Complications of bone tumors after multimodal therapy.

PURPOSE: To define and compare the complications of bone tumors after resection, extracorporeal irradiation and re-implantation, with or without radiotherapy. MATERIALS AND METHODS: Eighty patients (40 males and 40 females, ages 4-77 years) with 61 malignant and 19 benign bone tumors were evaluated for local and distant complications after treatment. Two groups of patients were studied: (1) 53 patients had resection without (43 patients) or with external beam radiotherapy (RadRx) (10 patients) and (2) 27 patients underwent extracorporeal irradiation and re-implantation without (22 patients) or with RadRx (5 patients). Patient follow-up varied from 1 month to 13.63 years with mean follow-up of 4.7 years. Imaging studies included bone and chest radiography, spin echo T1- and T2-weighted (or STIR) magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed tomography (CT) for thoracic and abdominopelvic metastases and 3-phase technetium-99m-labeled-methylene-diphosphonate (Tc99m MDP) scintigraphy for bone metastases. RESULTS: DCE-MRI differentiated the rapidly enhancing recurrences, residual tumors and metastases from the slowly enhancing inflammation, and the non-enhancing seromas and fibrosis. Recurrences, metastases (mainly to lung and bone), and seromas were greater than twice as frequent in patients after resection than after ECCRI. Although 11.3% of post-resection patients had residual tumor, no ECRRI-treated patient had residual tumor. In contrast, after ECRRI, infection was almost three times as frequent and aseptic loosening twice as frequent as compared with the post-resection patients. Bones treated with RadRx and/or ECRRI showed increased prevalence of fractures and osteoporosis. In addition, muscle inflammation was more common in the externally irradiated patient as compared with the patient who did not receive this therapy. However, another soft tissue complication, heterotopic ossification, was rare in the patient after RadRx, but 25.6% of patients after resection and 40.9% after ECRRI showed heterotopic ossification. Unusual complications after resection or ECRRI involved adjacent nerves with partial denervation, amputation neuroma, or entrapment (secondary to recurrence or fibrosis) after resection or ECRRI with or without RadRx. One patient developed a posterior tibial artery pseudoaneurysm after ECRRI. CONCLUSIONS: Follow-up of patients with benign and malignant bone tumors demonstrated the efficacy of DCE-MRI for distinguishing rapidly enhancing viable tumor from the slowly enhancing or non-enhancing benign processes after different therapies. Although recurrences, residual tumors, metastases and seromas were more common after resection, fractures, osteoporosis, infection, and muscular atrophy predominated in the ECRRI-treated patient. RadRx further predisposed post-resection and post-ECRRI patients to develop fractures, osteoporosis and infection and was the major cause of persistent muscle inflammation at MRI. Because complications can evolve and resolve years after treatment, the patients with bone tumors, particularly sarcomas, must receive life-time multimodal imaging for maximal diagnosis and treatment.

Post-treatment complications of soft tissue tumours.

