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Francesco Dimeco, Richard E. Clatterbuck, Khan W. Li, Edward F. McCarthy and Alessandro Olivi

✓ The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a recently described, currently evolving clinical entity that groups together several idiopathic disorders of bone and skin formerly described under a variety of names. Among the spectrum of possible locations for the bone lesions, there is no previous report in the literature of primary involvement of the skull vault. A patient with primary involvement of the calvaria in the setting of SAPHO syndrome is described here, which, to the authors' knowledge, is the first report of such localization. The clinically and radiologically benign evolution of the different stages of the bone lesions is presented. The authors suggest that the SAPHO syndrome should be considered in the differential diagnosis of lytic, sclerotic, or hyperostotic lesions of the skull, particularly before considering invasive diagnostic procedures.

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A brachial plexopathy due to myositis ossificans

Case report and review of the literature

John F. Reavey-Cantwell, Ira Garonzik, Michael P. Viglione, Edward F. M. McCarthy and Allan J. Belzberg

✓ Myositis ossificans (MO) is a disorder characterized by the intramuscular proliferation of fibroblasts and osteoblasts, with subsequent deposition of bone and cartilage. A typical clinical presentation involves traumatic injury to a young adult, usually localized to the thigh, buttock, or upper arm, with resultant MO and mildly restricted range of motion in adjacent joints. Rarely, MO is associated with peripheral neuropathies involving the radial, median, sciatic, and sural nerves. The authors present an unusual case of MO causing a brachial plexopathy. To their knowledge, this is the first description of such a presentation.

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Paul E. Kaloostian, Patricia L. Zadnik, Ahmed J. Awad, Edward McCarthy, Jean-Paul Wolinsky and Daniel M. Sciubba

Resection of metastatic pheochromocytomas may be complicated by transient postoperative neurological deficits due to hypotension. The authors report the first case of en bloc excision of a spinal pheochromocytoma with associated long-term hypertensive management off all medication. Interestingly, this is the first case of transient hypotension following en bloc resection of pheochromocytoma associated with temporary hypotension-associated neurological decline that resolved completely after correction of hypotension postoperatively. A 23-year-old man with a prior adrenalectomy for pheochromocytoma presented with focal thoracic pain. He had a known T-10 vertebral body lesion for which he received chemotherapy and radiation therapy. Imaging demonstrated increased destruction of the T-10 vertebral body, which was concerning for tumor growth. The patient underwent angiographic embolization followed by single-stage posterior en bloc vertebrectomy with placement of a cage and posterior instrumentation and fusion without event. However, approximately 24 hours after surgery, the patient's systolic blood pressure was consistently no higher than 70 mm Hg. During this time, he began suffering from severe bilateral lower-extremity weakness. His systolic blood pressure increased with dopamine, and his strength immediately improved. The patient's oral regimen of adrenergic blockade was stopped, and he recovered without event. Since that time, the patient has been symptom free and requires no antihypertensive medication. The role of en bloc resection for metastatic lesions of the spine is controversial but may be warranted in cases of metastatic pheochromocytoma. En bloc resection avoids intralesional tumor resection and thus may help prevent complications of hypertensive crisis associated with hormonal secretion and extensive blood loss, which are not uncommon with pheochromocytoma resection surgeries. Additionally, the role of en bloc spondylectomy in this setting may allow for metabolic treatment as patients with actively secreting tumors may no longer require antiadrenergic medications.

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Vertebral synovial chondromatosis

Report of two cases and review of the literature

Gary L. Gallia, Nirit Weiss, James N. Campbell, Edward F. McCarthy, Anthony P. Tufaro and Ziya L. Gokaslan

✓ Synovial chondromatosis is an uncommon disorder characterized by the formation of multiple cartilaginous nodules within the synovium, most commonly affecting large joints. Its involvement with the spine is rare; only six cases have been reported. The authors describe two patients with synovial chondromatosis involving the cervical spine. In the first case, synovial chondromatosis arose from the left C1–2 facet joint. This patient underwent a two-stage procedure including a posterior approach for tumor resection and occipitocervical fusion as well as a transmandibular circumglossal approach to the anterior craniocervical junction to complete the tumor removal. Interestingly, on histopathological examination, scattered foci of low-grade chondrosarcoma were intermixed within the synovial chondromatosis. To the authors' knowledge, this is the first report of secondary low-grade chondrosarcoma arising in vertebral synovial chondromatosis. In the second case, synovial chondromatosis involved the left C4–5 facet joint. Tumor resection and cervical fusion were performed via a posterior approach.

In this report, the authors describe the clinical presentation, radiographic findings, operative details, histopathological features, and clinicoradiological follow-up data obtained in these two patients and review the literature pertaining to this rare entity.

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Patricia L. Zadnik, Camilo A. Molina, Rachel Sarabia-Estrada, Mari L. Groves, Michele Wabler, Jana Mihalic, Edward F. McCarthy, Ziya L. Gokaslan, Robert Ivkov and Daniel Sciubba

Object

The goal of this study was to optimize local delivery of magnetic nanoparticles in a rat model of metastatic breast cancer in the spine for tumor hyperthermia while minimizing systemic exposure.

