ABSTRACT
BACKGROUND: Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. AIM: To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. METHODS: Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. RESULTS: Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%. CONCLUSIONS: Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner.
Subject(s)
Fatty Liver/diagnosis , Liver Diseases/diagnosis , Obesity/complications , Overweight/complications , Adolescent , Alanine Transaminase/metabolism , Child , Female , Follow-Up Studies , Gastroenterology/methods , Humans , Liver Diseases/physiopathology , Male , Mass Screening/methods , Non-alcoholic Fatty Liver Disease , Primary Health Care , Prospective Studies , Referral and Consultation , Sensitivity and SpecificityABSTRACT
PURPOSE: The retinoblastoma (RB) cell cycle regulatory pathway is known to be deregulated in virtually all known human tumors. The protein product of the RB gene, pRB, and its upstream regulator, p16, are among the most commonly affected members of this pathway. We investigated the prognostic significance of both pRB and p16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86-10. MATERIALS AND METHODS: Sixty-seven cases from RTOG 86-10 had immunohistochemically stained slides, judged interpretable for both p16 and pRB, available for analysis. Median follow-up was 8.9 years (range, 6.0 to 11.8 years) for surviving patients. Staining for each marker was then correlated with overall survival, local progression, distant metastasis, and disease-specific survival. RESULTS: Loss of p16 expression, as defined by expression was significantly associated with reduced overall survival (P =.039), disease-specific survival (P =.006), and higher risk of local progression (P =.0007) and distant metastasis (P =.026) in the univariate analysis. In the multivariate analysis, loss of p16 was significantly associated with reduced disease-specific survival (P =.0078) and increased risk of local failure (P =.0035) and distant metastasis (P =.026). A borderline association with reduced overall survival (P =.07) was also evident. Loss of pRB was associated with improved disease-specific survival on univariate (P =.028) and multivariate analysis (P =.043), but carried no other significant outcome associations. CONCLUSION: Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer.
Subject(s)
Cyclin-Dependent Kinase Inhibitor p16/metabolism , Prostatic Neoplasms/metabolism , Adult , Aged , Chi-Square Distribution , Disease Progression , Disease-Free Survival , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Metastasis , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Survival AnalysisABSTRACT
PURPOSE: When an initial retrospective review of malignant glioma patients (MG) undergoing brachytherapy was carried out using the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) criteria, it revealed that glioblastoma multiforme (GBM) cases benefit the most from implant. In the present study, we focused exclusively on these GBM patients stratified by RPA survival class and looked at the relationship between survival and implanted target volume, to distinguish the prognostic value of volume in general and for a given GBM class. METHODS AND MATERIALS: Between 1991 and 1998, 75 MG patients were treated with surgery, external beam radiation, and stereotactic iodine-125 (I-125) implant. Of these, 53 patients (70.7%) had GBMs, with 52 (98%) having target volume (TV) data for analysis. Stratification by RPA criteria showed 12, 26, 13, and 1 patients in classes III to VI, respectively. For analysis purposes, classes V and VI were merged. There were 27 (51.9%) male and 25 (48.1%) female patients. Mean age was 57.5 years (range 14-79). Median Karnofsky performance status (KPS) was 90 (range 50-100). Median follow-up time was 11 months (range 2-79). RESULTS: At analysis, 18 GBM patients (34.6%) were alive and 34 (65.4%) were dead. Two-year and 5-year survivals were 42% and 17.5%, respectively, with a median survival time (MST) of 16 months. Two-year survivals and MSTs for the implanted GBM patients compared to the RTOG database were as follows: 74% vs. 35% and 28 months vs. 17.9 months for class III; 32% vs. 15% and 16 months vs. 11.1 months for class IV; 29% vs. 6% and 11 months vs. 8.9 months for class V/VI. Mean implanted TV was 15.5 cc (range 0.8-78), which corresponds to a spherical implant diameter of 3.1 cm. Plotting survival as a function of 5-cc TV increments suggested a trend toward poorer survival as the implanted volume increases. The impact of incremental changes in TV on survival within a given RPA class of GBMs was compared to the RTOG database. Looking at absolute differences in MSTs: for classes III and IV, there was little effect of different TVs on survival; for class V/VI, a survival benefit to implantation was still seen at the target volume cutoff (TV > 25 cc). Within a given RPA class, no significant differences were found within class III; for class IV, the most significant difference was at 10 cc (p = 0.05); and for class V/VI, at 20 cc (p = 0.06). CONCLUSION: For all GBM patients, an inverse relationship between implanted TV size and median survival is suggested by this study. However, when GBM patients are stratified using the RTOG's RPA criteria, the prognostic effect of implant volume disappears within each RPA survival class. At the critical volume of 25 cc, which approximates an implant of 5-cm diameter (upper implantation limit of many CNS brachytherapy protocols), the "poorest" prognosis GBM patients stratified by RPA still demonstrate a survival benefit with implant. We suggest that any GBM patient meeting brachytherapy recognized size criteria be considered for I-125 implant.
