Model-based roentgen stereophotogrammetric analysis of the surface replacement trapeziometacarpal total joint arthroplasty.

The primary aim of this clinical and radiostereometric study was to study the migration pattern of the surface replacement trapeziometacarpal joint prosthesis (SRTMTMC, Avanta®, San Diego, CA). The secondary aims were to assess patient-related outcomes and prosthesis survival 5 years after surgery. Ten patients received the prosthesis. Radiostereometric radiographs were obtained 6 weeks, 6 months, 1 year and 5 years post-operatively and were analysed using model-based software. All patients completed DASH and Nelson Hospital scores at these follow-ups. Mean translations varied between 0.0 and 0.5 mm after 5 years. Rotation values could be calculated in six patients and mean rotations varied between -0.3 and 2.3°, although the precision of rotation values seems to be poor. The 5-year survival rate was 80%. Mean pre-operative DASH and Nelson Hospital scores were 53 (SD 14) and 51 (SD 13), respectively. Six months post-operatively, the DASH and Nelson Hospital scores had both significantly improved to 25 (SD 20) and 74 (SD 18) and remained high after 5 years. Implant stability was good 5 years post-operatively, and early migration did not predict implant failure in this study. LEVEL OF EVIDENCE: IV.

Feasibility of model-based Roentgen Stereophotogrammetric Analysis to evaluate early migration of the trapeziometacarpal joint prosthesis.

BACKGROUND: The purpose of this study was to determine the feasibility of Roentgen Stereophotogrammetric Analysis (RSA) in total joint arthroplasty of the trapeziometacarpal (TMC) joint of the thumb. METHODS: In five cadaveric hands the TMC-joint was replaced by the Surface Replacement Trapeziometacarpal prosthesis (SR™ TMC prosthesis; Avanta, San Diego, CA) and tantalum beads of 0.8 mm were implanted for RSA. RSA radiographs in two directions were made in ten positions to calculate the measurement error. Migration values from zero are indicative for the measurement error. The number of detected markers was recorded. RESULTS: The accuracy analysis showed that for the translations the mean measurement error varied between 0.003 mm (SD 0.057) and 0.055 mm (SD 0.133). For the rotations values ranged from 0.034° (SD 1.759) to 0.502° (SD 1.617). CONCLUSIONS: RSA analysis of the SR™ TMC prosthesis is feasible. The measurement error is good for the translations but high for the rotations. The latter is due to the close position of the markers relative to each other. Level of evidence III.

Mammography: interobserver variability in breast density assessment.

Our objective was to determine the interobserver variability of breast density assessment according to the Breast Imaging Reporting and Data System (BI-RADS) and to examine potential associations between breast density and risk factors for breast cancer. Four experienced breast radiologists received instructions regarding the use of BI-RADS and they assessed 57 mammograms into BI-RADS density categories of 1-4. The weighted kappa values for breast density between pairs of observers were 0.84 (A, B) (almost perfect agreement); 0.75 (A, C), 0.74 (A, D), 0.71 (B, C), 0.77 (B, D), 0.65 (C, D) (substantial agreement). The weighted overall kappa, measured by the intraclass correlation coefficient (ICC), was 0.77 (95% CI: 0.69-0.85). Body mass index was inversely associated with high breast density. In conclusion, overall interobserver agreement in mammographic interpretation of breast density is substantial and therefore, the BI-RADS classification for breast density is useful for standardization in a multicentre study.

Enhancement of initial stability of press-fit femoral stems using injectable calcium phosphate cement: an in vitro study in dog bones.

In this in vitro study we evaluated the initial stability of cementless femoral stems using an injectable calcium phosphate (Ca-P) cement. The cement was not used to form a cement mantle as is routinely done in PMMA cemented prostheses but functioned as an additive to fill the small gaps that exist between a press-fit placed titanium plasma sprayed implant and the bone bed. Six pair of Beagle femora were used in this study. In a random fashion, one femur of each pair was used for placement of a prosthesis without Ca-P cement, the contralateral was used for press-fit placement after injection of the calcium phosphate cement into the intramedullary canal. The reconstructions were placed in a MTS testing machine, tilted 15 degrees in varsus and 15 degrees of endorotation to obtain a physiological load on the femoral head. The load was applied stepwise from zero to a maximum of 100, 250 and 400 N, respectively. At each loading step the load was applied dynamically at a frequency of 1 Hz for 30 min. Between the loading steps, the load was removed for 10 min to allow elastic recovery. The stability of the stems was determined at each loading step with roentgen-stereophotogrammetric analysis. Results showed that with the prostheses without Ca-P cement the most important displacements were movement into varus (max. 818 microm under 400 N) and subsidence (max. 587 microm under 400 N). The displacements showed large variation. After unloading some elastic recovery occurred. In the specimens with Ca-P cement, displacements were negligible. As determined by an F-test the variations found were significantly smaller for the press-fit+Ca-P cement relative to the press-fit prosthesis at all loading steps (p<0.05). A paired t-test revealed significant differences in the mentioned displacements between the press-fit- and press-fit+Ca-P cement prosthesis at a loading with 400 N (P<0.05). On the basis of these results we conclude that the use of Ca-P cement increases the initial stability of press-fit inserted plasma-sprayed femoral prostheses and corrects for the high variability in displacements found with press-fit insertion of these femoral hip prostheses.

