Biomedical subjects
Publications and source records attributed to H J van der Woude.
A 23-year-old woman with an alveolar soft-part sarcoma of her calf with pulmonary metastases unresponsive to chemotherapy is described. Interferon (IFN) alpha-2b induced an impressive tumour response still ongoing after IFN treatment had to be stopped because of a psychosis. An explanation of this effect is still speculative.
A 49-year-old male presented with a painful progressive swelling in his right axillar region, without further complaints, which had been present for 2 weeks. On radiological examination a peripheral circumferential zone of mineralisation was seen in the right teres major muscle. An incision biopsy specimen showed a lesion of fibroblastic tissue in which areas of osteoid and fragmented lamellar bone tissue, without signs of malignancy. The diagnosis was myositis ossificans circumscripta. This is a rare benign ossifying lesion in skeletal muscles, mostly caused by a trauma and with an average age of occurrence between 20 and 30 years old. It must be differentiated from extra-skeletal osteosarcoma. The pathogenesis is unknown. Because it is a benign and self-limiting disorder, surgical excision is only necessary in case of mechanical hindrance. The patient's swelling partially regressed and he had no further complaints.
Explore the source record for details and available documents.
We investigated whether treatment with a long-acting beta2-agonist (LAbeta2) is associated with a decrease in patient compliance with regard to inhalation corticosteroids (ICS). Date on prescriptions collected by 15,760 patients suffering from airways disease were provided by 69 Dutch pharmacies. All prescriptions of ICS and LAbeta2 were analysed and divided in four groups by LAbeta2 use during 1997 and 1998. Date from 15,760 patients were available. In the 10,929 patients not treated with LAbeta2, compliance decreased slightly but not significantly. In 3281 patients receiving LAbeta2 compliance also decreased slightly but not significantly. In 404 patients, who used a LAbeta2 in 1997 and discontinued treatment in 1998, the compliance fell significantly (P<0.05). In 1147 patients who started to use a LAbeta2 in 1998, compliance with ICS significantly improved (P<0.05). These results suggest that the regular use of LAbeta2 improves compliance with ICS. Therefore, the concern that compliance with inhaled corticosteroid therapy will decrease under concomitant use of LAbeta2 appear to be unfounded.
BACKGROUND: In vitro the long acting beta2 agonist salmeterol can, in contrast to formoterol, behave as a partial agonist and become a partial antagonist to other beta2 agonists. To study this in vivo, the bronchodilating effect of salbutamol was measured during methacholine induced moderate to severe bronchoconstriction in patients receiving maintenance treatment with high dose long acting beta2 agonists. METHODS: A randomised double blind crossover study was performed in 19 asthmatic patients with mean forced expiratory volume in one second (FEV1) of 88.4% predicted and median concentration of methacholine provoking a fall in FEV1 of 20% or more (PC(20)) of 0.62 mg/ml at entry. One hour after the last dose of 2 weeks of treatment with formoterol (24 microg twice daily by Turbuhaler), salmeterol (100 microg twice daily by Diskhaler), or placebo a methacholine provocation test was performed and continued until there was at least a 30% decrease in FEV1. Salbutamol (50 microg) was administered immediately thereafter, followed by ipratropium bromide (40 microg) after a further 30 minutes. Lung function was monitored for 1 hour after provocation. RESULTS: There was a significant bronchodilating and bronchoprotective effect after 2 weeks of active treatment. The dose of methacholine needed to provoke a fall in FEV1 of > or = 30% was higher after pretreatment with formoterol (2.48 mg) than with salmeterol (1.58 mg) or placebo (0.74 mg). The difference between formoterol and salmeterol was statistically significant: 0.7 doubling dose steps (95% CI 0.1 to 1.2, p=0.016). The immediate bronchodilating effect of subsequently administered salbutamol was significantly impaired after pretreatment with both drugs (p<0.0003 for both). Three minutes after inhaling salbutamol the increase in FEV1 relative to the pre-methacholine baseline was 15.8%, 7.3%, and 5.5% for placebo, formoterol and salmeterol, respectively (equivalent to increases of 26%, 14%, and 12%, respectively, from the lowest FEV1 after methacholine). At 30 minutes significant differences remained, but 1 hour after completing the methacholine challenge FEV1 had returned to baseline values in all three treatment groups. CONCLUSION: Formoterol has a greater intrinsic activity than salmeterol as a bronchoprotective agent, indicating that salmeterol is a partial agonist compared with formoterol in contracted human airways in vivo. Irrespective of this, prior long term treatment with both long acting beta2 agonists reduced the bronchodilating effect of an additional single dose of salbutamol equally, indicating that the development of tolerance or high receptor occupancy overshadowed any possible partial antagonistic activity of salmeterol. Patients on regular treatment with long acting beta2 agonists should be made aware that an additional single dose of a short acting beta2 agonist may become less effective.