Subject(s)
Brachytherapy , Brain Neoplasms/mortality , Brain Neoplasms/radiotherapy , Glioblastoma/mortality , Glioblastoma/radiotherapy , Adolescent , Adult , Aged , Decision Making , Female , Follow-Up Studies , Humans , Iodine Radioisotopes/therapeutic use , Male , Middle Aged , Patient Selection , Prognosis , Radiopharmaceuticals/therapeutic use , Retrospective Studies , Survival AnalysisABSTRACT
The objective of this study was to determine the incremental labor costs or opportunity costs associated with the provision of immunizations in ambulatory care settings. A time and motion analysis of primary care health visits by pediatric patients was performed in 10 community clinics and 5 private primary care practices. These clinics and practices were located in areas designated as Health Professional Shortage Areas, with traditionally low immunization coverage rates and other unmet primary care needs. The outcome measure for this study was the comparative duration of the visit, contrasting well-child visits during which immunization was given with well-child visits during which no immunization was given. The results suggested that immunizations present an opportunity cost during well-child visits. The average time of patient-provider contact found in this study supports other findings showing that this time is now significantly longer than that reported in the past. In order for providers to comply with increased recommendations and requirements for preventive health care services, the allotted visit time, capitation rates, and overall clinic system effectiveness need to be reexamined.
Subject(s)
Child Health Services/economics , Health Care Costs/statistics & numerical data , Immunization/economics , Preventive Health Services/economics , California , Child Health Services/statistics & numerical data , Child, Preschool , Health Services Research , Humans , Immunization/statistics & numerical data , Medically Underserved Area , Office Visits/economics , Professional-Patient Relations , Salaries and Fringe BenefitsABSTRACT
BACKGROUND: As health care organizations face increasing pressure to institute quality assurance activities, the already-underfunded community clinics that treat the poor and underserved are challenged to perform these activities within tight constraints of human and financial resources. With pediatric immunizations as a marker, a workflow observation tool was used to identify causal processes affecting immunization delivery. METHODS: Ten clinics and five private practices, located in areas designated as health professional shortage areas, participated in the study, gaining access to a tool that would have been unaffordable to them from the private sector. Trained observers followed families through the clinic, using a 127-item workflow observation form--the Observational Checklist of Patient Encounters (OCPE)--assessing discrete activities that families encountered during the checkin/pre-exam, exam, discharge, and billing processes. A convenience sampling of the targeted population--children younger than three years of age--included observations of scheduled acute, scheduled well-child, follow-up, and walk-in visits. In the feedback session, a summary of each clinic's immunization delivery patterns was presented, with an emphasis on the individual health center's operational issues. RESULTS: The workflow observation tool was used to identify operational errors affecting both clinical and fiscal processes in each of the clinics that had not been previously apparent to either clinic management or the quality improvement (QI) teams. DISCUSSION: Feedback addressed and encouraged process-oriented improvements in response to the workflow observations, which were incorporated into the clinics' QI procedures. Twelve of the 15 clinics have formed process action teams to address QI issues on an ongoing basis.
Subject(s)
Immunization/standards , Quality Assurance, Health Care , Task Performance and Analysis , Age Factors , Ambulatory Care Facilities , Appointments and Schedules , Child, Preschool , Humans , Infant , Infant, Newborn , Medical Records , Medically Underserved Area , Office Visits , Outpatients , Primary Health Care , Private Practice , Research , Time FactorsABSTRACT
Spinal cord compression secondary to metastases is an infrequent complication of childhood cancer. We describe an infant with hepatoblastoma in whom cord compression developed because of extensive epidural metastases during treatment. This is a hitherto undescribed metastatic site for hepatoblastoma.
