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B Cushing

Publications and source records attributed to B Cushing.

At least 19 recordsLinked to original sources

DNA content of ovarian immature teratomas and malignant germ cell tumors.

OBJECTIVE: Ovarian germ cell tumors (GCT) show greater histologic and biologic heterogeneity than their testicular counterparts and remain poorly understood. Ploidy analysis was performed on ovarian GCT registered on Pediatric Oncology Group germ cell tumor protocols 9048 and 9049 to distinguish biologically distinct subsets of immature teratomas and malignant ovarian germ cell tumors. METHODS: Tumors from 22 patients (mean age 12 years) were analyzed and classified according to the submitting diagnosis; when pure samples of different histologic subtypes within a single tumor were possible, these were analyzed separately. Archival tissue was disaggregated and Feulgen stained; DNA index (DI) was determined by static image analysis utilizing internal normal cells as diploid controls. RESULTS: 26 histologic subtypes from 22 patients were analyzed. The tumors of 18 patients were composed of a single histologic subtype according to the submitting institution, including 6 dysgerminomas, 8 immature teratomas (IT), and 4 endodermal sinus tumors (EST). Two tumors contained both IT and EST components that were separately analyzed. Two tumors were classified as mixed germ cell tumors; 1 showed multiple intermingling subtypes unable to be separately analyzed and the second showed three histologic subtypes separately analyzed (IT, EST, embryonal carcinoma). From a total of 15 malignant histologic GCT subtypes in 14 patients, all but 2 demonstrated a DI of 1.4-2.4 (mean 1.85). Two diploid malignant GCT (1 EST, 1 dysgerminoma) were both associated with gonadoblastoma. Overall, 11 IT subtypes were analyzed and 9 were diploid (2 grade 1, 5 grade 2, and 2 grade 3). Two tumors originally submitted and classified as pure IT (grades 2 and 3) were aneuploid with a dominant diploid and a secondary aneuploid peak (both DI 1.7). On central review, both of these tumors demonstrated the presence of subtle patterns of EST that were unrecognized by the submitting institution and were much too small for separate analysis. Analysis of the 3 patients containing sufficient IT and EST to be separately analyzed all showed a diploid IT component and an aneuploid EST component. CONCLUSIONS: Analysis of ploidy data suggests that polyploidization is a consistent finding in malignant ovarian GCT arising in normal patients, similar to the data for adult testicular GCT. Immature teratomas in this pediatric population, however, are most commonly diploid, regardless of grade. The development of EST within an IT is associated with the development of an aneuploid clone. Therefore, the finding of such a clone in an IT may be of diagnostic utility, as EST may be difficult to recognize. Last, the development of a malignant GCT in patients with gonadal dysgenesis may be pathogenetically different from those arising in normal patients, in that polyploidization is not required.

Adolescent

Immature teratomas in children: pathologic considerations: a report from the combined Pediatric Oncology Group/Children's Cancer Group.

Pediatric germ cell tumors (n = 135) with a major component of immature teratoma (IT) registered on Pediatric Oncology Group/Children's Cancer Group treatment protocols from 1990 to 1995 were reviewed. Sixty cases were pure IT with no malignant component and 75 were mixed tumors with a major component of IT. Foci of yolk sac tumor (YST) were present in all 75 mixed tumors; additional malignant components were present in 15. The IT component was as follows: 47% grade 3, 29% grade 2, 24% grade 1. There were no significant correlations between tumor grade and patient age by specific subsets or overall (all p > 0.10). Significant correlations were detected between stage and the presence of foci of YST (p = 0.0145) and grade and the presence of foci of YST (p < 0.001). Serum alpha-fetoprotein concentrations were elevated at diagnosis in 96% of ovarian tumors with foci of YST and were mildly elevated (< 60 ng/dL) in only 16% of tumors without YST. Overall 2- to 6-year survival rate was 96% and was related to the presence of YST. Central pathologic review revealed aspects of morphologic diagnosis that were most frequently misinterpreted by contributing pathologists. These included the classification of differentiating tissues as immature and the failure to recognize two well-differentiated patterns of YST (the hepatoid pattern resembling fetal liver and the well-differentiated glandular pattern resembling fetal lung or intestine). Such foci were often overlooked. The authors conclude that the presence of microscopic foci of YST, rather than the grade of IT, per se, is the only valid predictor of recurrence in pediatric IT at any site.

