Results of titanium locking plate and stainless steel cerclage wire combination in femoral fractures

Background:

Some in vitro studies warn combining different metals in orthopedic surgery. The aim of this study is to determine the impact of combining titanium and stainless steel on bone healing and the clinical course of patients undergoing internal fixation of femoral fractures.

Materials and Methods:

69 patients with femoral fractures had polyaxial locking plate osteosynthesis. The locking plate was made of a titanium alloy. Two different cohorts were defined: (a) sole plating and (b) additional stainless steel cerclage wiring. Postoperative radiographs and clinical followup were performed at 6 weeks, 3 months and 12 months.

Results:

Cohorts A and B had 36 and 33 patients, respectively. Patient demographics and comorbidities were similar in both groups. In two cases in cohort A, surgical revision was necessary. No complication could be attributed to the combination of titanium and stainless steel.

Conclusion:

The combination of stainless steel cerclage wires and titanium plates does not compromise fracture healing or the postoperative clinical course.     

Tissue microarray-based screening for chromosomal breakpoints affecting the T-cell receptor gene loci in mature T-cell lymphomas

The pathogenesis of mature T-cell non-Hodgkin lymphomas (T-NHLs) is poorly understood. Analogous to B-cell lymphomas, in which the immunoglobulin (IgH) receptor loci are frequently targeted by chromosomal translocations, the T-cell receptor (TCR) gene loci are affected by translocations in a subset of precursor T-cell malignancies. In a large-scale analysis of 245 paraffin-embedded mature T-NHLs, arranged in a tissue microarray format and using improved FISH assays for the detection of breakpoints in the TCRalpha/delta, TCRbeta, and TCRgamma loci, we provide evidence that mature T-NHLs other than T-cell prolymphocytic leukaemia (T-PLL) also occasionally show a chromosomal rearrangement that involves the TCRalpha/delta locus. In particular, one peripheral T-cell lymphoma (not otherwise specified, NOS) with the morphological variant of Lennert lymphoma displayed a chromosomal translocation t(14;19) involving the TCRalpha/delta and the BCL3 loci. A second case, an angio-immunoblastic T-cell lymphoma (AILT), carried an inv(14)(q11q32) affecting the TCRalpha/delta and IgH loci. FISH signal constellations as well as concomitant comparative genomic hybridization (CGH) data were also suggestive of the occurrence of an isochromosome 7, previously described to be pathognomonic for hepatosplenic T-cell lymphomas, in rare cases of enteropathy-type T-cell lymphoma.     

Interferon β-1a and β-1b for patients with multiple sclerosis: updates to current knowledge

Introduction: Although multiple sclerosis (MS) remains incurable, interferon beta (IFNβ) has been at the forefront of treatment for many years. Different formulations of IFNβ allow for different levels of exposure: low-dose/frequency with some agents, and high-dose/frequency with others.

Areas covered: This review article discusses existing and emerging efficacy and safety data for IFNβ in MS. Clinical evidence of IFNβ efficacy has been generated and accumulated over many decades. During this time, key clinical trials have demonstrated the benefits of high-dose and/or high-frequency dosing of IFNβ-1a or β-1b, compared with lower levels of exposure, on outcome measures such as relapse rates, disability progression, disease progression and magnetic resonance imaging lesion outcomes.

IFNβ therapy is well tolerated and has one of the best characterized safety profiles of all first line therapies. The overall severity of adverse events (AEs) does not appear to be affected by different IFNβ exposures. Typical AEs that patients may experience with IFNβ are mild, reversible and manageable.

Expert commentary: IFNβ is one of the best characterized treatments for MS, with a large body of clinical and real-world evidence supporting the risk-benefit profile. High-dose/frequency regimens may provide better long-term outcomes.     

Tumor genetics and survival of thymic neuroendocrine neoplasms: A multi‐institutional clinicopathologic study

Thymic neuroendocrine tumors (TNET) are rare primary epithelial neoplasms of the thymus. This study aimed to determine clinically relevant parameters for their classification and for therapeutic decisions. We performed a comprehensive histological, clinical, and genetic study of 73 TNET cases (13 thymic typical carcinoids [TTC], 40 thymic atypical carcinoids [TAC], and 20 high‐grade neuroendocrine carcinomas [HGNEC] of the thymus), contributed by multiple institutions. The mean number of chromosomal imbalances per tumor was 0.8 in TTC (31% aberrant cases) versus 1.1 in TAC (44% aberrant cases) versus 4.7 in HGNEC (75% aberrant cases). Gains of 8q24 (MYC gene locus) were the most frequent alteration and one of the overlapping features between carcinoids and HGNEC. The 5‐year survival rates for TTC, TAC, and HGNEC were 100, 60, and 30%. The 10‐year survival rates for TTC and TAC were 50 and 30% (P = 0.002). Predictive mitotic cut‐off values for TTC versus TAC were 2.5 per 10 high‐power fields (HPF; indicating a higher death rate, P = 0.062) and 15 per 10 HPF (indicating higher risk of recurrence, P = 0.036) for separating HGNEC from TAC. We conclude that the current histopathologic classifications of TNET reflect tumor biology and provide important information for therapeutic management. © 2014 Wiley Periodicals, Inc.     

C-kit overexpression is not associated with KIT gene mutations in chromophobe renal cell carcinoma or renal oncocytoma

Introduction

C-kit overexpression has previously been described in chromophobe renal cell carcinoma (cpRCC) and renal oncocytoma (RO). However, so far no KIT mutations have been found. The objective of our study was to analyse c-kit in a large cohort of renal tumors and to perform KIT mutation analysis in a subset cpRCC and RO cases with overexpression of c-kit.