Subject(s)
Hepatoblastoma/secondary , Liver Neoplasms/diagnosis , Spinal Cord Compression/etiology , Spinal Neoplasms/secondary , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/therapeutic use , Embolization, Therapeutic , Fatal Outcome , Fluorouracil/administration & dosage , Hepatoblastoma/diagnosis , Hepatoblastoma/drug therapy , Humans , Infant , Liver Neoplasms/drug therapy , Magnetic Resonance Imaging , Male , Spinal Cord Compression/therapy , Spinal Neoplasms/diagnosis , Spinal Neoplasms/drug therapy , Vincristine/therapeutic useABSTRACT
PURPOSE: To date, numerous retrospective studies have suggested that the addition of brachytherapy to the conventional treatment of malignant gliomas (MG) (surgical resection followed by radiotherapy +/- chemotherapy) leads to improvements in survival. Two randomized trials have suggested either a positive or no survival benefit with implants. Critics of retrospective reports have suggested that the improvement in patient survival is due to selection bias. A recursive analysis by the RTOG of MG trials has stratified MG patients into 6 prognostically significant classes. We used the RTOG criteria to analyze the implant data at Wayne State University to determine the impact of selection bias. METHODS AND MATERIALS: Between July 1991 and January 1998, 75 patients were treated with a combination of surgery, radiotherapy, and stereotactic I-125 implant as primary MG management. Forty-one (54.7%) were male; 34 (45.3%) female. Median age was 52 years (range 4-79). Twenty-two (29.3%) had anaplastic astrocytoma (AA); 53 (70.7%), glioblastoma multiforme (GBM). Seventy-two patients had data making them eligible for stratification into the 6 RTOG prognostic classes (I-VI). Median Karnofsky performance status (KPS) was 90 (range 50-100). There were 14, 0, 14, 31, 12, and 1 patients in Classes I to VI, respectively. Median follow-up time for AA, GBM, and any surviving patient was 29, 12.5, and 35 months, respectively. RESULTS: At analysis, 29 (40.3%) patients were alive; 43 (59.7%), dead. For AA and GBM patients, 2-year and median survivals were: 58% and 40%; 38 and 17 months, respectively. For analysis purposes, Classes I and II, V and VI were merged. By class, the 2-year survival for implanted patients compared to the RTOG data base was: III--68% vs. I--76%; III--74% vs. 35%; IV--34% vs. 15%; V/VI--29% vs. V--6%. For implant patients, median survival by class was (in months): I/II--37; III--31; IV--16; V/VI--11. CONCLUSION: When applied to MG patients receiving permanent I-125 implant, the criteria of the RTOG recursive partitioning analysis are a valid tool to define prognostically distinct survival groups. As reflected in the RTOG study, a downward survival trend for the implant patients is seen from "best to worse" class patients. Compared to the RTOG database, median survival achieved by the addition of implant is improved most demonstrably for the poorer prognostic classes. This would suggest that selection bias alone does not account for the survival benefit seen with I-125 implant and would contradict the notion that the patients most eligible for implant are those gaining the most benefit from the treatment. In light of the contradictory results from two randomized studies and given the present results, further randomized studies with effective stratification are required since the evidence for a survival benefit with brachytherapy (as seen in retrospective studies) is substantial.
Subject(s)
Brain Neoplasms/radiotherapy , Glioma/radiotherapy , Iodine Radioisotopes/therapeutic use , Radiopharmaceuticals/therapeutic use , Adolescent , Adult , Aged , Bias , Brachytherapy , Brain Neoplasms/mortality , Brain Neoplasms/surgery , Child , Child, Preschool , Combined Modality Therapy , Female , Glioma/mortality , Glioma/surgery , Humans , Male , Middle Aged , Patient Selection , Prognosis , Retrospective Studies , Survival AnalysisABSTRACT
PURPOSE: In June 1992, POG began accrual to a phase III study, POG-9239, designed to compare the time to disease progression, overall survival, and toxicities observed in children with newly diagnosed brainstem tumor treated with 100 mg/m2 of infusional cisplatin and randomized to either conventional vs. hyperfractionated radiotherapy. METHODS AND MATERIALS: Patients eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the pons. Histologic confirmation of diagnosis was not mandatory, provided that the clinical and MRI scan findings were typical for a diffusely infiltrating pontine lesion. Treatment consisted of a six-week course of local field radiotherapy with either once a day treatment of 180 cGy per fraction to a total dose of 5400 cGy (arm 1) or a twice a day regimen of 117 cGy per fraction to a total dose of 7020 cGy (the second of the three hyperfractionated dose escalation levels of POG-8495) (arm 2). Because of previously reported poor results with conventional radiotherapy alone, cisplatin was included as a potential radiosensitizer in an attempt to improve progression-free and ultimate survival rates. Based on results of the phase I cisplatin dose escalation trial, POG-9139, 100 mg/m2 was chosen for this trial and was delivered by continuous infusion over a 120-hour period, beginning on the first day of radiotherapy and repeated during weeks 3 and 5. One hundred thirty eligible patients were treated on protocol, 66 on arm 1 and 64 on arm 2. RESULTS: The results we report are from