Child, Preschool

Thoracic neuroblastoma: what is the best imaging modality for evaluating extent of disease?

BACKGROUND: Thoracic neuroblastoma accounts for 15% of all cases of neuroblastoma. A minority of children with thoracic neuroblastoma will have dumbbell tumors, i.e., intraspinal extension, but only half these patients will have neurologic signs or symptoms. HYPOTHESIS: MR imaging is the single best test to evaluate the extent of thoracic and spinal disease in thoracic neuroblastoma after the diagnosis of a mass is established on plain film. MATERIALS AND METHODS: A retrospective multi-institutional investigation over 7 years of all cases of thoracic neuroblastoma (n = 26) imaged with CT and/or MR were reviewed for detection of the extent of disease. The chest film, nuclear bone scan, and other imaging modalities were also reviewed. The surgical and histologic correlation in each case, as well as the patients' staging and outcome, were tabulated. RESULTS: The chest radiograph was 100% sensitive in suggesting the diagnosis. MR imaging was 100% sensitive in predicting enlarged lymph nodes, intraspinal extension, and chest wall involvement. CT was 88% sensitive for intraspinal extension but only 20% sensitive for lymph node enlargement. CT was 100% sensitive in detecting chest wall involvement. Direct comparison of CT and MR imaging in six cases revealed no difference in detection of enlarged lymph nodes or chest wall involvement. Neither test was able to detect remote disease, as noted by bone scan. CONCLUSION: The chest film is 100% sensitive in suggesting the diagnosis of thoracic neuroblastoma; MR imaging appears to be the single best test for detecting nodal involvement, intraspinal extension, and chest wall involvement.

Adolescent

The prepubertal testis (prenatal and postnatal): its relationship to intratubular germ cell neoplasia: a combined Pediatric Oncology Group and Children's Cancer Study Group.

Seminiferous tubules adjacent to germ cell tumors (GCT) in prepubertal boys frequently contain increased germ cells with abundant, clear cytoplasm. These cells are placental alkaline phosphatase (PLAP) negative and are usually not considered to represent intratubular germ cell neoplasia (ITGCN). A recent case report found p53 and proliferating cell nuclear antigen (PCNA) positivity in such cells and equated these PLAP-negative cells with ITGCN. Because the proto-oncogene c-kit is also a marker of ITGCN, immunohistochemical tests for c-kit and PLAP were performed on 28 testes adjacent to prepubertal GCT in children aged 2 to 45 months. Additional slides from testes not associated with GCT from 18 preterm infants and children ages 19 weeks to 7 years were also tested. An adult testis with seminoma and ITGCN served as a positive control. PCNA, PLAP, and p53 were tested on available slides. No intratubular germ cells adjacent to GCT in prepubertal children were positive for PLAP or c-kit; five of seven were positive for PCNA; p53 was present in the two examined. These results indicate that germ cells adjacent to infantile GCT are proliferative but not neoplastic and offer additional evidence that intratubular germ cells and GCT in prepubertal boys are different from those of adolescents and adults.

Adult

Long-term outcomes after lower extremity trauma.

Previous studies have shown that over one-quarter of patients who were working before a severe lower extremity fracture had not returned to work by 12 months after injury. Disabilities also persisted in household management, recreation, and social interaction. The objective of this study was to determine whether recovery extended beyond 12 months. Three hundred nineteen patients who were previously working and were treated at three level I trauma centers for a severe lower extremity fracture were prospectively followed at 3, 6, and 12 months after injury. Patients were queried at each follow-up about their work status and completed the Sickness Impact Profile (SIP) at 6 and 12 months. The SIP is a widely used and well validated measure of general health status; it was used in this study to measure functional recovery across several domains of daily living. Patients who had not recovered by 12 months (i.e., 204 who were not working, working with limitations, or had limitations in performing other daily activities as measured by elevated scores on the SIP) were contacted again at 30 months and asked to complete an interview and the SIP. At 30 months, an estimated 82% of the study patients had returned to work (compared to 72% at 12 months). SIP scores improved only slightly from 6.4 at 12 months to 5.7 at 30 months. At 30 months, 64% of the patients had no disability (SIP scores less than 4), 17% had mild disability (SIP scores of 4 to 9), 12% had moderate disability (SIP scores of 10 to 19), and 7% had severe disability (SIP scores of 20 or higher). Although the majority of patients with persistent disabilities at 30 months had residual physical impairments at 12 months, the extent of impairment did not fully explain why some people had and had not recovered at 30 months after injury. The results confirm those of other studies that conclude that overall, outcomes after serious trauma are good when appropriate trauma and rehabilitation care are rendered. However, a minority of patients still report limitations at 30 months after injury, with one-fifth not returning to work.

