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Biomedical subjects

R Kotz

Publications and source records attributed to R Kotz.

At least 37 records · Page 2Linked to original sources

Proteins expressed in osteosarcoma and serum levels as prognostic factors.

Osteosarcoma is the most frequent highly malignant bone-tumor with a peak manifestation during the second and third decade of life. Although survival rate increased up to 60-70% within the last 20 years, the problem of non-response to chemotherapy remains. Initial tumor size and response to neoadjuvant chemotherapy are the most accepted prognostic factors used for postoperative stratification of chemotherapy. The identification of patients with a bad response to therapy at the time of diagnosis would facilitate already a preoperative stratification of chemotherapy or a more aggressive regime to increase survival. This review reflects on recently described molecular markers but not on clinical parameters in human osteosarcoma with respect to their prognostic potential. This includes p53, the p-glycoprotein, the multidrug resistance gene, the humen epidermal growth factor receptor and metallothionein expression. Heat shock proteins have recently become important in osteosarcoma because of their prognostic value and their role in drug resistance. A short overview of serological markers is also given. Further results on drug resistance and survival may be provided by ongoing studies, which investigate the role of proteins of the apoptotic and antiapoptotic families in human osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Expression of insulin-like growth factor-I (IGF-I) in aneurysmal bone cyst.

The effects of insulin-like growth factor-I on bone tissue and its role in bone development have been extensively investigated, but there is little information on its role in the pathogenesis of aneurysmal bone cyst. Therefore, using the techniques of immunohistochemistry and in situ hybridization, the authors studied the expression of insulin-like growth factor-I in 19 specimens of aneurysmal bone cyst. Insulin-like growth factor-I or specific mRNA sequences encoding for insulin-like growth factor-I were detectable in all specimens tested and were mainly localized in multinucleate giant cells. In contrast, only insignificant levels of insulin-like growth factor-I expression were detectable in normal human bone tissue. Taken together with the previously reported role of insulin-like growth factor-I in the pathogenesis of giant cell tumor, the findings of this study suggest that insulin-like growth factor-I may play a role in the pathogenesis of aneurysmal bone cyst.

Adolescent↗

Recurrence of curetted and bone-grafted giant-cell tumours with and without adjuvant phenol therapy.

AIMS: Giant-cell tumour of bone (GCT) represents 5% of all primary bone tumours. The aim of this study was to compare the outcome of GCT treated with or without phenol. METHODS: Out of 53 patients primarily treated for a giant-cell tumour, 47 were followed, with a median follow-up of 11 (range 4-43) years. All patients were disease-free at the latest follow-up. Of the 40 tumours (85%) located in long bones, 14 (35%) were treated by curettage and bone grafting and 12 (30%) by additional adjuvant phenol treatment. Fourteen patients (35%) received different therapies, including en-bloc resection, endoprosthesis, cement packing or other therapy. RESULTS: There were seven (17.5%) recurrences in long bones after a median of 12 (range 4-60) months, three (3/14, 21%) in the group treated without phenol and three (3/12, 25%) in the group with phenol. Of the seven tumours located in the axial skeleton, two patients died within the first year after surgery. The remaining five patients were followed, with a median follow-up of 12 (range 8-23) years. No patients had metastases or a multicentric tumour. CONCLUSIONS: Despite the different rates of recurrence reported in literature, this study suggests that local recurrence rate of giant-cell tumours located in long bones treated with or without phenol is similar. Adequate removal of the tumour seems to be a more important predictive factor for the outcome of surgery than the use of phenol as an adjuvant therapy.

Adolescent↗

A long-term review of the treatment of patients with Ewing's sarcoma in one institution.

