stromal cells, and immune infiltrates, all of which may constitute potential targets for anti-cancer drugs. Differences in the clinical and biological behaviour of JOS versus LBOS are likely to at least in part be due to differences in the microenvironment between the two sites. The present review provides a brief overview of the known pathophysiological parameters involved in JOS.

Surgical Outcome and Oncological Survival of Osteofibrous Dysplasia-Like and Classic Adamantinomas: An International Multicenter Study of 318 Cases.

BACKGROUND: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. METHODS: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. RESULTS: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years (median, 14.5 years) for OFD-AD and 32 years (median, 28 years) for AD; 53% of the patients were female. The mean tumor size in the OFD-AD and AD groups combined was 7.8 cm, measured histologically. Sixteen percent of the patients sustained a pathological fracture prior to treatment. Local recurrence was recorded in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD. Metastatic disease was found in 18% of the AD cases and fatal disease, in 11% of the AD cases. No metastatic or fatal disease was reported in the OFD-AD group. Multivariate Cox regression analysis demonstrated that uncontaminated resection margins (hazard ratio [HR] = 0.164, 95% confidence interval [CI] = 0.092 to 0.290, p < 0.001), pathological fracture (HR = 1.968, 95% CI = 1.076 to 3.600, p = 0.028), and sex (female versus male: HR = 0.535, 95% CI = 0.300 to 0.952, p = 0.033) impacted the risk of local recurrence. CONCLUSIONS: OFD-AD and AD are parts of a disease spectrum but should be regarded as different entities. Our results support reclassification of OFD-AD into the intermediate locally aggressive category, based on the local recurrence rate of 22% and absence of metastases. In our study, metastatic disease was restricted to the AD group (an 18% rate). We advocate wide resection with uncontaminated margins including bone and involved periosteum for both OFD-AD and AD. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Case report: histologic study of a human epiphyseal transplant at 3 years after implantation.

A 5-year-old boy underwent surgical excision of a Ewing's sarcoma of the proximal femur. Reconstruction was performed using an ipsilateral vascularized epiphyseal transplant and a femoral allograft. Local recurrence of the tumor necessitated hip disarticulation 3 years after the initial procedure. We then performed a histologic analysis of the transplant. The growth plate was still normal in structure but had richly vascularized hyperplastic layers. We observed bridging between the articular cartilage and the growth plate.

Clinical and densitometric efficacy of the association of interferon alpha and pamidronate in the treatment of osteoporosis in patients with systemic mastocytosis.

Osteoporosis accompanying severe mastocytosis leads to numerous compressed vertebrae. We treated four patients (mean age 52 years) with severe osteoporosis and mastocytosis proven by bone marrow biopsy (more than 40 mast cells/mm3), according to the following protocol: interferon alpha (IFN) 3 million units (MU) three times a week, reduced to 1.5 MU three times a week in the event of intolerance, and pamidronate (Pam) 90 mg/month in infusion. This treatment was given for 2 years. It was followed by Pam alone at a dose of 90 mg/month. After 3 or 4 years of treatment, no patient presented new vertebral or extravertebral fractures. The mean increase in bone mineral density (BMD) with IFN and Pam was 16.05+/-6.12% at the spine, 5+/-2.24% at the femoral neck, and 4.12+/-3.03% for the whole body; the increase or loss of BMD with Pam alone was +0.2+/-2.13% at the spine, -2.25+/-2.78% at the femoral neck, and -0.1+/-3.35% for the whole body. In one patient, the IFN dose was halved because of a flu-like syndrome, and in another IFN was discontinued at one year for the same reason. The association of IFN and Pam led to a major increase in bone marrow density in osteoporosis with concomitant mastocytosis and this gain was then maintained by monthly infusions of Pam.

[Angiosarcoma of the aorta]. / Angiosarcome épithélioïde de l'aorte.

Primary aortic tumors are extremely rare. A 73-year-old woman presented with a 8 kg weight loss associated with abdominal pain. Physical examination was normal. Laboratory tests disclosed increased acute phase reactants. Thoracic and abdominal CT scan showed diffuse splenic and renal hypodense lesions with thrombotic feature of the thoracic aorta extending on 9 cm length. Transesophageal echocardiography showed a large and heterogeneous floating mass advocating a thrombus developed on atheroma. Because of the high risk of embolism the patient underwent surgical replacement of the thoracic aorta. Histopathology revealed an epithelioid angiosarcoma of the aorta. A primary tumor of the aorta should be suspected in the presence of an intra-aortic process presenting features of thrombosis.

