Cytopathology in Finland.
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Biopsy, Fine-Needle↗
Biomedical subjects
T Toivonen
Publications and source records attributed to T Toivonen.
Intramedullary fixation of femoral cortical osteotomies with interlocked biodegradable self-reinforced poly-96L/4D-lactide (SR-PLA96) nails.
Femoral diaphyseal osteotomies of adult sheep were fixed with intramedullary (i.m.) biodegradable self-reinforced poly-96L/4D-lactide (SR-PLA96) nails (Phi 10.66-10.78 mmx195-199 mm) that were interlocked with four Phi 1.5 mm metallic Kirschner (K) wires. Hollow i.m. nails used in the pilot study resulted in implant failure and only two of these sheep were followed long term (18 months and 3 years). In the main study, solid nails were used and this resulted in consolidation in 5/6 cases and in one non-union due to failure of both proximal K wires at 3 weeks. Sheep in the main study were followed for 6 and 12 months. Femurs were studied radiographically, microradiographically, histologically and by oxytetracycline labelling. Good bone healing was achieved and histology showed only a mild tissue reaction to the implant at 6-18 months. At 3 years, the implant had almost degraded and numerous foamy macrophages were ingesting the disintegrated material. No accumulations of lymphocytes implying an immunological inflammatory reaction were seen. This investigation demonstrated that absorbable SR-PLA96 i.m. nails can be used together with interlocking metallic K wires in fixation of simple cortical osteotomies in large animals weighing up to 63 kg. The long-term biocompatibility should be studied in a larger population.
Animals↗
The sensitivity of axillary staging when using sentinel node biopsy in breast cancer.
AIMS: We aimed to study factors, which enhance the sensitivity of sentinel node biopsy. METHODS: Three hundred and sixty-three clinically node negative breast cancer patients with successful sentinel node biopsy were studied. All focally radioactive and/or blue nodes in the axilla were harvested. All palpably suspicious lymph nodes were also removed for a similar histological evaluation. RESULTS: Sentinel node metastases were found in 129 patients. The metastasis was detected in the three first retrieved sentinel nodes in 126 cases and in the fourth or fifth node in three cases. The 'hottest' sentinel node was not the involved one in 18 cases. Five patients with tumour negative sentinel nodes had metastases in other palpably suspicious nodes. CONCLUSIONS: Harvesting all focally radioactive and/or blue nodes and other palpably suspicious nodes minimises the false negative rate in sentinel node biopsy. Removal of more than five nodes does not significantly improve the sensitivity of axillary staging.
Adult↗
Intramedullary fixation of cortical bone osteotomies with absorbable self-reinforced fibrillated poly-96L/4D-lactide (SR-PLA96) rods in rabbits.
Osteotomies of the femoral diaphysis were fixed with absorbable self-reinforced fibrillated poly-96L/4D-lactide (SR-PLA96) intramedullary rods (4.5 mm x 50-60 mm) in 43 adult rabbits. Follow-up times varied from 3 weeks to 3 yr. After sacrifice histological, oxytetracycline-fluorescence and microradiographic studies of the bones were performed. Strength characteristics and changes in crystallinity and molecular weight of the rods were also measured. All osteotomies were evaluated radiographically. Thirty-six osteotomies (84%) healed uneventfully. The implant disappeared almost totally within 3 yr and histology showed only a minor foreign body reaction. From 6 weeks on, the bending force needed to break the osteotomy was comparable to the bending force needed to break the control bone. The shear strength of the rods displayed only minor changes for the first 24 weeks. Subsequently, the rods rapidly lost their strength and at 48 weeks there was practically no shear strength left, which is ideal for healing of an osteotomy. The present investigation demonstrated, that absorbable. fibrillated SR-PLA96-rods can be used for the intramedullar fixation of simple cortical bone osteotomies in rabbits. These results have encouraged us to continue our studies with the fixation of experimental cortical bone osteotomies in larger species.
Absorbable Implants↗
Tissue response to polyglycolide and polylevolactide pins in osteotomized cancellous bone.
