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M Beth McCarville

Publications and source records attributed to M Beth McCarville.

At least 19 recordsLinked to original sources
PubMed2008

Prolactinoma as the first manifestation of Gardner's syndrome.

Familial adenomatous polyposis (FAP) is an inherited condition causing numerous adenomatous colorectal polyps and a markedly elevated risk of colon cancer. FAP may be associated with various extracolonic manifestations such as desmoid fibromatosis and osteomas (termed Gardner's syndrome) and brain tumors, usually medulloblastoma or glioma [termed Brain Tumor Polyposis (BTP) syndrome type 2]. We describe a pediatric patient who initially presented with prolactinoma and later was found to have Gardner's syndrome. A germline mutation of the APC (adenomatous polyposis coli) gene was identified. Our case illustrates the association between prolactinoma and FAP, which may represent a rare subtype of Gardner's and BTP syndromes.

Child↗
PubMed2007

Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma.

BACKGROUND: Preclinical models show sequence-dependent synergy with the combination of temozolomide and irinotecan, and a Phase I trial has demonstrated the combination to be tolerable and active in children with relapsed solid tumors. Because responses were seen in patients with Ewing sarcoma (ES) on that trial, additional patients were treated with this combination following study completion. PROCEDURE: We reviewed data from all ES patients treated with temozolomide and irinotecan at four institutions, including seven patients treated on the above Phase I trial. RESULTS: Sixteen patients received a total of 95 courses, with a median of five courses per patient. All patients had either progressive disease (PD) during initial therapy (n = 5) or relapse within 2 years of diagnosis (n = 11). Twelve patients had metastatic disease at diagnosis, including 5 with bone and/or marrow metastases. Patients received oral temozolomide 100 mg/m(2)/day on days 1-5 plus intravenous irinotecan 10-20 mg/m(2)/day on days 1-5 and 8-12, with courses repeated every 21-28 days. We observed 1 complete, 3 partial, and 3 minor responses in 14 evaluable patients, with a median duration of response of 30 weeks. Planned 21-day courses were tolerable and no more toxic than 28-day courses. Myelosuppression was minimal despite heavy pretreatment. Grade 3-4 diarrhea occurred in 11% of courses and was related to higher irinotecan doses. Over 600 irinotecan doses were administered uneventfully at home. CONCLUSIONS: Temozolomide and protracted intravenous irinotecan given in 21-day courses was tolerable and active in patients with advanced ES. Home administration of irinotecan with temozolomide was safe and is reasonable palliative therapy. A formal Phase II study using a uniform dose and schedule is warranted to better define activity.

Administration, Oral↗
PubMed2006

Metastatic osteosarcoma.

BACKGROUND: The outcome of patients with metastatic osteosarcoma treated in two consecutive trials from 1986 to 1997 was analyzed to evaluate the efficacy of carboplatin-based multiagent chemotherapy and to identify prognostic factors. The initial study (OS-86) used ifosfamide, cisplatin, doxorubicin, and high-dose methotrexate, and the subsequent study (OS-91) used the same agents at similar doses, but carboplatin was substituted for cisplatin. METHODS: Twelve patients (median age, 15.1 yrs) were treated in OS-86 for osteosarcoma metastatic to the lung only (11 patients) or bone only (1 patient), and 17 patients (median age, 15.1 yrs) were treated in OS-91 for osteosarcoma metastatic to the lung only (12 patients), bone only (2 patients), lung and bone (2 patients), or other site (1 patient). RESULTS: Patients with metastatic disease enrolled in OS-86 and those with metastatic disease enrolled in OS-91 did not differ in terms of demographic features, histologic subtype, site of primary tumor, or site of metastases. There was a difference in survival according to treatment protocol (P = 0.054). All survivors (four of whom were enrolled in OS-86 and one of whom was enrolled in OS-91) had lung metastases only. Five-year survival estimates for patients with lung metastases only were 45.5 +/- 13.7% (OS-86) and 8.3 +/- 5.6% (OS-91) (P = 0.084). Unilateral lung metastases (P = 0.006), no more than three lung nodules (P = 0.014), and surgical remission (P = 0.001) were associated with improved survival probability. CONCLUSIONS: The poor outcome of patients with metastatic osteosarcoma treated in OS-91 justifies the use of cisplatin with its associated toxicity in patients with high-risk disease.

Adolescent↗
PubMed2006

Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma.