PURPOSE: To identify local and distant complications of patients with soft tissue tumours and evaluate their relationships to types of therapy. METHODS AND MATERIALS: Fifty-one patients (29 males and 22 females, ages 14-80 years) with 34 malignant and 17 benign soft tissue tumours were evaluated for local and distant complications after resection or amputation only (26 patients) or after the addition of radiotherapy (25 patients: 17 patients had external beam therapy, 7 patients had external beam therapy and brachytherapy, and one patient had extracorporeal irradiation and reimplantation). Duration of follow-up averaged 3.75 years for malignant tumours and 2.79 years for benign tumours. Follow-up studies included radiography, T1- and T2-weighted magnetic resonance (MR) imaging, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed tomography for thoracic and abdominal metastases, and 3-phase technetium-99m-labeled-methylene-diphosphonate scintigraphy for bone metastases. RESULTS: Recurrent tumours were 2.2 times more frequent in patients who had undergone their initial resection at an outside hospital as compared with those first treated at the university hospital. Nine of 11 recurrences occurred after marginal surgery. Metastases from soft tissue sarcomas, most commonly to lung (nine patients) and to bone and muscle (five patients), showed no specific relationship to type of therapy. DCE-MRI differentiated rapidly enhancing soft tissue recurrences (11 patients) and residual tumours (6 patients) from slowly enhancing muscle inflammation, and non-enhancing fibrosis and seromas that usually did not enhance. Seromas developed in 76% of patients who had postoperative radiation therapy and in 7.7% of patients who had only surgery. Subcutaneous and cutaneous oedema and muscle inflammation was at least four times more frequent after adjunct radiotherapy than after resection alone. Irrespective of the type of treatment, inflammatory changes in muscle and subcutaneous and cutaneous tissue and the majority of seromas were evident at the first follow-up study. Although seromas after resection and external beam therapy resolved with time, seromas after additional brachytherapy persisted. Inflammatory changes in muscle and cutaneous and subcutaneous tissue after resection alone disappeared by the second follow-up study, whereas these changes after radiotherapy resolved months to years after treatment. Fourteen of 51 patients showed MR findings of chronic muscular atrophy, predominantly located in the lower extremity. Heterotopic ossification was seen in three patients after resection and amputation without radiotherapy. Except for one patient with aggressive fibromatosis, bone and nerve complications occurred in patients with soft tissue malignancy. Twelve patients had osteoporosis. Six patients sustained fractures in irradiated osteoporotic bone of the lower extremity, and one patient had a vertebral fracture in radiographically normal but irradiated bone. In addition, one patient was found to have a medullary infarct in an irradiated femur. In nerve entrapment, DCE-MRI demonstrated the rapidly enhancing recurrent tumour or non-enhancing fibrosis surrounding the slowly enhancing nerve. T1- and T2-weighted MR images displayed the acute and chronic sequelae of nerve entrapment and nerve transection with denervation as T2-hyperintense acute muscle atrophy or T1-hypertense chronic fatty muscular atrophy with decrease in muscle volume. CONCLUSION: This study suggests a possible relationship between types of treatment of soft tissue tumours and subsequent complications. Postoperative radiotherapy was associated with a significant number of patients with seromas, muscle, cutaneous and subcutaneous inflammation, and fractures. Incomplete or difficult surgery resulted in residual or recurrent tumours and heterotopic ossification. Muscle atrophy and nerve entrapment were related to both treatments (resection alone or radiotherapy after resection). Diligent follow-up of patients with soft tissue tumours with recognition of these complications and their differentiation from recurrent or residual tumour can help guide clinical care and may negate the need for surgery when benign disease is defined.

Telomere biology in giant cell tumour of bone.

Giant cell tumour of bone (GCTB) is a benign bone tumour known for the unpredictable clinical behaviour of recurrences and, in rare instances, distant metastases. It consists of uniformly distributed osteoclastic giant cells in a background of mononuclear rounded and spindle-shaped cells. Cytogenetically, telomeric associations are the most common chromosomal aberrations, which, however, are normally almost exclusively found in high-grade malignancies. GCTB has often been regarded as a polyclonal tumour, but more recently a recurrent specific aberration was reported, which suggests a possible role for disturbed telomere maintenance. Here we further investigate telomere maintenance in GCTB using 19 samples from 19 patients. A combination of immunofluorescence and FISH was performed, applying antibodies directed against promyelocytic leukaemia body-related antigen and hTERT and using telomere peptide nucleic acid probes. The TRAP assay and telomere restriction fragment length analysis were performed for functional detection of telomerase activity and alternative telomere lengthening. Both osteoclastic giant cells and mononuclear cells showed positivity for hTERT and promyelocytic leukaemia body-related antigen. In most mononuclear cells, co-expression was present. The TRAP assay demonstrated heterogeneous telomerase activity, while telomere restriction fragment length analysis showed non-heterogeneous telomere lengths, indicating the absence of alternative telomere lengthening. Confocal microscopy showed stereometric co-localization of nucleolin with promyelocytic leukaemia body-related antigen in association with telomeres in the spindle-shaped cells. hTERT was more diffusely distributed throughout the nucleus. Our results show that GCTB demonstrates remarkable telomere maintenance of activated telomerase and inactivated alternative telomere lengthening in the presence of normal mean telomere restriction fragment lengths. These findings strongly suggest that these aggregates, while activating telomerase, are part of a structural telomere protective-capping mechanism rather than of a telomere-lengthening mechanism. Telomere maintenance could be considered an important key factor in the pathogenesis of GCTB.