Clear cell odontogenic carcinoma. A review.

INTRODUCTION: Clear cell odontogenic carcinoma (CCOC) is described as an exceptional and hard to diagnose malignant tumor which was first reported by Hansen in 1985. The purpose of this review article is to show that CCOC is a not that rare entity and to discuss its various aspects in order to enhance the diagnosis. MATERIAL AND METHODS: A search in the English language literature was performed using the Scopus, ScienceDirect, PubMed and Medline databases between 1985 and 2016. Data were collected on epidemiologic, clinical, radiographic, histological, immunohistochemistrical, cytogenetic, management, follow-up and prognosis features of CCOC. RESULTS: Sixty-five studies from which a total of 95 case reports were included in the review. CCOC was generally seen in the fifth decade and the most common site was mandibular. The most frequently found symptoms were swelling, tooth mobility and pain. Radiologically, the image was radiolucent and could look like a cyst or a periodontal lesion. In situ hybridization techniques frequently expressed a gene fission of EWSR1. The treatment was mostly a radical surgical excision of the tumor with or without adjuvant radiotherapy or chemotherapy. CCOC showed high rates of recurrence and mortality related with the presence of distance metastasis. DISCUSSION: Fission of EWSR1 gene could be the main element it the diagnosis of CCOC. A multidisciplinary approach, including a radiologist, pathologist and an oral & maxillofacial surgeon may be helpful in the evaluation and management of these lesions. With 95 reports found in English literature, we cannot say that CCOC is extremely rare anymore.

Clear cell odontogenic carcinoma, diagnostic difficulties. A case report.

INTRODUCTION: Clear cell odontogenic carcinoma (COCC) is a rare tumor described by Hansen et al. in 1985. The clinical and radiological manifestations are multiple and the diagnosis is histological. OBSERVATION: A 64-year-old patient consulted us for a right mandibular osteolytic lesion associated to a homolateral labial hypoesthesia. A biopsy was performed under local anesthesia. Histology was consistent with a metastatic lesion of clear kidney cell carcinoma, COCC, or odontogenic squamous tumor. Additional tests eliminated a metastatic lesion. A wide excision of the lesion by hemi-mandibulectomy associated with lymph node dissection and reconstruction by a fibula osteoseptocutaneous flap was performed. Presence of a fission of the EWSR1 gene on the histological examination of the surgical specimen made the diagnosis of COCC. DISCUSSION: Our observation illustrates the difficulty of diagnosing COCC. The new contribution of the cytogenetic techniques such as FISH-type techniques makes possible the improvement of the diagnosis.

Malignant tumours of the foot and ankle.

Most of tumours of the foot are tumour-like (synovial cyst, foreign body reactions and epidermal inclusion cyst) or benign conditions (tenosynovial giant cells tumours, planta fibromatosis). Malignant tumours of the soft-tissue and skeleton are very rare in the foot and their diagnosis is often delayed with referral to specialised teams after initial inappropriate procedures or unplanned excisions. The adverse effect of these misdiagnosed tumours is the increasing rate of amputation or local recurrences in the involved patients. In every lump, imaging should be discussed before any local treatment. Every lesion which is not an obvious synovial cyst or plantar fibromatosis should have a biopsy performed.After the age of 40 years, chondrosarcoma is the most usual malignant tumour of the foot. In young patients bone tumours such as osteosarcoma or Ewing's sarcoma, are very unusually located in the foot. Synovial sarcoma is the most frequent histological diagnosis in soft tissues. Epithelioid sarcoma or clear cell sarcoma, involve more frequently the foot and ankle than other sites. The classic local treatment of malignant conditions of the foot and ankle was below-knee amputation at different levels. Nowadays, with the development of adjuvant therapies, some patients may benefit from conservative surgery or partial amputation after multidisciplinary team discussions.The prognosis of foot malignancy is not different from that at other locations, except perhaps in chondrosarcoma, which seems to be less aggressive in the foot. The anatomy of the foot is very complex with many bony and soft tissue structures in a relatively small space making large resections and conservative treatments difficult to achieve. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160078. Originally published online at www.efortopenreviews.org.

