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Excessive centrosome abnormalities without ongoing numerical chromosome instability in a Burkitt's lymphoma.

Numerical and structural centrosome abnormalities are detected in various human malignancies and have been implicated in the formation of multipolar mitoses, chromosome missegregation, and chromosomal instability. Despite this association between centrosome abnormalities and cancerous growth, a causative role of centrosome aberrations in generating chromosomal instability and aneuploidy has not been universally established. We report here excessive numerical and structural centrosome abnormalities in a malignant Burkitt's lymphoma harboring the characteristic t(8;14) chromosomal translocation. Using conventional karyotyping and fluorescence in situ hybridization (FISH), we detected no signs of ongoing numerical chromosome instability, although the tumor displayed sporadic multipolar metaphases. These findings demonstrate that centrosome abnormalities are not a universal surrogate marker for chromosomal instability in malignant tumors. Moreover, our results suggest a model in which additional cellular alterations may be required to promote centrosome-related mitotic defects in tumor cells.

Adult↗

Genetic instability and divergence of clonal populations in colon cancer cells in vitro.

The accumulation of multiple chromosomal abnormalities is a characteristic of the majority of colorectal cancers and has been attributed to an underlying chromosomal instability. Genetic instability is considered to have a key role in the generation of genetic and phenotypic heterogeneity in cancer cells. To shed light on the dynamics of chromosomal instability in colon cancer cells, we have analyzed genetic divergence in clonal and subclonal derivates of chromosomally unstable (SW480) and stable (HCT116, LoVo) cell lines. Conventional G-banding karyotyping and arbitrarily primed PCR (AP-PCR) fingerprinting were used to calculate genetic distances among clones and parental cells, and to trace tree-type phylogenies among individual cells and clonal cell populations. SW480 cells showed enhanced karyotypic heterogeneity in clones as compared with parental cells. Moreover, genetic clonal divergence was also increased after two consecutive episodes of single-cell cloning, demonstrating that the homogeneity induced by the bottleneck of cloning is disrupted by genetic instability during clonal expansion and, as a consequence, heterogeneity is restored. These results demonstrate genetic drift in clonal populations originated from isolated cells. The generated cell heterogeneity coupled with selection provides the grounds for the reported feasibility of pre-neoplastic and neoplastic cells to generate new phenotypic variants with increased evolutionary potential.

Cell Line, Tumor↗

Centrosome amplification and chromosomal instability in feline lymphoma cell lines.

To evaluate the presence of centrosome amplification and the resulting chromosomal instability in cat tumors, a newly established feline lymphoma cell line and four already established feline lymphoma cell lines were examined using immunohistochemical analysis of centrosomes. The number of chromosomes were subsequently counted by metaphase spread. Moreover, to explore whether mutational inactivation of the p53 gene or inactivation of the P53 protein caused by mdm2 gene overexpression, occurred in the feline lymphoma cell lines, mutational analysis of the feline p53 gene was carried out. The expression of feline mdm2 mRNA was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Centrosome amplification and chromosomal instability was observed in three out of the five feline lymphoma cell lines. Of these three feline lymphoma cell lines, one had aberrations in the P53 amino-acid sequence, whereas the others had none. There was no significant difference in the expression of mdm2 mRNA between peripheral blood mononuclear cells (PBMC) obtained from a normal cat and that of the five feline lymphoma cell lines. These findings indicate that centrosome amplification also occurs in cat tumors and is strongly correlated with chromosomal instability, suggesting that the immunostaining of centrosomes could be an alternative method for the examination of the chromosomal instability. Furthermore, this study suggests the presence of unknown mechanism that leads to the centrosome amplification in feline lymphomas.

Animals↗

Glenohumeral joint instability in normal adolescents. Incidence and significance.

One hundred and fifty asymptomatic shoulders in 75 schoolchildren were studied. The shoulders were tested for instability and a hyperextensometer was used to assess joint laxity. Signs of instability were found in 57% of the shoulders in boys and 48% in girls; the commonest sign was a positive posterior drawer test which was found in 63 shoulders. A positive sulcus sign was found in 17 shoulders and 17 subjects had signs of multidirectional instability. General joint laxity was not a feature of subjects whose shoulders had positive instability signs.

Adolescent↗

Management of recurrent, complex instability of the elbow with a hinged external fixator.

