[Alveolar hemorrhage associated with sarcoidosis]. / Sarcoïdose médiastinopulmonaire associée à une hémorragie intra-alvéolaire.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease of unknown origin. We report an unusual case associated with alveolar haemorrhage. CASE REPORT: An 18-year-old caucasian man was admitted for recent dyspnea. He reported regular tobacco- and occasional cannabis smoking. Lung CT scan revealed mediastinal lymphadenopathy and lung nodules in both fields. Bronchoalveolar lavage recovered bloody alveolar fluid containing many siderophages. Because of rapid deterioration leading to acute respiratory failure, intravenous corticosteroid treatment was started. Improvement was obtained in few days and a diagnosis of sarcoidosis was established based on lymph node biopsy performed under mediastinoscopy. CONCLUSION: This unusual case and those reported in the literature give us the opportunity to describe the characteristics of alveolar haemorrhage associated with sarcoidosis.

[Spinal cord ischaemia and preoperative clopidogrel withdrawal in an arteriosclerotic patient]. / Accident ischémique médullaire associé à l'arrêt du clopidogrel chez une patiente artéritique.

We report the case of a motor impairment associated with bladder dysfunction several days after clopidogrel withdrawal in an arteriosclerotic woman scheduled for thoracotomy under general and thoracic epidural anaesthesia. Even if spinal artery syndrome may have a lot of aetiologies, we believe in a direct link between clopidogrel withdrawal and medulla ischaemia.

[Pulmonary artery stump thrombosis following pneumonectomy]. / Thrombose in situ du moignon artériel pulmonaire après pneumonectomie.

INTRODUCTION: Pulmonary artery stump thrombosis has been reported after pneumonectomy. The prevalence of risk factors for and outcome associated with this condition remain to be clearly evaluated. CASE REPORT: We describe three cases of pulmonary artery stump thrombosis occurring after pneumonectomy. No pulmonary embolism was observed despite the absence of anticoagulation therapy. The prevalence of arterial stump thrombosis after pneumonectomy has been estimated as 12%. It is often detected by CT scanning performed systematically as part of the routine follow up of lung cancer. Thrombus was identified as a filling defect with concave or convex margins, located at the bottom of the stump. DISCUSSION: Only one case of pulmonary embolism associated with pulmonary artery stump thrombosis has been described. The absence of complications associated with thrombus in this site suggests that anticoagulant therapy is not likely to be of benefit.

Hand-modelled composite prostheses after resection of peri-acetabular bone malignancies.

PURPOSE: To improve function after pelvic resection involving the acetabulum, using an anatomic composite implant built with screws and cement. MATERIAL AND METHOD: Since 1990, 66 patients with peri-acetabular bone malignancies have been treated by extensive resection followed by hand-modelled innominate prosthesis with partially constrained total hip prosthesis. The hand-modelled innominate prosthesis was made of a titanium cup, a set of long titanium screws and two or three packs of gentamycine-loaded cement. RESULTS: Many postoperative complications were observed: deep infection (14%), hip prosthesis dislocation (25%) and local recurrence (15%). Sixteen patients (25%) had to be reoperated. Nevertheless, at last follow-up, 62 patients still had composite prosthesis. The mean functional result, rated according to a modified Enneking's staging system, was 80% with unlimited walking without support, average hip flexion 100 degrees , length discrepancy less than 1 cm. DISCUSSION: These results were similar to those described in the literature for custom-made innominate prostheses and much better than those of alternative reconstructive procedures. Hand-modelled composite prostheses are cheaper, easier, more adaptable and enables better anchorage than custom-made prostheses. Such a procedure can be used even after total iliac wing resection. CONCLUSION: The advantages of such a procedure plead for its extensive use after acetabular resection. But long-term follow-up is necessary to validate indications.

[Hereditary multiple exostoses after 40 years of development: a case report]. / Maladie des exostoses multiples après 40 ans d'évolution: à propos d'un cas.

INTRODUCTION: Hereditary multiple exostoses is an autosomal dominant skeletal disorder with genetic heterogeneity and an estimated prevalence of 1/50,000 in western countries. Malignant degeneration is a rare (about 2%) but classical complication in patients with hereditary multiple exostoses. At least 3 loci identified as EXT 1, EXT 2 and EXT 3 are involved in this skeletal disease. EXEGESIS: The case of a 45-year old man is described with 15 years follow-up after resection of a well-differentiated chondrosarcoma (grade I), which arose from a right posterior pelvic exostosis. The observed radiological lesions remained relatively stable until now. The genetic mutation which is responsible for the disease was determined at the locus EXT 1. CONCLUSION: The present case report illustrates the natural history of hereditary multiple exostoses, especially since the patient underwent a malignant degeneration which could be resected without recurrence. The results of the genetic analysis contributed to the understanding of the pathophysiology of the disease.