Fourier Transform Infrared Imaging of focal lesions in human osteoarthritic cartilage.

Fourier Transform Infrared Imaging (FTIRI) is a new method for quantitatively assessing the spatial-chemical composition of complex materials. This technique has been applied to examine the feasibility of measuring changes in the composition and distribution of collagen and proteoglycan macromolecules in human osteoarthritic cartilage. Human cartilage was acquired post-operatively from total joint replacement patients. Samples were taken at the site of a focal lesion, adjacent to the lesion, and from relatively healthy cartilage away from the lesion. Sections were prepared for FTIRI and histochemical grading. FTIRI spectral images were acquired for the superficial, intermediate, and deep layers for each sample. Euclidean distance mapping and quantitative partial least squares analysis (PLS) were performed using reference spectra for type-II collagen and chondroitin 6-sulphate (CS6). FTIRI results were correlated to the histology-based Mankin scoring system. PLS analysis found relatively low relative concentrations of collagen (38 +/- 10%) and proteoglycan (22 +/- 9%) in osteoarthritic cartilage. Focal lesions were generally found to contain less CS6 compared to cartilage tissue adjacent to the lesion. Loss of proteoglycan content was well correlated to histological Mankin scores (r=0.69, p<0.0008). The evaluation of biological tissues with FTIRI can provide unique quantitative information on how disease can affect biochemical distribution and composition. This study has demonstrated that FTIRI is useful in quantitatively assessing pathology-related changes in the composition and distribution of primary macromolecular components of human osteoarthritic cartilage.

[Metastasis on previous hip arthroplasty: three cases]. / Métastase osseuse d'un cancer viscéral sur hanche prothésée: à propos de trois cas.

Three cases of metastasis on a previous total hip arthroplasty are reported. The hips had been operated a few years earlier for osteoarthritis. The patients then developed a carcinoma (kidney, prostate, breast) which disseminated producing bony metastases around the prosthesis which caused loosening. All three patients underwent a revision procedure for prosthesis replacement with a metaphysodyaphyseal implant. Carcinological resection was performed in one patient because the metastasis appeared to be unique. At last follow-up two years later, this patient was doing well.

Bone cysts: unicameral and aneurysmal bone cyst.

Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy.

Immunohistochemical assessment of human herpesvirus 8 infection in primary central nervous system large B cell lymphomas.

BACKGROUND/AIMS: Primary central nervous system large B cell lymphomas (PCNSLs) are frequently associated with Epstein-Barr virus (EBV) in patients with AIDS and less frequently in those without AIDS. Human herpesvirus 8 (HHV-8) has been detected in these tumours by the polymerase chain reaction (PCR) at low copy number, suggesting its presence in a cell compartment other than the malignant one. The aim of this study was to use immunohistochemistry to assess HHV-8 infection in a series of PCNSLs from patients with and without AIDS. METHODS: The antibody LN53, which reacts with the latent nuclear antigen 1 (LNA1) of HHV-8, was used on tissue sections from 35 patients (17 with and 18 without AIDS) with PCNSL. In addition, DNA was available for PCR (open reading frame 26 (ORF 26), ORF 72, ORF 75) in three patients (two without AIDS, one with AIDS). RESULTS: None of the 35 cases contained either DNA sequences or LNA1 positive cells. CONCLUSIONS: These results confirm the lack of HHV-8 infection in tumour cells of PCNSL. In addition, HHV-8 infected bystander cells do not express LNA1 latent protein in this setting.

Does vascular endothelial growth factor in the rheumatoid synovium predict joint destruction? A clinical, radiological, and pathological study in 12 patients monitored for 10 years.

OBJECTIVE: Synovial angiogenesis is at the epicenter of rheumatoid pannus development and is largely dependent on vascular endothelial growth factor (VEGF). We sought to determine whether the VEGF level in rheumatoid synovial tissue is a marker for disease severity. PATIENTS AND METHODS: Twelve patients with rheumatoid arthritis (RA) underwent a clinical and radiological evaluation at the time of a synovial biopsy done during joint surgery required by RA progression (T1) and, on average, 10 years later (T2). Immunohistochemistry was used to detect and quantitate VEGF in the synovial biopsy taken at T1. RESULTS: VEGF labeling was seen on endothelial cells and macrophages in all 12 synovial biopsies. The amount of endothelial-cell VEGF labeling (assessed semi-quantitatively) was significantly correlated with Larsen score progression during the 10-year follow-up. The amounts of endothelial cell or macrophage VEGF labeling was not correlated with the joint count, radiological stage of the biopsied joint or progression of this stage, Larsen scores at T1 or T2, presence of rheumatoid factor, or presence of extra-articular manifestations. CONCLUSION: Our results suggest that the amount of VEGF in the rheumatoid synovium may be a marker for joint destruction in patients with RA.