AIMS: The treatment of patients suffering from Ewing's sarcoma has changed over the last three decades. We report the analyses, significant prognostic factors, interdisciplinary approach and development of therapy in one institution in Austria. METHODS: One hundred and forty-two patients treated for Ewing's sarcoma between 1949 and 1994 were reviewed. Median follow-up was 8.5 years. Fifty-six patients were treated between 1949 and 1980 (group 1), and 86 patients between 1981 and 1994 (group 2). Patients in group 1 were treated with polychemotherapy. Patients in group 2 were treated with a neoadjuvant CESS (Cooperative Ewing's Sarcoma Study) regimen. In group 1, 24 patients underwent biopsy only, 32 patients had a definitive operation, 48 patients received either radiation therapy only or additional radiation therapy compared with in group 2: 6, 80 and 44 cases, respectively. RESULTS: Five-year overall survival (OS) increased from 27% to 57%. Significant prognostic factors for OS were pre-operative metastases (P=0.0001), tumour location (P=0.0048), type of chemotherapy (P=0.002) and response to chemotherapy (P=0.0004). Chemotherapy (P=0.037), tumour location (P=0.0017) and metastases at diagnosis (P=0.0025) were significant. CONCLUSION: The most effective treatment of Ewing's sarcoma is chemotherapy.

Adolescent↗

Long-term followup of uncemented tumor endoprostheses for the lower extremity.

Between 1982 and 1989, 100 primary lower limb reconstructions were done using the Kotz Modular Femur Tibia Reconstruction System after resection of a malignant tumor. In 32 patients a proximal femur prosthesis was implanted, in 40 patients a distal femur prosthesis was implanted, in 19 patients a proximal tibia component was implanted, in four patients a total femur prosthesis was implanted, and in five patients a total knee prosthesis was implanted. The Kaplan-Meier estimate of the overall survival rate of the prostheses was 85% after 3 years, 79% after 5 years, and 71% after 10 years. The most common reason for implant failure was aseptic loosening in 27% of patients (11 patients; range, 10-121 months) after the initial operation. The other reasons for revision surgery were implant fracture (n 5 4) and infection (n 5 4). Early repair of prostheses-related minor complications, such as worn polyethylene bushings, resulted in a statistically significant reduction of implant failure. After a median followup of 127.5 months after the initial surgery, 51 patients had died and eight patients were lost to followup. Forty-one patients were evaluated clinically and radiologically using the Musculoskeletal Tumor Society score and the radiologic implant evaluation system of the International Symposium on Limb Salvage; these 41 patients had a mean of 80% (range, 40%-100%) of the normal functional capability.

Adult↗

Growth prediction in extendable tumor prostheses in children.

Limb salvage procedures for malignant bone tumors of the lower limb in children usualy involve resection of at least one growing physis. To achieve equal leg length, reconstruction relies on accurate prediction of the remaining growth potential of the child. The current authors present the results of predicted growth versus actual prosthetic elongation observed in a group of 15 children fitted with extendable tumor endoprostheses of the lower limb who subsequently have reached skeletal maturity. All patients had at least one of the distal femoral or proximal tibial physes resected for a primary malignant bone tumor. Eight patients underwent distal femoral resection, four patients underwent proximal tibial resection, and three patients had total resection of the femur. All patients received custom-made Howmedica extendable prostheses. In two patients, a newly developed automatic elongation module was used. At followup, between 70 and 158 months, the patients achieved a mean elongation of the surgically treated limb of 10.4 cm (range, 1.1-19.5 cm), which exceeded the predicted growth by 24.3%. Final leg length discrepancies did not exceed 1 cm. Using incremental extendable tumor endoprostheses, individual adaptation of the elongation procedures could be achieved for equalization of leg length discrepancies in children after resection of primary malignant bone tumors of the lower limb.

Adolescent↗

The role of surgery and resection margins in the treatment of Ewing's sarcoma.

