[Bisphosphonates in the therapy of fibrous dysplasia. Relevant data and practical aspects]. / Bisphosphonate in der Therapie der fibrösen Dysplasie. Relevante Daten und praktische Aspekte.

Fibrous dysplasia covers a variety of rather different clinical pictures. Its therapy therefore has to be individually adapted. In addition to the orthopaedic surgeon, endocrinologists and craniofacial surgeons are also involved in the process. In the present contribution the role of modern bisphosphonates as a conservative treatment strategy is discussed with regard to the prevalent therapeutic possibilities. The literature as well as personal experience show them to be an especially valid option for the treatment of polyostotic fibrous dysplasia and the various syndromes.

Pathobiology of osteoarthritis: pathomechanisms and potential therapeutic targets.

Osteoarthritis, a degenerative joint disease, is the most disabling condition of the Western world. It affects first and foremost the articular cartilages and leads to a molecular and supramolecular destruction of the extracellular cartilage matrix. In addition, the cells, the chondrocytes, show severe alterations of their phenotype: they get anabolically and catabolically activated, change accordingly their gene expression pattern, lose their differentiated phenotype, and undergo focally cell death and cell degeneration. All these processes represent potential targets for therapeutic intervention and drug development. Apart from the cartilage itself, however, other joint tissues are also involved in the disease: thus, the synovial capsule and membrane as well as the subchondral bone account not only for most of the symptoms of the disease, but are also presumably involved in the progression of the degenerative process. Both, inflammation and stiffening within the joint capsule accelerate joint destruction. Stiffening of the subchondral bone increases the mechanical stress over the overlying cartilage during physiological movement. Altogether, there is a plethora of tissues, disease processes and targets for treating osteoarthritic joint degeneration, which will need to be followed up systematically in the future.

[Percutaneous radio-frequency ablation (PRFA) in painful metastases involving bone]. / Die perkutane Radiofrequenzablation (PRFA) bei symptomatischen sekundär-neoplastischen Knochenläsionen.

AIM: The aim of the study was to determine the efficacy of PRFA in the palliative treatment of symptomatic bone metastases in regard to pain reduction, safety, and quality of life. METHOD: Over a period of 11 months, ten PRFA were performed in eight patients with painful metastases involving bone, where conventional treatment with radiation therapy, chemotherapy, and treatment with analgesics had failed to reduce the pain efficiently. Pain was measured with the visual analogue scale (VAS: 0 to 10) for the day and night before PRFA was performed, and daily for 7 days after release from the hospital via a dietary book, and at the follow-up periods of 1, 3, 6 weeks and 3 and 6 months after PRFA. Additionally, quality of life was self-assessed by the patient via the health surveys IQOLA SF-36 and EORTC QLQ-C30, and via the Karnofsky Performance Scale (KPS) by the physician at each follow-up. The patients' analgesics use was also recorded at the follow-up intervals and complications were monitored. Analysis of the primary end point was undertaken with paired comparison procedures. RESULTS: Under conventional therapy, pain was specified by the patients as VAS min of 4.1 and VAS max of 9.3. Due to PRFA a reduction of the preinterventional pain (VAS) from 7.4 (+/- 1.9 SD) and 5.0 (+/- 2.7 SD) for day and night, subsequently, to 1.8 (+/- 1.6 SD, minus 75 percent) and 0.7 (+/- 0.7 SD, minus 86 percent) was achieved within one day after admission to the hospital. This significant reduction did not change during the whole follow-up period, and was also reflected in the ability to reduce analgesics and in the improvement of specific domains of SF-36 and QLQ-C30. However, no significant change was detected in the summary scales for mental and physical health. No serious complications were observed. CONCLUSION: PRFA of symptomatic bone metastases is a safe technology to reduce pain intractable to conventional therapy, even in terminally ill patients.

[Surgical therapy of pelvis and spine in primary malignant bone tumors]. / Operative Therapie am Becken und an der Wirbelsäule bei primär malignen Knochentumoren.

