Pseudotumors in Small-Head Metal-on-Metal Total Hip Arthroplasties at a Minimum Follow-Up of 20 Years

BackgroundMetal-on-metal (MOM) surfaces in total hip arthroplasty (THA) have been used widely. Serum cobalt and chromium levels have been the standard investigation for follow-up examinations, but magnetic resonance imaging (MRI) with metal artifact reducing sequences has shown good results in detecting pseudotumors. The aim of this study is to survey a significant correlation among MRI findings, serum metal levels, and clinical scores in patients with small-head MOM implants and if serum cobalt and chromium levels are sufficient in detecting patients with pseudotumors in the long-term follow-up.MethodsAt a minimum follow-up of 20 years, 26 patients (29 THAs) of the original 98 patients (105 THAs) included in this study between November 1992 and May 1994 were available for follow-up examination. Clinical scores, serum metal ion levels, and MRIs were obtained.ResultsWe found mean serum cobalt levels of 1.87 μg/L (±3.44) and chromium levels of 2.23 μg/L (±2.96) and very good clinical and functional results (mean Harris Hip Score 88.6) in the long-term follow-up. Pseudotumors were detected in MRIs of 21 hips. There were no significant differences between patients with or without pseudotumors regarding serum metal levels and the correlation for clinical outcome scores, demographic data, and cup inclination. The cumulative rate of survival was still at 91.4% at 22.8 years.ConclusionThis study presents the first published data on small-head MOM hips, comparing metal ion levels, pseudotumors, clinical, and radiological results in a follow-up period of more than 20 years and reveals that serum metal levels are not significantly higher in patients with pseudotumors.Level of EvidenceTherapeutic Level III     

Photodynamic Diagnosis in Non–Muscle-Invasive Bladder Cancer: A Systematic Review and Cumulative Analysis of Prospective Studies

Context

The clinical benefit of photodynamic diagnosis (PDD) with 5-aminolevulinic acid or hexaminolevulinate in addition to white-light cystoscopy (WLC) in bladder cancer has been discussed controversially.

Objective

To assess in a systematic review the effect of PDD in addition to WLC on (1) the diagnosis and (2) the therapeutic outcome of primary or recurrent non–muscle-invasive bladder cancer investigated by cystoscopy or transurethral resection.

Evidence acquisition

An electronic database search of Medline, Embase, the Cochrane Library, and CancerLit was undertaken, plus hand searching of relevant congress abstracts and urologic journals. Trials were included if they prospectively compared WLC with PDD in bladder cancer. The review process followed the guidelines of the Cochrane Collaboration. Two reviewers evaluated independently both trial eligibility and methodological quality and data extraction.

Evidence synthesis

The primary end point of diagnostic accuracy was additional detection rate. The primary end points of therapeutic outcome were residual tumour at second resection and recurrence-free survival (RFS). Seventeen trials were identified. Twelve diagnostic trials used WLC and PDD with the same patients. Seven reported results for the subgroup of patients with carcinoma in situ (CIS). Five randomised trials studied therapeutic outcome. The results were combined in random effects meta-analyses if end points, designs, and populations were comparable. Twenty percent (95% confidence interval [CI], 8–35) more tumour-positive patients were detected with PDD in all patients with non–muscle-invasive tumours and 39% (CI, 23–57) more when only CIS was analysed. Heterogeneity was present among diagnostic studies even when the subgroup of patients with CIS was investigated. Residual tumour was significantly less often found after PDD (odds ratio: 0.28; 95% CI, 0.15–0.52; p < 0.0001). RFS was higher at 12 and 24 mo in the PDD groups than in the WLC-only groups. The combined p value of log-rank tests of RFS was statistically significant (0.00002).

Conclusions

PDD detects more bladder tumour–positive patients, especially more with CIS, than WLC. More patients have a complete resection and a longer RFS when diagnosed with PDD.     

Phase 3 Study of Adjuvant Radiotherapy Versus Wait and See in pT3 Prostate Cancer: Impact of Pathology Review on Analysis

Background

In a randomised trial, radical prostatectomy (RP) followed by adjuvant radiotherapy (aRT) was compared with RP alone in patients with pT3 pN0 prostate cancer with or without positive margin at local pathology (German Cancer Society trial numbers ARO 96-02/AUO AP 09/95).