BACKGROUND: Survivors of Hodgkin lymphoma and other patients who receive neck irradiation are at increased risk of thyroid cancer. Ultrasonography provides an inexpensive and non-invasive method of thyroid screening, but the clinical significance of thyroid nodules detected by ultrasound screening is uncertain. PROCEDURE: We reviewed the demographics, clinical characteristics, method of detection, and outcome of patients who developed thyroid nodules after treatment for pediatric Hodgkin lymphoma at our institution. One radiologist reviewed all imaging studies. RESULTS: Sixty-seven children treated for Hodgkin lymphoma from 1962 to 2001 developed thyroid nodules. The study group represented 9,024 person-years of follow-up after the diagnosis of Hodgkin lymphoma and 581 person-years after diagnosis of a thyroid nodule. A median of 10.5 years (range, 0.2-24.8 years) elapsed between the diagnoses of Hodgkin lymphoma and thyroid nodule(s). All but one patient had received neck irradiation for Hodgkin lymphoma, with a median thyroid radiation dose of 35 Gy (range, 12-45 Gy). Thyroid nodules were found to be malignant in seven patients (10%), at a median of 16.2 years (range, 8.4-23.7 years) after diagnosis of Hodgkin lymphoma. Only one malignancy was found through screening ultrasonography. All patients with thyroid cancer remained disease-free at 0.4-16.2 years of follow-up. CONCLUSIONS: Thyroid nodules are common in Hodgkin lymphoma survivors treated with neck irradiation, but the majority of these lesions have an indolent clinical course and do not undergo malignant transformation. Only patients with a palpable mass or clinical symptoms need more extensive evaluation, including Doppler-flow ultrasonography and fine-needle aspiration.

Disease-Free Survival↗
PubMed2006

Efficacy of zoledronate against neuroblastoma.

BACKGROUND: We investigated the antitumor and antiosteoclastic effects of zoledronate against human neuroblastoma in vitro and in a murine model of bone metastasis. METHODS: Antitumor activity of zoledronate against neuroblastoma cell lines was assessed by evaluating proliferation, apoptosis, and cell-cycle progression. A murine model of bone invasion was used to assess antiosteoclastic and antitumor activity in vivo. Mice were followed by radiographic and bioluminescence imaging. RESULTS: Treatment of human neuroblastoma cells resulted in a decrease in cell count, increase in apoptosis, and arrest of cell-cycle progression. In the model of bone invasion, mice were treated weekly with zoledronate or vehicle control 10 days after tumor cell inoculation. Five weeks later, radiographs revealed a large degree of osteolytic disease in control mice. Impressively, mice treated with zoledronate demonstrated minimal radiographic changes at this time. Bioluminescence imaging of these mice revealed a significant restriction of tumor growth during the course of therapy. CONCLUSIONS: Zoledronate exhibits significant antitumor activity against human neuroblastoma cells in vitro, prevents development of osteolytic lesions, and restricts tumor growth in a murine model of bone metastasis. These results suggest that clinical investigation of zoledronate or similar bisphosphonates as adjuvant therapy in neuroblastoma patients is warranted.

Animals↗
PubMed2006

Case reports: polymethylmethacrylate lung embolus after limb-salvage surgery of the distal femur.

Limb-salvage surgery for malignant tumors frequently involves reconstruction with an endoprosthesis anchored to bone by using third-generation cementing techniques. A 10-year-old boy with osteosarcoma had a pulmonary embolus caused by polymethylmethacrylate after having limb-salvage surgery that used high-pressure cementing techniques. He experienced transient postoperative chest pain, and a new wedge-shaped radiodense pulmonary lesion appeared on a computed tomography scan of the chest. A thoracotomy for resection of suspected metastatic osteosarcoma revealed a pulmonary infarct caused by cement embolization. Awareness of this potential complication should prompt investigation of possible pulmonary embolism and may prevent unnecessary thoracotomy.

Biopsy↗
PubMed2006

Distinguishing benign from malignant pulmonary nodules with helical chest CT in children with malignant solid tumors.

