Pekka Tervahartiala

Effect of the Tyrosine Kinase Inhibitor STI571 in a Patient with a Metastatic Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumors are a group of mesenchymal neoplasms that arise from precursors of the connective-tissue cells of the gastrointestinal tract.1 They occur predominantly in middle-aged and older persons, and approximately 70 percent of the tumors are found in the stomach, 20 to 30 percent are found in the small intestine, and less than 10 percent are found elsewhere in the gastrointestinal tract.1 Recent studies have shown that cells in gastrointestinal stromal tumors express a growth factor receptor with tyrosine kinase activity termed c-kit. This receptor, the product of the proto-oncogene c-kit, can be detected by immunohistochemical staining for .xa0.xa0.

Treatment of severe spondylolisthesis in adolescence with reduction or fusion in situ: long-term clinical, radiologic, and functional outcome.

Study Design. Retrospective follow-up study with two cohorts: one treated with reduction and the other with fusion in situ. Objective. To assess the long-term effects of reduction versus fusion in situ on lumbar spine in children and adolescents with severe L5 isthmic spondylolisthesis. Summary of Background Data. Severe isthmic spondylolisthesis is commonly treated with fusion in situ, but modern surgical techniques and instrumentation permit the reduction of a severely slipped fifth lumbar vertebra. Advocates of one or another of these procedures present different claims to defend their choice. However, to our knowledge, no long-term results of the reduction maneuver exist. Methods. Between 1983 and 1991, 22 adolescents with severe (more than 60%) slip were treated surgically. In 11 of them, reduction was performed with a Magerl/Dick transpedicular device, followed by fusion posteriorly from L4 or L5 to S1 and anteriorly from L5 to S1. In the others, fusion was performed in situ posteriorly from L4 (n = 7) or L5 (n = 4) to S1 and anteriorly from L5 to S1. The average age of patients at surgery was 14.7 years (range 10.7–18.5). Radiographs obtained before surgery, after surgery, and at the final follow-up evaluation were assessed for quality of fusion. In addition, magnetic resonance imaging was obtained at the last follow-up visit. Average follow-up time was 14.8 years (range 11.6–18.7). Physical examination, spinal mobility, and nondynamometric trunk strength measurements were used to assess, and Oswestry Disability Index and Scoliosis Research Society scores were used to calculate outcome at the last follow-up visit. Results. In the reduction group, mean Oswestry Disability Index was 7.2 (range 0–20) and in the fusion in situ group, was 1.6 (range 0–4) (P = 0.0096). The Scoliosis Research Society total score averaged 90.0 (range 39–107) in the reduction group and 103.9 (range 93–120) in the fusion in situ group (P = 0.046). At the last follow-up evaluation, mean vertebral slip had decreased from the preoperative value of 90% to 57% in the reduction group but remained the same (80% vs. 78%) in the fusion in situ group (P = 0.04 and 0.013, respectively, for preoperative and postoperative comparison). On magnetic resonance imaging, disc degeneration above the fusion was more common in the reduction group (P = 0.004). None of the patients had spinal stenosis above the fusion. Nerve root canal impingement at the L5–S1 level was more common in the fusion in situ group (P = 0.03), but all patients were free of L5 nerve root symptoms. There was no difference in spinal mobility or trunk strength measurements between the groups. Conclusions. The fusion in situ group seems to perform better in almost all clinical parameters measured. These findings suggest that fusion in situ should be considered as a method of choice in severe L5 isthmic spondylolisthesis.

Posterolateral, anterior, or circumferential fusion in situ for high-grade spondylolisthesis in young patients: a long-term evaluation using the Scoliosis Research Society questionnaire.