Objective

A pathology review was performed on 85% of RP specimens of patients to investigate the influence of pathology review on the analysis.

Design, setting, and participants

Patients post-RP (n = 385) were randomised before achieving an undetectable prostate-specific antigen (PSA) level to either wait and see (n = 192) or 60 Gy aRT (n = 193). Of 307 patients with undetectable PSA after RP, 262 had pathology review. These results were included prospectively into the analysis.

Outcome measurements and statistical analysis

Agreement between local and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic reliability for the different parameters was analysed by Cox regression model. Event-free rates were determined by Kaplan-Meier analysis with a median follow-up of 40 mo for the wait-and-see arm and 38.5 mo for the aRT arm.

Results and limitations

There was fair concordance between pathology review and local pathologists for seminal vesicle invasion (pT3c: 91%; κ = 0.76), surgical margin status (84%; κ = 0.65), and for extraprostatic extension (pT3a/b: 75%; κ = 0.74). Agreement was much less for Gleason score (47%; κ = 0.42), whereby the review pathology resulted in a shift to Gleason score 7. In contrast to the analysis of progression-free survival with local pathology, the multivariate analysis including review pathology revealed PSMs and Gleason score >6 as significant prognostic factors.

Conclusions

Phase 3 studies of postoperative treatment of prostate cancer should be accomplished in the future with a pathology review. In daily practice, a second opinion by a pathologist experienced in urogenital pathology would be desirable, in particular, for high-risk patients after RP.     

Revascularized fibula for tibia replacement in adamantinoma

Adamantinoma of long bones is one of the rarest of malignant bone tumors; it is commonly located in the middle or lower third of the diaphysis of the tibia. A case with multiple occurrences affecting both the tibia and fibula is presented. En bloc resection with wide operative margins was performed, and a large tibial defect of 23 cm was effectively bridged by a revascularized free fibular flap. At 13 months follow-up, there was no sign of local recurrence or metastasis, and the patient was mobile.     

Detailed pathological changes of human lumbar facet joints L1–L5 in elderly individuals

Facet joints play an important role in intervertebral load transmission and are crucial for rotational kinematics. Clinically, the role of facet joints as a possible source of low back pain is seen as controversial and at present is not sufficiently investigated. In this study, human lumbar facet (zygapopyhysial) joints from donors with advanced age were analyzed macroscopically, for degenerative changes. The aim was to determine the extent and morphology of degenerative changes in these joints. Lumbar facet joints (L1–L5) of 32 donors were studied (mean age 80.1±11.2 years). Joint capsules were carefully removed and joint surfaces (5 zones) examined using magnifying glasses and probes. In the result, the majority of facet joints showed cartilage defects of varying extent. Defects were located mostly at the margins of the articular surface, the central zone being relatively well preserved. Defect localization was different between superior (most cartilage defects in superior zone) and inferior (most defects inferiorly) facets. Further, defects were more severe caudal (level of L5) and in older persons. Osteophytes were present in up to 30%, located mostly at the latero-dorsal enthesis of the joint capsule on the superior facet. In conclusion, most margins of the articular facets are subject to degenerative changes in the lumbar spine of elderly persons, the topographical pattern being different in superior and inferior facets. This observation can be explained by the segmental motion patterns during extension/flexion movements of the facets. Sometimes, due to the marginal extension, it is obvious that not all changes can be assessed by CT or MRI.     

Penetrating keratoplasty in patients with atopic dermatitis with and without systemic cyclosporin A