time of diagnosis through October 1997. For patients treated on arm 1, the median time to disease progression (defined as time to off study) was 6 months (range 2-15 months) and the median time to death 8.5 months (range 3-24 months); survival at 1 year was 30.9% and at 2 years, 7.1%. For patients treated on arm 2, the corresponding values were 5 months (range 1-12 months) and 8 months (range 1-23 months), with 1- and 2-year survival rates at 27.0% and 6.7%, respectively. Evaluation of response by MRI at 4 or 8 wks post treatment was available in 108 patients and revealed a complete response in 1 patient of each Rx arm, a partial response (> 50% decrease in size) in 18 patients of arm 1 and 15 patients of arm 2, minimal to no response (stable) in 25 patients of arm 1 and 23 patients of arm 2, and progressive disease in 13 patients of arm 1 and 12 patients of arm 2. The pattern of failure was local in all patients. Morbidity of treatment was similar in both Rx arms, with no significant toxicity (including hearing loss) reported. Autopsy was performed in 6 patients, and confirmed the presence of extensive residual tumor in these cases. CONCLUSION: The major conclusion from this trial is that the hyperfractionated method of Rx 2 did not improve event-free survival (p = 0.96) nor did it improve survival (p = 0.65) over that of the conventional fractionation regimen of Rx 1, and that both treatments are associated with a poor disease-free and survival outcome.
Subject(s)
Brain Neoplasms/radiotherapy , Brain Stem , Dose Fractionation, Radiation , Glioma/radiotherapy , Adolescent , Adult , Brain Neoplasms/mortality , Child , Child, Preschool , Female , Glioma/mortality , Humans , Male , Prospective Studies , Survival Rate , Treatment OutcomeABSTRACT
PURPOSE: To determine the efficacy and toxicity of permanent 125iodine implants for recurrent malignant gliomas. METHODS AND MATERIALS: Between January 1989 and January:, 59 patients with histologically confirmed recurrent malignant gliomas (22 nonglioblastoma malignant gliomas, 37 glioblastoma multiforme at the time of implant) received a permanent 125iodine implant. Patients ranged in age from 13-74 years. The median ages for the overall group, nonglioblastoma (nonGBM), and glioblastoma (GBM) groups was 47 years, 39 years, and 53 years, respectively. RESULTS: With a median follow-up of 40 months, the median survival for the 59 total patients is 1.34 years; nonGBM 2.04 years, GBM 0.9 years. Factors predictive for poor prognosis were GBM histology, age 60 years or more, target volume 17 cc or more, and/or tumor location within the corpus callosum or thalamus. Reoperations have been performed in 24 (40%) patients; 15 (25%) for tumor progression; 3 (5%) for radiation necrosis; 2 (3%) for skull necrosis/infection, and 4 (7%) for other reasons (Ommaya reservoir insertion, catheter removal, hematoma evacuation). CONCLUSION: Permanent 125iodine implants in selected patients with recurrent malignant gliomas are associated with reasonable long-term survival and a low risk of complications. Given the low incidence of radiation necrosis, future plans are to increase dose rate and/or total dose delivered with the permanent implant.
Subject(s)
Brain Neoplasms/radiotherapy , Glioma/radiotherapy , Iodine Radioisotopes/therapeutic use , Neoplasm Recurrence, Local/radiotherapy , Radiopharmaceuticals/therapeutic use , Adolescent , Adult , Aged , Brain Neoplasms/mortality , Female , Follow-Up Studies , Glioma/mortality , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Survival AnalysisABSTRACT
Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gyx4 fractions. After 4-6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7-9 months from diagnosis) and four patients remain alive (5-38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses.
Subject(s)
Brachytherapy , Brain Neoplasms/radiotherapy , Glioma/radiotherapy , Iodine Radioisotopes/administration & dosage , Mesencephalon , Neuroectodermal Tumors, Primitive/radiotherapy , Pons , Brain Neoplasms/diagnosis , Brain Stem , Child , Child, Preschool , Drug Implants , Female , Glioma/diagnosis , Humans , Infant , Iodine Radioisotopes/adverse effects , Iodine Radioisotopes/therapeutic use , Magnetic Resonance Imaging , Male , Neuroectodermal Tumors, Primitive/diagnosis , Stereotaxic Techniques , Survival Analysis , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Managed care organizations (MCOs) are being recruited to support school health services delivered in school clinics. Schools without clinics already provide numerous health services and could provide more if they had support from managed care organizations. This article describes the first two years of a San Diego-based collaborative consisting of MCOs, school districts, and other health care agencies. By establishing trust, developing overriding principles, and creating an interagency communication infrastructure, this collaborative has encouraged shared management of many student health issues. Because the agreements apply to all schools, programs can reduce high rates of absenteeism district-wide and avoid unnecessary doctor appointments for common health problems. These collaborative agreements are designed to be financially self-sustaining. However, data collection, the logistics of obtaining parental consent, and getting health professionals to communicate with each other in new ways remain to be significant challenges.