PURPOSE: To retrospectively assess whether computed tomographic (CT) findings can indicate the benign or malignant nature of pulmonary nodules in pediatric patients with malignant solid primary tumors. MATERIALS AND METHODS: With institutional review board approval, waived parental and patient consent, and HIPAA compliance, the authors determined the incidence of malignancy among 81 pulmonary nodules that were sampled at biopsy within 3 weeks after chest CT (January 1999 to September 2003) in 41 young patients with malignant solid tumors. Three radiologists independently and retrospectively reviewed these scans and the available previously obtained scans, classifying nodules as benign, malignant, or indeterminate on the basis of their number, unilateral versus bilateral distribution, size, margins (indistinct vs distinct), calcification, growth, and associated adenopathy. These classifications were compared with nodule histologic type, and interreviewer agreement was assessed. RESULTS: The median patient age was 14.8 years (mean, 13.7 years; range, 5-21 years). Twenty-four of the 41 patients (58%) had at least one biopsy-proved malignant nodule. Four (10%) patients had both benign and malignant nodules; 17 (42%) had only benign nodules. Reviewer 1 classified 65% (39 of 60) of nodules correctly; reviewer 2, 57% (37 of 65); and reviewer 3, 67% (43 of 64). Interreviewer agreement was slight to moderate (kappa </= 0.43, P </= .03). In contrast to findings in adults, sharply defined nodules in younger individuals were more likely to be malignant (P = .03) and nodule size was not associated with malignancy (P >/= .32). CONCLUSION: The frequency of benign nodules and the inconsistency of predictions based on CT features suggest the need for better predictors of pulmonary nodules being malignant or benign, so as to reduce unnecessary thoracotomy in pediatric patients with solid malignancy. .

Adolescent↗
PubMed2006

Angiogenesis inhibitors in a murine neuroblastoma model: quantitative assessment of intratumoral blood flow with contrast-enhanced gray-scale US.

PURPOSE: To quantify intratumoral ultrasonographic (US) contrast agent flow at gray-scale imaging as a measure of functional tumor vascularity in an orthotopic murine neuroblastoma model treated with angiogenesis inhibitors. MATERIALS AND METHODS: After Institutional Animal Care and Use Committee approval, retroperitoneal neuroblastomas were established in mice with unmodified NXS2 cells (n = 13) or with cells engineered to overexpress an angiogenesis inhibitor--either tissue inhibitor of matrix metalloproteinase-3 (n = 22) or a truncated soluble form of the vascular endothelial growth factor receptor-2 (truncated soluble fetal liver kinase-1; n = 13). When tumors were approximately 600 mm3, contrast material-enhanced gray-scale US was performed, and the imaging was recorded on cine clips. Regions of interest within tumors were analyzed off-line to determine postcontrast change in signal intensity (SI) from baseline to initial peak (deltaSI), rate of SI increase from baseline to initial peak (RSI), and contrast material washout. The Mann-Whitney test was used to evaluate potential differences in these US parameters between treatment groups. The mean intratumoral endothelial cell (CD34) and pericyte (smooth muscle actin [SMA]) counts at immunohistochemical analysis were also evaluated. Spearman correlation test was used to investigate the relation between US parameters and these histologic markers. RESULTS: The deltaSI and RSI were lower in tumors overexpressing an angiogenesis inhibitor than in control tumors (all P < .03). Contrast material washout did not differ between groups. For the entire cohort, the RSI correlated with the immunohistochemical assessment of tumor vascularity (SMA and CD34 counts) (P < .003). CONCLUSION: Quantification of intratumoral flow of a US contrast agent at gray-scale imaging shows promise for monitoring tumor vascular response to antiangiogenic therapy.

Albumins↗
PubMed2006

PET/CT characterization of fibroosseous defects in children: 18F-FDG uptake can mimic metastatic disease.

OBJECTIVE: The purpose of this study was to characterize the anatomic appearance and metabolic activity of nonossifying fibromas, fibrous cortical defects, and cortical desmoids on PET/CT images. CONCLUSION: Over a 14-month period, we identified eight nonossifying fibromas, four fibrous cortical defects, and two cortical desmoids in 330 children who underwent PET/CT for the evaluation of a known or suspected malignancy. CT, conventional radiography, MRI, or clinical follow-up was used to confirm the diagnoses of these fibroosseous lesions. Eleven of the 14 children underwent multiple PET/CT examinations; thus, 34 studies were included. The lesions showed variable metabolic activity as indicated by 18F-FDG uptake: 19 PET/CT examinations showed lesions with mild 18F-FDG uptake, eight showed moderate 18F-FDG uptake, and seven showed intense uptake. When PET reveals metabolically active osseous abnormalities in children who are at risk for bone metastases, benign fibroosseous lesions should be considered in the differential diagnosis before additional diagnostic procedures are undertaken. Benign fibroosseous lesions may be metabolically active and thus mimic metastatic osseous disease in children with underlying malignancies. Correlative CT or other anatomic imaging can confirm the benign nature of these lesions.

Adolescent↗
PubMed2005

Typhlitis in childhood cancer.