Osteosarcoma with extensive calcified pleural metastases at diagnosis.

We report the case of an 18 year old woman presenting with shortness of breath and pain in the left shoulder. Imaging of the lungs revealed pleural effusion and calcification of the left pleura. An osteosarcoma of the left humerus was the final diagnosis. A review of the literature reveals that calcified pleural metastatic disease in cases of osteosarcoma has been infrequently reported. Other causes of pleural calcification are briefly discussed.

[Results of an inverted shoulder prosthesis after resection for tumor of the proximal humerus]. / Résultats d'une prothèse d'épaule inversée après résection pour tumeur de l'humérus proximal.

PURPOSE OF THE STUDY: Treatment of primary bone tumors of the proximal humerus is a major challenge, both in terms of oncological cure and limitation of functional handicap. Extracorporal radiation and reimplantation have provided satisfactory results for the treatment of bone tumors and the inverted shoulder prosthesis has be found to be effective in treating rotator cuff deficiency. We therefore assessed patients treated with a combination of these two treatments in order to search for a better functional outcome. MATERIAL AND METHODS: Conservative resection of the tumor with reconstruction using an inverted shoulder prosthesis was performed in six patients with a tumor of the proximal humerus of type Ia or Ib in the Malawer classification or type S3-S4-S5 in the Musculoskeletal Tumor Society classification. Patients whose tumor involved the deltoid or the glenohumeral joint were not considered for this procedure. The series included four men and two women (4 left and 2 right shoulders) aged 51 years on the average at the time of surgery. RESULTS: Mean follow-up was 12 months. The mean age- and sex-adjusted Constant score was 74% (70-85%). The patients were generally satisfied and were able to continue their daily activities. There were two displacements, one of which was diagnosed immediately and reduced without anesthesia. An abduction pad was worn for six months after reduction. The post-operative period was uneventful. No local recurrence has been observed. DISCUSSION: Our results compared favorably with other therapeutic options for resection-reconstruction reported in the literature: functional outcome was better and more predictable, at least in the short term; oncological results were satisfactory although the follow-up is short, particularly for the three primary malignant tumors. It is known however that the long-term oncology result depends on the quality of the resection and the efficacy of the extracorporeal radiation. Shoulder motion outcome was the least satisfactory in patients who experienced peri-operative complications. We were unable to find any relation between less satisfactory functional outcome and the number of surgical procedures for local recurrence before extracorporeal radiation and arthroplasty (deltoid dystrophy). Normal deltoid function appeared to be crucial for optimal functional outcome with this prosthesis which allows sacrifice of the rotators. The rate of complications was low and recovery of active shoulder movement was more rapid. Despite the short-term nature of these results, and despite the risk of loosening, the inverted shoulder prosthesis appears to be an interesting therapeutic option for these patients.

Parosteal osteosarcoma of the humerus.

The authors report the case of a 50-year-old man who presented with nontraumatic swelling of the left upper arm. The diagnosis of parosteal osteosarcoma of the humerus was made after diagnostic workup. A long diaphyseal segment of the humerus containing the tumor was resected with a healthy margin of soft tissues and was irradiated extracorporeally with a single dose of 30 Gray. The bony segment was then reimplanted after removal of the tumor using plate and screw fixation. Loosening of the proximal screws after one year required additional fixation and autologous cancellous bone grafting. The patient has a nearly three-year-follow-up and there are no signs of tumor recurrence or metastasis. The proximal osteotomy has healed nicely; the distal fixation osteotomy exhibits delayed healing. The pathogenesis of parosteal osteosarcoma is discussed.

Neurofibromatosis, gigantism, elephantiasis neuromatosa and recurrent massive subperiosteal hematoma: a new case report and review of 7 case reports from the literature.

