Biomedical subjects
Publications and source records attributed to R Kotz.
1. Clearly specify the hypothesis to be investigated using clinically meaningful objective endpoints. 2. Collect all patients' data in a reliable and consistent manner. 3. Use statistically appropriate procedures to analyze the data. 4. Conclusions should be able to support all claims of safety and effectiveness that are to be made.
PURPOSE: The aim of this retrospective analysis was to investigate the prognostic significance and optimal measures of tumor size in osteosarcoma treated with intensive neoadjuvant chemotherapy. PATIENTS AND METHODS: Initial anterior-posterior (AP) and lateral x-ray films of 128 patients treated within the trials Cooperative Osteosarcoma Study (COSS)-80, -82, and -86, were evaluated for the following three tumor diameters: length, width, and depth. Metastasis-free survival (MFS) analyses were performed in univariate and multivariate models with one, two, and three dimensions of the tumor as absolute or relative measures (tumor length, referred to bone length, plane and volume to body-surface area). RESULTS: Univariate analyses of MFS showed a high prognostic significance of all absolute measures. Relative measures, at best, showed a comparable predictive value. Cox regression analysis indicated the high prognostic significance of absolute tumor volume (ATV; P < .0001) and histologic response (P < .0001). None of 19 patients with an ATV < or = 70 cm3 and only four of 53 with an ATV < or = 150 cm3 relapsed, while in patients with an ATV more than 150 cm3, the relapse rate remained 40% to 60%, irrespective of further increase in volume. CONCLUSION: Initial tumor size is an important and easily obtainable prognostic factor in osteosarcoma and may serve as a basis for risk-adapted therapy. It is best represented by the absolute three-dimensional measure ATV. There is a cut-off point regarding the incidence of metastases at a tumor volume of approximately 150 cm3 as calculated from two-plane x-ray films.
22 women and 2 men with a mean age of 75 (51-90) years underwent replacement of the proximal femur for failed total hip arthroplasty by a modular femoral resection endoprosthesis (KMFTR). The indications were bone loss in aseptic loosening (n 8), fracture (n 12) and Girdlestone hips (n 4). After a mean follow-up of 5 (2-10) years, the Harris Hip Score improved from an average of 17 (4-43) to 79 (50-97). In 19 patients, the proximal femur was kept as an autograft and was wrapped around the resection parts of the modular prosthesis as a cortical sleeve. Bone formation in these 19 hips took place in 18 at the dorsal, in 17 at the medial, in 8 at the lateral and in 7 at the ventral aspect of the femur. The bone bridge formed within the first year and persisted in amount and distribution during the time of observation. In the 5 patients without a remaining cortical sleeve around the resection parts of the prosthesis, no bone bridge was formed. These 5 patients showed stress-shielding at the prosthesis-bone-junction. Until now, none of the 24 patients has undergone additional surgery.
The oncologic and functional outcome was reviewed in 21 consecutive patients who underwent limb salvaging surgery for periacetabular sarcoma using a new surgical approach and different types of reconstruction between 1972 and 1990. Histologic diagnosis in 86% showed osteosarcomas, chondrosarcomas, and Ewing's tumors. Age ranged from 10.0 to 61.5 years (mean age, 32.9 years). The resection margin was wide in 15 patients but marginal in 2 patients and intralesional in 4 patients. All of the latter patients died of their disease. In all cases where 3-dimensional imaging was used, wide resection margins could be achieved, whereas this was possible only in 50% of the cases with conventional imaging techniques. Seven patients died of their disease 3 to 15 months after surgery, 2 died of chemotherapy induced sepsis, and 2 patients died perioperatively. At followup, 8 patients had no evidence of disease (mean, 57.6 months; range, 12-190 months), and 2 patients were alive with disease. Fourteen patients could be observed for at least 12 months (mean, 41.1 months) and were functionally evaluated according to Enneking's criteria. If extensive resection was necessary, the best results were found if the defect had been reconstructed with a custom made prosthesis. The results were only satisfactory after implantation of saddle prostheses and poor with allografts or when no reconstruction of the bone defect was done.