BACKGROUND: Typhlitis is increasingly recognized in children undergoing chemotherapy but is poorly characterized. The authors investigated the demographic, clinical, and imaging (ultrasonography and computed tomography [CT] scans) variables related to the diagnosis, risk, and outcome of typhlitis. METHODS: The authors reviewed the records of patients who had typhlitis (bowel wall thickness > or = 0.3 cm plus clinical findings) during treatment at St. Jude Children's Research Hospital (Memphis, TN) between 1990 and 2001. They assessed whether duration of typhlitis was related to bowel wall thickness, extent of colonic involvement, ascites, demographics, primary diagnosis, symptoms of typhlitis, or duration of neutropenia. To identify risk factors for typhlitis, the authors compared the demographic data and previous drug therapy of 78 patients who had typhlitis and 1231 identically treated children who did not. RESULTS: Of 3171 children, 83 (2.6%) developed typhlitis. Frequent symptoms were abdominal pain (91%), fever (84%), abdominal tenderness (82%), and diarrhea (72%). Twelve percent of the patients were not neutropenic. Duration of typhlitis was associated with bowel wall thickness measured by ultrasonography (n = 68; P = 0.05) but not CT scan (n = 48; P = 0.67) and was associated with duration of neutropenia (P = 0.02), fever (P = 0.01), and abdominal tenderness (P = 0.04). Age >16 years at cancer diagnosis was the only demographic factor associated with typhlitis (P = 0.03). Two patients died of typhlitis. CONCLUSIONS: Ultrasonography was a useful imaging modality for children with suspected typhlitis. The classic triad of abdominal pain, fever, and neutropenia may be absent. The severity of typhlitis was related to the duration of neutropenia and the presence of fever or abdominal tenderness.

Adolescent↗
PubMed2005

PET/CT in the evaluation of childhood sarcomas.

OBJECTIVE: Our objective was to review our preliminary experience with PET/CT in evaluating childhood sarcomas including rhabdomyosarcoma (n = 28), the Ewing's sarcoma family of tumors (n = 14), nonrhabdomyosarcoma soft-tissue sarcoma (n = 9), osteosarcoma (n = 8), chondrosarcoma (n = 1), and embryonal sarcoma (n = 1). CONCLUSION: We found PET/CT useful in depicting an unknown primary rhabdomyosarcoma and detecting unsuspected and unusual metastatic sites of childhood sarcomas. It was useful in monitoring response to chemotherapy, radiation therapy, and radiofrequency ablation and aided the postoperative evaluation of tumor resection sites.

Child↗
PubMed2004

Outcome after local recurrence of osteosarcoma: the St. Jude Children's Research Hospital experience (1970-2000).

BACKGROUND: Despite improvements in therapy for osteosarcoma, approximately 4-10% of patients experience a local recurrence and have a poor prognosis. METHODS: The authors analyzed prognostic factors for survival in 26 patients with a local recurrence of osteosarcoma who were treated between 1970 and 2000. RESULTS: The initial surgical procedure was amputation in 20 patients (76.9%) and limb salvage in 6 patients (23.1%). The median time from the diagnosis of osteosarcoma to local recurrence was 1.2 years (range, 1.2 months-6.1 years). Eleven patients (42.3%) developed an isolated local recurrence and 15 patients (57.7%) developed local and distant recurrence. The 5-year estimate of postrecurrence survival (PRS) (+/- 1 standard error) for the 26 patients was 19.2% +/- 7.7%. Recurrence > or = 2 years from the time of diagnosis was found to predict a better outcome (5-year PRS of 50.0% +/- 20.4%) compared with earlier recurrence (10.0% +/- 5.5%) (P = 0.037). Patients with negative margins after initial surgery were found to have improved survival (5-year PRS of 33.3% +/- 13.6%) compared with patients with positive margins (7.1% +/- 4.9%) (P = 0.015). Patients who underwent complete surgical resection at the time of recurrence were found to have a better PRS (5-year PRS of 41.7% +/- 14.2%) compared with patients who did not undergo surgery (0% +/- 0%) (P < 0.001). CONCLUSIONS: The prognosis for patients after local recurrence of osteosarcoma is poor. Complete surgical resection at the time of recurrence is essential for survival. Positive margins at the time of initial surgical resection and early recurrence appear to be poor prognostic factors.

Adolescent↗
PubMed2004

Phase I trial of temozolomide and protracted irinotecan in pediatric patients with refractory solid tumors.