Materials and methods

We studied the immunohistochemical expression of c-kit on tissue microarrays containing formalin-fixed, paraffin-embedded samples of 948 patients with renal tumors. CpRCC and RO cases with c-kit overexpression (n = 23) were analyzed for KIT mutations in exons 9, 11, 13, 14, 15, and 17.

Results

Expression of c-kit was found in 6/642 (0.9%) clear cell RCC, 3/154 (1.9%) papillary RCC, 54/69 (78.3%) cpRCC, 37/45 (82.2%) RO and 2/30 (6.7%) of other unclassified tumor types. In none of the RO and cpRCC cases analyzed, a KIT gene mutation was found.

Conclusion

C-kit expression is found in the majority of cpRCC and RO, but these tumors do not harbor the usual c-kit activating mutations. This may have implications for the use of tyrosine kinase inhibitors in patients with advanced cpRCC and c-kit expression.     

Recurrent genetic aberrations in thymoma and thymic carcinoma

Apart from single reported aberrant karyotypes, genetic alterations in thymic epithelial neoplasms have not been investigated so far. In this study, 12 World Health Organization classification type A thymomas (medullary thymomas), 16 type B3 thymomas (well-differentiated thymic carcinomas), and nine type C thymomas, all of them primary thymic squamous cell carcinomas, were analyzed by comparative genomic hybridization and fluorescence in situ hybridization. With the exception of one single case, type A thymomas did not reveal chromosomal gains or losses in comparative genomic hybridization. In contrast, all type B3 thymomas showed chromosomal imbalances, with gain of 1q, loss of chromosome 6, and loss of 13q occurring in 11 (69%), six (38%), and five (31%) of 16 cases, respectively. In primary thymic squamous cell carcinoma, the most frequent chromosomal losses were observed for 16q (six of nine cases, 67%), 6 (4 of 9, 44%), and 3p and 17p (three of nine each, 33%), whereas recurrent gains of chromosomal material were gains of 1q (5 of 9, 56%), 17q, and 18 (three of nine each, 33%). This study shows that the distinct histological thymoma types A and B3 exhibit distinct genetic phenotypes, whereas type B3 thymoma and primary thymic squamous cell carcinoma partially share genetic aberrations. In addition to the possible tumorigenic role, the deletion in type B3 thymoma of chromosome 6, harboring the HLA locus, might play a role in the pathogenesis of paraneoplastic autoimmunity characteristic of thymoma.     

Microarray analysis identifies distinct gene expression profiles associated with histological subtype in human osteosarcoma

Osteosarcoma is the most common primary malignant bone tumour. Currently osteosarcoma classification is based on histological appearance. It was the aim of this study to use a more systematic approach to osteosarcoma classification based on gene expression analysis and to identify subtype specific differentially expressed genes. We analysed the global gene expression profiles of ten osteosarcoma samples using Affymetrix U133A arrays (five osteoblastic and five non-osteoblastic osteosarcoma patients). Differential gene expression analysis yielded 75 genes up-regulated and 97 genes down-regulated in osteoblastic versus non-osteoblastic osteosarcoma samples, respectively. These included genes involved in cell growth, chemotherapy resistance, angiogenesis, steroid- and neuropeptide hormone receptor activity, acute-phase response and serotonin receptor activity and members of the Wnt/ß-catenin pathway and many others. Furthermore, we validated the highly differential expression of six genes including angiopoietin 1, IGFBP3, ferredoxin 1, BMP, decorin, and fibulin 1 in osteoblastic osteosarcoma relative to non-osteoblastic osteosarcoma. Our results show the utility of gene expression analysis to study osteosarcoma subtypes, and we identified several genes that may play a role as potential therapeutic targets in the future.     

Comparison of the results of the Weil and Helal osteotomies for the treatment of metatarsalgia secondary to dislocation of the lesser metatarsophalangeal joints

We retrospectively reviewed the outcome of 30 patients who were treated surgically for metatarsalgia resulting from dislocation of one or more lesser metatarsophalangeal (MTP) joints. We used two treatments, including an osteotomy of the metatarsal head (Weil osteotomy, N = 15) or an osteotomy of the metatarsal shaft (Helal osteotomy, N = 15). Before surgery, all patients had been treated with various nonoperative modalities for a minimum of 6 months. Between 1991 and 1993, 15 consecutive patients underwent a Helal osteotomy (22 metatarsals), and 15 consecutive patients were subsequently treated between 1994 and 1995 with a Weil osteotomy (25 metatarsals). All patients were evaluated clinically and radiographically at a mean follow-up period of 22 months (range, 12-39 months), noting especially persistent subluxation or dislocation, recurrent metatarsalgia, and transfer lesions. Patients managed with a Weil osteotomy had significantly higher satisfaction (P = 0.049), lower incidence of recurrent metatarsalgia (0 vs. 27%, P = 0.107), and fewer transfer lesions (0 vs. 41%, P = < 0.001) than those managed with a Helal osteotomy. Furthermore, those managed with the Weil procedure had a higher percentage of radiographic reduction and maintenance of the MTP joint dislocation (21 of 25, 84%; vs. 8 of 22, 36%; P = 0.002) than those managed with the Helal procedure. In the Weil group, there was also no malunion or pseudoarthrosis; in the Helal group there were five malunions and three pseudoarthroses. Although the follow-up period for the Weil osteotomy (15 months) was shorter than that for the Helal osteotomy (26 months), the former group had higher American Orthopaedic Foot and Ankle Society forefoot scores, which were significantly different from the results attained with the Helal osteotomy. A telephone update was performed on the Weil osteotomy group at an average of 27 months postsurgery, and no patient had experienced changes since the clinical follow-up. We concluded that the Weil procedure is a satisfactory method for correcting metatarsalgia caused by dislocation of the MTP joint and that, because of the high complication rate, the Helal osteotomy is not an acceptable procedure for correcting this condition.