Despite standardization of surgical treatment of primary malignant tumors of the pelvis and spine, prognosis in these centrally located tumors still is inferior compared to those located in the extremities. This fact may be attributed to delayed diagnosis in many cases and the resulting increase in tumor volume as well as to difficulties of resection due to the anatomical situation. The frequency of local recurrence after resection of primary malignant tumors is reported to be between 4 and 41% and the 5-year survival rate below 40%. Whereas the latter has remained almost unchanged during the past 20 years, amputation has been replaced by limb-salvage surgery except for a minimal amount of less than 10%. For reconstruction, biological techniques are increasingly preferred to endoprosthetic replacement or use of bulk allografts because of the high complication rate. Even in the spine wide resections are feasible provided at least one lamina is healthy in order to prepare and save the neural structures without touching the tumor. Compared to the widely used technique of curettage, en bloc resection may provide a significantly better oncologic result with respect to local tumor control. Failure of the dorsoventral stabilization with delayed union is the most frequent complication of these challenging procedures. In order to improve the long-term prognosis of these groups of patients in the future, early diagnosis and immediate admission to a specialized tumor service has to be attempted.

[Histologic grading of chondrosarcoma. A qualitative and quantitative analysis of 74 cases of the Hamburg bone tumor register]. / Zur histologischen Gradeinteilung der Chondrosarkome. Eine qualitative und quantitative Analyse an 74 Fällen des Hamburger Knochentumorregisters.

Chondrosarcomas are frequent malignant bone tumors. Aside from different subtypes, such as dedifferentiated, mesenchymal and clear-cell chondrosarcoma, chondrosarcomas (classical chondrosarcoma) show different grades of differentiation. The borderline between chondroma and classical chondrosarcoma is not clearly defined. The same chondrosarcoma can be graded differently at different institutes. Standardized therapy concepts are currently in preparation. As the Hamburg Bone Tumor Registry is often consulted for chondrogenic tumors, the histological criteria are based on a series of 74 chondrosarcomas recorded there. The emphasis has been laid on a classification which can be used in daily routine and which is reproducible and in agreement with the classifications of other international groups. Grade I chondrosarcomas (50%) can be distinguished only by growth criteria. The nuclei are small and show high chromatin density. Grade II chondrosarcomas (42%) have medium-sized, regular nuclei with loose chromatin structure. The chondrocytes of grade III cases (8%) show polymorphic nuclei. Binucleas forms, the number of mitoses and cellularity all show considerable overlap for all three grades. So far there are no immunohistological and molecular biological methods for reliable differentiation. The therapeutic consequences of the classification into grades are thorough curettage, in the case of grade I tumors, or complete resection, for grade II and III cases. The long-term results, however, need to be confirmed by a larger number of cases. From 1991 to 1995 the method was applied and proved to be easily practicable in daily diagnostic routine. Some 104 cases of classical chondrosarcomas (grade I 53%, grade II 39%, grade III 8%) were analyzed. Two pathologists both assigned the same grade in 90% of cases.

[Solitary bone cysts. Morphologic variation, site, incidence and differential diagnosis]. / Solitäre Knochenzysten. Morphologische Variationsbreite, Lokalisation, Häufigkeit und Differentialdiagnose.

Analysis of 402 solitary bone cysts demonstrates the wide morphological variation of this cystic lesion with regard to histology and radiology. Aside from metaphyseal location in femur (33%) and humerus (23%), solitary bone cysts are also often located in calcaneus (11%), tibia (11%) and pelvis (10%). Most patients are in the second decade of life. Differentiation between this benign lesion and malignant bone tumors is very important in daily clinical routine. The diagnosis cannot be based solely on radiological findings because of the variation of solitary bone cysts and the special forms, such as calcifying solitary bone cyst. Therefore, exact histological diagnosis is of particular importance.

Extraskeletal osteosarcoma with a highly malignant course. A case report.