Because of the enormous progress in surgery in the treatment of patients with tumors, the current study analyzed the influence of wide surgical resection margins on the outcome of patients with Ewing's sarcoma. Between 1980 and 1994, 86 patients were treated with systemic therapy and surgery (biopsy in six patients, tumor resection in 80 patients). Forty-four patients also had radiation therapy. The 5-year overall survival was 56.8% (5-year disease-free survival, 59.4%). The 5-year overall survival after radical or wide resection was 60.2% (5-year disease-free survival, 58.2%), in comparison with 40.1% (46.7%) after marginal or intralesional resection. Two patients with inadequate resection margins had local recurrences. In addition to the influence of neoadjuvant chemotherapy for higher survival rates (5-year overall survival with a good response was 80.2% versus 41.7% with a poor response), adequate surgical margins significantly affect the outcome for patients with Ewing's sarcoma.

Adolescent↗

[Analysis of the migration of cementless all-metal hip endoprosthesis].

Since September 1997, 58 patients have received a newly developed all-metal hip prosthesis at the department of orthopaedic surgery, University Hospital Vienna. In a retrospective study, the migration profile of 26 acetabular components of these prostheses with all-metal cups was evaluated. A total of 25 patients (10 men, 15 women, mean age 61 years) who had been operated on earlier than 11 months previously were studied. Indications included coxarthrosis (15), congenital dysplasia of the hip (7), post-traumatic coxarthrosis (3), and change of the implant due to infection (1). Twenty-three patients (7 men, 16 women; mean age 63 years) with 25 metal-backed polyethylene implants and matched demographic data, indications and cup size, served as the group for comparison. The mean duration of follow-up for both groups was 14 months. For analysis of migration a modified version of Dickob's method for digital measurement of comparative hip radiographs was used. Measurements were performed three times by one examiner. Migration values of more than 2.0 mm were regarded as a sign of possible cup loosening. After 13 to 20 months the average migration was -0.10 mm in horizontal and 0.18 mm in vertical direction for all-metal prostheses, and -0.20 mm horizontally and 0.47 mm vertically for the other group. Mean migration values exceeded the critical limit of 2.0 mm in two patients in the all-metal group, one of whom also had clinical signs of cup loosening. The covariance analysis of the highest migration levels of each patient revealed no significant differences between the groups; the postoperative Harris hip score was 98 points (range, 93-100) in the all-metal group and 97 (range, 92-100) in the other. Provided metal is carefully processed and cups are initially stable, the all-metal implants have equivalent in-growth as expressed by the migration analysis, and thus constitute an alternative therapeutic modality without polyethylene components.

Adult↗

Treatment of extra-abdominal desmoid tumors with interferon-alpha with or without tretinoin.

BACKGROUND AND OBJECTIVES: Surgery is the main treatment for extra-abdominal desmoid tumors, but the results of further management remain uncertain. Therefore, a retrospective analysis was undertaken to evaluate the toxicity and efficacy of treatment with interferon-alpha (IFN-alpha) +/- tretinoin in this setting. METHODS: Thirteen patients with extra-abdominal desmoid tumors and a median age of 32 years (range, 15-73) received IFN-alpha. Seven of these patients received a combination of IFN-alpha and tretinoin in order to test further enhancement. RESULTS: After a mean observation period of 27 +/- 15 months (mean +/- standard deviation) under treatment with IFN-alpha +/- tretinoin, local control was seen in 11 of 13 patients (85%). Seven patients had no evidence of disease at a mean disease-free interval of 22 +/- 18 months; in two patients progressive disease occurred after only 7 and 9 months, respectively, of observation. In another four patients, progression of the desmoid tumor was stabilized. CONCLUSIONS: The data of this retrospective, nonrandomized study on therapy with IFN-alpha +/- tretinoin suggest that such treatment may be effective in prolonging the disease-free interval of patients after intralesional or marginal surgery. Because of the encouraging response rate, this regimen appears to be another nonsurgical treatment alternative.

Adolescent↗

Heat shock protein 72 expression in chondrosarcoma correlates with differentiation.