A transcondylar osteotomy of the distal femur was fixed with a self-reinforced polyglycolide pin in one hind leg and with a self-reinforced polylevolactide pin in the other hind leg of 49 rats. The intact femurs of eight rats that did not have surgical treatment were used as controls. The tissue reaction to the implant and the consolidation of the osteotomy were examined radiographically, histologically, histomorphometrically, microradiographically, and using oxytetracycline fluorescence studies. The followups were from 1 to 52 weeks. A vigorous osteostimulatory tissue response to self-reinforced polyglycolide pins and self-reinforced polylevolactide pins was observed 1 week after fixation. This reaction reached its highest value 24 weeks after self-reinforced polyglycolide pin fixation and 6 weeks after self-reinforced polylevolactide pin fixation. The highest values of the mean trabecular bone area fraction, 27.9% for self-reinforced polyglycolide pins and 28.1% for self-reinforced polylevolactide pins, were measured at 48 weeks. At 12 weeks there was a peak of phagocytizing macrophages in the specimens with self-reinforced polyglycolide pin fixation. During the followup, total phagocytosis of self-reinforced polyglycolide pins was seen, but only a few signs of degradation of self-reinforced polylevolactide pins were observed. Both polymeric implants seemed to possess osteostimulatory properties, and the biocompatibility and clinical relevance proved to be acceptable.
Absorbable Implants↗
Biodegradation and strength retention of poly-L-lactide screws in vivo. An experimental long-term study in sheep.
BACKGROUND AND AIMS: Poly-L-lactide implants have gained popularity in the fixation of fractures and osteotomies in the past decade. The aim of the present experimental long-term study was to examine the degradation and strength retention of self-reinforced poly-L-lactide (SR-PLLA) lag-screws and the bone tissue response. MATERIAL AND METHODS: A total of 27 young adult sheep were used. Self-reinforced poly-L-lactide (SR-PLLA) lag-screws of 6.3 mm were implanted in the left proximal femur of nine sheep. At two, three and five years three of the sheep were sacrificed and the degradation was studied radiologically, microradiographically and histologically. For the strength retention measurements five SR-PLLA lag-screws of 6.3 mm and five lag-screws of 4.5 mm were implanted in the subcutaneous tissue of the five sheep and lag-screws of 6.3 mm for the pull-out test in the left proximal femur of 20 sheep. At 0, 12, 18, 24, 32, and 36 weeks bending and shear strength, molecular weight and pull-out measurements were performed. RESULTS: At five years no SR-PLLA material could be seen. The implant area was surrounded by high density bone with bone ingrowth in the screw area. At 36 weeks the bending strength of the 6.3 mm screws had decreased from 257.9 MPa to 36.4 MPa and the shear strength from 131.8 MPa to 19.8 MPa. The pull-out strength of the lag-screws of 6.3 mm in diameter decreased from 1507 N to 331 N in 24 weeks. CONCLUSIONS: SR-PLLA lag-screws showed high initial values, a controlled strength retention and gradual degradation process making the use of them safe also in demanding fixations.
Absorbable Implants↗
SR-PLLA and SR-PGA miniscrews: biodegradation and tissue reactions in the calvarium and dura mater.
The biocompatibility and degradation of self-reinforced poly-L-lactide (SR-PLLA) and polyglycolide (SR-PGA) miniscrews, vs titanium miniscrews, was studied in frontal bone osteotomies in 20 lambs, where they were used for plate fixation. At follow-up at 4, 6, 12, 26, 52 and 104 weeks, no clinical foreign body reaction, infection or other complications had occurred. Histologically, PGA material was hydrolyzed and fragmented at 4-6 weeks and was resorbed by 12 weeks, whereas the SR-PLLA miniscrews retained their integrity and holding power for 26 weeks and were mostly resorbed at 2 years. According to histological and histomorphometric analyses and plain film radiography, the degradation of PGA miniscrews was accompanied by a typical non-specific foreign-body reaction and initial transient osteolysis with decreased osteoid formation around the screw channel, but compensatory intense osteoid formation and bone remodelling followed after resorption of the polymer. The foreign body reactions to PLLA and titanium were considerably milder. All miniscrews were commendably strong and could be satisfactorily tightened against the plate. SR-PLLA miniscrews offer fixation stability for half a year, whereas rapidly degrading SR-PGA miniscrews may be used when short-term fixation is needed.
Absorbable Implants↗
Cathepsin-D, urokinase plasminogen activator and type-1 plasminogen activator inhibitor in early breast cancer: an immunohistochemical study of prognostic value and relations to tenascin-C and other factors.
