Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.     

Histogram analysis of MR imaging-derived cerebral blood volume maps： combined glioma grading and identification of low-grade oligodendroglial subtypes

BACKGROUND AND PURPOSE： Inclusion of oligodendroglial tumors may confound the utility of MR based glioma grading. Our aim was, first, to assess retrospectively whether a histogram-analysis method of MR peifusion images may both grade gliomas and differentiate between low-grade oligodendroglial tumors with or without loss of heterozygosity （LOH） on 1p/19q and, second, to assess retrospectively whether low-grade oligodendroglial subtypes can be identified in a population of patients with high-grade and low-grade astrocytic and oligodendroglial tumors.     

Segmental limb reconstruction after tumor resection

Limb salvage of large segmental and osteoarticular defects after tumor resection has become the standard of care for most patients with musculoskeletal tumors because overall survival is the same when compared with that seen in amputation patients. This study examines limb salvage for the surgical management of large segmental defects in terms of local recurrence, complications, and functional outcome in both primary and metastatic lesions. We retrospectively identified 32 patients with benign or malignant tumors of bone who underwent resection and limb salvage reconstruction by means of a custom or modular metal implant between 1985 and 1995. The most common tumor sites were the proximal femur (41%), distal femur (37.5%), and proximal humerus (12.5%). Primary bone lesions accounted for 18 patients (56%); metastatic disease accounted for 14 patients (44%). Osteosarcoma (n = 11) and chondrosarcoma (n = 3) were the most frequent primary tumors. The overall limb salvage rate (91%) was high, yet complications (28%) were common. Except for 3 patients who underwent amputation after prosthetic failure, all surviving patients were independent with or without assistive devices at latest follow-up. In patients with advanced metastatic disease, average survival was 7.6 months. No cases of aseptic loosening or implant breakage were observed in patients followed up for 2 years or more. Treatment after tumor resection with a limb salvage prosthetic reconstruction has shown good functional outcomes with an acceptable complication rate. This modality, therefore, offers patients a more favorable functional outcome with a more energy-efficient gait when compared with limb amputation.     

Preoperative versus postoperative radiation therapy for soft-tissue sarcomas

In this article, we report results from a retrospective consecutive series of 117 patients with soft-tissue sarcomas treated with adjuvant radiation and surgical resection at 2 associated institutions. Fifty-nine patients received preoperative radiation; 58 patients received postoperative radiation. Mean clinical follow-ups were 6.1 years and 8.4 years, respectively. Nineteen (32.2%) of 59 patients in the preoperative group and 17 (29.3%) of 58 patients in the postoperative group had wound complications (P = .89). Three (5.1%) of 59 sarcomas in the preoperative group and 7 (12.1%) of 58 sarcomas in the postoperative group recurred locally (P = .19). Improved local disease control and other potential advantages of using preoperative radiation make this a preferred adjuvant treatment.     

Paget's disease of bone in patients younger than 40 years

Paget's disease of bone, although common in the United States, is relatively rare in patients younger than 40 years. In a large archival series, 10% of patients with Paget's disease of bone were younger than 40 years. Pain followed by pathologic fracture was the most common presenting complaint in this group of patients. There was no gender difference comparing the younger group with the older group of patients. Of the 521 patients in this series, only 10 were African-American; the others were Caucasians. Seven African-American patients were in the group of patients who were younger than 40 years. Appendicular and monostotic bone involvement was more frequent in the younger age group although these differences were not statistically significant. The incidence of malignant transformation in pagetic bone was high (30.3%), and is a reflection of the high volume of uncommon tumor referrals to our consultation service. However, there were no cases of associated malignancies in the group of patients younger than 40 years.     

Intraspinal anomalies associated with isolated congenital hemivertebra: the role of routine magnetic resonance imaging

BACKGROUND: Previous studies have demonstrated high rates of intraspinal anomalies in patients with congenital scoliosis; however, various authors have not considered the presence of an isolated hemivertebra to be sufficient reason for further evaluation with magnetic resonance imaging. Consequently, the rate of magnetic resonance imaging-detected intraspinal anomalies and subsequent neurosurgical intervention in patients with a single hemivertebra is unknown. Therefore, we studied all patients with a hemivertebra, after eliminating patients with a myelomeningocele, to compare those who had a single hemivertebra with those who had a complex hemivertebral pattern. METHODS: A retrospective review of the history, physical examination findings, and magnetic resonance imaging findings for patients who had presented with at least one hemivertebra, excluding those who had a myelomeningocele, was conducted to identify the prevalence of intraspinal anomalies as seen on magnetic resonance imaging and the rate of subsequent neurosurgical intervention. Additionally, the diagnostic value of the history and the physical examination in predicting the presence of intraspinal anomalies was determined. RESULTS: One hundred and sixteen patients with congenital scoliosis and a curve that included at least one hemivertebra were identified. Seventy-six of these patients had had magnetic resonance imaging and were included in the present study. The mean age of these patients at the time of presentation was 4.9 years, and the mean duration of follow-up was 7.7 years. Twenty-nine patients had an isolated hemivertebra, and forty-seven patients had a complex hemivertebral pattern. Eight (28%) of the twenty-nine patients with an isolated hemivertebra and ten (21%) of the forty-seven patients with a complex hemivertebral pattern had an intraspinal anomaly that was detected with magnetic resonance imaging. Overall, an abnormal finding on the history or physical examination demonstrated an accuracy of 71%, a sensitivity of 56%, a specificity of 76%, a positive predictive value of 42%, and a negative predictive value of 85% for the diagnosis of an intraspinal anomaly. Three patients with an isolated hemivertebra and five patients with a complex hemivertebral pattern underwent neurosurgical intervention. All eight patients who underwent neurosurgical intervention had had detection of an intraspinal anomaly with magnetic resonance imaging, whereas only four of these patients (two of whom had an isolated hemivertebra and two of whom had a complex hemivertebral pattern) had had an abnormal finding on either the history or the physical examination. CONCLUSIONS: Patients who have an isolated hemivertebra and those who have a complex hemivertebral pattern have similar rates of intraspinal anomalies that are detected with magnetic resonance imaging and similar rates of subsequent neurosurgical intervention. The history and physical examination findings are not predictive of intraspinal anomalies. Therefore, a magnetic resonance imaging evaluation of the entire spine should be considered for all patients with congenital scoliosis, including those with an isolated hemivertebra.