Teddy Holmström

Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders

From 1990 to 1997, 113 eligible patients with classical osteosarcoma received neo-adjuvant chemotherapy consisting of high-dose methotrexate, cisplatin and doxorubicin. Good histological responders continued to receive the same therapy postoperatively, while poor responders received salvage therapy with an etoposide/ifosfamide combination. With a median follow-up of 83 months, the projected metastasis-free and overall survival rates at 5 years are 63 and 74%, respectively. Independent favourable prognostic factors for outcome were tumour volume < 190 ml, 24-h serum methotrexate > 4.5 microM and female gender. The etoposide/ifosfamide replacement combination did not improve outcome in the poor histological responders. In conclusion, this intensive multi-agent chemotherapy results in > 70% of patients with classical osteosarcoma surviving for 5 years. The data obtained from this non-randomised study do not support discontinuation and exchange of all drugs used preoperatively in histological poor responders. As observed in previous Scandinavian osteosarcoma studies, female gender appears to be a strong predictor of a favourable outcome.

Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII

Abstract From 1990 to 1997, 113 eligible patients with classical osteosarcoma received neo-adjuvant chemotherapy consisting of high-dose methotrexate, cisplatin and doxorubicin. Good histological responders continued to receive the same therapy postoperatively, while poor responders received salvage therapy with an etoposide/ifosfamide combination. With a median follow-up of 83 months, the projected metastasis-free and overall survival rates at 5 years are 63 and 74%, respectively. Independent favourable prognostic factors for outcome were tumour volume 4.5 μM and female gender. The etoposide/ifosfamide replacement combination did not improve outcome in the poor histological responders. In conclusion, this intensive multi-agent chemotherapy results in >70% of patients with classical osteosarcoma surviving for 5 years. The data obtained from this non-randomised study do not support discontinuation and exchange of all drugs used preoperatively in histological poor responders. As observed in previous Scandinavian osteosarcoma studies, female gender appears to be a strong predictor of a favourable outcome.

Three‐year follow‐up of the use of a levonorgestrel‐releasing intrauterine system in hormone replacement therapy

Background. The efficacy of a levonorgestrel‐releasing intrauterine system in opposing endometrial proliferation and in preventing bleeding was studied in peri‐ and postmenopausal women receiving estrogen replacement therapy.

Intrauterine and subdermal progestin administration in postmenopausal hormone replacement therapy

OBJECTIVE To compare the effects of intrauterine and subdermal administration of levonorgestrel on control of bleeding and on the endometrium in postmenopausal hormone replacement therapy. INTERVENTIONS Nineteen women started continuous oral E2 valerate therapy (2 mg daily) together with continuous parenteral progestin therapy. The subjects randomly received either a subdermal levonorgestrel-releasing implant (n = 9) or an intrauterine device (IUD) releasing levonorgestrel (n = 10). MAIN OUTCOME MEASURES Serum concentrations of estrone, E2, FSH, sex hormone-binding globulin (SHBG) and levonorgestrel were followed. Endometrial biopsies and transvaginal ultrasonography were used to evaluate the endometrium. The subjects kept daily records of bleeding. The observation time was 1 year. RESULTS Serum concentrations of the hormones mentioned above and SHBG were similar in both groups during the observation time, but the patterns of bleeding differed. In the IUD group there were 0.9 days (mean, range 0 to 4 days) of spotting and no days of bleeding during the last month of the follow-up year. In the implant group there were 8 days (mean, range 0 to 25 days) of spotting and 3.4 days (mean, range 0 to 14 days) of bleeding. In histological examination there was uniform atrophy in the endometrial samples from the IUD group, and a weak or absent progestin effect in the implant group. CONCLUSIONS In spite of similar serum levonorgestrel concentrations, local intrauterine administration of levonorgestrel resulted in better control of bleeding and in more effective endometrial suppression than subdermal administration.

Intraosseous Lipoma of the Calcaneus: Report of a Case and a Short Review of the Literature

One case of an intraosseous lipoma of the calcaneus bone is presented together with a short review of the literature. Only 20 cases of tumors in the extremities have so far been published. The typical X-ray picture shows a cystic, sharply demarcated cavity, which macroscopically at operation is filled with yellowish, adipose tissue. In the present case and one previously published a central sclerotic mass was observed. The histological picture is typical, with mature adipose tissue mixed with a few degenerated bone trabeculae.

The Healing of Experimental Fractures by Compression Osteosynthesis: I. Torsional Strength

Biomechanical properties of osteotomized rabbit tibio-fibular bones fixed with 6-hole stainless steel AO/DCP plates were investigated with torsional loading 3 to 24 weeks postoperatively. During the first 9 weeks maximum torque capacity, energy absorption and torsional rigidity increased, reflecting progressive bony union between the fractured bone ends. From 9 to 24 weeks the values of torque capacity and energy absorption decreased, whereas torsional rigidity seemed to reach a steady state without further significant changes. For the three parameters considered, the mean percentage differences between the osteotomized plated bones and their paired-sham-operated controls were 69, 64 and 80 per cent, respectively. The results suggest that internal fixation of fractured bones provides conditions for undisturbed fracture healing, but that subsequently the rigid nature of the implant has an adverse effect on the cortical bone, which slowly loses strength. Thus the optimal time for removal of the plate seems to be shortly after the fracture has healed and before the bony tissue had been weakened by secondary changes, such as cancellous transformation and spatial rearrangement of the tubular bone.