Methods

A syngeneic mammary adenocarcinoma was implanted into the L-6 vertebral body of 69 female Fischer rats. Suspensions of 100-nm starch-coated iron oxide magnetic nanoparticles (micromod Partikeltechnologie GmbH) were injected into tumors 9 or 13 days after implantation. For nanoparticle distribution studies, tissues were harvested from a cohort of 36 rats, and inductively coupled plasma mass spectrometry and histopathological studies with Prussian blue staining were used to analyze the samples. Intratumor heating was tested in 4 anesthetized animals with a 20-minute exposure to an alternating magnetic field (AMF) at a frequency of 150 kHz and an amplitude of 48 kA/m or 63.3 kA/m. Intratumor and rectal temperatures were measured, and functional assessments of AMF-exposed animals and histopathological studies of heated tumor samples were examined. Rectal temperatures alone were tested in a cohort of 29 rats during AMF exposure with or without nanoparticle administration. Animal studies were completed in accordance with the protocols of the University Animal Care and Use Committee.

Results

Nanoparticles remained within the tumor mass within 3 hours of injection and migrated into the bone at 6, 12, and 24 hours. Subarachnoid accumulation of nanoparticles was noted at 48 hours. No evidence of lymphoreticular nanoparticle exposure was found on histological investigation or via inductively coupled plasma mass spectrometry. The mean intratumor temperatures were 43.2°C and 40.6°C on exposure to 63.3 kA/m and 48 kA/m, respectively, with histological evidence of necrosis. All animals were ambulatory at 24 hours after treatment with no evidence of neurological dysfunction.

Conclusions

Locally delivered magnetic nanoparticles activated by an AMF can generate hyperthermia in spinal tumors without accumulating in the lymphoreticular system and without damaging the spinal cord, thereby limiting neurological dysfunction and minimizing systemic exposure. Magnetic nanoparticle hyperthermia may be a viable option for palliative therapy of spinal tumors.

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Patricia Zadnik, Rachel Sarabia-Estrada, Mari L. Groves, Camilo Molina, Christopher Jackson, Edward McCarthy, Ziya L. Gokaslan, Ali Bydon, Jean-Paul Wolinsky, Timothy F. Witham and Daniel M. Sciubba

Object

Metastatic spine disease is prevalent in cancer victims; 10%–30% of the 1.2 million new patients diagnosed with cancer in the US exhibit spinal metastases. Unfortunately, treatments are limited for these patients, as disseminated disease is often refractory to chemotherapy and is difficult to treat with surgical intervention alone. New animal models that accurately recapitulate the human disease process are needed to study the behavior of metastases in real time.

Methods

In this study the authors report on a cell line that reliably generates bony metastases following intracardiac injection and can be tracked in real time using optical bioluminescence imaging. This line, RBC3, was derived from a metastatic breast adenocarcinoma lesion arising in the osseous spine of a rat following intracardiac injection of MDA-231 human breast cancer cells.

Results

Upon culture and reinjection of RBC3, a statistically significantly increased systemic burden of metastatic tumor was noted. The resultant spine lesions were osteolytic, as demonstrated by small animal CT scanning.

Conclusions

This cell line generates spinal metastases that can be tracked in real time and may serve as a useful tool in the study of metastatic disease in the spine.

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Bridget J. McCarthy, Faith Davis, Sally Freels, Tanya S. Surawicz, Denise Damek, James Grutsch, Herman R. Menck and Edward R. Laws Jr.

Factors affecting the survival rate in patients with meningiomas were explored using the National Cancer Database (NCDB), which includes tumors from approximately 1000 hospitals participating in the American College of Surgeons tumor registry program. Analysis included over 9000 cases diagnosed from 1985 to 1988 and 1990 to 1992. Survival estimates were computed and prognostic factors were identified using a proportional hazards model. The overall 5-year survival rate was 69% and it declined with age. This rate was 81% in patients aged 21 to 64 and 56% for patients 65 years of age or older. When patients were grouped by the histological type of their tumors, those with benign tumors had an overall 5-year survival rate of 70%, whereas the overall 5-year survival rates in patients with atypical and malignant meningiomas were 75% and 55%, respectively. Prognostic factors for benign tumors included age at diagnosis, tumor size, whether treated surgically, hospital type, and radiation therapy; for malignant tumors, age at diagnosis, whether treated surgically, and radiation therapy were statistically significant. The 5-year rate for recurrence of symptoms (regardless of the method of treatment) was 18.2% for those with benign tumors and 27.5% for those with malignant tumors. In patients whose benign tumor had been completely removed, the 5-year rate of tumor recurrence was 20.5%. Although not population-based, the NCDB has the potential for providing pertinent information regarding patient characteristics and methods of treatment for benign, as well as malignant, brain tumors.