There is the possibility that during treatment with inhaled long-acting beta2-agonists that a loss of perception of dyspnoea might occur and that the forced expiratory volume in one second (FEV1) might fall precipitously during bronchial provocation. This study investigated these possibilities during methacholine provocation, continued until there was > or =30% fall in FEV1, mimicking a moderate asthma attack. Nineteen asthmatic patients were asked to score their dyspnoea as a Borg score during provocation with methacholine. One hour prior to this provocation, the patients used the last morning dose of 14 days treatment with either formoterol (twice daily 24 microg by Turbuhaler), salmeterol (twice daily 100 microg by Diskhaler) and placebo in a double-blind, randomized, double-dummy, cross-over design. The perception of dyspnoea, expressed as the Borg score divided by the change in FEV1 at > or =30% fall in FEV1, was similar on the three test days at 0.067, 0.076 and 0.074%(-1) after formoterol, salmeterol and placebo treatment, respectively (p=0.16). The slope of the methacholine dose response curve did not differ (p=0.52). In conclusion, no suggestion was found for an abnormal perception of dyspnoea or an exaggerated fall in forced expiratory volume in one second during provocation with methacholine under long-acting beta2-agonist treatment.
We present an overview of the imaging modalities in bone tumors. The imaging strategies of preoperative work-up, monitoring the effect of chemotherapy and the detection of recurrences by long-term follow-up are discussed.
Multiple enchondromatosis (Ollier's disease) is a nonhereditary disease characterized by multiple central (medullary) cartilaginous bone tumors of unknown pathogenesis. It usually involves the extremities with a unilateral predominance, and sarcomatous transformation may occur. We report an autopsy-based genetic study of a 34-year-old man presenting in early adolescence with multiple enchondromas of the extremities, predominantly left-sided, compatible with Ollier's disease. Twelve years after presentation, malignant transformation to a high grade chondrosarcoma occurred in a tibial enchondroma. The patient died after widespread metastatic disease. Loss of heterozygosity (LOH), in the tibial chondrosarcoma and its metastases, was identified exclusively on chromosome bands 13q14 and 9p21, while being absent in the femoral enchondroma analyzed. Similarly, p53 overexpression was identified immunohistochemically in the tibial chondrosarcoma and its metastases, while being absent in the femoral enchondroma; LOH at 17p13 however, was not demonstrable. It is hypothesized that inactivation of putative tumor suppressor genes at 9p21 and 13q14, and overexpression of p53, identified in the chondrosarcoma and its metastases, but absent in enchondroma, may be related to sarcomatous transformation in Ollier's disease.
Rheumatologists may be incidentally confronted by bone and soft tissue lesions presenting in and around joints that require early recognition and appropriate referral. The diagnostic and therapeutic management of patients with musculoskeletal tumors is critically dependent on a multidisciplinary approach. Advances, particularly in the fields of histopathology, molecular (cyto)genetics and radiologic imaging techniques, have resulted in significant improvements in reaching a correct (differential) diagnosis, essential for implementing optimal treatment modalities. Magnetic resonance imaging is becoming increasingly important in planning preoperative and postoperative management strategies, and should precede all invasive procedures. Improvements in the fields of immunohistochemistry, together with the realization that certain tumor groups may be associated with specific genetic alterations, has significantly improved diagnostic accuracy. Additionally, the presence of certain genetic alterations within the tumoral genome have been found to be of prognostic value, and the hereditary context recognized for a number of specific bone and soft tissue tumors should be taken into account in the management of a patient with such a neoplasm. It is envisaged that an increasing understanding of the molecular biology and histogenesis of individual musculoskeletal tumor types will lead to tailor-made therapeutic options and consequently prognostic improvements. This update serves to highlight some important recent developments in fundamental and diagnostic aspects of musculoskeletal tumors.