Adolescent

The Sickness Impact Profile as a tool to evaluate functional outcome in trauma patients.

Because the ultimate goal of trauma care is to restore injured patients to their former functional status, reliable evaluation of functional status is needed to assess fully the effectiveness of trauma care. We hypothesized that the Sickness Impact Profile (SIP), a widely used measure of general health status, would be a useful tool to evaluate the long-term functional outcome of trauma patients and that the SIP would identify unexpected problems in the recovery process and groups of patients at high risk for long-term disability. A prospective cohort of 329 patients with lower extremity fractures admitted to three level I trauma centers were interviewed using SIP at 6 and 12 months postinjury. Patients with major neurologic injuries were excluded. Overall SIP scores and each of the component subscores may range from 0 (no disability) to 100. In this series, the mean overall SIP was 9.5 at 6 months and 6.8 at 12 months, compared with a preinjury baseline of 2.5. At 12 months, 52% of patients had no disability (SIP 0 to 3), 23% mild disability (4 to 9), 16% moderate disability (10 to 19), and 9% severe disability ( > or = 20). Disability was widely distributed across the spectrum of activities of daily living, including physical functioning (mean score of 5.5), psychosocial health (mean score of 5.5), sleeping (mean score of 10.0), and work (mean score of 21.0). The SIP scores did not correlate with Injury Severity Score.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living

Trauma data bases.

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Databases, Factual

Gut failure--predictor of or contributor to mortality in mechanically ventilated blunt trauma patients?

UNLABELLED: Thirty-seven ventilator-dependent blunt trauma patients (ISS 36 +/- 15) were randomized at 24 hours after injury to receive parenteral (TPN) (n = 15), enteral (TEN) (n = 12), or parenteral plus enteral (PN/EN) (n = 10) nutrition. The TEN and PN/EN patients had endoscopically placed transpyloric feeding tubes. Patients who had nutritional complications were two TPN (13%), three TEN (25%), and five PN/EN (50%). Enteral complications were tube occlusion (two), failed duodenal intubation (one), patient extubation of feeding tube (one), gastric reflux (two), and abdominal distention (two). Mortality rates were not different between the groups, but were significantly related to the nutrition-associated complications (p = 0.01): four deaths in ten (40%) with complications and one death in 27 (3.7%) without complications. All four deaths associated with complications occurred in the four with gastric reflux or abdominal distention. No deaths occurred in the other 18 TEN or PN/EN patients (p = 0.0001). Of the four deaths, three were associated with ARDS and respiratory infection (75%). CONCLUSIONS: In mechanically ventilated blunt trauma patients, endoscopic transpyloric tube placement and feeding has a substantial failure rate (36%). Intolerance to duodenal feeding has a remarkably high mortality (100%) in patients in whom gut dysfunction may be a manifestation of injury severity or directly affect survival.

Adult

Inflammatory markers: superior predictors of adverse outcome in blunt trauma patients?