The authors report the case of a 13-year-old patient with neurofibromatosis (NF-I), who suffered blunt trauma to the left tibia in 1993. The diagnosis of subperiosteal hematoma was made. Treatment consisted of temporary rest. There was a recurrence in 1996, and the subperiosteal hematoma was drained. In 1997, a shortening osteotomy of the left tibia was performed. However, massive gigantism with elephantiasis of the left leg remained, causing a serious functional and cosmetic problem. In 1999, the leg was amputated above the knee. The literature is reviewed and 7 case reports are compared. The pathogenesis of subperiosteal hematoma is discussed.

Recurrent massive subperiosteal hematoma in a patient with neurofibromatosis.

The authors report the case of a 13-year-old neurofibromatosis (NF-I) patient who suffered a blunt trauma in 1993. The diagnosis of subperiosteal hematoma was made. The pathogenesis of subperiosteal hematoma is discussed.

Technetium-99m-MDP scintigraphy and long-term follow-up of treated primary malignant bone tumors.

UNLABELLED: Local malignant bone tumor excision followed by high-dose extracorporeal irradiation (300 Gy) and subsequent reimplantation is a unique technique for treatment of primary bone and cartilage tumors. The long-term scintigraphic findings of irradiated bone autografts in relation to clinical patient data were reviewed retrospectively. METHODS: Thirty-seven patients (12 women, 25 men; age range 13.0-66.7 yr; average age 29.1 yr) were studied. Postsurgical anatomopathological diagnoses included osteosarcoma, 20 patients; chondrosarcoma, 7 patients; and other less-frequent primary osteogenic tumors, 10 patients. Three hundred ninety 99mTc-methylene diphosphonate (MDP) whole-body scans performed between 3 mo and 18.3 yr (mean 6.5 yr) after treatment were reviewed. RESULTS: The 10-yr actuarial survival rate was 78%. After a mean period of 19.4 mo, 6 patients developed a local recurrence, and MDP scintigraphy detected the recurrence in 4. Distant metastases developed in 11 patients (30%), of which 10 were nonosseous. Initially, all autografts appeared as photon-deficient areas. Diffusely increased bone uptake was present at osteotomy sites and at articulating surfaces contiguous with autografts within the first few months after surgery. Of all 25 patients with adequate follow-up, 7 showed persistent decreased uptake up to 129 mo after surgery. The other patients developed partial tracer uptake after 19.6 mo, on average. In 6 patients, scintigraphic images consistent with complete revascularisation were noted later (mean 31.5 mo). Local, sometimes multiple, complications were noted in 22 patients, mainly mechanical graft-related (15) or infections (11). Scintigraphic sensitivity for mechanical complications was 100%. Significantly more fractures and collapses were seen when partial tracer uptake suggestive of revascularisation occurred. Altered bone stress gave rise to focal and diffuse scintigraphic abnormalities, often in the spine and lower extremities. In recent literature, similar clinical complication patterns are found for massive allografts. CONCLUSION: Skeletal scintigraphy is a sensitive technique for evaluating long-term follow-up of massive grafts to treat primary malignant bone tumors. Revascularisation and partial bone ingrowth are not sufficient conditions for a lower complication rate.

Examination of the back using the Bunnell scoliometer in a Belgian school population around puberty.

The present study was designed to determine whether quantified clinical measurement of the back would provide arguments supporting a biomechanical cause of adolescent idiopathic scoliosis (AIS). Two hundred ninety-two healthy girls (9 to 16 years) and 191 healthy boys (11 to 18 years) were examined clinically with the use of the Bunnell scoliometer. The inter- and intraobserver measurement error was determined. The accuracy of the Bunnell scoliometer as a biomorphological measurement method is good (variation coefficient +/- 10%). The measurement error is not influenced by the site of the rib hump or the type of scoliosis, but by the magnitude of the deformity to be measured. The present study confirms that the threshold for differentiating a physiological from a pathological gibbosity is 5 degrees C, as advanced by Bunnell (1984). The Bunnell measurement shows no statistically significant differences between boys and girls, although the standard deviation of the measurement in the declive segment is larger in girls. In all spinal segments measured, the scoliometer values show the same evolution in the boys and girls of the various age groups. Although the larger standard deviation in the declive segment in girls favors the existence of a physiological scoliosis, the present study shows no evolution in the various spinal segments for the age groups studied, and therefore does not substantiate the biomechanical etiopathogenic theories for the development of AIS.