PURPOSE: Heat shock proteins (hsp) are involved in tumor immunity, and a correlation with survival, occurrence of metastases, and drug resistance has been reported. It was the aim of this study to investigate the expression of heat shock proteins in chondrosarcomas and chondromas. METHODS: Hsp expression was investigated immunohistochemically on paraffin-embedded sections of 37 consecutive patients (24 male and 13 female, mean age 48 years) with chondrosarcoma and of ten patients (six male, four female, mean age 36 years) with chondroma. RESULTS: Chondromas showed a positive staining for hsp27 in 100%, for hsp60 in 30%, for hsp72 in 80%, for hsp73 in 80%, and for hsp90 in 90%. In chondrosarcoma a decreased expression was found for hsp27 (62% positive, P<0.05) and hsp72 (43% positive, P<0.05), whereas no significant difference to chondromas was detected in the expression of hsp60 (49% positive), hsp73 and hsp90 (73% and 81% positive, respectively). In addition, hsp72 expression showed a correlation with differentiation of the tumors (P<0.05); the lowest hsp72 expression was found in G3 chondrosarcomas (only 13% positive). No correlation with respect to differentiation was found for the expression of the other hsps. CONCLUSIONS: This study shows a different expression of hsps in chondrosarcomas and chondromas. Together with the correlation of hsp72 expression with low differentiation, this finding could lead to new experimental and diagnostic strategies.

Adolescent↗

Serum antibodies against the heat shock protein 60 are elevated in patients with osteosarcoma.

Osteosarcoma is the most frequent malignant bone tumor, mainly occurring in the second and third decade of life. Diagnosis is limited to clinical symptoms, radiology and histology, but so far no diagnostic laboratory tests are available. Heat shock proteins (hsp), highly conserved proteins performing vital intracellular chaperoning functions and preventing cells from death, have been shown to be involved in tumor immunity. We analyzed 75 sera from 23 patients with high-grade osteosarcoma, 8 patients with chondrosarcoma, 10 patients with Ewing's sarcoma, 5 patients with soft tissue sarcoma, 11 patients with benign bone tumors at the time of diagnosis and from 18 healthy controls with an indirect one-site enzyme linked immunosorbent assay (ELISA) for the presence of anti-hsp60 and 70 antibodies. In these assays 10/23 osteosarcoma patients (43%) had anti-hsp60 antibodies with a mean +/- S.D. titer of 0.382 +/- 0.243 U/ml. Only one of the 18 healthy controls (1/18, 5.6%; titer 0.22 U/ml), two of the Ewing's sarcoma patients (2/10, 20%; titer 0.2 +/- 0.09 U/ml), two of the patients with a benign bone tumor (2/11, 18%; titer 0.22 +/- 0.16 U/ml) and one of the chondrosarcoma patients (1/8, 12.5%; titer 0.14 U/ml) were positive, whereas all others, including all soft tissue sarcomas were negative throughout. Anti-hsp60 antibodies in patients with osteosarcoma are therefore significantly increased (p < 0.05). 19/23 (83%) of osteosarcoma biopsy specimens expressed hsp60 immunohistochemically and all specimens from patients with a positive anti-hsp60 serum titer expressed hsp60. The level of the anti-hsp60 antibodies did not correlate with clinical parameters such as response to preoperative chemotherapy, duration of symptoms, age, gender, tumor size, serum alkaline-phosphatase levels and metastases. Although no difference in anti-hsp70 antibodies could be observed between sera from patients and healthy controls, a positive correlation was found for the presence of anti-hsp70 serum antibodies and lung metastases at the time of diagnosis in osteosarcoma patients. These data suggest an increase of anti-hsp60 antibodies at the time of first diagnosis of osteosarcoma. These findings should therefore give rise to further investigations on a group of new markers for the diagnosis of osteosarcoma.

Adolescent↗

Antibodies to heat shock protein 90 in osteosarcoma patients correlate with response to neoadjuvant chemotherapy.

Autoantibodies to the heat shock protein 90 (Hsp 90) have been reported as prognostic marker in breast cancer patients. Sera from 20 high-grade osteosarcoma patients were tested at the time of diagnosis by enzyme-linked immunosorbent assay. Presence of anti-Hsp90 antibodies correlated with a better response to neoadjuvant chemotherapy (P < 0.01), whereas the absence correlated with development of metastases. These data suggest that anti-Hsp90 antibodies might be of predictive value in human osteosarcoma.