We have treated 16 patients with recurrent complex elbow instability using a hinged external fixator. All patients had instability, dislocation or subluxation of the ulnohumeral joint. The injuries were open in eight patients and were associated with 20 other fractures and five peripheral nerve injuries. Two patients had received initial treatment from us; 14 had previously had a mean of 2.1 unsuccessful surgical procedures (1 to 6). The fixator was applied at a mean of 4.8 weeks (0 to 9) after the injury and remained on the elbow for a mean of 8.5 weeks (6 to 11). After treatment we found the mean range of flexion-extension to be 105 degrees (65 to 140). At a final follow-up of 23 months (14 to 40), the mean Morrey score was 84 (49 to 96): this translated into one poor, three fair, ten good and two excellent results. Complications included one fractured humeral pin, one temporary palsy of the radial nerve, one recurrent instability, one wound infection, one severe pin-track infection and one patient with reflex sympathetic dystrophy. Although technically demanding, the use of the fixator is an important advance in the management of recurrent complex elbow instability after failure of conventional treatment.

Adult↗

The use of ultrasound in determining the initiation of treatment in instability of the hip in neonates.

We have evaluated the effect of the use of ultrasound in determining the initiation of treatment in neonatal instability of the hip. A total of 99 newborn infants (1.5% of all live births) with neonatal hip instability did not have treatment from birth, but were re-examined at eight to 15 days. In the 31 who had persisting clinical instability and ultrasound abnormality, treatment was then started with a Frejka pillow. The hips in the remaining 68 infants showed spontaneous clinical stabilisation and improvement of the ultrasound findings. Treatment was therefore withheld. There was a marked trend towards normal development in mildly unstable hips, whereas no hips with severe instability did so spontaneously. Further follow-up showed normal development in all the hips which had been treated, and in all except five of the 68 untreated infants. These five infants showed persistent hip dysplasia on both ultrasound and radiological examination at four to five months of age. Treatment with an abduction splint was then started and their hips developed normally. Ultrasound is very useful in deciding on treatment if the examiners have adequate experience with the method. Its use substantially reduces the rate of treatment. Spontaneous resolution occurred in more than half of the unstable hips. Since five of the untreated infants developed hip dysplasia a strict follow-up is essential to identify and treat these cases.

Female↗

Conditional coalescent trees with two mutation rates and their application to genomic instability.

Humans have invested several genes in DNA repair and fidelity replication. To account for the disparity between the rarity of mutations in normal cells and the large number of mutations present in cancer, an hypothesis is that cancer cells must exhibit a mutator phenotype (genomic instability) during tumor progression, with the initiation of abnormal mutation rates caused by the loss of mismatch repair. In this study we introduce a stochastic model of mutation in tumor cells with the aim of estimating the amount of genomic instability due to the alteration of DNA repair genes. Our approach took into account the difficulties generated by sampling within tumoral clones and the fact that these clones must be difficult to isolate. We provide corrections to two classical statistics to obtain unbiased estimators of the raised mutation rate, and we show that large statistical errors may be associated with such estimators. The power of these new statistics to reject genomic instability is assessed and proved to increase with the intensity of mutation rates. In addition, we show that genomic instability cannot be detected unless the raised mutation rates exceed the normal rates by a factor of at least 1000.

Computational Biology↗

Zebrafish genomic instability mutants and cancer susceptibility.

Somatic loss of tumor suppressor gene function comprising the second hit of Knudson's two-hit hypothesis is important in human cancer. A genetic screen was performed in zebrafish (Danio rerio) to find mutations that cause genomic instability (gin), as scored by Streisinger's mosaic-eye assay that models this second hit. The assay, based on a visible test for loss of wild-type gene function at a single locus, golden, is representative of genomewide events. Twelve ENU-induced genomic instability (gin) mutations were isolated. Most mutations showed weak dominance in heterozygotes and all showed a stronger phenotype in homozygotes. Trans-heterozygosity for 7 of these mutations showed greatly enhanced instability. A variety of spontaneous tumors were found in heterozygous adults from all gin lines, consistent with the expectation that genomic instability (mutator) mutations can accelerate carcinogenesis. The incidence of spontaneous cancer at 30-34 months was increased 9.6-fold in heterozygotes for the mutant with the strongest phenotype, gin-10. Tumors were seen in skin, colon, kidney, liver, pancreas, ovary, testis, and neuronal tissues, with multiple tumors in some fish. The study of these mutants will add to our understanding of the mechanisms of somatic loss of gene function and how those mechanisms contribute to cancer susceptibility.