OBJECTIVE: To assess whether variables reflective of early metabolic responses to injury are predictors of outcome in critically ill trauma patients. DESIGN: Clinical inception cohort study comparing conventional measures of injury severity with early host response markers for the correlation of each with outcome. These data are prospectively collected in a group of patients being evaluated in a nutritional support investigation. SETTING: Intensive care unit (ICU) of a major Level I trauma center. PATIENTS: Seventeen blunt trauma patients, aged 18 to 60 yrs with an Injury Severity Score of > or = 15, requiring early mechanical ventilation. INTERVENTIONS: Blood and urine samples were routinely obtained from patients undergoing nutritional support by one of three routes. MEASUREMENTS AND MAIN RESULTS: Conventional assessment was consistent with moderate severity and variation: Injury Severity Score, 41 +/- 15; Glasgow Coma Score, 11 +/- 4; admission circulating lactate concentration, 4.8 +/- 2.2 mmol/L; and first 24-hr transfusion requirement, 3.1 +/- 2.9 L. The mean concentrations of inflammatory marker during the first week were: cholesterol, 2.67 +/- 0.80 mmol/L (103.2 +/- 31 mg/dL); C-reactive protein, 23 +/- 11 mg/dL; transferrin, 1.44 +/- 0.47 g/L; glucose, 9.21 +/- 2.27 mmol/L (166 +/- 41 mg/dL); albumin, 26 +/- 5 g/L; and nitrogen loss, 24 +/- 9 g/d. Hospital outcome variables were: ventilator days, 17 +/- 7; ICU days, 26 +/- 10; hospital days, 38 +/- 15; occurrence rate of adult respiratory distress syndrome (ARDS), 35%; infections, 82%; multiple organ failure, 71%; and total of hospital plus professional charges, $125,000 +/- $56,000. A significant (p < .05), but weak, correlation existed between all seven outcome variables and the inflammatory markers: ventilator days with cholesterol and C-reactive protein; ICU days with transferrin; total stay with cholesterol; ARDS with C-reactive protein; infections with glucose, cholesterol, and nitrogen loss; multiple organ failure with albumin and C-reactive protein; and financial charges with glucose. However, a significant correlation existed between only two of seven outcome variables and conventional measures of severity: multiple organ failure with lactate and financial charges with transfusion requirement. CONCLUSION: Readily obtainable inflammatory marker measurements may better reflect the summation effects of the early perfusion deficit and tissue injury in the blunt trauma patient compared with conventional measures of injury severity.

Adult

Safety belt restraints and compartment intrusions in frontal and lateral motor vehicle crashes: mechanisms of injuries, complications, and acute care costs.

A 3-year prospective study examined 76 frontal (F) and 45 lateral (L) motor vehicle crash (MVC) patients with regard to seatbelt restraint use and occupant compartment contact and intrusion injuries. These 121 MVC victims with multiple injuries (39 belted [B] and 82 non-belted [NB]), admitted to a level I trauma center, were studied by accident reconstruction and medical data analysis. They had a MVC mean impact velocity (delta V) of 30 +/- 11 mph and an injury Severity Score of 29 +/- 12. Proper restraint use reduced brain injury in F MVCs (30% FB vs. 47% FNB) but had no effect in L MVCs (63% LB vs. 30% FB [p < 0.06]). Belt use did not protect against lung, liver, spleen, pelvis, or lower extremity (LE) injury. These appeared to be more a function of crash direction, with LE injuries higher in F crashes (p < 0.04) and pelvis injuries (p < 0.001) higher in L crashes. In FB crashes, however, properly used safety restraints were the primary cause of bowel or colon injuries (p < 0.006). Belts did not prevent thoracic or abdominal solid organ injuries in L crashes. Contact-intrusions (CI) of the car occupant compartment in F crashes were the main cause of brain (A-pillar), lung and liver (steering wheel and instrument panel), and LE (toepan) injuries; but in L crashes, side-door CI caused lung, aorta, liver, and pelvic injuries. In contrast, contact-only (CO) injuries of the steering assembly were mainly responsible for injuries to the lung, heart, and liver in F crashes, and side-door CO for lung, liver, and spleen injuries in L crashes. Deaths and complications after injury were higher among F MVC occupants, or when delta V was > or = 30 mph. Hospital and professional costs reflect the complex care needed for victims of multiple injuries: FB, $99,000; FNB, $95,000; LB, $75,000; LNB, $79,000; total, $10.7 million. Present vehicle safety standards are not adequate, and structural design changes are needed to improve restraints and protect occupants from intrusion-related injuries.

Abdominal Injuries

Occult malignancy in neonatal sacrococcygeal teratomas. A report from a Combined Pediatric Oncology Group and Children's Cancer Group study.