The penetration and absorption of ibuprofen (CAS 15687-27-1) from a topical gel and oral tablets were tested in an open study, performed in 17 patients with degenerative knee disorders requiring an operation. Patients administered the topical test preparation (ibugel, 3 x 375 mg ibuprofen daily) or the standard oral preparation (2 x 600 mg ibuprofen daily) for 3 days prior to the operation. Samples of blood, synovial fluid, muscle, fasciae and subcutis were obtained during the operation (15 h after the last administration) and analysed for ibuprofen content using a validated HPLC method. Different absorption profiles were observed for topical and oral administration. Oral administration led to higher concentrations in the plasma, synovial fluid and fasciae, while higher levels in the muscle and subcutis were found after topical administration. After topical application, the concentrations in the fasciae, muscle and subcutis were significantly higher than those in the blood plasma and synovial fluid (p < 0.05). Very low levels of ibuprofen were observed in the subcutis after oral administration. This can be explained by the different pathways. This study demonstrated that concentrations of ibuprofen in the various biological samples were still within therapeutically effective levels 15 h after topical or oral administration. By use of an oral comparison group, it has been possible to show that the concentrations in times directly under the site of topical application lie in the same order of magnitude as those found after preoral treatment. Therapy of intra-articular inflammatory and degenerative joint diseases requires oral administration of non-steroidal anti-inflammatory drugs (NSAIDs). However, based on the results of this study, topical therapy with NSAIDs can be recommended for soft tissue rheumatism and periarticular insertion tendinopathia.
The case histories of all patients with osteosarcoma of the trunk entered into the consecutive studies COSS 80 through COSS 86 of the Cooperative German/Austrian Osteosarcoma Study Group (COSS) were analyzed in order to evaluate their clinical characteristics and the impact of modern neoadjuvant therapy on prognosis. They were compared to those of all patients with extremity osteosarcoma treated according to the same protocols. While tumors of the trunk comprised only 32 (4.8%) of 665 primary classical osteosarcomas, secondary osteosarcomas were much more likely to be located in bones of the axial skeleton (6 of 18, 33%). Patients with primary osteosarcoma of the axial skeleton were older (mean: 20.8 vs. 15.2 years, P < 0.01) and were more likely to present with metastases at diagnosis (34% vs 12%, P < 0.001) than those with primary extremity osteosarcoma. In contrast to extremity tumors, local surgical treatment failure was very common in osteosarcomas of the trunk. Complete tumor removal was achieved in less than half of all evaluable cases. The prognosis of eight patients with localized primary axial osteosarcoma and effective surgical local control was not inferior to that of 483 equally evaluable patients with extremity tumors. In conclusion, while secondary systemic spread of axial osteosarcoma may be avoided in patients treated with multiagent chemotherapy, successful treatment is often barred by primary metastatic disease and inability to control the local tumor site.
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We analyzed in 17 patients the outcome of various surgical techniques for reconstruction of the extension apparatus after resection of the proximal tibia and tumor prosthesis implantation. The mean follow-up period was 5 (1.5-11) years. Knee extension and flexion strength were measured isokinetically by dynamometer and muscle activities of the vastus medialis, the vastus lateralis and the rectus femoris muscles determined by means of EMG. Muscle function of the operated leg was compared to that of the contralateral extremity by using various surgical techniques: fibula transposition, transposition of the gastrocnemius muscle, and combination technique. The results concerning the operated leg were compared within the 3 groups and the activity and strength of both legs were compared to those of a control group of healthy subjects matched for age and weight. The strength of extensor muscles of the healthy leg was greater than that of the control group in flexion position (60 degrees-90 degrees); the hamstring strength values were within the normal range. The strength of extensor muscles of the operated leg differed between groups II and III at 90 degrees in favor of group II (p < 0.01) and at 60 degrees to 20 degrees (p < 0.001) in favor of group III. Expressed in percentage ranges (nonoperated leg set at 100 percent) the flexor muscles averaged 30 percent, the extensor muscles represented on average 12 percent (9-17 percent) in group I, 9 percent (5-18 percent) in group II and 16 percent (6-26 percent) in group III, depending on the knee angle.(ABSTRACT TRUNCATED AT 250 WORDS)
From 1986 to 1991 we fitted 20 children with endoprostheses after resection of malignant bone tumours of the leg; six have reached skeletal maturity and are the subject of this study. Reconstruction of defects in growing limbs in which the eventual shortening can be predicted requires the use of extendable prostheses. The mean age at operation was 11 years (9.2 to 13.7) and the average follow-up period was 6.3 years (4.3 to 7.6). The diagnosis was osteosarcoma in five patients and Ewing's sarcoma in one. All tumours were Enneking stage-IIB. When seen for follow-up all patients were free from disease. The extendable implants used included the Pafford-Lewis prosthesis and the Kotz Modular Femur Tibia Reconstruction system with a compatible, newly-designed growth module. Telescope-like elongation of the prostheses was performed by insertion of a screwdriver through a small skin incision. Active epiphyseal growth in the adjacent growth plate was preserved by using prosthetic stems with a smooth surface. The mean length gained was 13.15 cm (4.5 to 19.5) requiring 53 planned procedures. Seven revision operations were necessary for complications. Functional evaluation showed excellent and good results in all cases. Stress-shielding at the site of anchorage of the prosthesis was more pronounced than in adults. Implantation of extendable endoprostheses in children provides a reasonable alternative to rotationplasty, but limb salvage requires more operations.