Use of injectable calcium-phosphate cement for the fixation of titanium implants: an experimental study in goats.

This in vivo study evaluated the fixation of two types of titanium implants with the use of an injectable calcium-phosphate (CaP) cement. The cement was either used to create a cement mantle (Type A implant) or as an additive to press-fit placed titanium plasma sprayed implants (Type B implant). The implants were placed in trabecular bone of the medial femoral condyle of goats and left in place for 2 and 10 weeks. Mechanical evaluation of the implant fixation was done by torque testing. This showed that for the Type A implants the calcium-phosphate cement's performance was significantly inferior (P < 0.05) to that of polymethylmethacrylate cement fixation. For the two-week Type B implants a significant increase (P < 0.05) in failure load was found for calcium-phosphate cemented implants compared with just press-fitted Type B implants. Histological evaluation revealed that for Type A implants, failure during torque testing occurred at the implant-cement interface. In contrast, for Type B implants, failure occurred in the bone-implant interface for press-fit-placed devices and in the cement layer for CaP-cemented devices. Further, the CaP cement was found to be overgrown with new formed bone already after 2 weeks of implantation. The cement showed resorption due to regular bone remodeling. On the basis of these observations, it was concluded that the use of injectable CaP cement might facilitate earlier loading of press-fit inserted titanium implants. Nevertheless, the results have to be confirmed in dynamical mechanical as well as loaded in vivo studies.

In vivo bone response to porous calcium phosphate cement.

We conducted an in vivo experiment to evaluate the resorption rate of a calcium phosphate cement (CPC) with macropores larger than 100 microm, using the CPC called Biocement D (Merck Biomaterial, Darmstadt, Germany), which after setting only shows pores smaller than 1 microm. The gas bubble method used during the setting process created macroporosity. Preset nonporous and porous cement implants were inserted into the trabecular bone of the tibial metaphysis of goats. The size of the preset implants was 6 mm and the diameter of the drill hole was 6.3 mm, leaving a gap of 0.3 mm between implant surface and drill wall. After 2 and 10 weeks, the animals were euthanized and cement implants with surrounding bone were retrieved for histologic evaluation. Light microscopy at 2 weeks revealed that the nonporous implants were surrounded by connective tissue. On the cement surface, we observed a monolayer of multinucleated cells. Ten weeks after implantation, the nonporous implants were still surrounded by connective tissue. However, a thin layer of bone now covered the implant surface. No sign of cement resorption was observed. In contrast, the porous cement evoked a completely different bone response. At 2 weeks, bone formation had already occurred inside the implant porosity. Bone formation even appeared to occur as a result of osteoinduction. Also, at their outer surface, the porous implants were completely surrounded by bone. At 2 weeks, about 31% of the initial cement was resorbed. After 10 weeks, 81% of the initial phosphate cement was resorbed and new bone was deposited. On the basis of these observations, we conclude that the creation of macropores can significantly improve the resorption rate of CPC. This increased degradation is associated with almost complete bone replacement.

Histological evaluation of the bone response to calcium phosphate cement implanted in cortical bone.