PURPOSE: To differentiate between benign and malignant cartilaginous tumors with fast contrast material-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: In 37 patients, fast contrast-enhanced MR images were obtained in eight enchondromas, 11 osteochondromas, and 18 chondrosarcomas. Start of enhancement-early, within 10 seconds after arterial enhancement; delayed, between 10 seconds and 2 minutes; late, after 5 minutes on spin-echo images-and progression of enhancement were represented with three types of time-signal intensity curves. Findings were correlated with the surgical specimen in 27 cases, curettage material in three cases, and biopsy combined with long-term follow-up findings in seven cases. RESULTS: Start of enhancement and the combination of start and progression of enhancement correlated significantly (P <.001) with benign and malignant tumors. Early enhancement was seen in chondrosarcoma, not seen in enchondroma, and seen in osteochondroma only when growth plates were unfused. The sensitivity was 89%, specificity 84%, positive predictive value 84%, and negative predictive value 89%. Differentiation of malignancy from benignity on the basis of early and exponential enhancement was possible with a sensitivity of 61%, specificity 95%, positive predictive value 92%, and negative predictive value 72%. CONCLUSION: Preliminary results show that in the adult population fast contrast-enhanced MR imaging may assist in differentiation between benign and malignant cartilaginous tumors.
Diagnostic imaging is pivotal in the initial detection, characterization, staging and post-treatment follow-up of patients with high-grade osteogenic and Ewing's sarcoma. In the present review article, conventional and new imaging modalities are discussed with regard to the monitoring of the effect of neoadjuvant chemotherapy in such patients. Presurgical monitoring of response to chemotherapy may have an impact on modification of neoadjuvant treatment protocols, on patient selection for the performance and timing of limb-salvage surgery and on planning of radiation therapy (in non-operated Ewing's sarcomas) and selection of postoperative chemotherapy regimens. Dynamic contrast-enhanced MR imaging, as part of a routine MR protocol, assists in the detection of the most viable parts of the tumour and serves as an initial standard for follow-up of the metabolic activity of the tumour during and after chemotherapy, both in small intraosseous tumours and in tumours with an associated soft tissue mass. In combination with selected morphological features, dynamic imaging parameters are therefore advocated for monitoring the effect of neoadjuvant chemotherapy in patients with osteogenic and Ewing's sarcoma.
OBJECTIVE: To identify specific features of chondroblastic osteosarcoma on gadopentetate dimeglumine (Gd)-enhanced magnetic resonance (MR) imaging. DESIGN AND PATIENTS: Nine patients with chondroblastic osteosarcoma and a control group of 20 patients with conventional central osteosarcoma were included in this study. The histopathological findings of the surgical specimens were compared with enhancement patterns on static Gd-enhanced MR images. RESULTS: In chondroblastic osteosarcoma septonodular and peripheral rim enhancement represented tumour with a pure chondroid matrix. Non-enhancing and heterogeneous enhancing areas represented tumour with both chondroid and osteoid matrix. In the tumours in the control group enhancement was predominantly heterogeneous but in one it was homogeneous. All these areas corresponded to necrotic or viable osteoid tumour tissue or fibrovascular tissue in areas of necrosis. CONCLUSION: Gd-enhanced MR imaging can assist in obtaining diagnostic biopsy material of chondroblastic osteosarcoma by identifying both osteoid- and chondroid-forming areas.