Animals↗

Molecular testing for microsatellite instability and its value in tumor characterization.

Molecular analysis of tumor tissue has become a rapidly expanding field in medical research, exploiting the advantages of new technologies adapted to high-throughput examination of genetic alterations, gene and protein expression patterns. Only exceptionally, these approaches have found their way into routine clinical diagnosis and therapy. Microsatellite instability testing has been established as a very powerful tool to identify patients with hereditary nonpolyposis colorectal cancer, one of the most common familial cancer syndromes. In addition, there is emerging evidence that microsatellite instability analysis may become increasingly important for the clinician, having considerable impact on patients' prognosis as well as therapeutic decisions, at least in colorectal cancer patients. A better understanding of the microsatellite instability phenotype, its pathogenesis and implications for the course of the disease will pave the way for novel diagnostic and therapeutic strategies specifically tailored to microsatellite-unstable tumors. This review summarizes the current significance of molecular testing for microsatellite instability in several tumor entities and provides prospects of future developments.

Animals↗

Centrosomes, genomic instability, and cervical carcinogenesis.

High-risk human papillomavirus (HPV)-associated carcinogenesis of the uterine cervix is a particularly useful model to study basic mechanisms of genomic instability in cancer. Cervical carcinogenesis is associated with the expression of two high-risk HPV-encoded oncoproteins, E6 and E7. Aneuploidy, the most frequent form of genomic instability in human carcinomas, develops as early as in nonmalignant cervical precursor lesions. In addition, cervical neoplasia is frequently associated with abnormal multipolar mitotic figures, suggesting disturbances of the cell-division process as a mechanism for chromosome segregation defects. Spindle poles are formed by centrosomes, and the high-risk HPV E6 and E7 oncoproteins can each induce abnormal centrosome numbers. These two HPV oncoproteins, however, induce centrosome abnormalities through fundamentally different mechanisms and, presumably, with different functional consequences. High-risk HPV E7, which targets the pRB tumor suppressor pathway, can provoke abnormal centrosome duplication in phenotypically normal cells. On the contrary, cells expressing the HPV E6 oncoprotein, which inactivates p53, accumulate abnormal numbers of centrosomes in parallel with multinucleation and nuclear atypia. These two pathways are not mutually exclusive, since co-expression of HPV E6 and E7 has synergistic effects on centrosome abnormalities and chromosomal instability. Taken together, these findings support the general model in which chromosomal instability arises as a direct consequence of oncogenic insults and can develop at early stages of tumor progression.

Animals↗

Chromosomal instability and delayed apoptosis in long-term T-lymphocyte cultures irradiated with carbon ions and x rays.

In this study, we examined genomic instability induced by 250 kV X rays and 100 MeV/nucleon carbon ions in long-term lymphocyte cultures from two healthy donors. Two biological end points, delayed apoptosis and chromosomal instability, were studied in descendants of cells irradiated with three different doses of the particular radiation up to 22 population doublings. The delayed apoptosis showed no clear dependence on radiation dose, culture time or radiation quality. A persistent significant increase in the rate of apoptosis up to 36 days after X irradiation was observed for a dose of 4 Gy in donor 1 only. For both donors and radiations, de novo aberration yields were significantly increased in comparison to control values up to day 36. For both radiations, chromosome-type aberrations were seen more frequently than chromatid-type aberrations in both donors up to 22 days postirradiation. In both donors, carbon ions were more effective than X rays with respect to the induction of chromosome instability. A dose of 0.25 Gy of carbon ions corresponding to 1.4 ion traversals per cell nucleus was effective in the induction of instability in our cell system.

Apoptosis↗

Spontaneous and radiation-induced genomic instability in human cell lines differing in cellular TP53 status.