[Periosteal Ewing's sarcoma]. / Sarcome d'Ewing périosté

Periosteal Ewing's sarcoma is a histologically typical Ewing's sarcoma arising in the periosteum with no involvement of the medullary canal or cancellous bone. We describe four cases in our experience and review the literature, recalling the usual computed tomography diagnostic criteria and the therapeutic consequences. Prognosis of periosteal Ewing's sarcoma is generally better than for ordinary Ewing's sarcoma. In order to avoid inoculating the canal, the operator must strictly avoid perforating the cortical during the biopsy. At surgical resection, cortical resection can be partial maintaining a continuous diaphysis; this should be examined as a possibility for young patients in order to avoid the problems encountered with massive reconstruction followed by chemotherapy.

[Diagnosis and treatment of malignant bone fibrohistiocytoma]. / Diagnostic et traitement des histiocytofibromes malins de l'os.

Malignant fibrous histiocytoma (MFH) and giant cells sarcoma arise from fibrous tissue and histiocytic cells evenly distributed in all age group, except children much less common than osteosarcoma and chondrosarcoma. They most commonly localize in the major long bones (femur, tibia, humerus) and in pelvis. Pain and sometimes swelling are the most frequent symptoms but pathologic fractures are rather common. Medical imaging shows a purely osteolytic tumor centrally or eccentrically located, ill defined with a permeative or even moth eaten patterns. Periosteal reaction is scarce or absent. Osteogenic reaction or tumor calcifications are absent. Outcome was historically better than those of osteosarcoma but hangs on the grading of tumors; low grade sarcoma have a regional evolution while high grade malignant histiocytofibroma are threatened with metastases. Therapy must be adapted to the histological grading and the extent of the illness. Low grade localized MFH are best treated by wide resection. High grade MFH are preferentially treated by a comprehensive multidisciplinary approach with preoperative chemotherapy including high dose methotrexate, wide resection and postoperative chemotherapy. With such a treatment, nearly 80% of patients seen with localized tumor of the limb can be cured and keep a functional limb.

[Hand on composite prosthesis after resection of peri-acetabular sarcoma]. / Résultats des prothèses composites au ciment après résection acétabulaire pour sarcome.

PURPOSE OF THE STUDY: To improve function after pelvic resection involving theacetabulum we have used an anatomic composite implant built with screws and cement. MATERIAL AND METHOD: Since 1990, 27 patients with peri-acetabular bone sarcoma have been treated by extensive resection followed by "hand on innominate prosthesis with constrained total hip prosthesis. The hand on innominate prosthesis was made of a titanium cup, a set of long titanium screws and 2 or 3 packs of gentamycin loaded ciment. RESULTS: Many postoperative complications were observed; deep infection (15 p. 100), hip prosthesis dislocation (33 p. 100) and local recurrence (17 p. 100). Nine patients (33 p. 100) had to be reoperated. Nevertheless at last follow up 24 patients still had their composite prosthesis. The mean functional result, rated according to a modified Enneking's staging system, was 83 p. 100 with unlimited walking without support, average hip flexion 100 degrees, length discrepancy less than 1 centimeters. DISCUSSION: These results were similar to those described in the literature for custom made innominate prosthesis and much better than those of alternative reconstructive procedures. Hand on composite prosthesis is cheaper, easier, more adaptable and enables better anchorage than custom-made prosthesis. Such a procedure can be used even after total iliac wing resection. CONCLUSIONS: The advantages of such procedure pleads for using it extensively after acetabular resection. But long term follow up is necessary to validate indications.

Pharmacokinetic modelling of ifosfamide administered by continuous infusion on 5 days at the dose of 6 g/m2.