We describe a method of partial limb salvage for the treatment of large primary malignant tumours of the arm. The tumour-bearing area is resected as a cylindrical segment and the distal arm is then replanted with the necessary shortening. The method is suitable for stage-IIB tumours with or without neurovascular involvement which, because of their extent, could otherwise be adequately treated only by amputation. From 1987 to 1992 we used this method in 12 patients with primary malignant bone or soft-tissue sarcomas. Wide resection margins were achieved in all, but six patients died from their disease at a mean of 21.5 months (6 to 48), none with any local recurrence. Five patients have no evidence of disease at a mean follow-up period of 52.2 months (22 to 78), and one was lost to follow-up at 48 months postoperatively when there was no evidence of disease. The results of the functional evaluation of ten patients with a follow-up of over ten months were excellent in one, good in six and fair in three, by the criteria of Enneking (1987). Recovery after nerve reconstruction was satisfactory in all cases with sensation S3 or higher and motor function M2+ or higher. Detailed evaluation of hand function on the Millesi score rated only 22% (9.6% to 33.7%) as compared with the contralateral side, but the patients were satisfied and refused further operations for the improvement of function. These oncological and functional results allow us to recommend resection-replantation as a valuable alternative to amputation for the treatment of primary malignant tumours of the arm.
We evaluated pressure distribution patterns under the feet during gait in 20 patients after resection of malignant bone tumor and endoprosthetic replacement of the distal femur. In all cases, a modular cementless, hinged prosthesis had been used. The examination was performed after 4 (1-6) years. Shortened contact phase, decreased peak pressure, and reduced force-time integral during gait analysis were observed on the operated side. Peak pressure in the heel and the toe regions was decreased and the load (force-time integral) in the metatarsal heads and the big toe regions was reduced. There was a positive correlation between load under the foot and knee extension strength, measured isokinetically.
An high-performance liquid chromatographic method with column switching for the detection of less than 4 ng of methotrexate in the urine of oncologic nurses is described. Urine samples were purified by solid-phase extraction on silica-bonded phenyl columns, eluting impurities with ethyl acetate. After elution from the column, the analyte was concentrated ten-fold, evaporating the solvent. On a strong anion-exchange column (Nucleosil 100 SB), methotrexate was separated from the remaining interfering substances, was then switched to a reversed-phase column (LiChrospher 100 RP-18e), and finally eluted by a linear gradient in a solvent system consisting of ammonium formate buffer (pH 2.7) and acetonitrile. Absorbance was monitored at 310 nm. This method has proved to be suitable for detecting traces of methotrexate in urine in order to individualize risks and to reduce further the occupational safety hazard for hospital personnel.
Using high-dose methotrexate, doxorubicin, and cisplatinum (or BCD) for adjuvant chemotherapy in osteosarcoma of the extremities, we achieved 8-year metastasis-free survival rates of 60-70%. No relapse has been observed after that time. A dose of 12 g/m2 of high-dose methotrexate seems superior to 6 g; doxorubicin was found to be indispensable for efficient therapy and administering ifosfamide in addition seemed to be beneficial. Primary chemotherapy appeared to be safe and to facilitate surgery. The response on chemotherapy provided valuable prognostic information. Salvage of poor responders by alternative postsurgical chemotherapy was unsuccessful. Intraarterial, as opposed to intravenous, use of cisplatinum, in addition to systemic three-drug chemotherapy, did not improve the local tumor response rate. The local failure rate was low (4.7%); it was higher, however, after limb-salvage procedures than after amputation and rotationplasty (11.1% vs. 2.2%, p < 0.05). The outcome after local failure was almost universally fatal. The most intriguing late sequelae of chemotherapy were cardiomyopathy due to doxorubicin and hearing loss due to cisplatinum. Given the limited number of effective drugs, it might be difficult to further improve the cure rate and also to diminish late toxicity. Exploration of the most effective but least toxic mode of drug administration might be one possibility. Another might be reduction of the cumulative doses and therapy duration, while simultaneously increasing the dose rate.