Study Design. A retrospective, comparative follow-up study. Objective. To compare clinical and radiographic outcomes after posterolateral, anterior, or circumferential fusion in situ for high-grade spondylolisthesis in children and adolescents. Summary of Background Data. Controversial opinions still exist about the surgical treatment of severe isthmic spondylolisthesis. There are no long-term comparative studies of different fusion in situ techniques in these patients. Methods. A total of 21 patients treated using posterolateral, 23 using anterior, and 26 using the circumferential fusion technique without instrumentation for high-grade isthmic spondylolisthesis (≥50% slip) participated. Their mean age at surgery was 14.4 years (range 8.0–19.6). The follow-up rate was 84% after a mean of 17.2 years (range 10.7–26.0). Radiographs were obtained before surgery, at 2-year follow-up, and at final follow-up. The Scoliosis Research Society (SRS) and Oswestry Disability Index questionnaires were completed, and a physical examination was performed at the final follow-up visit. Results. Progression of lumbosacral kyphosis (≥10°) was found in 9 (43%), 3 (13%), and 3 (12%) patients of the posterolateral, anterior, and circumferential fusion groups, respectively (P = 0.017). The SRS total score averaged 89.7 (range 56–105) in the posterolateral, 93.2 (range 66–114) in the anterior, and 100.0 (range 71–117) in the circumferential fusion groups (P = 0.021). Patients in the circumferential fusion group had better values for pain (P = 0.023) and function from back condition domains (P = 0.079) than patients in the posterolateral or anterior groups. The Oswestry Disability Index averaged 9.7 (range 0–62) in the posterolateral, 8.9 (range 0–32) in the anterior, and 3.0 (range 0–16) in the circumferential fusion groups (P = 0.035). Conclusions. Circumferential fusion provided significantly better long-term clinical, radiographic, and SRS total score than posterolateral or anterior fusion for high-grade isthmic spondylolisthesis.

Scoliosis research society outcome instrument in evaluation of long-term surgical results in spondylolysis and low-grade isthmic spondylolisthesis in young patients.

Study Design. A retrospective follow-up study of low-grade (slip ≤ 50%) isthmic spondylolisthesis after posterior or posterolateral fusion in young patients. Objective. To evaluate the usefulness of the Scoliosis Research Society questionnaire and compare it with Oswestry Disability Index and radiographic parameters in patients with isthmic spondylolisthesis. Summary of Background Data. A few studies have examined long-term patient outcome using validated questionnaires or compared it with radiographic parameters after surgery for isthmic spondylolisthesis in young patients. The Scoliosis Research Society questionnaire provides patient-oriented information on back pain, cosmetic aspects, patient satisfaction, and level of activity and might therefore be suitable for evaluation of surgical outcome after isthmic spondylolisthesis in young patients. However, there are no studies assessing the usefulness of the Scoliosis Research Society questionnaire for these patients. Methods. One hundred and eight patients treated at a mean (range) age of 15.9 (range, 8.1–19.8) years with posterior (n = 29) or posterolateral (n = 79) in situ fusion for isthmic spondylolisthesis participated in the present study. The follow-up rate was 83% after a mean of 20.8 (range, 15.1–25.9) years. The mean age at follow-up observation was 36.7 years. Radiographs were obtained before surgery, at 2-year follow-up observation, and at final follow-up review. The Scoliosis Research Society and Oswestry Disability Index questionnaires were completed, and a physical examination was performed at the final follow-up visit. Results. Nonunion after primary operation was found in 10 (34%) patients after posterior fusion and in 10 (13%) patients after posterolateral fusion (P = 0.0017). The mean (range) anterior slip was 25.2% (0–50%) before surgery and 24.2% (0–78%) at final follow-up observation. Lumbosacral kyphosis increased significantly during the follow-up period. The Scoliosis Research Society questionnaire yielded a total of 94.0 (range, 44–114) points. On the Scoliosis Research Society questionnaire, 14 (14%) patients reported back pain often or very often at rest. The Oswestry Disability Index scores averaged 8.2 (range, 0–68). There was a significant correlation between the Scoliosis Research Society total score and the Oswestry Disability Index. The percentage slip showed significant inverse correlations with the scores for appearance in clothes, attractiveness, and self image (Scoliosis Research Society questions 5, 14, and 15). Conclusions. Long-term clinical and radiographic outcomes after posterolateral fusion of low-grade spondylolisthesis were satisfactory. Cosmetic aspects of this deformity should be included as one of the outcome measurements, since cosmetic questions on the Scoliosis Research Society questionnaire showed inverse correlations between the amount of slip at final follow-up observation. The Scoliosis Research Society questionnaire could be used as a primary patient-oriented outcome tool after back surgery in young patients.