Cytosolic determinations of cathepsin-D (cath-D), urokinase plasminogen activator (uPA) and its specific inhibitor PAI-1 have shown an association with adverse prognosis in breast cancer. Our aim was to study the distribution of these markers in small axillary node-negative breast carcinomas using immunohistochemistry and relate the semiquantitative results to known prognostic factors, the expression of tenascin-C (Tn-C) in invasion border of the tumour and prognosis. All the 158 women (159 tumours) were treated with breast conserving surgery and postoperative radiotherapy. Cytoplasmic immunoreactivity for cath-D was seen in carcinoma cells in 47% and in stromal cells in 44%. Nearly all tumours expressed uPA and PAI-1, which were categorized to cytoplasmic expression in carcinoma cells and diffuse stromal expression and quantified -/+/++/ and further dichotomized for purposes of analysis. Expression of uPA and PAI-1 in stromal fibroblasts was recorded as -/+. Cytoplasmic and stromal cell cath-D contents were associated with grade, proliferation, Tn-C expression in the tumour invasion border and the development of distant metastasis. In multivariate analysis stromal cath-D proved to be an independent prognostic factor for metastasis. Stromal expression of uPA was associated with an increased risk of local recurrence; otherwise high levels of uPA did not associate with other prognostic factors nor with prognosis. Fibroblastic expression of PAI-1 showed an association with both local and distant disease recurrence. However, no consistent association between the immunohistochemically quantified uPA and PAI-1 and prognosis was found. In conclusion, immunohistochemical determination of cath-D seems to be a viable method to predict a higher risk of metastasis but not local recurrence in small axillary node-negative breast carcinomas.
Biomarkers↗
Biodegradable semirigid plate and miniscrew fixation compared with rigid titanium fixation in experimental calvarial osteotomy.
OBJECT: To determine the biocompatibility and suitability of resorbable plates and miniscrews, consolidation of symmetrical, bilateral frontal bone craniotomies that had been closed using various methods was studied in 20 growing lambs. METHODS: Bone fixation with a flexible, punched polylactide plate and four slowly degradable, self-reinforced poly-levolactide (SR-PLLA) or rapidly degradable, self-reinforced polyglycolide (SR-PGA) miniscrews (10 animals in each group) was compared intraindividually with rigid fixation by using a titanium miniplate and four miniscrews. Plain x-ray films, magnetic resonance images, histological studies, and histomorphometric studies were obtained at 4 to 104 weeks. CONCLUSIONS: No dislocation, instability, clinical foreign body reactions, infections, or loss of fixation were observed. Bone consolidation of the 2.35-mm-wide craniotomy lines was incomplete; connective tissue-filled defects through the bone were observed in 13 of 28 lines at 26 to 52 weeks. Statistical analyses based on histomorphometric studies showed no difference in consolidation with SR-PLLA miniscrew and titanium plate/screw fixation or between the two resorbable fixation methods. Fixation with rapidly degradable SR-PGA miniscrews resulted in less effective consolidation than on the contralateral titanium-treated side (p<0.05), but the bone segment was thicker (p<0.005). The SR-PGA miniscrews had disappeared by 6 weeks, the polyactide plate by 104 weeks, and the SR-PLLA miniscrews had been mostly resorbed at 104 weeks. Passive translocation of the titanium plates and screws into the bone tissue was seen at 52 and 104 weeks. In rapidly growing lamb frontal bone, comparable consolidation results, without complications, can be achieved with semi-rigid resorbable fixation compared with rigid metallic fixation.
Absorbable Implants↗
Tissue response to polyglycolide and polylactide pins in cancellous bone.
An absorbable self-reinforced polyglycolide (SR-PGA) pin, 2.0 mm in diameter and 15 mm in length, was implanted in the trabecular bone areas of the distal femur of 51 rats and a biodegradable self-reinforced poly-L-lactide (SR-PLLA) pin of the same size was inserted into the distal femur of the other hind leg of the same rats. The intact femora of eight non-operated rats were used as controls. Tissue reaction to the implants was examined within standardized sample fields radiographically, histologically, histomorphometrically, microradiographically and using oxytetracycline fluorescence studies. The follow-up periods of the groups consisting of five operated rats and one intact control rat were 1, 3, 6, 12, 24, 36, 48 and 52 weeks. Eleven extra rats were operated on to ensure five samples in each follow-up group for the final analyses. The first signs of degradation of the SR-PGA pin were seen at 3 weeks, and the pin was totally degraded by 36 weeks. No signs of degradation of the SR-PLLA pin were observed during the follow-up period. Active new bone formation was seen close to the implant profile at 1 week in both groups. At 12 weeks the mean fractional osteoid formation surface was statistically significantly (P < 0.01) higher in the SR-PGA-implanted specimens than in the SR-PLLA-implanted specimens. At that time there were also statistically significantly (P < 0.05) more phagocyting macrophages in the SR-PGA-implanted specimens than in the SR-PLLA-implanted specimens, which is in accordance with the degradation behaviour of both implants. The biocompatibility of polyglycolide and polylactide proved to be good.