A case of a highly malignant extraskeletal osteosarcoma is reported. Although biopsy is not considered necessary in cases of heterotopic calcification when the aetiology is known, malignancy should be suspected when the cause is questionable.

[Pathomorphology of malignant chondrogenic bone tumors--an analysis of 94 cases from the Hamburg Bone Tumor Register (1974-1989)]. / Pathomorphologie der malignen chondrogenen Knochentumoren--eine Analyse von 94 Fällen des Hamburger Knochentumorregisters (1974-1989).

89 central and 5 periosteal chondrosarcomas identified between 1974-1989 were reviewed in a retrospective study. The purpose of this study was to examine the morphological characteristics of different types of chondrosarcomas and to describe remarkable features of location, age distribution and male to female ratio. We distinguish four types of centrally located chondrosarcoma: classical chondrosarcomas, dedifferentiated chondrosarcomas, mesenchymal chondrosarcomas and clear cell chondrosarcomas. Five periosteal chondrosarcomas were represented. Classical chondrosarcomas as well as clear cell chondrosarcomas indicate a significant predominance of males; no sex predilection in dedifferentiated and mesenchymal chondrosarcomas was seen. Nearly 60% of classical and mesenchymal chondrosarcomas occur in the trunk. 85% of dedifferentiated chondrosarcomas are located in the long bones of the limbs. The most common location of clear cell chondrosarcoma is the proximal part of the femur. There is a marked predilection for mesenchymal chondrosarcomas in the second and third decades of life. The mean age of patients with classical chondrosarcomas was 54 years, but clear cell chondrosarcomas occur 10 years earlier and dedifferentiated chondrosarcomas 10 years later. Characteristically, classical chondrosarcomas produce a pure chondroid matrix with variable differentiation of tumour chondrocytes. The most important histological feature of the dedifferentiated chondrosarcoma is the close association of two different cellular components. One of these consists of cartilage, which is generally well differentiated. In most of our cases the second component showed features of osteosarcoma (50%). Mesenchymal chondrosarcoma is characterized by concentric infiltration of cartilage islands by small tumour cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme and immunohistochemistry on undecalcified bone and bone marrow biopsies after embedding in plastic: a new embedding method for routine application.

A simplified method of low temperature methyl and butyl methacrylate embedding (up -20 degrees to -15 degrees C) is demonstrated using a proper redox system of benzoyl peroxide and aromatic amine. This method combines the morphological superiority of plastic-embedded bone tissue and bone marrow sections with the advantages of specific enzyme histochemical and immunochemical markers. The method permits good preservation of morphological details, the survival of antigenic determinants and the retention of enzyme activities. The specimens were fixed in 1.6% formaldehyde and 5% sucrose in 0.02 M phosphate buffer at pH 7.4, washed in 0.02 M phosphate buffer and 5% sucrose, dehydrated with acetone and impregnated with monomers of embedding medium. All these steps were carried out at +4 degrees C. The method presented is especially suitable for enzyme histological and immunohistological diagnosis of primary and secondary bone tumours, soft tissue tumours, as well as myelo- and lymphoproliferative disorders of bone marrow biopsies. Examples are demonstrated with mono- and polyclonal antibodies and reaction products of hydrolytic enzymes.

Morphological typing of chondrosarcoma: a study of 94 cases.

