Arthroskopisch gestützte Behandlung der aseptischen Hüftkopfnekrose

Objective

Preservation of the hip joint function by treatment of the avascular necrosis of the femoral head in adults or at least avoiding progression.

Indications

Avascular necrosis of the femoral head in adults in Steinberg stages I–III. In patients with Steinberg stage IVa (subchondral collapse ≤?15% of the articular surface, depression <?2 mm) hip joint salvage therapy in early stages of femoral head collapse.

Contraindications

Manifest osteoarthritis of the hip joint. Joint infection. Relative contraindications: subchondral collapse >?15% of the articular surface or depression >?2 mm (Steinberg stage IVb and above). Persisting risk factors for a progression of avascular necrosis (e.g., alcohol abuse, chemotherapy, local irradiation, high-dose cortisone therapy) and obesity (BMI >?40).

Surgical technique

Arthroscopy of the hip joint in case of cartilage defects and/or potential collapse of the femoral head. Without collapse of the femoral head and absence of severe damage of the cartilage: core decompression using a guiding sleeve through a lateral approach (Steinberg II, III). Subsequently curettage of the necrotic area through a central drill hole and insertion of autogenic bone cylinders using an OATS harvester (Steinberg II b/c, III b/c). In Steinberg stage IVa, reconstruction of the outline of the femoral head is attempted by reduction of the impressed portion (under intraoperative fluoroscopy).

Postoperative management

Limited weight bearing (10 kg) of the operated leg for 6 weeks. In cases of large necrotic defects located directly beneath the subchondral bone (Steinberg IIIc) as well as subchondral collapse with flattening of the femoral head (Steinberg IVa) limited weight bearing (10 kg) for 12 weeks.

Results

Early results of femoral head preserving therapy in 53 patients (56 hips, consecutively treated between June 2004 and December 2009) after 33?±?20 months: success rate (no arthroplasty, no reoperation, no radiological progress associated with clinical symptoms) 86% for patients treated with Steinberg stages I–III. Failure of the head preserving therapy with concern to the mentioned criteria depending on the initial Steinberg stage: 0 (0%) for stage I, 2 (10%) for stage II, 3 (25%) for stage III, and 4 (31%) for stage IVa.     

Management der fehlgeschlagenen vorderen Schulterstabilisierung

Background

Shoulder dislocations are common injuries and recurrent dislocations after primary stabilization are also relatively common. Therefore, every shoulder surgeon should know how to handle this condition properly.

Objective

The aim of this article is to present the current knowledge about the management of failed anterior shoulder stabilization including the treatment of humeral and glenoid bone defects.

Methods

The results are based on the current study results in the literature concerning arthroscopic and open shoulder revision stabilization.

Results

The redislocation rate after arthroscopic revision stabilization is between 4.5 and 25% after exclusion of osseous defects. When bony Bankart lesions with a defect size of more than 25% of the glenoid width are prevalent, the redislocation rate increases significantly. Therefore, these defects have to be addressed separately with bony reconstruction procedures. Bony defects of the humerus occasionally have to be addressed, but comparative and prospective long-term studies are rare.

Conclusion

For the management of failed anterior stabilization a detailed investigation of the cause of the failure should be carried out. Specific therapy of the pathology can then be carried out to optimize patient treatment and reduce the risk for redislocation.     

Arthroskopische Resektion des Akromioklavikulargelenks

Objective

Arthroscopic resection of the painful and degenerative altered acromioclavicular (AC) joint without destabilization of the joint and therefore pain relief and improvement in function.

Indications

Conservative failed therapy of painful AC joint osteoarthritis. Impingement caused by caudal AC joint osteophytes. Lateral clavicular osteolysis.

Contraindications

General contraindications (infection, local tumor, coagulation disorders), higher grade instability of the AC joint (resection only together with stabilization).

Surgical technique

Diagnostic glenohumeral arthroscopy. Treatment of accompanying lesions (subacromial impingement, rotator cuff, long head of biceps). Subacromial arthroscopy with bursectomy (partial) and visualization of the AC joint. Resection of caudal osteophytes. Localization of the anterior portal using a spinal needle in the outside-in technique. Resection of 2–3 mm of the acromial side and the 3–4 mm of the clavicular side with shaver/acromionizer.

Results

An isolated open AC joint resection was performed in 9 studies and an arthroscopic resection in 6 studies. Good and very good results were obtained in 79?% (range 54–100?%) in open resection and 91?% (range 85–100?%) in arthroscopic resections. Patients were able to return to activities of daily life more quickly after arthroscopic resections than after open surgery.     