Long-term outcome after posterolateral, anterior, and circumferential fusion for high-grade isthmic spondylolisthesis in children and adolescents: magnetic resonance imaging findings after average of 17-year follow-up.

Study Design. A cross-sectional study to evaluate the long-term result of posterolateral (PLF), anterior (AF), and circumferential fusion (CF) for isthmic spondylolisthesis. Objectives. To assess the long-term effects of PLF, AF, or CF for high-grade isthmic spondylolisthesis on lumbar spine in children and adolescents by using MRI. Summary of Background Data. Short- and mid-term clinical and plain radiographic results of isthmic spondylolisthesis and of PLF, AF, and CF in severe slip are well documented. The long-term effect of the fusion on soft tissues, on the intervertebral discs inside and above fusion in particular, is, however, unclear. Methods. Between 1977 and 1991, PLF (n = 21), AF (n = 22), or CF (n = 24) was performed on 67 patients (42 females, 25 males) with high-grade (slip ≥50%) isthmic spondylolisthesis. The average age of patients at the time of operation was 14.4 (range, 8.9–19.6) years. Clinical, spinal mobility and trunk strength in addition to MRI and plain radiograph examinations were performed on these patients after an average follow-up time of 17.3 years (range, 10.7–26.0 years). Results. Three (14%) patients in the PLF and AF groups, but none in the CF group, reported back pain often or very often at rest. The mean Oswestry Disability Index (ODI) was 9.7 (range, 0–62) in the PLF, 8.1 (0–32) in the AF, and 2.3 (0–14) in the CF group (P < 0.05). The mean slip before surgery was 66% (range, 50%–100%) and at the last follow-up visit 66% (range, 26%–106%). Disc degeneration was most common in the PLF group (P = 0.0014) and inside the fusion and in the lowest moving intervertebral disc spaces in all subgroups. Only 1 patient had an asymptomatic prolapse. In MR images, none of the patients had lumbar central canal stenosis inside or above the fusion. In contrast, the spinal canal was wide at the spondylolysis and spondylolisthesis level in 23 (34%) patients. Of the patients, 19 (28%) patients (32 neural foramens) had severe narrowing of the neural foramen with impingement of the nerve root. No patients had clinically confirmed L5 nerve root symptoms. Muscle degeneration was found in 29 (43%) of patients. Longer fusion and muscle degeneration, but not disc degeneration, were associated with lower performance in spinal mobility and trunk-strength measurement tests. Conclusions. The clinical outcome was best in the CF group as measured by ODI. Degenerative changes were most commonly found at the level of the slip and above the fusion level. The prevalence of disc prolapses was low. Spinal fusion for isthmic spondylolysis is not associated with central canal stenosis above the fusion. Radiologic nerve root stenosis was common but asymptomatic. Mild muscle atrophy was common.

Long-term clinical, functional and radiological outcome 21 years after posterior or posterolateral fusion in childhood and adolescence isthmic spondylolisthesis

Long-term radiological studies have shown that a high rate of fusion can be achieved with posterolateral spondylodesis. Radiological findings, however, do not always correlate with patient satisfaction and outcome. No studies have been conducted on the long-term results of functional outcome, including spinal mobility and trunk strength measurements, after operative treatment of spondylolysis and spondylolisthesis, as compared with the reference population. Of 129 consecutive patients with isthmic spondylolisthesis operated on with spondylodesis between 1977 and 1987, 107 (83%) participated in the study. Posterior spondylodesis was performed in 29 (27%) patients and posterolateral spondylodesis in 78 (73%) patients. The average follow-up time was 20.9 years (range 15.1–26.2 years). Radiographs obtained preoperatively and at the 2-year and final follow-ups were assessed for quality of the fusion and degenerative changes. Outcome was assessed at the last follow-up by physical examination, spinal mobility and non-dynamometric trunk strength measurements, and calculation of Oswestry disability index (ODI) scores. The fusion rate was 66% after posterior fusion and 83% after posterolateral fusion. Degenerative changes in the lumbar intervertebral discs above the fusion level were noted in 13 (12%) patients. At the final follow-up 14% of patients reported back pain often or very often. The mean ODI score was 7.6 (0–68). Moderate disability was found in 6% of patients and severe disability in 1%; one patient was crippled. No correlation was found between disc degeneration or solidity of the fusion and the ODI score. Non-dynamometric trunk strength measurements corresponded with the reference values. Lumbar flexion, but not extension, was diminished when compared with that of the reference population. The overall long-term clinical outcome is good in patients with spondylolysis and spondylolisthesis operated on with posterior or posterolateral fusion. The clinical and radiological outcomes do not, however, appear to correlate with each other. Lumbar flexion is diminished, but the patients perform, on average, as well as the general population in non-dynamometric trunk strength measurements.