Intramedullary fixation of forearm fractures in adults.

The authors present a retrospective study of acute fractures of the diaphysis of the radius or ulna, or both, in adults treated by intramedullary nailing. Seventy diaphyseal fractures in 38 patients (30 men and 8 women) were treated by intramedullary fixation. The mean age of the patients was 31.5 years. Union occurred in 66 fractures (94%). The average union-time was 73 days. Compared with the results published by other authors, using the same evaluation criteria, union-time with the intramedullary technique was shorter than with other techniques. Union-rates and functional results were similar to those in comparable studies. Closed nailing does have many advantages, including early union, low incidence of infection, small scars, less blood loss, and short operating time with minimal surgical trauma.

Thallium-201 accumulation in myositis ossificans and in juxta-articular ossification.

We present the findings on 201Tl and 99mTc-MDP scintigraphy in three patients suffering from heterotopic ossification (two patients presenting with myositis ossificans and one patient presenting with juxta-articular ossification in combination with myositis ossificans). Since resection of the lesions has to be delayed until stabilization, 99mTc-MDP is often used as a parameter of lesional activity, although it is not optimal. For this clinical problem, we evaluated 201Tl scintigraphy as a marker of metabolic activity. In addition to the well-documented uptake of 99mTc-MDP, marked accumulation of 201Tl was observed in all heterotopic ossification sites. Hence, our results support the use of 201Tl scintigraphy in the therapeutic management and monitoring of conditions associated with ectopic ossification. On the other hand, although myositis ossificans is sometimes clinically, radiographically and even histologically confused with extraosseous osteogenic sarcoma, 201Tl accumulation may not be a helpful factor in the differential diagnosis due to the presence of tracer accumulation in both disorders.

Static, dynamic and first-pass MR imaging of musculoskeletal lesions using gadodiamide injection.

Forty-five patients with known or suspected musculoskeletal tumors were examined with static and dynamic MR imaging to evaluate the safety, tolerability and diagnostic utility of gadodiamide injection and to assess the diagnostic value of dynamic MR imaging and parametric "first-pass" (FP) images. The proportion of patients presenting more diagnostic information on the contrast-enhanced compared to the precontrast spin-echo examinations was determined. The dynamic enhancement characteristics were evaluated with time-intensity curves and parametric images of the FP enhancement rate. The tolerance of gadodiamide injection was good. Contrast enhancement was useful for delineating tumor from muscle, and differentiating viable from necrotic tissue and cystic from solid lesions. Malignant tumors showed a significantly higher slope value, earlier onset of enhancement, and higher maximum enhancement than benign lesions. However, slope values could not be used to predict the malignant potential of a lesion, due to overlap between highly vascular benign and low vascular malignant lesions. By displaying highly vascular areas, parametric FP images provided useful information on the most active part in a tumor before biopsy and for assessing the incorporation of bone-chip allografts. Static, dynamic and FP MR imaging using gadodiamide injection appears safe and provides useful information for diagnosis, biopsy and follow-up of musculoskeletal lesions.

Benign and malignant musculoskeletal lesions: dynamic contrast-enhanced MR imaging--parametric "first-pass" images depict tissue vascularization and perfusion.

PURPOSE: To assess the diagnostic value of parametric magnetic resonance images that display the first pass (FP) of gadopentetate dimeglumine. MATERIALS AND METHODS: Dynamic, contrast material-enhanced, fast low-angle shot MR imaging was performed of 100 musculoskeletal lesions in 36 female and 64 male patients (aged 9-81 years [mean, 34 years]). The highest slope value of the time-intensity curve was calculated pixel by pixel and displayed on the FP image, with a gray-scale value equal to the slope value. Tissue vascularization and perfusion were evaluated at pathologic and angiographic examinations in 33 lesions. RESULTS: A significant difference (P < .001) was found between the FP slope values of benign (mean, 36.2% per second) and malignant (mean, 67.4% per second) lesions. FP images depicted tissue vascularization and perfusion rather than benignity or malignancy, because there is an overlap in the slope values of highly vascular benign lesions and malignant lesions. CONCLUSION: FP images provide diagnostically useful information by depicting tissue vascularization and perfusion.

