Survival in patients operated on for pathologic fracture: implications for end-of-life orthopedic care.

PURPOSE: Life expectancy is routinely used as part of the decision-making process in deciding the value of surgery for the treatment of bone metastases. We sought to investigate the validity of frequently used indices in the prognostication of survival in patients with metastatic bone disease. METHODS: The study prospectively assessed 191 patients who underwent surgery for metastatic bone disease. Diagnostic, staging, nutritional, and hematologic parameters cited to be related to life expectancy were evaluated. Preoperatively, the surgeon recorded an estimate of projected life expectancy for each patient. The time until death was recorded. RESULTS: Kaplan-Meier survival analyses indicated that the survival estimate, primary diagnosis, use of systemic therapy, Eastern Cooperative Oncology Group (ECOG) performance status, number of bone metastases, presence of visceral metastases, and serum hemoglobin, albumin, and lymphocyte counts were significant for predicting survival (P < .004). Cox regression analysis indicated that the independently significant predictors of survival were diagnosis (P < .006), ECOG performance status (P < .04), number of bone metastases (P < .008), presence of visceral metastases (P < .03), hemoglobin count (P < .009), and survival estimate (P < .00005). Diagnosis, ECOG performance status, and visceral metastases covaried with surgeon survival estimate. Linear regression and receiver-operator characteristic assessment confirmed that clinician estimation was the most accurate predictor of survival, followed by hemoglobin count, number of visceral metastases, ECOG performance status, primary diagnosis, and number of bone metastases. Nevertheless, survival estimate was accurate in predicting actual survival in only 33 (18%) of 181 patients. CONCLUSION: A better means of prognostication is needed. In this article, we present a sliding scale for this purpose.     

The prognostic significance of postoperative residual tumor in ependymoma

Between 1970 and 1989, 29 patients with intracranial ependymomas were evaluated and treated at the Children's Hospital in Boston. With a median follow-up of 82 months, the actuarial survival rates at 5 and 10 years were 61 +/- 10% and 46 +/- 12%, respectively. Anaplastic histological findings were uncommon (2 of 29). Initial postoperative radiotherapy was given to 25 patients, with a median tumor dose of 5360 cGy. With a median time to recurrence of 22 months, local failure (within 2 cm of original enhancing mass) was the predominant pattern of relapse (15 of 16 failures). The presence of radiographic residual disease seen on postoperative magnetic resonance imaging or computed tomographic scans was the most important prognostic variable for patients with intracranial ependymoma. Analysis of the 19 patients who underwent postoperative imaging revealed a 75 +/- 15% 5-year freedom from progressive disease for 9 patients with no residual disease, as compared with 0% freedom from progressive disease for the 10 patients with gross residual disease (P = 0.03). In contrast, the surgical assessment of residual disease was not significant (P = 0.4). Age at presentation was also a significant prognostic factor. The overall actuarial survival rate at 12 years for infants 24 months or younger at diagnosis was 0%, as compared with 62 +/- 13% for older patients (P = 0.03). For non-anaplastic ependymomas, complete surgical resection followed by local-field, high-dose (greater than 54 Gy) radiotherapy appears to offer the greatest chance for long-term survival. Because of the markedly reduced survival rate for patients with radiologically apparent postoperative disease, maximal surgical resection and novel therapeutic endeavors appear warranted for this high-risk group. Future protocols should use postoperative imaging, not operative reports, to stratify patients with ependymoma.     

Quercetin attenuates UV- and H(2)O(2)-induced decrease of collagen type I in cultured human lens epithelial cells.

Ultraviolet (UV) radiation is related to cataract formation. The dynamics of matrix proteins play crucial roles in cell proliferation, cell migration, and the remodeling of lens capsule and, possibly, cataract formation. However, the change of dynamics of matrix proteins, such as collagens, in lens cells in response to UV radiation has not been investigated. Using cultured human lens epithelial cells, we, for the first time, demonstrate that UV radiation induces a decrease of collagen type I in a time- and dose-dependent manner. Hydrogen peroxide (H(2)O(2)) also induces a collagen type I decrease in a similar pattern. We observed that UV and H(2)O(2) induce JNK and its downstream component, c-Jun, activation in both a time- and dose-dependent manner. The pharmacologic inhibitor of JNK or JNKi inhibits UV-induced JNK and c-Jun activation and attenuates a UV-induced decrease of collagen type I. Quercetin, a well known antioxidant, also protects against a UV- and H(2)O(2)-induced decrease of collagen type I in a dose-dependent manner. Quercetin inhibits UV- and H(2)O(2)-induced JNK and c-Jun activation. Collectively, we conclude that quercetin attenuates both a UV- and H(2)O(2)-induced decrease of collagen type I via the inhibiting of JNK/c-Jun activity. Understanding the cellular-signaling pathways involved in the UV- and H(2)O(2)-induced decrease of collagen type I may reveal potential therapeutic targets for the UV-induced cataract.     

Eye movements of stutterers

As a consequence of recent inquiries into the brainstem activity of stutterers, saccades and pursuit were evaluated in stutterers and their matched normals while silent and talking. No ocular motor instabilities or aberrations caused by speech were found. Saccadic latencies and gains for the stutterers were normal, but peak velocities were higher and durations were shorter. This finding is consistent with hypotheses of speech dysfluency proposed by others. The gains of these fast saccades were kept normal by an adaptive decrease in the duration of the neural pulse producing the saccade. It is proposed that these fast saccades are a result of increased excitatory input to the burst cells in the brainstem.     

Cervical spine instability in children with Goldenhar's syndrome.

OBJECTIVE: To study the vertebral involvement of the cervical spine, in particular the stability of C1-C2, in children with proven Goldenhar's syndrome. DESIGN: A case review. SETTING: The Children's Hospital of Eastern Ontario, Ottawa. PATIENTS: Eight children who had a minimum of 2 out of 3 Goldenhar criteria plus other strong associations with the syndrome and for whom detailed radiographic spinal assessment, including flexion-extension views of the cervical spine and computed tomography of the congenital anomalies, were available. OUTCOME MEASURES: Radiographic findings. RESULTS: Seven children demonstrated cervical spine anomalies. Of particular concern was the high incidence of C1-C2 instability in 3 children, 2 of whom required occiput to C2 fusion. The presence of hemivertebrae and failures of segmentation were most common and resulted in thoracic scoliosis, leading to spinal fusion in 2 children. CONCLUSIONS: In patients with Goldenhar's syndrome the cervical spines must be monitored carefully for C1-C2 subluxation before any proposed surgery for other malformations associated with the syndrome, so that any instability can be identified to avoid cord impingement during a general anesthetic.