Adolescent↗

Abdominosacral resection of recurrent rectal cancer in the sacrum.

PURPOSE: Resection of the sacrum is the only curative therapy of isolated sacral recurrence after primarily resected rectal cancer. The aim of the study was to assess whether there is a benefit in terms of overall survival, morbidity, and mortality when sacrum resection is performed more radically and in cooperation between colorectal and orthopedic surgeons. Possible prognostic factors were also assessed. METHODS: Twelve consecutive patients who underwent interdisciplinary partial sacral resection were included in a retrospective cohort study. Furthermore, overall survival rate and survival time were calculated. RESULTS: Histologic examination showed tumor-free resection margins in all cases. Extended resection was necessary in seven patients, including total pelvic exenteration in two. No perioperative death occurred and no patient required early reoperation. Complications were observed in 42 percent of patients, mainly caused by poor wound healing. All patients experienced relief from pain. One-year and three-year overall survival rates were 50 and 17 percent, respectively. The overall mean survival time was 21.7 months. Patients who died of recurrent disease within one year either underwent former resection for locoregional recurrence, had extensive local recurrent tumors affecting pelvic visceral structures, or retrospectively suffered from metastatic sacral tumor manifestation. CONCLUSION: The mortality and morbidity rates observed in the present study seem to justify partial sacral resection as a means to achieve palliation of perineosacral pain in spite of rare overall long-term survival.

Adenocarcinoma↗

Combined treatment of metastatic osteosarcoma of the spine.

We report on a 28-year-old male with a single metastasis of an osteosarcoma in the twelfth thoracic vertebra occurring 9 years after initial diagnosis of the primary tumour in the left distal femur and neoadjuvant treatment according to a modified T-10 protocol. After pre-operative second-line combination chemotherapy with doxorubicin, carboplatin and etoposide leading to regression of the primarily inoperable metastasis wide resection of the tumour employing total spondylectomy was done. The duration of response had been 65 months since the end of subsequent postoperative chemotherapy with the same regimen.

Adult↗

Aneurysmal bone cyst. A population based epidemiologic study and literature review.

Aneurysmal bone cyst is a rare nonneoplastic expansile osteolytic bone lesion of unknown etiology. To the best of the authors' knowledge, no epidemiologic study concerning its incidence has been reported. The authors performed a retrospective, population based analysis of 94 patients with primary aneurysmal bone cyst and a literature review of 1002 patients regarding gender and age predilection. The annual incidence of primary aneurysmal bone cyst was 0.14 per 10(5) individuals. The male to female ratio was 1:1.04, and the median age was 13 years (range, 1-59 years). The results of this study and data compiled from the literature show that aneurysmal bone cysts occur significantly more often in female patients.

Adolescent↗

Intra-articular hyaluronic acid: duration of effect and results of repeated treatment cycles.

An open-label, multicenter study was designed to evaluate the effects of intra-articular (IA) hyaluronic acid in patients given a diagnosis of osteoarthritis of the knee. Patients (n = 108) received five weekly IA injections of hyaluronic acid 20 mg (Hyalgan) under sterile conditions, and were observed for up to 12 months after the last injection. Some patients received a second series of injections after 4 to 8 months. For the 59 patients who were observed for 12 months after the first treatment cycle, evaluation of pain according to a visual analog scale showed significant improvements lasting 12 months, with pain during load, pain at rest, and duration of walking ability compared with a baseline evaluation. Patients who required a second treatment cycle showed a further amelioration. Significant improvements were also seen in knee function and in global evaluations by both patient and investigators. Relief of symptoms of osteoarthritis of the knee was seen as early as 4 weeks after treatment in 68% of patients receiving IA hyaluronic acid. In 55% of these patients, relief was maintained until the end of the 12-month follow-up.

Adjuvants, Immunologic↗