Treatment of unstable fractures, dislocations and fracture-dislocations of the cervical spine with Senegas plate fixation.

The results of the anterior approach to the cervical spine for the treatment of fractures and dislocations by arthrodesis and Senegas plate fixation are described. Twenty-two patients underwent a one- or two-level arthrodesis of the cervical spine. Their mean age was 42 years. The injuries were subdivided using the radiological classification described by Harris. In the group of patients who presented with a complete neurological deficit below the level of injury, there was only one patient who deteriorated. X ray examination 1 year after surgery showed fusion in 17 patients (100%). In contrast to some recent cadaveric and animal studies in which the anterior approach and fixation were found to be less stable than posterior fusion, our results obtained with this method are excellent, despite the fact that post-operative immobilization was limited. Problems with the anterior approach did not arise in these 22 patients. Alignment was always acceptable and fusion was achieved within one year in all cases.

First-pass images of musculoskeletal lesions: a new and useful diagnostic application of dynamic contrast-enhanced MRI.

The purpose of this study was to evaluate the diagnostic value of parametric images which display the first-pass of Gd-DTPA after intravenous bolus injection. Single slice dynamic contrast-enhanced MRI (Turbo-FLASH) with a temporal resolution of 2.41 s was performed in 40 benign and malignant musculoskeletal lesions. Parametric 'first-pass' images were obtained by using a new postprocessing technique, derived from a home written computer program, which calculated the steepest slope of the time-intensity curve pixel by pixel. First-pass images provided qualitative and quantitative information, which was useful for diagnosis and therapy. Demonstration of the areas with the highest vascularization was very helpful in planning the best biopsy site in 6 patients and to delineate tumor from peritumoral muscle edema in 4 patients. In 10 patients the first-pass images provided additional information, which was not visible on the conventional spin-echo images. The most promising application was the ability to evaluate the response to preoperative chemotherapy in a patient with Ewing's sarcoma. Although a highly statistically significant difference (p < 0.001) was found between the first-pass slope values of benign and malignant lesions, the sensitivity (77%) and specificity (71%) of this method were too low to permit a definite differentiation of highly vascular benign from malignant lesions. Pathologic examination of 17 lesions, performed in the plane of the first-pass image, showed a good correlation between the first-pass slope values and the vascularization of the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Ossification of the transverse atlantoid ligament in rheumatoid arthritis.

Ossification of the transverse atlantoid ligament (TAL) is rare. A few cases have been reported by Wackenheim and Dietemann and others. Calcification of the TAL has also been seen in calcium pyrophosphate dihydrate deposition disease. It is important to differentiate this condition from traumatic lesions of the dens axis.

Molecular cytogenetic analysis of a complex t(10;22;11) translocation in Ewing's sarcoma.

Fluorescence in situ hybridization (FISH) using chromosome-specific plasmid libraries and chromosome region-specific DNA markers allowed the characterization of a t(10;22;11) (p11.2;q12;q24) in a Ewing's sarcoma (ES). This study illustrates the usefulness of molecular cytogenetic analysis of ES, especially for determining the localization of the translocated 11q24-25 segment in complex or variant translocations.

Kashin-Beck's disease.

A case of Kashin-Beck's disease is presented. It is an acquired, disabling, polyarthritic, degenerative condition of early onset, sometimes leading to a variable degree of dwarfism. It occurs endemically in certain Asian areas. Treatment is, if possible, preventive. In the established disease the therapy is that of any other form of secondary osteoarthritis. Reconstructive surgery and removal of loose bodies may be needed in severe cases (11). Early detection, facilitated by careful family history taking, is a prime requisite, especially in non-endemic areas (7).