The aim of this study was to investigate the physicochemical and biological properties of a newly developed calcium phosphate cement (CaP cement) implanted in cortical bone. CaP cement was injected as a paste into tibia cortical bone defects in goats. Polymethylmethacrylate (PMMA) bone cement was used as a control. The animals were killed after 3 days, 2, 8, 16 and 24 weeks. X-ray diffraction and Fourier transform infrared spectroscopy performed at retrieved samples showed that the CaP cement had set as a carbonate apatite and remained stable over time. Light microscopic evaluation showed that after 2 weeks the cement was in tight contact with the bone without any inflammatory reaction or fibrous encapsulation. At later time points, the CaP cement implants were totally covered by a thin layer of bone and osteoclasts, present at the interface, which were clearly resorbing the cement. At locations where CaP cement was resorbed, new bone was deposited. Transmission electron microscopy revealed that indeed a seamless contact existed between CaP cement and bone, as characterized by the occurrence of an electron dense line of 50-60 nm thick that covered the CaP cement. Osteoblasts, in contact with the cement, were depositing new bone. Although the bulk of the material was still in situ after 24 weeks, the progressive osteoclast resorption of the cement followed by new bone formation suggests that all of the material may be replaced eventually. In contrast to the CaP cement, the PMMA reference cement was always surrounded by a thin fibrous capsule. The results indicate that the investigated CaP cement is biocompatible, osteoconductive as well as osteotransductive and is a candidate material for use as a bone substitute.

Soft-tissue response to injectable calcium phosphate cements.

In this study, the soft tissue reaction to two newly developed injectable calcium phosphate bone cements (cement D and W) was evaluated after implantation in the back of goats. For one of the cements (cement D) the tissue reaction was also investigated after varying the concentration of accelerator Na(2)HPO(4) in the cement liquid (resulting in cement D1 and D2). Eight healthy mature female Saanen goats were used. The cement was applied 10min after mixing while it was still moldable and plastic. The material was given a standardized cylindrical shape. Thirty-two implants of each cement formulation were inserted and left in place for 1, 2, 4, and 8weeks. At the end of the study, eight specimens of each material and healing period were available for further analysis. Two specimens were used for X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) and six specimens were used for light microscopical evaluation. XRD and FTIR showed that the cements did set as microcrystalline carbonate apatite with the disappearance of monetite from the cements during implantation. Histological analysis showed that after 8weeks of implantation around all materials a thin soft-tissue capsule was formed (thickness ranging from 5 to 15 cell layers) with almost complete absence of inflammatory cells. Only in some specimens a slightly higher inflammatory reaction was observed. This was due to cement surface defects and a zone of dispersed particles near the cement-soft tissue interface. There was almost no resorption of the material after 8 weeks of implantation. In a few 4 and 8weeks samples, small areas of calcification were found in the fibrous capsule surrounding the implants. On the basis of our observations, we conclude that the tested cements were biocompatible and can be used next to soft tissue.

Trabecular bone response to injectable calcium phosphate (Ca-P) cement.

The aim of this study was to investigate the physicochemical, biological, and handling properties of a new developed calcium phosphate (Ca-P) cement when implanted in trabecular bone. Ca-P cement consisting of a powder and a liquid phase was implanted as a paste into femoral trabecular bone of goats for 3 days and 2, 8, 16, and 24 weeks. The cement was tested using three clinically relevant liquid-to-powder ratios. Polymethylmethacrylate bone cement, routinely used in orthopedics, was used as a control. The Ca-P cement was easy to handle and was fast setting with good cohesion when in contact with body fluids. X-ray diffraction at the different implantation periods showed that the cement had set as an apatite and remained stable over time. Histological evaluation after 2 weeks, performed on 10 microm un-decalcified sections, showed abundant bone apposition on the cement surface without any inflammatory reaction or fibrous encapsulation. At later time points, the Ca-P cement implants were totally covered by a thin layer of bone. Osteoclast-like cells, as present at the interface, had resorbed parts of the cement mass. At locations where Ca-P cement was resorbed, new bone was formed without loss of integrity between the bone bed and the cement. This demonstrated the osteotransductive property of the cement, i.e., resorption of the material by osteoclast-like cells, directly followed by the formation of new bone. Histological and histomorphometrical evaluation did not show any significant differences between the Ca-P cement implanted at the three different liquid/powder ratios. The results indicate that the investigated Ca-P cement is biocompatible, osteoconductive, as well as osteotransductive and is a candidate material for use as a bone substitute.

Variable heavy chain gene analysis of follicular lymphomas: correlation between heavy chain isotype expression and somatic mutation load.