PURPOSE: The purpose is to estimate the maximum-tolerated dose (MTD) of temozolomide and irinotecan given on a protracted schedule in 28-day courses to pediatric patients with refractory solid tumors. EXPERIMENTAL DESIGN: Twelve heavily pretreated patients received 56 courses of oral temozolomide at 100 mg/m(2)/day for 5 days combined with i.v. irinotecan given daily for 5 days for 2 consecutive weeks at either 10 mg/m(2)/day (n = 6) or 15 mg/m(2)/day (n = 6). We assessed toxicity, the pharmacokinetics of temozolomide and irinotecan, and the DNA repair phenotype in tumor samples. RESULTS: Two patients experienced dose-limiting toxicity (DLT) at the higher dose level; one had grade 4 diarrhea, whereas the other had bacteremia with grade 2 neutropenia. In contrast, no patient receiving temozolomide and 10 mg/m(2)/day irinotecan experienced DLT. Myelosuppression was minimal and noncumulative. No pharmacokinetic interaction was observed. Drug metabolite exposures at the MTD were similar to exposures previously associated with single-agent antitumor activity. One complete response, two partial responses, and one minor response were observed in Ewing's sarcoma and neuroblastoma patients previously treated with stem cell transplant. Responding patients had low or absent O(6)-methylguanine-DNA methyltransferase expression in tumor tissue. CONCLUSIONS: The MTD using this schedule was temozolomide (100 mg/m(2)/day) and irinotecan (10 mg/m(2)/day), with DLT being diarrhea and infection. Drug clearance was similar to single-agent values, and clinically relevant SN-38 lactone and MTIC exposures were achieved at the MTD. As predicted by xenograft models, this combination and schedule appears to be tolerable and active in pediatric solid tumors. Evaluation of a 21-day schedule is planned.

Adolescent↗
PubMed2004

Significance of appendiceal thickening in association with typhlitis in pediatric oncology patients.

BACKGROUND: The management of pediatric oncology patients with imaging evidence of appendiceal thickening is complex because they are generally poor surgical candidates and often have confounding clinical findings. OBJECTIVE: We sought to determine the significance of appendiceal thickening in pediatric oncology patients who also had typhlitis. Specifically, we evaluated the impact of this finding on the duration of typhlitis, its clinical management, and outcome. MATERIALS AND METHODS: From a previous review of the management of typhlitis in 90 children with cancer at our institution, we identified 4 with imaging evidence of appendiceal thickening. We compared colonic wall measurements, duration of typhlitis symptoms, management, and outcome of patients with appendiceal thickening and typhlitis to patients with typhlitis alone. RESULTS: There was no significant difference in duration of typhlitis symptoms between patients with typhlitis only (15.6+/-1.2 days) and those with typhlitis and appendiceal thickening (14.5+/-5.8 days; P=0.9). Two patients with appendiceal thickening required surgical treatment for ischemic bowel, and two were treated medically. Only one patient in the typhlitis without appendiceal thickening group required surgical intervention. There were no deaths in children with appendiceal thickening; two patients died of complications of typhlitis alone. CONCLUSION: Our findings suggest that appendiceal thickening does not predict a prolonged course of typhlitis in pediatric oncology patients, but it may indicate an increased risk of serious complications from this disease process.

Adolescent↗
PubMed2004

Comparison of transcranial Doppler sonography with and without imaging in the evaluation of children with sickle cell anemia.

OBJECTIVE: High blood flow velocity in the middle cerebral artery or distal internal carotid artery, as measured by nonduplex transcranial Doppler sonography, predicts stroke in children with sickle cell anemia. However, velocities measured using the more widely available duplex transcranial Doppler imaging equipment may not be comparable. We sought to determine the magnitude and significance of the potential differences. SUBJECTS AND METHODS: We performed 55 paired examinations with duplex imaging and nonduplex nonimaging sonography machines on 53 children with sickle cell anemia. Examinations were performed consecutively by three sonographers blinded to the results of the opposing study. Velocities were measured in five clinically relevant vessels. RESULTS: Time-averaged mean maximum (TAMx) velocity measurements obtained with the duplex equipment were significantly lower than those made with the nonduplex equipment for all vessels except the posterior cerebral artery. The mean differences were 10.9% (p < 0.0001) in the middle cerebral artery, 12.7% (p = 0.002) in the anterior cerebral artery, 2.2% (p = 0.69) in the posterior cerebral artery, 21.0% (p < 0.0001) in the distal internal carotid artery, and 15.3% (p < 0.0001) at the bifurcation of the distal internal carotid artery. CONCLUSION: If TAMx velocities measured with duplex equipment are used to assign stroke risk in children with sickle cell anemia, we suggest that 180 cm/sec or more should be considered abnormal, and 153-179 cm/sec, as conditional. These values are 10% lower than those obtained from the nonduplex equipment used in the Stroke Prevention Trial in Sickle Cell Anemia study.

Adolescent↗