Absorption↗
Tissue response to bioabsorbable self-reinforced polylevolactide and polyglycolide pins implanted intra-articularly and directly into the bone on different levels. An experimental study on rats.
Self-reinforced poly-L-lactide (SR-PLLA) and self-reinforced polyglycolide (SR-PGA) pins were implanted intra-articularly and directly into the bone of the distal femur of rats at three levels: above, on the same level, and under the surface. For the controls only channels were drilled, or the controls were not operated at all. The follow-up times were 3, 6, and 12 weeks for SR-PGA and 3, 6, 12, and 24 weeks for SR-PLLA. The macroscopic appearance and histologically the villus reaction, the mononuclear phagocytosis and giant cells, the neutrophils, the lymphocytes, the plasma cells, the eosinophils, and the mast cells were analyzed. In the histologic analysis, the most favorable implantation depth was found to be under the surface where the contact between the implants and bone was best, and the orifice was covered with new trabecular bone at 3 weeks. This was especially seen in intra-articular implantation. In general, the tissue responses were mild, and could also be explained in the statistical analysis by a normal postoperative tissue response and faster biodegradation of PGA.
Absorbable Implants↗
Expression of tenascin-C in intraductal carcinoma of human breast: relationship to invasion.
Tenascin-C (Tn-C) is an extracellular matrix glycoprotein that appears in areas of epithelial-mesenchymal interaction during fetal development and in neoplasia. The immunohistochemical expression of Tn-C and its relationship to histology, nuclear grade, microinvasion, oestrogen (ER) and progesterone receptors (PR), and to cell proliferation measured by Ki-67 expression were studied in 89 intraductal breast carcinomas (DCIS). Periductal Tn-C was noted in 87% and stromal Tn-C in 25% of the tumours. Stromal expression was associated with moderate to strong periductal expression and microinvasion. Periductal expression was associated with comedo-type, nuclear grade, microinvasion, Ki-67 expression, and lack of PR. The distribution of Tn-C was compared in DCIS and in the intraductal component from another series of small axillary node-negative invasive breast carcinomas (n = 44). Tn-C was present in the stroma of pure DCIS in 25% and in the intraductal component of the other series in 82%. Thus, stromal or moderate to strong periductal Tn-C expression in DCIS may relate to early invasion. DCIS with weak periductal or missing Tn-C expression may be a subgroup with benign behaviour.
Adult↗
Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence.
We have recently demonstrated an association between distant metastasis and the expression of the extracellular matrix glycoprotein tenascin-C (Tn-C) in the invasion border of small axillary node-negative breast carcinomas. Our purpose was to assess the relationship between the expression of Tn-C in the tumour invasion border and several histopathological and biological variables and to compare their usefulness in predicting local and distant disease recurrences. The original patient group consisted of 143 women with axillary node-negative breast cancer (one bilateral) treated with breast-conserving surgery and post-operative radiotherapy, and followed for a median of 8 years. Because of the small number of recurrences an additional group of 15 similarly treated women with recurrent breast cancer was also studied. The size of the tumour, its histology, including a possible intraductal component, and grade were re-evaluated. The expression of erbB-2, p53, Ki-67 and Tn-C was evaluated by immunohistochemistry. Ploidy and S-phase fraction (SPF) were assessed by flow cytometry. The only statistically significant prognostic factor for local recurrence was Tn-C expression in the invasion border. For metastasis Ki-67 positivity, tumour size and Tn-C expression in the invasion border were statistically significant, but Ki-67 positivity was the only independent prognostic factor. Tn-C expression in the invasion border was associated with a higher proliferation rate measured by Ki-67 and SPF, which is consistent with the suggested growth-promoting activity of Tn-C. Tn-C may be a useful marker in selecting patients for adjuvant therapies to reduce the rate of both local and distant cancer recurrences.
Adult↗
Intraosseous plating: a new method for biodegradable osteofixation in craniofacial surgery.