We evaluated quadriceps muscle mass and knee extension strength in 21 patients after resection and endoprosthetic replacement of the distal femur for malignant bone tumor. In all cases, a modular cementless, hinged prosthesis had been used. The mean follow-up period was 4 (2-9) years. Muscle mass was measured ultrasonographically, and strength isokinetically with a Cybex 6000 dynamometer. All the data for the operated side are given as percentage of the non-operated side. The average quadriceps mass was 48 (27-70) percent. The average peak torque was 31 (14-48) and 36 (18-55) percent at the speed of 30 degrees/s and 90 degrees/s, respectively. The reduction in extension strength became greater with increasing flexion. There was a moderate correlation between muscle mass and muscle strength. Most of the patients who had kept more than 40 percent of the quadriceps mass had more than 30 percent peak torque. Patients with excellent function (Enneking 1987) had more quadriceps muscle mass and higher strength than those that were merely good with the borderline at about 40 percent muscle mass.
One hundred twenty-two patients with tuberculous or pyogenic spondylitis were investigated retrospectively. Patient histories, laboratory tests, and radiographic findings were compared statistically between the two groups. Significant differences were calculated for the interval between onset of symptoms and diagnosis, erythrocyte sedimentation rate, mean vertebral loss at discharge, and sclerosis of the vertebral bodies involved. Open or closed biopsy was performed in 91 patients. The result provided a clear distinction between tuberculous and pyogenic spondylitis in 62.2%, either by means of histology or by culture growth. In pyogenic spondylitis, staphylococci were the most predominant bacteria isolated. Neurologic deficits were demonstrated in 17.8% of patients with tuberculous spondylitis and 22.7% with pyogenic spondylitis. At follow-up examinations, only two patients still had a motor deficit. Additionally, pain, gibbus formation, and bony fusion were evaluated, but no significant differences were found. The combination of several unspecific findings such as patient history, erythrocyte sedimentation rate, and radiographic assessment can lead to the correct diagnosis. A definitive diagnosis is established by means of biopsy, histologic evidence, and bacterial culture.
Eighteen patients with tumors of the leg underwent limb saving operations. The large tissue defects were covered by flaps. The use and advantages of these flaps are discussed.
In the Department of Orthopedics at the University of Vienna, tumor endoprostheses have been implanted after resections of tumors of the upper extremities since 1974 and of the knee joint since 1976. For replacement of the humerus after tumor resection, a system of modular tumor endoprostheses was developed very early. Initially, it was ceramic and later on made of titanium alloys, which were also implanted in combination with custom-made prostheses with cementless stem-plate fixation in 57 patients until February 1990. In 43 of these patients (75.4%) adequate resection (2 radical and 41 wide) had been performed. Of 49 patients with a follow-up period of at least 24 months, 36 patients had a mean disease-free survival time of 106.1 months. Between 1976 and 1981, 16 custom-made endoprostheses were used after tumor resection of the knee joint. Since 1982 we have used a modular system of tumor endoprostheses suitable for replacement of the proximal and distal femur, proximal tibia, total femur and total knee joint. Of 75 patients who had been operated on up to February 1990, 67 patients (89.3%) had undergone adequate resection (2 radical and 65 wide). Out of 32 of these patients, 24 (75%) exhibited a disease-free survival time of at least 24 months (mean 48.2 months). Out of 213 patients with resection/reconstruction (160 endoprostheses), 77.8% had a survival time of at least 24 months, a results which is considerably better than in 146 patients with amputation in which case the respective value was 69.4%.(ABSTRACT TRUNCATED AT 250 WORDS)
A new triple osteotomy, polygonal pelvic osteotomy (PPO), is described for use in dysplastic hips. The hip joint must be congruous with a centre-edge (CE) angle between +20 degrees and -10 degrees. Templates are used before and during operation which allow precise correction of the position of the acetabulum. The geometry of the osteotomy and a special compression plate achieve sufficient stability to permit early mobilisation. Surgery is indicated in adolescents and young adults if pain persists for at least two months. The surgical exposure, operative technique and postoperative management are presented, with the two-year results in nine cases.