Magnetic resonance imaging, because of its exquisite soft tissue contrast, has dramatically improved the ability to preoperatively stage primary osseous and soft tissue neoplasms. This technique also has allowed the monitoring of the effects of chemotherapy and the screening for recurrence of neoplasms. The role of magnetic resonance imaging in the preoperative evaluation of the patient with a suspected primary osseous or soft tissue neoplasm is outlined, instances where magnetic resonance imaging potentially may make a specific diagnosis are outlined, the importance of gadolinium enhancement as an adjunct to native magnetic resonance imaging is stressed, and an algorithm for followup of patients after chemotherapy or definitive surgical treatment is presented. In all cases, the magnetic resonance images should be correlated with the plain film, which is still an important aspect of the diagnosis of osseous lesions.
PURPOSE: To prospectively analyze the value of fast, dynamic, subtraction magnetic resonance (MR) imaging in the characterization of musculoskeletal tumors. MATERIALS AND METHODS: In 175 consecutive patients with a musculoskeletal mass, dynamic contrast-enhanced subtraction MR imaging was performed after administration of 0.1 mmol per kilogram of body weight gadopentetate dimeglumine or gadoteridol. A turbo gradient-echo technique was used, with a temporal resolution of 1-3 seconds. The interval between arterial and early tumor enhancement, the pattern (peripheral or diffuse) of enhancement, and the progression of tumor enhancement, as visualized on time-signal intensity curves, were assessed. MR enhancement features were related to the histopathologic diagnoses. RESULTS: Differentiation of benign from malignant soft-tissue masses was possible with a sensitivity of 91% and specificity of 72% based on start of enhancement, a sensitivity of 73% and specificity of 97% based on peripheral or diffuse enhancement, and a sensitivity of 86% and specificity of 81% based on progression of enhancement. Benign bone tumors could not be accurately differentiated from malignant bone tumors on the basis of the three defined parameters (sensitivity, 63%-76%; specificity, 50%-76%). CONCLUSION: Dynamic, contract-enhanced, subtraction MR images may be useful to differentiate malignant from benign soft-tissue masses.
MR imaging has had an unparalleled impact on the treatment of patients with musculoskeletal sarcoma. Basically, the high accuracy of local staging has made the introduction of reconstructive and limb salvage procedures instead of amputation of disarticulation available to the majority of patients with musculoskeletal sarcoma. Pre-operative work-up with MRI is not only more accurate, but also much faster and cheaper than the conventional work-up. Staging is the single most important reason for performing MR imaging in patients with musculoskeletal tumours. The impact of MR specificity is less dramatic but the benefit to the patient is an increased safety margin. When diagnostic errors with devastating consequences are made nowadays, it is usually because the proper protocol has not been followed. A patient with a potentially malignant, or equivocal, musculoskeletal mass deserves to have a combined radiographic-MRI examination prior to invasive procedures. MRI does not currently have a major impact on chemotherapy decisions and colour Doppler ultrasound has a higher accuracy than MRI. However, selected cases, i.e. intraosseous tumours, dynamic Gd-enhanced MRI, can replace colour Doppler ultrasound.
The magnetic resonance (MR) changes after one cycle of chemotherapy were compared with the prechemotherapy studies in 39 patients with osteosarcoma, in order to identify MR changes which can be used to assess early response to chemotherapy. Measurements of total tumour volume, signal intensity, and tumour enhancement of the intra- and extraosseous tumour component were performed. Change in the amount of oedema was subjectively assessed. Changes observed were correlated with histopathological response. Changes in tumour volume and of the signal intensity of the extraosseous tumour component on T2-weighting were the only two parameters which correlated significantly (P < 0.05) with histopathological response. Increase of tumour volume is the most significant parameter and indicates poor response (sensitivity 89%, specificity 73%). Only one good responder showed increase of tumour volume. Decreased or stable tumour volume was observed in both good and poor responders. Increase of signal intensity was found exclusively in five poor responders (sensitivity 100%, specificity 23%). Decreased or stable signal intensity was observed in both good and poor responders. Changes in the amount of oedema and contrast enhancement could not predict response at an early stage. We conclude that increase of tumour volume and increase of T2 signal intensity of extraosseous tumour can be predictive for poor response. MR criteria are not helpful in the early identification of good responders.