BACKGROUND: We aimed to create a model for Ifosfamide (IFX) pharmacokinetics for drug monitoring in order to improve protocol dose intensity. MATERIAL AND METHODS: We studied ifosfamide pharmacokinetics in 12 patients aged 8-19 years. Sixteen courses were modelled (6 g/m2, on 5 days). The auto-induction of ifosfamide was taken into account in the model. Ifosfamide measurement was performed on serum samples by gas chromatography with thermo-ionic detection. Two pharmacokinetic models were compared. The following parameters were estimated: volume of distribution (Vd), clearance at the beginning of the induction (CLi), clearance extrapolated to infinity (CLf), clearance at the end of infusion (CL120), a rate constant (Kc) indicating the clearance variation with time and the lag time (Lag) indicating the time elapsed between the start of infusion and the start of induction. The Wilcoxon test was used to investigate possible differences between models. We tested the hypothesis that Boddy's model is an acceptable simplification of Levy's model. RESULTS: Four of six parameters were significantly different between the two models (p = 0.05). The best curve fitting was obtained using the Levy's model which provided the following estimates, Cli = 2.46 +/- 0.94 L.h-1.m-2, CLf = 5.22 +/- 1.02 L.h-1.m-2, Kc = 0.024 +/- 0.014 h-1, Vd = 18.84 +/- 5.04 L and Lag = 4.86 +/- 6.61 h. The most important difference is found for the distribution volume. CONCLUSION: Levy's model is more accurate and takes into account the integration of clearance.

The importance of systematic histological examination after loosening of an implant.

A 65-year-old man presented with a painful hip five years after a cemented replacement. Histological examination of a biopsy taken from tissue surrounding the femoral implant showed infiltration of a squamous-cell carcinoma. Further investigation revealed a primary growth in the left lung. This rare example of a metastasis in relation to a joint replacement illustrates the necessity for histological examination of the tissue adjacent to a loose prosthesis.

Expanding prostheses in conservative surgery for lower limb sarcoma.

Conservative resection of bone sarcoma in the lower limbs in children is very likely to be followed by a progressive problem of leg length inequality resulting from removal of the growth cartilage. To overcome this we have been using an expanding prosthesis and we report our experiences during the period 1985-1996. The prostheses are made of titanium and comprise 3 parts: an articular component, an expanding mechanism, and tibial and femoral stems. The degree of possible lengthening of the prostheses is virtually unlimited, and they can be inserted in children of 5 or more years of age. We report the use of 28 prostheses in patients aged from 5 to 18 years, of which 4 were tibial, 5 total femur, and 16 distal femur. There were 6 Ewing's sarcoma, 21 osteosarcoma, and 1 synovial sarcoma. The average follow-up was for 5 years. Five patients died from their disease, and 21 benefited from an average lengthening of 2.6 cm (range: 2 mm-120 mm). Using the Société Européenne des Tumeurs Osseouses (EMSOS) criteria, the functional results were excellent or very good in 16, fair in 7 and bad in 5. Five patients developed an infection; one required amputation and the others received a new expanding prosthesis. We conclude that an expanding prosthesis is an excellent alternative to amputation in young children. However, the risk of infection associated with repeat surgery has led us to develop a prosthesis which can be lengthened externally, without the need for reopening the wound.

Prognostic factors in patients with localized Ewing's sarcoma: the effect on survival of actual received drug dose intensity and of histologic response to induction therapy.

To bring to the fore the most important prognostic factors in Ewing's sarcoma (ES) with current protocols, we studied the classical prognostic factors, dose intensity (DI) of actual received drugs, age and histological response to induction therapy and their correlation in 39 patients with localized ES treated from 11/85 to 06/95 to identify eventual predictors of event-free survival (EFS). Inclusion criteria were age 35 yr or less, definitive local treatment by our team and chemotherapy including at least 4 drugs: vincristine (VCR), dactinomycin (DACT), doxorubicin (DOXO) cyclophosphamide (CPX). The endpoint was the absence of relapse. Parameters related to the status of patients were tested using the Chi square test or Fisher's exact test. The non parametric Kruskal-Wallis test was used for quantitative data. When necessary stratified analysis was done using the Mantel Cox test. With a median follow-up of 7 yr, overall survival (OS) and EFS were both 67% at 7 yr. According to univariate analysis, the significant predictors of survival were the DI of VCR and DACT, the histological response to preoperative chemotherapy (CT), the patient's age (< 18 yr DFS: 84%; > 18 yr DFS: 38%). The risk of metastases was almost tenfold higher in patients with low received DI of VCR (DFS 40% versus 95%) and of DACT (DFS 48% versus 94%). The prognostic value of primary tumor characteristics (tumoral volume or location) was erased by the comprehensive treatment. Following multivariate analysis, the actual received DI of VCR (p < 0.02) and DACT (p < 0.03) and the histological response to preoperative CT (p < 0.05) were retained as the only significant independent predictors of EFS. Taking into account the actual received DI of VCR and DACT, the prognostic value of age disappears. In conclusion, this study points out the main role of the drug DI in ES (particularly VCR and DACT) and of histological response to preoperative CT.