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Bridget J. McCarthy, Faith G. Davis, Sally Freels, Tanya S. Surawicz, Denise M. Damek, James Grutsch, Herman R. Menck and Edward R. Laws Jr.

Object. To explore factors affecting the survival rate in patients with meningiomas, the authors used the National Cancer Data Base (NCDB), which includes tumors from approximately 1000 hospitals participating in the American College of Surgeons tumor registry program.

Methods. Analysis included over 9000 cases diagnosed from 1985 to 1988 and 1990 to 1992. Survival estimates were computed and prognostic factors were identified using a proportional hazards model. The overall 5-year survival rate was 69% and it declined with patient age. This rate was 81% in patients aged 21 to 64 years and 56% for patients 65 years of age or older. When patients were grouped by the histological type of their tumors, those with benign tumors had an overall 5-year survival rate of 70%, whereas the overall 5-year survival rates in patients with atypical and malignant meningiomas were 75% and 55%, respectively. Prognostic factors for benign tumors included age at diagnosis, tumor size, whether treated surgically, hospital type, and radiation therapy; for malignant tumors, the prognostic factors included: age at diagnosis, whether treated surgically, and radiation therapy. These factors were statistically significant. The 5-year rate for recurrence of symptoms (regardless of the method of treatment) was 19.2% for those with benign tumors and 32.4% for those with malignant tumors. In patients whose benign tumor had been completely removed, the 5-year rate of tumor recurrence was 20.5%.

Conclusions. Although not population-based, the NCDB has the potential for providing pertinent information regarding patient characteristics and methods of treatment for benign, as well as malignant, brain tumors.

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Wesley Hsu, Ahmed Mohyeldin, Sagar R. Shah, Colette M. ap Rhys, Lakesha F. Johnson, Neda I. Sedora-Roman, Thomas A. Kosztowski, Ola A. Awad, Edward F. McCarthy, David M. Loeb, Jean-Paul Wolinsky, Ziya L. Gokaslan and Alfredo Quiñones-Hinojosa

Object

Chordoma is a malignant bone neoplasm hypothesized to arise from notochordal remnants along the length of the neuraxis. Recent genomic investigation of chordomas has identified T (Brachyury) gene duplication as a major susceptibility mutation in familial chordomas. Brachyury plays a vital role during embryonic development of the notochord and has recently been shown to regulate epithelial-to-mesenchymal transition in epithelial-derived cancers. However, current understanding of the role of this transcription factor in chordoma is limited due to the lack of availability of a fully characterized chordoma cell line expressing Brachyury. Thus, the objective of this study was to establish the first fully characterized primary chordoma cell line expressing gain of the T gene locus that readily recapitulates the original parental tumor phenotype in vitro and in vivo.

Methods

Using an intraoperatively obtained tumor sample from a 61-year-old woman with primary sacral chordoma, a chordoma cell line (JHC7, or Johns Hopkins Chordoma Line 7) was established. Molecular characterization of the primary tumor and cell line was conducted using standard immunostaining and Western blotting. Chromosomal aberrations and genomic amplification of the T gene in this cell line were determined. Using this cell line, a xenograft model was established and the histopathological analysis of the tumor was performed. Silencing of Brachyury and changes in gene expression were assessed.

Results

The authors report, for the first time, the successful establishment of a chordoma cell line (JHC7) from a patient with pathologically confirmed sacral chordoma. This cell line readily forms tumors in immunodeficient mice that recapitulate the parental tumor phenotype with conserved histological features consistent with the parental tumor. Furthermore, it is demonstrated for the first time that silencing of Brachyury using short hairpin RNA renders the morphology of chordoma cells to a more differentiated-like state and leads to complete growth arrest and senescence with an inability to be passaged serially in vitro.

Conclusions

This report represents the first xenograft model of a sacral chordoma line described in the literature and the first cell line established with stable Brachyury expression. The authors propose that Brachyury is an attractive therapeutic target in chordoma and that JHC7 will serve as a clinically relevant model for the study of this disease.

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Daniel M. Sciubba, Rory J. Petteys, Sophia F. Shakur, Ziya L. Gokaslan, Edward F. McCarthy, Michael T. Collins, Matthew J. McGirt, Patrick C. Hsieh, Clarke S. Nelson and Jean-Paul Wolinsky

En bloc spondylectomy represents a radical resection of a spinal segment most often reserved for patients presenting with a primary extradural spine tumor or a solitary metastasis in the setting of an indolent, well-controlled systemic malignancy. The authors report a case in which en bloc spondylectomy was conducted to control a metabolically active spine tumor. A 56-year-old woman, who suffered from severe tumor-induced osteomalacia, was found to have a fibroblast growth factor-23–secreting phosphaturic mesenchymal tumor in the T-8 vertebral body. En bloc resection was conducted, leading to resolution of her tumor-induced osteomalacia. This case suggests that radical spondylectomy may be beneficial in the management of metabolically or endocrinologically active tumors of the spine.