OBJECTIVE: The purpose of this study was to use color Doppler flow imaging to predict the response to preoperative chemotherapy in patients with Ewing's sarcoma or high-grade osteosarcomas early in treatment. SUBJECTS AND METHODS: Color Doppler flow imaging was done in 31 patients before, during, and after chemotherapy. In each phase of treatment, semiquantitative changes in intratumoral blood flow, changes in maximum intratumoral Doppler shifts, and changes in resistive indexes of arteries feeding limbs that contained tumors relative to contralateral normal arteries were compared with the histopathologic response, as evaluated on the resected specimens. RESULTS: Before chemotherapy, pathologic flow was found in the extraosseous component of all but two patients. Resistive indexes in arteries that fed tumors were significantly lower (p < .001) than the resistive indexes in the contralateral normal arteries. Histopathologic response could not be predicted on the basis of the initial measurements of Doppler shifts and resistive indexes taken before or after the first cycle of chemotherapy. Histopathologic response could be predicted after the second cycle of chemotherapy. After the second cycle of chemotherapy, the resistive index in the arteries that fed tumors increased in eight of nine good respondents but did not change or decreased in eight of nine poor respondents (p = .03). Lower intratumoral Doppler shifts were measured in six of 10 good respondents but also in five of 13 poor respondents (p = .07). After the full course of chemotherapy, persistent lower resistive indexes were measured in the arteries that fed tumors in all poor respondents but one. Intratumoral flow and Doppler shifts further decreased in all good respondents but one. Changes in Doppler shifts (p = .001) and resistive indexes (p < .001) were statistically significant between good and poor respondents, irrespective of the tumor type studied. CONCLUSION: Decreased or unaltered resistive index in the arteries that feed tumors in addition to persistent intratumoral flow and high-frequency Doppler shifts after two cycles of chemotherapy suggest poor histologic response to chemotherapy in osteosarcoma and Ewing's sarcoma. An increased resistive index after two cycles is indicative of good response.
OBJECTIVE: This study analyzed the value of dynamic contrast-enhanced and subtraction MR images in detecting residual viable tumor before surgery, with emphasis on timing of enhancement, in patients with high-grade osteosarcoma and Ewing's sarcoma after neoadjuvant chemotherapy. SUBJECTS AND METHODS: Twenty-one patients with proved osteosarcoma or Ewing's sarcoma were treated with neoadjuvant chemotherapy followed by surgery. After IV administration of gadopentetate dimeglumine, dynamic enhancement patterns on preoperative MR images were compared with corresponding areas on histologic sections of the resected specimens. On dynamic subtraction images obtained with high temporal resolution (1.5-3 sec), the interval between arrival of the bolus of contrast agent in an artery and start of tumoral enhancement was used to distinguish residual viable tumor. Early enhancing foci (interval artery-tumor < 6 sec) and late or nonenhancing areas seen on MR images were correlated with the histopathologic findings in these areas of the resected specimens. RESULTS: Early and progressively enhancing structures seen on MR images corresponded to feeding arteries, physeal vessels, or residual viable tumor at specific preferential sites on corresponding histologic sections of the resected specimens. Tumor foci as small as 3-5 mm2 could be detected on dynamic MR images. Remnant viable tumor was often located subperiosteally and at the margins of the tumor. Occasionally, active periosteal reaction without presence of viable tumor contributed to early enhancement. Late and gradually enhancing or nonenhancing areas corresponded histopathologically to regions of chemotherapy-induced necrosis, mucomyxoid degeneration, or fibrosis. Alternatively, late or nonenhancing areas were associated with reactive changes such as edema, hemorrhage, or osteomyelitis or with tumor-related extracellular matrices such as abundant osteoid or chondroid. Viable tumor areas with scarce formation of matrix on microscopy, such as small cell osteosarcoma areas or Ewing's sarcoma, showed early enhancement with rapid washout of contrast agent on the dynamic MR images. CONCLUSION: Fast dynamic contrast-enhanced sequences are essential for identifying residual tumor before surgery. A short time interval of less than 6 sec between arterial enhancement and tumoral enhancement strongly correlates with presence of viable tumor. Both therapy-related alterations of tissue and tumor-related matrices must be considered when late or lack of enhancement is noted on dynamic MR images.