Structural chromosomal rearrangements are commonly observed in tumor karyotypes and in radiation-induced genomic instability. Here we report the effects of TP53 deficiency on karyotypic stability before and after irradiation using related cells and clones differing in cellular TP53 status. The parental cell line, TK6, is a TP53 wild-type human B-lymphoblastoid line with a highly stable karyotype. In the two TK6 derivatives used here, TP53 has been inactivated by biochemical means (expression of HPV16 E6; TK6-5E) or genetic means (allelic inactivation; NH32). Biochemical inactivation of TP53 (TK6-5E) had little effect on the spontaneous karyotype, whereas allelic inactivation of TP53 (NH32) resulted in a modest increase in spontaneous karyotypic instability. After 2 Gy gamma irradiation, the number of unstable clones derived from TP53-deficient cells was significantly elevated compared to the TP53 wild-type counterpart. Extensively destabilized clones were common after irradiation in the set of clones derived from NH32 cells, and one was observed in the set of TK6-5E clones; however, they were never observed in TK6-derived clones. In two of the irradiated NH32 clones, whole chromosomes or chromosome bands were preferentially involved in alterations. These results suggest that genomic instability may differ both quantitatively and qualitatively as a consequence of altered TP53 expression. Some of the results showing repeated and preferential chromosome involvement in aberrations support a model in which instability may be driven by cis mechanisms.

Aneuploidy↗

Clonally expanded T-cell populations in atomic bomb survivors do not show excess levels of chromosome instability.

Radiation-induced genomic instability has been studied primarily in cultured cells, while in vivo studies have been limited. One major obstacle for in vivo studies is the lack of reliable biomarkers that are capable of distinguishing genetic alterations induced by delayed radiation effects from those that are induced immediately after a radiation exposure. Here we describe a method to estimate cytogenetic instability in vivo using chromosomally marked clonal T-cell populations in atomic bomb survivors. The basic idea is that clonal translocations are derived from single progenitor cells that acquired an aberration, most likely after a radiation exposure, and then multiplied extensively in vivo, resulting in a large number of progeny cells that eventually comprise several percent of the total lymphocyte population. Therefore, if chromosome instability began to operate soon after a radiation exposure, an elevated frequency of additional but solitary chromosome aberrations in clonal cell populations would be expected. In the present study, six additional translocations were found among 936 clonal cells examined with the G-band method (0.6%); the corresponding value with multicolor FISH analysis was 1.2% (4/333). Since these frequencies were no higher than 1.2% (219/17,878 cells), the mean translocation frequency observed in control subjects using the G-band method, it is concluded that chromosome instabilities that could give rise to an increased frequency of persisting, exchange-type aberrations were not commonly generated by radiation exposure.

Breast Neoplasms↗

Instability of the elbow treated with semiconstrained total elbow arthroplasty.

The results of nineteen semiconstrained modified Coonrad-Morrey total elbow arthroplasties performed in nineteen patients to treat instability were evaluated at an average of seventy-two months (range, twenty-five to 128 months) postoperatively. Preoperatively, all patients had either a flail elbow or gross instability of the elbow that prevented useful function of the extremity. The instability of sixteen elbows was the result of a traumatic injury or of the treatment of such an injury. The most recent result was satisfactory for sixteen elbows and unsatisfactory for three. The average overall Mayo elbow performance score increased from 44 points preoperatively to 86 points postoperatively. At the most recent follow-up examination, no elbow was unstable. The average arc of flexion was from 25 degrees (range, 0 to 60 degrees) to 128 degrees (range, 30 to 142 degrees), which represented a 58-degree increase from the preoperative average arc. Sixteen patients had little or no pain after the arthroplasty. There were four complications in four patients. Three complications (loosening of the humeral component in one patient and a fracture of the ulnar component in two) occurred postoperatively; all three were treated with a revision procedure. The other complication (a fracture of the olecranon) occurred intraoperatively and was treated with tension-band fixation; the most recent outcome was not affected. Radiographically, one patient had complete (type-V) radiolucency about the humeral component. None of the nine patients for whom true anteroposterior radiographs were available had evidence of wear of the bushings. The bone graft behind the anterior flange of the humeral prosthesis was mature in fourteen elbows, incomplete in two, and resorbed in two. One patient was excluded from this analysis because radiographs were not available. Instability of the elbow resulting in the inability to use the extremity is a challenging clinical situation. However, in patients who are more than sixty years old and in selected patients who are less than sixty years old but who have extensive loss of bone as a result of severe injury, have had multiple operations, or have rheumatoid arthritis, total elbow arthroplasty with a linked, semiconstrained prosthesis reestablishes a mobile, stable joint without premature loosening or failure of the components. In our experience, the use of customized implants, maintenance of the muscular attachments to the epicondyles, and reconstruction of the epicondyles to the implant were unnecessary.

Arthroplasty, Replacement↗

Shoulder arthroplasty for arthritis after instability surgery.