Thoracic and lumbar spine in diastrophic dysplasia : A clinical and magnetic resonance imaging analysis

Study Design. Cross-sectional study to evaluate the thoracic and lumbar spine in patients with diastrophic dysplasia (DD). Objectives. To find the causative factors behind the spinal deformities and restricted mobility of the spine. Summary of Background Data. Typical findings in this skeletal dysplasia are short-limbed stature, multiple joint contractures, early degeneration of joints, and spinal deformities such as cervical kyphosis, scoliosis, and exaggerated lumbar lordosis. The pathogenic mechanism of scoliosis is unknown. Methods. A physical examination was performed on 88 patients (55 females, 33 males) with an average age of 31 years (range, 3–56). Magnetic resonance (MR) images from T2 to S1 and radiographs were obtained. Degree of scoliosis was measured according to Cobb from standing radiographs.The anatomy of the medulla and the size of the spinal canal were assessed. The transverse dural tube area was measured from L2 to S1. Disc space, degeneration, and protrusions were evaluated. Vertebral abnormalities, if any, facet joint degeneration and the state of the spinal muscles were also assessed. Results. Physical examination showed diminished mobility of the spine. Scoliosis was noted in 70 patients with an average of 42° (range, 11–188°). The mean transverse area of the dural tube ranged from 94 mm2 at L2–L3 to 57 mm2 at L5–S1. The area was smaller at all levels compared with reference values (P < 0.001). One patient had severe thoracic and lumbar spinal stenosis. Five patients had compression of neural structures in the lumbar spinal canal in MR images, but had no clinical symptoms. All patients exhibited narrowed disc heights and a decrease in the signal intensity of discs on T2-weighted images. The prevalence of disc protrusions was low; three patients had a prolapse in the lumbar spine. Two patients displayed vertebral anomalies. All patients also had muscular atrophy and degenerative-like facet joint hypertrophy. The severity of these changes increased with age. Conclusions. Abnormal disc structure and rapid degeneration explain the diminished decreased mobility of the spine and may be a causative factor in the development of scoliosis. Muscular atrophy may be caused by reduced physical activity and rigid spinal deformities. The spinal canal is narrowed, but symptomatic lumbar spinal stenosis is uncommon.

Spine After Solid Organ Transplantation in Childhood : A Clinical, Radiographic, and Magnetic Resonance Imaging Analysis of 40 Patients

Study Design. A cross-sectional study of the spine in 40 young adults after solid organ transplantation in childhood. Objective. To evaluate the impact of organ transplantation and long-term immunosuppressive treatment on growing spine using magnetic resonance imaging (MRI). Summary of Background Data. A review of the current literature reveals no systematic evaluation of the spine after transplantation in childhood. Methods. A total of 40 adult patients (mean age 22.1 years, range, 16.0–27.0), who received either kidney, liver, or heart transplant as children, were evaluated. Mean follow-up after transplantation was 11.2 years (range 3.0–18.0). All patients filled in a questionnaire, underwent an interview and physical examination, as well as had MRI of the spine. Standing spinal radiographs were taken from patients with a rib hump ≥6°. Results. There were 8 (20%) patients who had a history of vertebral fracture. Eleven (28%) patients reported frequent back pain at rest. There were 15 (38%) patients who had scoliosis >10° (range 10°–69°). On MRI, narrowed disc spaces were noted in 32 (80%) patients, and irregular endplates were noted in 24 (60%). There were 14 (35%) patients who had at least 1 compressed or wedged vertebra (>20%). Patients treated for acute rejection had wedged vertebrae, speckled or black disc spaces, and irregular endplates more often than patients without rejections. Males had wedged vertebrae more often than females (P = 0.0067). Conclusions. Back pain, scoliosis, wedged vertebrae, and narrowed, degenerated disc spaces are common after solid organ transplantation in childhood.