The expansion of follicular lymphomas (FLs) resembles, both morphologically and functionally, normal germinal center B-cell growth. The tumor cells proliferate in networks of follicular dendritic cells and are believed to be capable of somatic hypermutation and isotype switching. To investigate the relation between somatic mutation and heavy chain isotype expression, we analyzed the variable heavy (V(H)) chain genes of 30 FL samples of different isotypes. The V(H) genes of the FLs were heavily mutated (29.3 mutations on average). In addition, isotype-switched lymphomas contained more somatic mutations than immunoglobulin M-positive lymphomas (33.8 mutations per V(H) gene versus 23.0, respectively). In all but one of the FLs, the ratios of replacement versus silent mutations in the framework regions were low, independent of the absolute number of somatic mutations and the level of intraclonal variation. Analysis of relapse samples of 4 FLs showed no obvious increase in somatic mutation load in most FLs and a decrease in intraclonal variation in time. In 3 of 4 cases, we obtained evidence for selection of certain subclones, rather than clonal evolution. Our findings question if intraclonal variation is always a reflection of ongoing somatic hypermutation. This may have implications for the concept of antigen-driven lymphomagenesis. (Blood. 2000;95:2922-2929)

Conventional bladder wash cytology performed by four experts versus quantitative image analysis.

Bladder wash cytology provides superior results for the detection of bladder malignancies than does voided urine analysis. Image analysis systems have been developed for quantification of cytologic features. In this study, routine bladder wash cytology is compared with an automated image analysis system (QUANTICYT). We studied a random set of 100 bladder wash samples from a population of 1614 patients in follow-up after bladder cancer. Four experienced pathologists interpreted the same 100 Papanicolaou-stained slides. Cytologic and image analysis results were compared for prediction of a cystoscopic lesion, histologic abnormalities, and tumor recurrence. After application of receiver operating characteristic curves, prediction of a cystoscopic lesion by cytology and image analysis was comparable. Both the image analysis system and the cytologic examination detected all of the high-grade lesions. Image analysis was superior to cytologic analysis for the prediction of tumor recurrence after normal findings at cystoscopic examination.

[Potential cornea, heart valve, bone and skin donors in 5 Dutch hospitals far outnumber actual donors]. / Aantal potentiële hoornvlies-, hartklep-, bot- en huiddonors in vijf Nederlandse ziekenhuizen veel groter dan aantal daadwerkelijke donors.

OBJECTIVE: To determine the number of potential cornea, heart valve, bone and skin donors among patients who died in Dutch hospitals, in comparison with the number of actual donors. DESIGN: Descriptive. SETTING: Five hospitals in the western part of the Netherlands. MATERIAL AND METHODS: The medical records of patients who died in 1989 were reviewed. Children younger than 4 weeks were excluded from the study. On the basis of criteria used by the Eurotransplant and Bio Implant Services Foundations and those of the skin bank of the Dutch Burns Foundation, it was determined if the deceased were medically suitable as cornea, heart valve, bone or skin donor. RESULTS: Data were collected on 2150 of 2369 deceased (90.8%), mean age 69.5 (17.0) (SD) years. Medical criteria for cornea donation were met in 72% of the cases, 6.8% of these became actual donors. The figures for heart value donors were 4.3% and 9.7% respectively, and for bone donors 2.7% and 0%. The percentage of potential skin donors could not be determined, because essential data were missing from the medical records. After extrapolation the number of donors among all patients who died in Dutch hospitals in 1989 amounted to 35,046 potential cornea donors, 2,093 potential heart valve donors and 1,314 potential bone donors. CONCLUSION: Only a very small proportion of the potential tissue donors were referred to Eurotransplant and Bio Implant Services. Therefore, waiting lists for tissue transplantation are not necessary.

The effect of estriol on the cytology of urethra and vagina in postmenopausal women with genito-urinary symptoms.

In a double-blind, randomised trial, 62 postmenopausal women with genito-urinary symptoms were treated with oestriol or matching placebo for 4 weeks. Estriol (Synapause-E3, Nourypharma Nederland) was given orally for 4 weeks in a single daily dose (8 mg/day first week, 4 mg/day second and third week, 2 mg/day fourth week). The influence of estriol on the vaginal and urethral epithelium was assessed by using the karyopycnotic index and the maturation value. As we expected, it was confirmed that estriol has a remarkably beneficial effect on the vaginal epithelium. This also applies to the epithelium of the urethra, although the effect is much less obvious.

Prognostic factors in bladder carcinoma: histologic parameters and expression of a cell cycle-related nuclear antigen (Ki-67).