Gene dosage effects in chronic lymphocytic leukemia

To understand the influence of chromosomal alterations on gene expression in a genome-wide view, chromosomal imbalances detected by single nucleotide polymorphism (SNP) chips were compared with global gene expression in 16 cases of chronic lymphocytic leukemia (CLL). A strong concordance between chromosomal gain or loss and increased or reduced expression of genes in the affected regions was found, respectively. Regions of uniparental disomy (UPD) were rare and had usually no consistent influence on gene expression, but in one instance, a large UPD was associated with a downregulation of most genes in the affected chromosome. The frequently deleted miRNAs, MIRN15A and MIRN16-1, did not show a reduced expression in cases with monoallelic deletions. The BCL2 protein, considered to be downregulated by these miRNAs, was upregulated not only in CLL with biallelic deletion of MIRN15A and MIRN16-1, but also in cases with monoallelic deletion. This suggests a complex regulation of BCL2 levels in CLL cells. Taken together, in CLL, a global gene dosage effect exists for chromosomal gains and deletions and in some instances for UPDs. We did not confirm a consistent correlation between MIRN15A and MIRN16-1 expression levels and BCL2 protein levels, indicating a complex regulation of BCL2 expression.     

Diminished CXCR5 expression in peripheral blood of patients with Sjögren's syndrome may relate to both genotype and salivary gland homing

Genetic investigations of Sjögren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. C‐X‐C motif chemokine receptor 5 (CXCR5) is a chemokine receptor expressed on B and T cell subsets, and binds the chemotactic ligand C‐X‐C motif chemokine ligand 13 (CXCL13). In this study we aimed to link the genetic association with functional effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait loci analysis of the 11q23.3 locus was performed using B cell mRNA expression data from genotyped individuals. Lymphocyte surface markers were assessed by flow cytometry, and CXCL13 levels by a proximity extension assay. CXCR5⁺ and CXCL13⁺ cells in minor salivary glands were detected using immunohistochemistry. Our results demonstrated that SS‐associated genetic polymorphisms affected the expression of CXCR5 (P < 0·01). Notably, a decreased percentage of CXCR5⁺ cells, with lower CXCR5 expression, was observed for most circulating B and T cell subsets in SS patients, reaching statistical significance in CD19⁺CD27⁺immunoglobulin (Ig)D⁺ marginal zone (P < 0·001), CD19⁺CD27⁺IgD^– memory (P < 0·05) and CD27‐IgD double‐negative (P < 0·01) B cells and CD4⁺CXCR3^–CCR6⁺ Th17 cells (P < 0·05). CXCL13 levels were increased in patient plasma (P < 0·001), and immunohistochemical staining revealed expression of CXCL13 and higher numbers of CXCR5⁺ cells (P < 0·0001) within focal infiltrates and interstitially in salivary glands of SS patients. In conclusion, we link a genetic susceptibility allele for SS to a functional phenotype in terms of decreased CXCR5 expression. The decrease of CXCR5⁺ cells in circulation was also related to homing of B and T cells to the autoimmune target organ. Therapeutic drugs targeting the CXCR5/CXCL13 axis may be useful in SS.     

Ten novel MSH2 and MLH1 germline mutations in families with HNPCC

Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer-susceptibility syndromes. Germline mutations in mismatch repair genes are associated with the clinical phenotype of HNPCC. We report ten novel germline mutations, three in MSH2 and seven in MLH1. All but one mutation have been found in families fulfilling criteria of the Bethesda guidelines; four of them additionally fulfilled the Amsterdam criteria I or II. Eight mutations were considered pathogenic and predictive diagnostics in healthy family members at risk shall be undertaken; these include five frameshift mutations leading to premature stop codons, in MSH2: c.1672delT (p.S558Xfs) and c.2466_2467delTG (p.C822X) and in MLH1: c.1023delG (p.R341Xfs), c.1127_1128dupAT (p.K377Xfs) and c.1310delC (p.P437Xfs); three mutations leading to splice aberrations, in MSH2: c.1661G>C (r.1511_1661del) and in MLH1: c.677+3A>C (r.589_677del) and c.1990-2A>G predicted to result in a splice site defect. The remaining two mutations are unclassified variants with assumed pathogenicity: one missense mutation in the highly conserved ATPase domain of MLH1 (c.122A>G [p.D41G]) and one in-frame insertion of twelve nucleotides in MLH1 (c.2155_2156insATGTGTTCCACA [p.I719delinsNVFHI]). These two mutations were not found in 102 alleles of healthy control individuals. The corresponding tumors from all patients showed a high level of microsatellite instability (MSI-H). Immunohistochemistry (IHC) revealed complete loss of expression of the affected protein in the tumor cells from all but three patients. The tumors from the patients with the mutations c.1127_1128dupAT and c.1990-2A>G showed a reduction of expression of the MLH1-protein, rather than complete loss. In the tumor from the patient with the missense mutation c.122A>G [p.D41G] a normal expression of the proteins coded by MLH1 and MSH2 was noticed.     