Cervical spine in diastrophic dysplasia: an MRI analysis.

In this cross-sectional study, we evaluated the cervical spine in patients with diastrophic dysplasia (DD) by using magnetic resonance imaging (MRI). From 90 (57 female, 33 male) patients of different ages (0.3-56.0 years), T1- and T2-weighted images were obtained. The craniocervical junction and status of the medulla were examined, and the transverse areas of dural tube and medulla were measured. Alignment of the cervical spine, vertebral abnormalities, and disc changes also were evaluated. The cervical spinal canal was moderately narrowed, particularly in adults. The transverse areas of the medulla and especially of the dural tube were smaller compared with a normal population (p < 0.0001). There was no stenosis of the foramen magnum in patients with DD, but the spinal canal was narrowed. Degenerative changes were common. In all age groups, intervertebral discs were dark and disc heights were narrowed. Three (3%) patients (two children, one adult) had cervical kyphosis. Compression of the medulla was noted in association with severe cervical kyphosis in one child and one adult. Typical findings of the cervical spine in DD were exceptionally wide foramen magnum, narrowed spinal canal and early degenerative changes, and in older age groups, especially midcervically narrowed spinal canal. Severe cervical kyphosis caused medullar compression. The intervertebral discs developed abnormally. Abnormal disc structure may be one etiologic factor in the development of cervical kyphosis. Early and rapid progression of the degenerative changes is a normal finding in patients with DD, regardless of their age, and this also explains the stiffness of the cervical spine in clinical examination.

No correlation between patient outcome and abnormal lumbar MRI findings 21 years after posterior or posterolateral fusion for isthmic spondylolisthesis in children and adolescents

Between 1977 and 1987, posterior (n=29) or posterolateral (n=73) fusion was performed for mild to moderate (slip <50%) isthmic spondylolisthesis on 102 patients (46 females, 56 males). The patients’ average age at the time of operation was 15.9 (range, 8.1–19.8) years. Clinical (physical examination and Oswestry disability index (ODI)) and radiological (MRI and plain radiographs) examinations were performed on these patients after an average follow-up time of 21.0 (range, 26.2–15.1) years. In the radiographs, the mean slip preoperatively was 27% (range, 5–50%) and at the last follow-up visit 26% (range, 5–78%). Inside the fusion, there were a total of 148 intervertebral discs, 121 (82%) of them had decreased signal intensity in T2-weighted MR images and 113 (76%) were narrowed. Above the fusion level, 27 (27%) discs were speckled and 27 (27%) were black; 21 (21%) intervertebral disc spaces were narrowed. Two levels above the fusion level the numbers were 8 (8%), 16 (16%) and 16 (16%), respectively. Six (6%) patients had a prolapse. Degenerative facet joint hypertrophy above fusion was seen at 80 (79%) of the levels studied. When compared to healthy subjects higher frequency of disc and facet joint degeneration was found. In MR images, none of the patients had lumbar spinal stenosis inside or above the fusion. Narrowing of one or both of the neural foramina at the level of the L5–S1 interververtebral disc was noted in 32 (31%) patients. Seventeen (17%) of the patients had, usually mild, muscular atrophy of the psoas and 33 (32%) of the paraspinal muscles. There was no difference in frequency of abnormal MRI findings between patients (n=93) with ODI 20 or less compared with patients (n=9) with ODI more than 20. In situ fusion due to isthmic spondylolsthesis at adolescence is associated with moderate degenerative changes in the lumbar spine during a 20-year follow-up. Changes were most commonly found at the level of the spondylolisthesis and above fusion level. Neural foramina stenosis seems to be associated with spondylolisthesis and its severity to severity of the slip. Muscle atrophy tended to be mild. However, there was no correlation between patient outcome (ODI) and abnormal lumbar MRI findings.