Reconstruction of anterior cruciate ligament with carbon fiber An experimental study on pigs

During a follow-up period of 16 weeks in 18 pigs, macroscopical and histological studies revealed inva sion of fibroblasts and mesenchymal cells around the carbon fiber prosthesis inserted to replace the ACL but scarce tissue ingrowth into the prosthesis proper. There was no adherence of the carbon ligament onto the bony channels. The peak tensile strength of the reconstructed ligament was about one third of the paired normal ACL ligament during the 16 week exper iment.

Biologic anchorage of cruciate ligament prosthesis: Bone ingrowth and fixation of the Gore-Tex® ligament in sheep

The biologic fixation and strength of fixation of the polytetrafluoroethylene (PTFE) Gore-Tex ligament prosthesis was investigated in sheep knees. The device was inserted to replace the anterior cruciate ligament according to the recommended technique. Histological bone tunnel evaluation together with mechanical tensile studies were done at 6, 12, and 18 months. Already at 6 months the pull-out load of the prosthesis exceeded that of the normal ligament, and this finding persisted up to 18 months postoperatively. At 6 months there was marked fibrous tissue ingrowth into the prosthesis, and at 12 months trabecular bone had replaced the fibrous tissue between the interstices of the filaments; at 18 months bone even penetrated into the individual porous fibers of the prosthesis. The intra-articular part of the prosthesis was surrounded and partly invaded by undifferentiated connective tissue, with no recognizable macrophages or other inflammatory cells. In this experiment, the biocompatibility and porosity of the Gore-Tex prosthesis seemed optimal to permit ingrowth from surrounding fibrous and osseous tissues and firm anchorage into the bone tunnels.

Endometrial response to hormone replacement therapy as assessed by expression of insulin-like growth factor-binding protein-1 in the endometrium *

OBJECTIVE To assess endometrial response to parenteral levonorgestrel in hormone replacement therapy by means of morphological criteria and immunohistochemical staining of insulin-like growth factor-binding protein-1 (IGFBP-1). DESIGN Endometrial samples were collected from 35 postmenopausal women after 12 to 22 months of continuous combined estrogen-progestin therapy. All subjects were treated with parenteral progestin. A group of 8 women was treated with a subdermal levonorgestrel-releasing implant, and 27 women had a levonorgestrel-releasing intrauterine device (IUD). Sections of formalin-fixed paraffin-embedded biopsies were used for immunohistochemistry and after hematoxylin-eosin staining for routine histologic examination. RESULTS Atrophic epithelium with pronounced decidual reaction in the stroma was detected by histologic examination in all endometrial samples obtained from 27 women treated with the levonorgestrel-releasing IUD. In contrast, the endometrium was proliferative in seven of eight (87.5 percent) biopsies obtained from women treated with the levonorgestrel-releasing implant. Immunoreactive IGFBP-1 was detected in decidualized stromal cells in all endometrial samples obtained during intrauterine levonorgestrel therapy, whereas only one of eight samples obtained from women treated with subdermal levonorgestrel exhibited weak staining for IGFBP-1. CONCLUSIONS Our data show that both the morphological and biochemical response of post- menopausal endometrium to parenteral levonorgestrel was strikingly different, depending on the route of progestin administration, and that the decidual reaction and epithelial atrophy induced by intrauterine levonorgestrel were associated with expression IGFBP-1 in decidualized stromal cells.

Endometrial effect of transdermal estradiol and progestin ST-1435 * in postmenopausal women †

OBJECTIVE To study the endometrial effect of the transdermal synthetic progestin ST-1435. DESIGN Prospective. SETTING City Maternity Hospital, Helsinki, Finland. PATIENTS Eleven postmenopausal women used transdermal estradiol (E2) patches for 6 weeks immediately before a vaginal operation for prolapse. For the last 10 days, 1 mg of ST-1435 transdermally in a gel was combined to the treatment. MAIN OUTCOME MEASURES Blood samples were taken to follow serum concentrations of E2, follicle-stimulating hormone, and ST-1435. Endometrial samples for histologic examination were collected during the operation to evaluate the effect of the progestin. RESULTS Transdermal absorption of ST-1435 resulted in reasonably constant serum concentrations of ST-1435 in each subject. A progestin effect on the endometrium was seen in 9 of 10 samples obtained. One sample did not show any progestin effect in spite of adequate ST-1435 levels, but this patients E2 concentrations were low. CONCLUSIONS When the estrogen stimulation was adequate, the transdermal ST-1435 induced a progestin effect on the endometrium, i.e., it had an end-organ effect.