BACKGROUND: We are not aware of any large published studies regarding the intermediate to long-term results of shoulder arthroplasty performed for the treatment of osteoarthritis after instability surgery. Therefore, we reviewed the results of this procedure, the risk factors for an unsatisfactory outcome, and the rates of failure in our patients. METHODS: Between January 1, 1978, and December 31, 1997, thirty-three patients (thirty-three shoulders) with glenohumeral arthritis after instability surgery were treated with a shoulder arthroplasty at our institution. Two patients were excluded from the study: one died less than two years postoperatively, and one had not been managed by the senior surgeon. The remaining thirty-one patients, including twenty-one patients who had had a total shoulder arthroplasty and ten who had had a hemiarthroplasty, were followed for a minimum of two years (mean, seven years) or until the time of revision surgery. The mean age at the time of the shoulder arthroplasty was forty-six years. RESULTS: Shoulder arthroplasty was associated with significant pain relief (p < 0.001) as well as significant improvement in external rotation (from 4 degrees to 43 degrees; p < 0.001) and active abduction (from 94 degrees to 141 degrees; p < 0.001). There was not a significant difference between the hemiarthroplasty group and the total shoulder arthroplasty group with regard to postoperative external rotation, active abduction, or pain. According to a modification of the rating system of Neer et al., there were four excellent, two satisfactory, and four unsatisfactory results in the hemiarthroplasty group and three excellent, five satisfactory, and thirteen unsatisfactory results in the total shoulder arthroplasty group. Three patients in the hemiarthroplasty group and eight patients in the total shoulder arthroplasty group underwent revision surgery. The estimated survival of the components (and 95% confidence interval) was 97% (91% to 100%) at two years, 86% (74% to 99%) at five years, and 61% (42% to 86%) at ten years. CONCLUSIONS: The data from the present study suggest that shoulder arthroplasty for the treatment of osteoarthritis of the glenohumeral joint following instability surgery in this relatively young group of patients provides pain relief and improved motion but is associated with high rates of revision surgery and unsatisfactory results due to component failure, instability, and pain due to glenoid arthritis.

Adult↗

Glenoid rim morphology in recurrent anterior glenohumeral instability.

BACKGROUND: Knowledge regarding the morphology of the glenoid rim is important when patients with recurrent anterior glenohumeral instability are assessed. Ordinary imaging techniques are not always sensitive enough to demonstrate the morphology of the glenoid rim accurately. We developed a method of three-dimensionally reconstructed computed tomography with elimination of the humeral head to evaluate glenoid morphology. The purpose of the present study was to quantify glenoid osseous defects and to define their characteristics in patients with recurrent anterior instability. METHODS: The morphology of the glenoid rim in 100 consecutive shoulders with recurrent unilateral anterior glenohumeral instability was evaluated on three-dimensionally reconstructed computed tomography images with the humeral head eliminated. The configuration of the glenoid rim was evaluated on both en face and oblique views. Concurrently, we also investigated seventy-five normal glenoids, including both glenoids in ten normal volunteers. Shoulders without an osseous fragment at the anteroinferior portion of the glenoid were compared with the contralateral shoulder in the same patient to determine if the glenoid morphology was normal. In shoulders with an osseous fragment, the fragment was evaluated quantitatively and its size was classified as large (>20% of the glenoid fossa), medium (5% to 20%), or small (<5%). Finally, all 100 shoulders were evaluated arthroscopically to confirm the presence of the lesion at the glenoid rim that had been identified with three-dimensionally reconstructed computed tomography. RESULTS: Investigation of the normal glenoids revealed no side-to-side differences. Investigation of the affected glenoids revealed an abnormal configuration in ninety shoulders. Fifty glenoids had an osseous fragment. One fragment was large (26.9% of the glenoid fossa), twenty-seven fragments were medium (10.6% of the glenoid fossa, on the average), and twenty-two were small (2.9% of the glenoid fossa, on the average). In the forty shoulders without an osseous fragment, the anteroinferior portion of the glenoid appeared straight on the en face view and it appeared obtuse or slightly rounded, compared with the normally sharp contour of the normal glenoid rim, on the oblique view, suggesting erosion or a mild compression fracture at this site. Arthroscopic investigation revealed a Bankart lesion in ninety-seven of the 100 shoulders and an osseous fragment in forty-five of the fifty shoulders in which an osseous Bankart lesion had been identified with the three-dimensionally reconstructed computed tomography. In the shoulders with distinctly abnormal morphology on three-dimensionally reconstructed computed tomography, the arthroscopic appearance of the anteroinferior portion of the glenoid rim was compatible with the appearance demonstrated by the three-dimensionally reconstructed computed tomography. CONCLUSIONS: We introduced a method to evaluate the morphology of the glenoid rim and to quantify the osseous defect in a simple and practical manner with three-dimensionally reconstructed computed tomography with elimination of the humeral head. Fifty percent of the shoulders with recurrent anterior glenohumeral instability had an osseous Bankart lesion; 40% did not have an osseous fragment but demonstrated loss of the normal circular configuration on the en face view and an obtuse contour on the oblique view, suggesting erosion or compression of the glenoid rim.