Possible monocytic origin of chondrosarcoma: in vitro transdifferentiation of HLA-DR blood monocyte-like cells from a patient with chondrosarcoma, into neo-fibroblasts and chondrocyte-like cells.

Nodules and multilayered areas composed of fibroblasts and chondrocyte-like cells embedded in an abundant extracellular matrix appeared spontaneously in in vitro culture of mononucleated blood cells taken from a patient with chondrosarcoma. Using specific antibodies it was demonstrated that the neo-fibroblasts which developed in the culture resulted from a direct transdifferentiation of monocytes expressing HLA-DR specificity. The experiment was carried out twice, once before surgery and then two years later. In both cases the spontaneous transdifferentiation of HLA-DR monocytes into neo-fibroblasts was observed. Previously it was shown that normal monocytes were also able to give rise in vitro to neo-fibroblasts. However, the latter are normally rapidly destroyed by cell-cell contact with T-cells. Normal T-cells adhere to normal neo-fibroblasts by which they are finally engulfed. As a result, the neo-fibroblasts lose their fibroblastic shape, no longer adhere to their support and die. Therefore the abnormal proliferation and persistence of neo-fibroblasts in pathological situations such as the present case may result either from an intrinsic defect in monocytes, T-cells or both. The question is whether or not this transdifferentiation process observed in vitro accounts for the development of chondrosarcoma in vivo. The present results suggest that in vivo chondrosarcoma may start in a necrotic zone (resulting for instance from trauma) and attract HLA-DR monocytes, where they accumulate and transdifferentiate into neo-fibroblasts and chondrocyte-like cells. The uncontrolled transdifferentiation of these HLA-DR monocytes resulting from a dysregulation of the immune system is probably linked to the malignant process which may have a retroviral origin. The question is raised regarding the embryologic origin of this special sub-population of blood monocytes in which pluripotential capabilities are retained; its origin may differ from that of the other circulating monocytes.

Influence of methotrexate dose intensity on outcome of patients with high grade osteogenic osteosarcoma. Analysis of the literature.

BACKGROUND: The authors surveyed the published clinical trial literature on the subject of localized high grade osteosarcoma in order to develop new hypotheses dealing with drug-dose combinations in the treatment of this disease. METHODS: A computerized literature search was conducted to identify all available published reports of the clinical trials using high dose methotrexate (MTX) in multidrug protocols treating osteosarcoma. Thirty studies, including discussion of high dose MTX (> 7.5 g/m2 per course) and precise quantification of 5-year disease free survival (DFS), fulfilled the inclusion criteria of this dose-intensity analysis. The total number of patients treated in eligible studies was 1909. Correlation among the planned total doses, the dose intensities of the drugs, and the 5-year DFS were tested by regression analysis. RESULTS: No correlation of any other drug dose or dose intensity with DFS appeared as important as the MTX finding. In multivariate analysis, the dose intensity of MTX was found to be the one most correlated with DFS. This correlation appeared to hold for adjuvant and neoadjuvant trials. CONCLUSIONS: The dose intensity of MTX seems to be a major factor in predicting the outcome of patients with localized high grade osteosarcoma.

[Carcinoid thymus tumor at an advanced age: diagnostic value of mediastinal needle biopsy with computerized tomography]. / Tumeur carcinoïde du thymus à un âge avancé: intérêt diagnostique de la ponction-biopsie médiastinaie sous tomodensitométrie.

Carcinoid tumour of the thymus is a rare neuroendocrine tumour particularly at an advanced age. The authors report a case of a mediastinal mass in a man aged 85, the mass had remained asymptomatic for a long time. It was decided to achieve a diagnosis because the tumour was causing local compression: a mediastinal needle biopsy under computerised tomographic control confirmed that this was a carcinoid tumour and a study of the biopsy material using an electron microscope showed neurosecretory granules. A sternotomy enabled the tumour to be excised but a post-operative Pseudomonas pneumonia led to the death of the patient. This case underlines the diagnostic place of mediastinal needle biopsy in the presence of a mediastinal tumour. The technique can be carried out under computerised tomography or ultrasonography and this can be associated with a study of the biopsy specimen using electron microscopy which enables the diagnosis to be made before any therapeutic decisions. The treatment of choice of a carcinoid tumour of the thymus is surgery which confirms the tumour limits and also its thymic origin. Tumour excision can be completed using radiotherapy or even chemotherapy.