A total of 316 biopsies from patients with bladder carcinoma who entered a trial of the genito-urinary group of the European Organization for Research and Treatment of Cancer (EORTC) were reviewed. The histological data were subsequently correlated with the clinical course. A strong correlation between the number of mitoses and the time of first recurrence, muscle invasion, and death was noted. Next the expression of Ki-67 in frozen sections from 49 transitional cell carcinomas (TCCs) and the DNA content of the tumour cells were determined. The frequency of Ki-67-positive tumour cells increased with tumour grade and stage. Grade II TCCs and superficially infiltrating TCCs showed a wide range of Ki-67 scores. There was a significant difference in Ki-67 score between non-infiltrating (Ta) and superficially infiltrating (T1) grade II TCCs. All DNA-aneuploid carcinomas but also 15 out of 36 DNA-diploid tumours contained more than 10 per cent Ki-67-positive cells. Only some of these tumours were DNA-aneuploid or -tetraploid. The results indicate that the number of Ki-67-positive cells in grade II tumours may be a useful aid in separating grade II TCCs with a favourable prognosis from those with a poor clinical outcome.

Cytokeratin expression patterns in metastatic transitional cell carcinoma of the urinary tract. An immunohistochemical study comparing local tumor and autologous metastases.

The cytokeratin (CK) expression patterns of local, ie, primary or recurrent, high-grade-malignant transitional cell carcinomas (TCCs) of the human urinary tract and autologous lymphogenic and hematogenic metastases (n = 33) were compared. Special attention was paid to CK expression in the tumor invasion front and other areas where tumor-stroma interaction occurred to visualize cell populations with a metastatic phenotype. For this purpose, polypeptide-specific monoclonal antibodies to CKs 4, 7, 8, 10, 13, 14, 16, 17, 18, and 19 were used, employing the immunoperoxidase method. Results show that: 1) An increased expression of CK8 and CK18 is seen in the TCC tumor cells at the interface with peritumoral stroma in the tumor invasion front and with intratumoral stroma ('interface phenomenon'). Other than reflecting a quantitative change, this phenomenon might be explained by unmasking of CK8 and CK18 epitopes occurring in these regions. 2) Although in general the expression of CK13 in local TCC is decreased with increase of histopathologic parameters for progression, ie, grade and stage, an extensive proportion of CK13-positive tumor cells still can be found in some TCCs, even in metastases. 3) Morphologically recognizable types of aberrant differentiation in TCC, i.e., pseudosarcomatous or squamous differentiation and marked loss of differentiation, show altered expression of many of the CKs studied.

Flow cytometric and histomorphometric analysis of limitations of clinical breast cytomorphometry.

The clinical value and limitations of a previously described cytomorphometric method, based on nuclear size and anisonucleosis, for evaluation of routine fine-needle aspiration of the breast were assessed in a series of 313 histologically investigated primary breast lesions. Limitations were analyzed by histomorphometry and DNA flow cytometry in 116 consecutive cases of histologically confirmed breast carcinoma. Eighty per cent of histologically proven malignant tumours were classified cytomorphometrically as malignant and no false-positive results were encountered. For benign lesions a benign cytomorphometric classification was reached in 66% of the cases. Histomorphometry showed that on the whole the assignment of histologically malignant tumours to a non-malignant cytomorphometric classification was determined by smaller nuclei and not by sampling error. Tumours assigned to a malignant cytomorphometric classification had on average significantly higher DNA indices than did tumours not assigned to a malignant cytomorphometric classification (P less than 0.001). The mean-nuclear areas in cytomorphometry and histomorphometry were strongly correlated with DNA indices indicated by DNA flow cytometry (P less than 0.001 for both). The present findings show that this cytomorphometric method is appropriate for routine quality control of a cytological diagnosis of malignancy in FNA of the breast. However, an inconclusive result in 15-25% of the tumours is inevitable.

[Neurofibromatosis and a tumor of Vater's papilla]. / Neurofibromatosis en een tumor bij de papil van Vater.

A male aged 57 is reported with neurofibromatosis presenting with a tumour in the periampullary region. Pathologic examination revealed a neuroendocrine tumour of the carcinoid type. A review of the literature suggests that neurofibromatosis patients are at significant risk for developing a periampullary tumour which is nearly always of neuroectodermal origin. To date, surgical excision is the only curative therapy. Therefore, early diagnosis is of major importance. In all patients with neurofibromatosis presenting with jaundice, gastrointestinal bleeding or abdominal pain, a periampullary tumour should be considered. A review is presented of the latest developments concerning the DNA-based mutation causing this disorder. In family members, DNA linkage studies should be carried out, and they should be periodically screened, e.g. with gastroduodenoscopy.