Adolescent↗

The efficacy of ultrasound in the evaluation of dynamic scapholunate ligamentous instability.

BACKGROUND: The accuracy of diagnostic imaging modalities that are currently used to evaluate dynamic scapholunate ligamentous instability is equivocal. Ultrasound is commonly used for a wide variety of diagnostic purposes in orthopaedics. The purpose of the present study was to determine the efficacy of ultrasound in the diagnosis of dynamic scapholunate ligamentous instability. METHODS: Two groups of individuals were prospectively studied. Group A included patients with a clinical diagnosis of unilateral dynamic scapholunate ligamentous instability, and Group B included asymptomatic volunteer control subjects. Dynamic ultrasound examinations of the dorsal portion of the scapholunate ligament in both wrists of all individuals were performed by radiologists. The radiologists were blinded with regard to the group to which each person belonged as well as with regard to the affected wrist in the patients in Group A. Arthroscopic examinations of the affected wrist in all of the patients in Group A were then performed by surgeons who were blinded with regard to the results of the ultrasound examination, and the results of the arthroscopic and ultrasound examinations were compared. The ability of ultrasound to discern asymptomatic from symptomatic individuals was also determined. RESULTS: Over a period of 1.5 years, a total of sixty-four wrists were evaluated in fourteen patients (Group A) and eighteen normal subjects (Group B). All fourteen nonaffected wrists in Group A and all thirty-six wrists in Group B were correctly identified as normal with use of ultrasound. Of the fourteen affected wrists in Group A, thirteen were found to have scapholunate ligament laxity on the basis of arthroscopy (twelve wrists) or arthrotomy (one wrist); six of these thirteen wrists had been correctly identified as abnormal with use of ultrasound (a true-positive result), and seven had false-negative results. There was one true-negative result. The ability of ultrasound to differentiate between normal and abnormal wrists was significant (p < 0.001). For the sixty-four wrists, statistical analysis revealed that ultrasound had a sensitivity of 46.2%, a specificity of 100%, and an accuracy of 89.1%. CONCLUSIONS: We conclude that ultrasound has a high specificity and accuracy but a low sensitivity for the evaluation of dynamic scapholunate ligamentous instability, and we recommend its use as an adjunct to other diagnostic modalities for this purpose.

Adult↗

Posterior instrumentation surgery for craniocervical junction instabilities: an update.

The surgical treatment of craniocervical junction (CCJ) instability has recently undergone significant development and change. Posterior instrumentation surgery has been the mainstay of treatment of CCJ instability, and is the focus of this review. For the treatment of atlantoaxial instability, C1-2 transarticular screw fixation has shown good stability, and has been regarded as the "gold standard" procedure. Because of potentially hazardous complications including vertebral artery injury, however, C-1 lateral mass-C-2 pedicle screw fixation is gaining popularity. For treatment of atlantooccipital instability, occipitocervical fixation using screw constructs (combined with either rods or plates) has shown more stability than sublaminar wiring techniques, and has been utilized more frequently. Both innovation in material engineering and in vitro biomechanical studies have contributed significantly to the development of more rigid internal fixation devices, and as a result, many patients who would have been treated conservatively with external orthosis are treated nowadays with instrumentation surgery, resulting in earlier ambulation, shortened hospital stay, and earlier recovery into social activities. New surgical techniques and instruments, however, need to stand the test of time to see whether they are free from long-term adverse events. The rapid turnover of new surgical techniques and hardware has made it difficult for less experienced surgeons to keep up with the latest developments. Conventional techniques can be safer and less technically demanding than newer techniques for those who are not familiar with them.

Cervical Vertebrae↗