PURPOSE: Clinical experience suggests that atopic dermatitis is a considerable risk factor in penetrating keratoplasty. The scientific evidence, however, has been equivocal. Systemic cyclosporin A reduces the threat of immune reactions and simultaneously improves atopic dermatitis. The purpose of this study was to evaluate to what extent and for how long systemic cyclosporin A improves graft prognosis in patients with atopic dermatitis. PATIENTS AND METHODS: Between November 1986 and July 1994, 173 penetrating keratoplasties were performed on keratoconus patients without skin disease (I). Fifteen penetrating keratoplasties were performed on patients with keratoconus associated with slight atopic dermatitis (II), 24 on patients with keratoconus associated with severe atopic dermatitis (III), and 13 on patients with keratitis in atopic dermatitis but without keratoconus (IV). Systemic cyclosporin A was administered for at least 6 months in groups III and IV. Clear graft survival was estimated according to Kaplan and Meier, and statistical significance was evaluated via log-rank test. RESULTS: Six months/6 years postoperatively 99.5 and 96.5% (I), 80 and 80% (II), 96 and 83.2% (III), and 100 and 65.8% (IV) of the grafts were clear. Only the differences between the survival curve of group I and the curves of each of groups II-IV were statistically significant (p < 0.001). CONCLUSIONS: To our knowledge, this is the first study proving that atopic dermatitis with and without keratoconus deteriorates graft prognosis statistically significantly. The application of systemic cyclosporin A improves graft prognosis in atopic dermatitis as long as the drug is applied, and this effect slowly fades thereafter.     

The new malononitrilamide immunosuppressant FK778 prolongs corneal allograft survival in the rat keratoplasty model

PURPOSE: Aim of this study was to prove the efficacy and safety of the new malononitrilamide immunosuppressive FK778 in prolonging clear graft survival following allogeneic orthotopic keratoplasty in rats. METHODS: Sixty-seven penetrating keratoplasties were performed using Fisher and Lewis rats as donors and recipients, respectively: group 1 (n=11), allogeneic control without therapy; group 2 (n=12), syngeneic control; group 3 (n=11), mycophenolate mofetil (MMF) 40 mg/kg bodyweight; group 4 (n=12), FK778 5 mg/kg bodyweight; group 5 (n=12), FK778 10 mg/kg bodyweight; and group 6 (n=9), FK778 20 mg/kg bodyweight. Four animals in each group were killed for immunohistological evaluation on day 14. Therapy was administered orally for 18 days. The grafts were evaluated every three days by means of a scoring system including opacity, oedema, and vascularization. Time to rejection was analysed with the Kaplan-Meier survival analysis and compared with the log-rank test. The densities of infiltrating immune cells were compared statistically using the non-parametric Mann-Whitney test. RESULTS: Mean rejection-free graft survival was 11.4 days in group 1 (allogeneic control), 100 days (total follow-up time) in group 2 (syngeneic control), 24.0 days in group 3 (MMF 40 mg/kg), 15.7 days in group 4 (FK778 5 mg/kg), 19.1 days in group 5 (FK778 10 mg/kg), and 25.4 days in group 6 (FK778 20 mg/kg) (P<0.005). CONCLUSIONS: Systemic immunosuppression with FK778 prolongs graft survival in the rat keratoplasty model. FK778's efficacy is comparable with that of MMF in preventing immunologic graft rejection.     

Eccentric fixation in Stargardt's disease assessed by Tübingen perimetry

PURPOSE: To measure eccentric fixation characteristics in visual fields of patients with Stargardt's disease. METHODS: The positions of fixation loci (FL) in the visual field were determined by Tübingen perimetry (TP), using the position of the blind spots in 173 patients. Altogether, 669 visual fields were measured at baseline and during follow-up. Twenty patients were also examined by scanning laser ophthalmoscope (SLO). RESULTS: Ninety-five of 173 patients showed a ring scotoma with central fixation in at least one test, which could persist for up to 18.8 years. The median age for a 50% chance of the development of eccentric fixation was 23.6 years. One hundred four patients (203 eyes) used eccentric fixation in at least one eye; in 154 eyes, the FL was placed below the scotoma and in 33 eyes to the left of it, in 11 to the right of it, and in 5 above it. Once the FL was chosen, it remained within the same visual field area at subsequent tests, varying on average by 1.76 degrees. Compared with SLO results, the mean distance between FL and PRL was 1.90 degrees. CONCLUSIONS: It is possible to determine the position of the FL by perimetry with sufficient accuracy if the blind spot is well delimited. Stargardt patients can keep central fixation for different time intervals before changing to an eccentric FL. Most of them show an FL below the central scotoma, which is considered favorable for horizontal reading.