Dose escalation with pharmacokinetics monitoring in methotrexate chemotherapy of osteosarcoma.

This paper evaluates the influence of pharmacokinetics monitoring of HDMTX in the treatment of localized operable previously untreated high grade osteosarcoma. 44 patients (group 1) received a T10 protocol with dose adapted only to age. 27 other patients (group 2) had a pharmacokinetics monitored dose adaptation of MTX. The pharmacokinetics monitoring leads to higher dosage, higher area under the concentration/time curve and permits higher toxicity to be avoided. The higher dose intensity of MTX gave higher histologic response rate (66% compared to 45%) and higher 5 year disease free survival (92% compare to 76%). HDMTX treatment of osteosarcoma should be dose adapted to indivi-dual pharmacokinetics.

[Mitral surgery by superior biatrial septotomy]. / Chirurgie mitrale par bi-atrio-septotomie supérieure.

The superior biatrial septotomy approach consists of two semicircular right atrial and septal incisions joined at the superior end of the interatrial septum and extended across the dome of the left atrium, allowing exposure of the mitral valve by reflecting the ventricular side using stay sutures. From 1991 to 1993, 81 patients underwent mitral valve surgery by this technic. Mitral valve operation was combined with other cardiac procedures in 30 patients (37%) and was performed as a second operation in 21 patients (25.9%). Duration of cardiopulmonary bypass and aortic occlusion was not significantly different from that of patients operated via a conventional left atrial approach. The five hospital deaths (6.2%) were not related to this operative approach. Only 2 patients (3.3%) with preoperative in sinus rythm were discharged in atrial fibrillation after operation. In one patient (1.6%), atrioventricular block appeared at late follow-up. There were no cases of bleeding, atrioventricular nodal dysfunction or intra-atrial shunting related to the approach. This approach provides excellent exposure of the mitral valve even in unfavorable situations such as a small left atrium, dense adhesions from previous procedures or a previously implanted aortic prosthesis, without damage to various cardiac structures due to excessive traction. No retractor or vena cava repair are required. These data support a wide application of the superior biatrial septotomy approach in mitral valve surgery.

[Peri-operative chemotherapy during resection of pulmonary metastases of sarcoma]. / Chimiothérapie périopératoire lors des résections de métastases pulmonaires de sarcomes.

The objective of this prospective study was to evaluate the mortality and morbidity of sarcoma pulmonary metastasis resection with continuous chemotherapy. Ifosfamide was administered at the daily dose of 1200 mg/m2/24 h. Twenty-six resections of pulmonary sarcoma were performed from December 1990 to April 1992. The primary lesion was already resected in all patients. Peri-operatory chemotherapy was started 30 minutes before surgery and continued for 6 days. Chemotherapy was associated with an uroprotector, antiemetic drugs and adequate hydration. Patients had a mean age of 30.6 years. The delay between initial and thoracic surgery was 81 months. The following was performed: tumorectomy (32), wedge (18), lobectomy (7), diaphragm resection (1), left pneumectomy (1). All patients had the 6-days chemotherapy course. None of the patients died. Respiratory failure following superinfection, but not necessitating assisted ventilation, was observed in one case. The following adverse events were noted: nausea (34.6%), uncomplicated cystitis (15.4%), leucopenia (7.6%), fever (3.8%). Mean duration of hospitalization was 11.8 days. Chemotherapy adverse effects did not result in significant morbidity. Bronchial fistula was not observed. Following the results of this pilot study, we feel that perioperatory chemotherapy can be added to sarcoma pulmonary metastasis resection surgery without increasing patient morbidity and mortality.

[Recurrent mobile thrombus of the ascending aorta diagnosed by transesophageal echocardiography]. / Thrombus mobile récidivant de l'aorte ascendante diagnostiqué par échocardiographie transoesophagienne.

The authors report the case of a 32 year old woman with no risk factors for thromboembolism apart from a raised Lipoprotein (a) level, in whom a mobile thrombus of the ascending aorta was diagnosed only by transoesophageal echocardiography after multiple episodes of systemic embolism. After surgical excision the thrombus recurred and death ensued on the 17th postoperative day after multiple visceral embolism despite adequate anticoagulant therapy. This is a rare condition, the outcome of which seems often to be fatal, due to early recurrence irrespective of the treatment (anticoagulant or platelet antiaggregant therapy). This case illustrates the value of systematic transoesophageal echocardiography for the investigation of cerebral or peripheral ischaemic episodes without carotid artery disease and raises the problem of the best way of treating this pathology.