Biodegradable miniplates and screws offer special possibilities for surgical techniques because the removal operation is avoided. In areas beneath thin skin, intraosseous plating could be preferable to avoid palpability and transient swelling during resorption. The tissue reaction to a 0.5-mm-thick self-reinforced poly-L-lactide (SR-PLLA) plate fixed with an SR-PLLA miniscrew was studied histologically and histomorphometrically after implantation into the calvarium of six young sheep. After follow-up periods of 6, 20, and 52 weeks, no signs of adverse tissue reaction such as clinically manifest foreign body reaction or histologically manifest osteolysis were noted. By 52 weeks the implants were largely in direct contact with remodeled, dense bone tissue. No signs of fragmentation or resorption were noted in the intraosseous parts of the implants, whereas the screw head had been fragmented and was undergoing resorption at 52 weeks. The screw head is unnecessary in this plating method and could have been removed with a hot wire loop. The excellent biocompatibility of the mechanically strong, resorbable SR-PLLA plate with miniscrew fixation provides a possibility for intraosseous plating in less loaded craniofacial areas, especially in areas with very thin soft-tissue coverage.
Absorption↗
Expression of tenascin in invasion border of early breast cancer correlates with higher risk of distant metastasis.
Tenascin (Tn) is an extracellular matrix glycoprotein transiently expressed in epithelial-mesenchymal interaction areas during embryogenesis. Tn is expressed in a limited manner in adult tissues but emerges during wound healing and tumorigenesis. We have studied Tn expression by immunohistochemistry in 137 small node-negative breast cancers treated with breast-conserving surgery and post-operative radiotherapy during 1985-1989. None of the patients had undergone any adjuvant hormonal therapy or chemotherapy. Stromal Tn expression itself could not predict distant metastasis. However, Tn staining in the area of the invasion border seemed to be a strong predictor of distant metastasis, with an estimated 5-year metastasis-free survival (MFS) of 85% in Tn-positive cases compared to 98% in Tn-negative ones. The prognostic impact of Tn in the invasion border on MFS was stronger than that of tumour size and grade. This staining appears to be a useful adjunct for the estimation of breast-cancer metastasis.
Breast Neoplasms↗
Intraosseous cellular response to biodegradable fracture fixation screws made of polyglycolide or polylactide.
As biodegradable pins and screws have increasingly been used in the internal fixation of fractures, sterile inflammatory reactions have occasionally occurred. The aim of the present experimental study was to assess the cellular response within cancellous bone to biodegradable polyester screws. In 45 rabbis a transverse distal femoral osteotomy was fixed with a 4.5 x 30 mm screw made either of polyglycolide (PGA, in 20 rabbits) or polylactide (PLA, in 25 rabbits). The follow-up times were 3, 6, 12, 36 or 48 weeks. The time-related and spatial characteristics of the cellular response were examined histomorphometrically using standardised sample fields under polarised-light microscopy. Polymorphonuclear granulocytes and mononuclear round cells were scarce in all follow-up groups. The occurrence of phagocytic cells (mononuclear macrophages and foreign-body giant cells) was highest in the PGA-fixed 12-week specimens. The giant cells seemed to adhere to the implant surface at an early stage, whereas the ultimate digestion and clearing of the decomposing polymeric material later on were performed by macrophages invading the implant body. No PGA was left in the 36-week specimens, while the gross geometry of the PLA screws was still intact at 48 weeks. In conclusion, the inflammatory response to these polymers was quite mild. Thus it seems probable that some other additional factors must influence the occurrence of the clinical inflammatory reactions.
Animals↗
Preliminary study of porous hydroxylapatite particle containment with a curved biodegradable implant in the sheep mandible.
A conventional augmentation method without a splint was compared with the use of a biodegradable polyglycolide (PGA) splint as a container of hydroxylapatite (HA) particles. With the PGA splint there was a 35% rate of dehiscence of the incision, leading to loss of HA particles. Based on microradiographic measurements, the HA was retained better on the side augmented by the conventional technique. Toward the end of 24 weeks, however, a decrease of augmentation and in the quantity of HA was seen with both methods. According to the histologic studies, there was evidence of HA phagocytosis by osteoclast-type cells. In the histomorphometric studies after 24 weeks of follow-up, new bone ingrowth was 12% without and 10% with the PGA splint. Although the planimetric studies showed the PGA splint to be a good container, the material still requires further development.
Alveolar Ridge Augmentation↗
[Sparing breast cancer surgery].
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Adult↗