Ninety-four chondrosarcomas of the Hamburg Bone Tumour Registry were reviewed in a retrospective study. The purpose of this study was to examine the morphological characteristics of different types of chondrosarcomas and to describe distinctive features of location, the age distribution and the male to female ratio. Central chondrosarcomas can be divided into classical chondrosarcomas, dedifferentiated chondrosarcomas, mesenchymal chondrosarcomas and clear-cell chondrosarcomas. Five periosteal chondrosarcomas were represented. Classical chondrosarcomas and clear-cell chondrosarcomas show a significant predominance of males; no sex predilection was seen in dedifferentiated and mesenchymal chondrosarcomas. Nearly 60% of classical and mesenchymal chondrosarcomas occur in the trunk. Eighty-five percent of dedifferentiated chondrosarcomas are located in the long bones of the limbs. Clear-cell chondrosarcomas arise in the proximal part of the femur. There is a marked predilection for mesenchymal chondrosarcomas in the second and third decades of life. The average age of patients with classical chondrosarcomas was 54 years, but clear-cell chondrosarcomas occur 10 years earlier and dedifferentiated chondrosarcomas 10 years later. Characteristically, classical chondrosarcomas produce a pure chondroid matrix with variable differentiation of tumour chondrocytes. The most important histological feature of the defifferentiated chondrosarcoma is the close association of two different cellular components. One of these consists of cartilage, which is generally well differentiated. In most of our cases the second component showed features of osteosarcoma (50%). Mesenchymal chondrosarcoma is characterized by concentric infiltration of cartilage islands by small tumour cells. Clear-cell chondrosarcomas show regions of cartilaginous tumour and areas of closely packed, glycogen-rich, large tumour cells with distinct boundaries. Osteoid formation and multinucleated giant cells are present in clear-cell areas. Knowledge of this group of tumours is indispensable for correct histological diagnosis and typing and is important in the design of surgical therapy and the prediction of biological behaviour.

[Computer-assisted data analysis of injuries of the skeletal system in polytrauma patients]. / Computergestützte Datenanalyse von Verletzten des knöchernen Bewegungsapparates beim polytraumatisierten Patienten.

The data of 366 patients with multiple injuries were evaluated by application of data processing over a period of seven years. Age and sex distribution, location and combination of injuries, mortality, mechanism of accident, diagnostics as well as therapy were analysed. 91.3% of our patients had injuries of the skeleton. The male to female ratio was 2:1. In 55.4% the age of the patients ranged from 10 to 39 years. The mortality rate of all patients was 27.2%. In the third decade only 16.9% of the patients died. Whereas the mortality of the patients in the 1. decade as well as between the 7. and 9. decades of life was very high (33% and 50%). Most of the skeletal injuries were located in the shank (24% open fractures). The mortality rate increases with the number of injuries (Table III). Patients with concomitant injuries, such as head injuries and fractures of the extremities were the most common combination of multiple injuries. 20% of the patients in this group died. Patients with combined injuries of the head, chest, abdomen and skeleton had highest mortality (57%). X-ray examination of the skull, chest, extremities and mainly of the spine and pelvis should be subjects of routine diagnostics. In patients who were suspected of having a blunt abdominal trauma, the first diagnostic technique will be ultrasound. On account of the various number of concomitant injuries as well as the patients individuality, the estimation of prognosis by systems for the classification of the severity of injury is fraught with difficulties. The analysis of the evaluated data showed that previously small number of variables may predict the prognosis of the course of disease.

[Clear cell chondrosarcoma--clinico-pathological report of an additional case]. / Das Klarzellchondrosarkom--klinisch-pathologischer Bericht eines weiteren Falles.

On account of the rarity and its histologic features, the clear-cell chondrosarcoma is a particular entity. Up to the present, 98 cases have been reported in the literature. In the present report one case located in the proximal femur will be discussed. Approximately 60% of these tumors are situated in the mentioned region. Including one referred case, which will not be described in detail, 100 cases have been recognized. Clear-cell chondrosarcoma is radiographically indistinguishable from benign lesions or chondroblastoma. Therefore the histologic examination is crucial for the diagnosis. The histologic characteristics preclude the diagnosis of chondroblastoma. Clear-cell chondrosarcoma is characterized by regions of chondroid matrix and areas of closely packed, glycogen-rich large tumor cells with distinct boundaries. The centrally located nuclei are large with marked polymorphism, surrounded by abundant clear PAS positive cytoplasm. The chondroid matrix is lacking. Osteoid formation and multinucleated giant cells are present in clear-cell areas. In spite of the low malignancy there is still a metastatic potential. Therefore the type of surgical treatment is very important. En bloc excision with wide margins is the treatment of choice. The knowledge about this tumor is crucial for adequate surgical therapy.