The management of chordomas and chondrosarcomas involving the cranial base remains controversial. The options for therapy include biopsy, partial resection, radical resection, and various forms of radiotherapy. In this article, we analyze the outcome of 60 patients with cranial base chordoma or chondrosarcoma treated with extensive surgical resection between 1984 and 1993. Forty-six patients had chordomas, and 14 had low-grade chondrosarcomas; 50% of these patients had been treated previously. Preoperative studies included computed tomography, magnetic resonance imaging, cerebral angiography, and balloon occlusion test of the internal carotid artery, as indicated. Magnetic resonance imaging was performed on all patients during follow-up. The surgical approaches used for tumor resection were predominantly the following: subtemporal, transzygomatic, transcavernous, and transpetrous apex; subtemporal and infratemporal; extended frontal; and extreme lateral transcondylar. Staged operations with a combination of approaches were used when necessary (52% of cases) to remove a tumor more completely. Statistical analysis was done by the chi 2 test and correlation matrix. Sixty-seven percent of the patients had total or near-total resection. Twenty percent of the patients received postoperative radiotherapy. Eleven patients died during the postoperative follow-up period, nine with chordomas and two with chondrosarcomas. Three patients died because of systemic complications within 3 months after surgery, five died because of tumor recurrence, one died from unrelated causes, and two died from late complications of radiotherapy. The recurrence-free survival rate for all tumors was 80% at 3 years and 76% at 5 years. Chondrosarcomas had a better prognosis than chordomas (recurrence-free survival rates, 90% at 5 years and 65% at 5 years, respectively; P = 0.09). Patients who had undergone previous surgery had a greater risk of recurrence (5-year recurrence-free survival rate, 64%) than did patients who had not undergone previous surgery (5-year recurrence-free survival rate, 93%; P < 0.05). Patients with total or near-total resection had a better 5-year recurrence-free survival rate (84%) than did patients with partial or subtotal resection (64%) (P < 0.05). Postoperative leakage of cerebrospinal fluid was the most frequent complication (30% of patients) and was found to increase the risk of permanent disability. Patients who had undergone previous radiotherapy had a greater risk of death in the postoperative period (within 3 months of their operations) and during follow-up. However, total or near-total resection did not increase the rate of postoperative disability.(ABSTRACT TRUNCATED AT 400 WORDS)
Meta-analytic methods were used to integrate the findings of a sample of Monte Carlo studies of the robustness of the F test in the one- and two-factor fixed effects ANOVA models. Monte Carlo results for the Welch (1947) and Kruskal-Wallis (Kruskal & Wallis, 1952) tests were also analyzed. The meta-analytic results provided strong support for the robustness of the Type I error rate of the F test when certain assumptions were violated. The F test also showed excellent power properties. However, the Type I error rate of the F test was sensitive to unequal variances, even when sample sizes were equal. The error rate of the Welch test was insensitive to unequal variances when the population distribution was normal, but nonnormal distributions tended to inflate its error rate and to depress its power. Meta-analytic and exact statistical theory results were used to summarize the effects of assumption violations for the tests.
The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level. We extended this approach to the case of a novel, patient-specific ABM that we generated for vocal fold inflammation, with the ultimate goal of identifying individually optimized treatments. ABM simulations reproduced trajectories of inflammatory mediators in laryngeal secretions of individuals subjected to experimental phonotrauma up to 4 hrs post-injury, and predicted the levels of inflammatory mediators 24 hrs post-injury. Subject-specific simulations also predicted different outcomes from behavioral treatment regimens to which subjects had not been exposed. We propose that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains.
Neurological deterioration is commonly seen after surgical excision of clival meningiomas; however, an understanding of the risk factors associated with postoperative deterioration can lead to improvements in outcome. In 75 patients with clival meningiomas operated on over a 7-year period, the following data were studied; preoperative variables such as presenting Karnofsky scale score, age, sex, and prior operations or radiation therapy. Radiological findings on magnetic resonance imaging or arteriography, such as the development of the arachnoidal cleavage plane between tumor and the brain stem, brainstem edema, tumor size, extent of compression on the brain stem, vascular encasement, and blood supply from the basilar artery were among other data studied. In addition, intraoperative findings such as development of the arachnoid plane, vascular encasement, and the difficulty of dissection were noted. Finally, each patient's neurological and functional statuses were recorded at 1 week postoperatively and at follow-up examinations. Early postoperative functional deterioration occurred in 45 patients (60%) and ranged from mild (30 patients) to severe (three patients). Significant improvement had occurred by the time of follow-up examination in all but four patients; however, permanent postoperative dysfunction was present in 12 patients. Statistical analysis revealed significant correlations between early functional deterioration and preoperative Karnofsky scale scores, male gender, radiological findings of the absence of an arachnoid plane, edema of the brain stem, and arteriographic supply from the basilar artery. Operative features included difficulty with dissection, an absent arachnoidal cleavage plane, and incomplete tumor resection. Permanent functional deterioration was statistically associated with the following: blood supply from the basilar artery, difficulty of dissection, incomplete tumor resection, and early postoperative dysfunction. Logistical regression analysis revealed that the most important risk factor for early postoperative deterioration was tumor size. Patients with large or giant tumors had a 6.7 to 13 times greater risk of functional deterioration, respectively, than patients with small- or medium-sized tumors. Excluding tumor size, the most important factor for permanent deterioration was blood supply from the basilar artery. Patients in this category had a 4.4 times greater risk of permanent functional deterioration. Three stages of tumor relationship to the brainstem arachnoid and pial membranes are proposed. Based on the results of this clinical study of clival meningiomas, suggestions are made for changes in the management strategy of these difficult lesions.
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