Vestibular schwannomas: correlations between magnetic resonance imaging and histopathologic appearance.

BACKGROUND: The indication for surgery of vestibular schwannomas (VS) remains controversial and depends on several factors. The ability to predict their patterns of growth would allow better surgical planning. This growth may depend on tumoral proliferation but also depends on dystrophic changes. OBJECTIVE: The aim of this study was to evaluate the role of magnetic resonance imaging (MRI) in predicting the evolution of VS. For this purpose, the authors attempted (1) to compare the MRI appearance of VS with its histopathologic features, (2) to correlate the MRI appearance of VS and its histopathologic features with its size, and (3) to evaluate the index of proliferation (IP) of each VS. PATIENTS AND METHODS: Thirty VS were studied with MRI before surgery. The VS were measured and classified as homogeneous, heterogeneous, and cystic. After surgery, IP was evaluated with immunohistochemical study using MIB-1 monoclonal antibody, and compared with tumor size. Pathologic studies evaluated the prevalence of Antoni type A and type B tissue, the amount of fibrosis, and the presence of siderin-loaded macrophages, xanthomatous cells, and cysts. RESULTS: The IP was low (0.2%-2.2%) and was not correlated with VS size. On MRI, 13 VS were homogeneous, 12 heterogeneous, and 5 cystic. The 13 homogeneous VS were smaller and were predominantly made of Antoni type A tissue. The 12 heterogeneous and 5 cystic VS were larger and were predominantly made of Antoni type B/mixed tissue. Heterogeneous and cystic VS showed significantly more hemosiderin deposits. There was a significant relation between the amount of hemosiderin deposits and the mean size of VS. Microscopic cysts were observed only in VS with cystic MRI appearance. Fibrosis was present in all tumors regardless of their size and MRI appearance. CONCLUSION: A heterogeneous MRI aspect (correlated with larger mean size) not only is related to the ratio of type A to type B tissue but also is caused by other pathologic changes, mainly hemosiderin deposits and cystic formation. Increasing tumor size probably depends less on IP than on dystrophic changes (hemosiderin, cysts) and/or on the presence of type B tissue.

[Anaphylactic shock caused by pancuronium and vecuronium]. / Choc anaphylactique au pancuronium et au vécuronium.

A case is reported of anaphylactic shock due to vecuronium occurring in a patient who had already had such a shock, due then to pancuronium, during a previous general anaesthesia. The need for a full immuno-allergological investigation, the occasional efficiency of the anti-histamine premedication, and crossed allergies between muscle relaxants are stressed. It is noted that an anaphylactic shock can be seen on first using a new molecule, as the patient can have been sensitized to it by other muscle relaxants. This case was the first to be described of an anaphylactic shock due to vecuronium bromide.

[Continuous administration of vancomycin in patients with severe burns]. / Vancomycine en administration continue chez le grand brûlé.

OBJECTIVES: In the severely burned patient, a marked, rapid fall in serum concentrations is often observed after intermittent infusion of vancomycin at the usual dose of 30 mg/kg. This specific "jagged" pharmokinetic course with inadequate residual concentrations raises the problem of the efficacy of this time-dependent antibiotic. Studies in patients in general resuscitation units have shown the interest of vancomycin administration in continuous infusion. METHODS: We analyzed variations in serum concentrations of vancomycin during continuous infusion in 18 patients with burns involving a mean of 40% total body surface and reported the doses necessary to maintain serum vancomycin at therapeutic levels; the possible correlations between serum vancomycin concentrations, burn parameters, age and renal function; and clinical and biological tolerance. RESULTS: Higher initial doses were required in burn patients (40 mg/kg in patients aged under 60) than in other patients. Impairment of renal function is a contra-indication of continuous infusion. CONCLUSION: This mode of administration has the advantage of ensuring greater efficacy by preventing fluctuations in serum concentrations.