Apparent genotype–phenotype correlation in childhood,adolescent, and adult Chediak‐Higashi syndrome

Chediak‐Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, bleeding tendency, and progressive neurological dysfunction. Most patients present in early childhood and die unless treated by bone marrow transplantation. About 10–15% of patients exhibit a much milder clinical phenotype and survive to adulthood, but develop progressive and often fatal neurological dysfunction. Very rare patients exhibit an intermediate adolescent CHS phenotype, presenting with severe infections in early childhood, but a milder course by adolescence, with no accelerated phase. Here, we describe the organization and genomic DNA sequence of the CHS1 gene and mutation analysis of 21 unrelated patients with the childhood, adolescent, and adult forms of CHS. In patients with severe childhood CHS, we found only functionally null mutant CHS1 alleles, whereas in patients with the adolescent and adult forms of CHS we also found missense mutant alleles that likely encode CHS1 polypeptides with partial function. Together, these results suggest an allelic genotype–phenotype relationship among the various clinical forms of CHS. © 2002 Wiley‐Liss, Inc.     

Consistent mutation status within histologically heterogeneous lung cancer lesions

Mattsson J S M, Imgenberg‐Kreuz J, Edlund K, Botling J & Micke P
(2012) Histopathology  61, 744–748 Consistent mutation status within histologically heterogeneous lung cancer lesions Aims: Activating epidermal growth factor receptor (EGFR) and KRAS mutations characterize molecular subgroups of non‐small‐cell lung cancer (NSCLC) with a strong predictive value for response to EGFR inhibitor therapy. However, the temporal occurrence and clonal stability of these mutations during the course of cancer progression are debated. The aim of this study was to characterize the presence of EGFR and KRAS mutations in histologically different areas of primary NSCLC lesions. Methods and results: Formalin‐fixed paraffin‐embedded cancer specimens from six cases with EGFR mutations and five cases with KRAS mutations were selected from a pool of primary resected NSCLC patients. From each tumour, three morphologically distinct areas were manually microdissected and analysed for the presence of mutations. The results demonstrated consistent EGFR and KRAS mutation status in the different histological areas of all primary tumours. Conclusions: The results support the concept that activating EGFR and KRAS mutations are oncogenic events that are consistently present throughout the primary tumour independently of histological heterogeneity. Thus, for molecular diagnostics, any part of the tumour is likely to be representative for EGFR and KRAS mutation testing.     

Novel twelve-generation kindred of fatal familial insomnia from germany representing the entire spectrum of disease expression

We present a novel large German kindred of fatal familial insomnia (FFI) consisting of three branches and comprising more than 800 individuals of 12 generations, the largest pedigree of any familial prion disease known today. There is a wide spectrum of clinical presentations leading to misdiagnoses of Olivo-Ponto-Cerebellar Atrophy (OPCA), Parkinson's or Alzheimer's disease in addition to Creutzfeldt-Jakob disease (CJD) and Gerstmann-Str?ussler-Scheinker (GSS) syndrome. Molecular genetic analysis of the prion protein gene (PRNP) confirmed the mutation D178N segregating with methionine at the polymorphic codon 129 of PRNP in all 7 patients examined. This polymorphism at codon 129 is supposed to discriminate between familial CJD (fCJD) and FFI; the 129M allele determines FFI and 129V fCJD. Furthermore, heterozygosity at this site appears to induce prolonged disease duration as compared to the homozygous condition. The variability of the clinical and pathological findings documented for our patients indicates the difficulty in establishing the diagnosis of FFI on clinical and on pathological grounds alone. In three cases (IX-97, XI-21, V-2) followed up by us prospectively insomnia was an early and severe symptom; however, in case notes analyzed retrospectively this symptom was frequently missed. In contrast to previous reports and in agreement with recent studies we cannot confirm a clear relationship between the status of the M/V polymorphism at codon 129 and the age-of-onset of this disease.