PURPOSE: Six children who had mature or immature sacrococcygeal teratomas diagnosed in the newborn period have since been registered on a Pediatric Oncology Group/Children's Cancer Group germ cell study with recurrent malignant neoplasia [pure yolk sac tumor (YST) or teratoma with yolk sac elements]. RESULTS: Four of the children have responded to therapy, one has died, and one has been lost to follow-up. Review of the slides from five of the original tumors identified microscopic foci of YST in four. CONCLUSIONS: Detection of such foci in neonatal tumors is important because serum alpha-fetoprotein concentrations may not be helpful since they may normally be high in the newborn period due to fetal production.

Antineoplastic Combined Chemotherapy Protocols

Imaging of Wilms' tumor: what is important!

The imaging of Wilms' tumor needs to be quite focused so that the oncologist and surgeon can most precisely stage the patient before operation. The imager needs to be exact about the extent of the primary tumor and define any invasion into the adjacent soft tissues. The ability to detect nodal disease is quite difficult but clearly influences the preoperative approach and staging. Children with large tumors extending across the midline in whom primary resection may lead to tumor spillage are prime candidates for preoperative chemotherapy, and the imager has significant input in making this decision. The imager must define metastases in the lungs and the liver and evaluate the risk of bilateral tumor (particularly metachronous) by searching the index kidney for multifocal lesions or nephroblastomatosis in either kidney.

Child

Phase I study of a 120-hour continuous intravenous infusion of 5-fluorouracil in pediatric patients with recurrent solid tumors: a Pediatric Oncology Group study.

To determine the maximum tolerated dose of 5-fluorouracil administered as a 120-hour continuous intravenous infusion to pediatric patients, we performed a phase I study using a starting dosage of 900 mg/m2/day. The maximum tolerated dosage (MTD) was 1,100 mg/m2/day. At this dosage level 40% of courses were complicated by grade 3 mucositis. Three additional patients were treated at the dosage level of 1,000 mg/m2/day after the MTD was determined. We recommend the dosage level of 1,000 mg/m2/day for phase II studies of 5-fluorouracil administered as a 120-hour continuous intravenous infusion to pediatric patients.

Adolescent

Phase I evaluation of diaziquone in childhood cancer. A Pediatric Oncology Group study.

We conducted a phase I clinical study of aziridinylbenzoquinone (Diaziquone, AZQ) given as a 4 hour infusion weekly X 4. Forty-five children with recurrent acute leukemia and 33 children with various advanced solid tumors participated. Severe myelosuppression was the dose limiting toxic effect, occurring in all patients at the upper dose levels. Gastrointestinal and hepatic toxicities were infrequent and not severe. No allergic reactions occurred. Objective tumor regression was noted in 3 of 25 patients with a CNS tumor and in 6 of 45 patients with acute leukemia. For phase II trials the recommended dosage of Diaziquone given by this schedule is 18 mg/M2/week X 4 for patients with a solid tumor, and is 30 mg/M2/week X 4 for children with acute leukemia.

Adolescent

Recurrence of Wilms tumor after apparent cure.

The recurrence of Wilms tumor after a 5-year disease-free interval is rare. We present two patients who had recurrent disease after a disease-free interval of greater than 7 years. Three additional patients, registered with the National Wilms Tumor Study who had a recurrence after 5 years, are also described. Of these three patients, two had nephroblastomatosis. Because more patients are achieving long-term survival, careful surveillance after apparent "cure" is recommended, particularly if nephroblastomatosis is identified in the original nephrectomy specimen.

Child, Preschool

Asymptomatic intracardiac metastasis from osteosarcoma: a case report with literature review.

Osteosarcoma very rarely metastasizes to the heart. Thirteen cases have been reported in the literature so far. Diagnosis in some of these cases was made during investigation for severe cardiac failure and in most of them at autopsy. Our patient, a 13-year-old girl, showed right pulmonary metastases on chest x-ray 1 year after above knee amputation for osteosarcoma of the distal femur. Routine preoperative computerized axial tomography (CT Scan) revealed a calcified lesion in the heart in addition to the pulmonary metastases. She was very active and completely asymptomatic. Two-dimensional echocardiography, angiography, and right and left heart catheterizations were done. This revealed a large mobile metastatic lesion in the right ventricle. The intraventricular tumor was successfully removed, and 12 days later she had a second thoracotomy for removal of pulmonary metastases. Nine months after her intraventricular metastasis was removed she developed a solitary right pulmonary metastasis. This was successfully resected. Now, 10 months later, she is disease free and completely asymptomatic.

Adolescent