Subject(s)
Delivery of Health Care, Integrated/organization & administration , Health Maintenance Organizations/organization & administration , School Health Services/organization & administration , Adolescent , California , Child , Delivery of Health Care, Integrated/standards , Guidelines as Topic , Health Maintenance Organizations/standards , Humans , Lice Infestations/prevention & control , Mass Screening/organization & administration , Physical Examination , Program Development , Program Evaluation , Psychological Tests , Referral and Consultation/organization & administration , Scalp Dermatoses/prevention & control , School Health Services/standards , School Health Services/statistics & numerical data , Tuberculin Test/standardsABSTRACT
BACKGROUND: Radiation-induced necrosis (RIN) of the brain is a complication associated with the use of aggressive focal treatments such as radioactive implants and stereotactic radiosurgery. In an attempt to treat patients with central nervous system (CNS) RIN, ten patients received hyperbaric oxygen treatment (HBOT). METHODS: Patients presented with new or increasing neurologic deficits associated with imaging changes after radiotherapy. Necrosis was proven by biopsy in eight cases. HBOT was comprised of 20-30 sessions at 2.0 to 2.4 atmospheres, for 90 minutes-2 hours. Sites of RIN included the brain stem (n = 2), posterior fossa (n = 1), and supratentorial fossa (n 7). Histologic types included brain stem glioma (n = 2), ependymoma (n = 2), germinoma (n = 2), low grade astrocytoma (n = 1), oligodendroglioma (n = 1), glioblastoma multiforme (n = 1), and arteriovenous malformation (n = 1). RESULTS: Initial improvement or stabilization of symptoms and/or imaging findings were documented in all ten patients studied and no severe HBOT toxicity was observed. Four patients died, with the cause of death attributed to tumor progression. Five of six surviving patients were improved by clinical and imaging criteria; one patient was alive with tumor present at last follow-up. CONCLUSIONS: HBOT may prove to be an important adjunct to surgery and steroid therapy for CNS RIN.
Subject(s)
Brain Injuries/etiology , Brain Injuries/therapy , Hyperbaric Oxygenation , Radiation Injuries/therapy , Radiotherapy/adverse effects , Adolescent , Adult , Brain Injuries/pathology , Brain Neoplasms/radiotherapy , Child , Child, Preschool , Female , Humans , Magnetic Resonance Imaging , Male , NecrosisABSTRACT
Four unrelated patients are described with a syndrome that included developmental delay, seizures, ataxia, recurrent infections, severe language deficit, and an unusual behavioral phenotype characterized by hyperactivity, short attention span, and poor social interaction. These manifestations appeared within the first few years of life. Each patient displayed abnormalities on EEG. No unusual metabolites were found in plasma or urine, and metabolic testing was normal except for persistent hypouricosuria. Investigation of purine and pyrimidine metabolism in cultured fibroblasts derived from these patients showed normal incorporation of purine bases into nucleotides but decreased incorporation of uridine. De novo synthesis of purines and cellular phosphoribosyl pyrophosphate content also were moderately decreased. The distribution of incorporated purines and pyrimidines did not reveal a pattern suggestive of a deficient enzyme activity. Assay of individual enzymes in fibroblast lysates showed no deficiencies. However, the activity of cytosolic 5'-nucleotidase was elevated 6- to 10-fold. Based on the possibility that the observed increased catabolic activity and decreased pyrimidine salvage might be causing a deficiency of pyrimidine nucleotides, the patients were treated with oral pyrimidine nucleoside or nucleotide compounds. All patients showed remarkable improvement in speech and behavior as well as decreased seizure activity and frequency of infections. A double-blind placebo trial was undertaken to ascertain the efficacy of this supplementation regimen. Upon replacement of the supplements with placebo, all patients showed rapid regression to their pretreatment states. These observations suggest that increased nucleotide catabolism is related to the symptoms of these patients, and that the effects of this increased catabolism are reversed by administration of uridine.
Subject(s)
Attention Deficit Disorder with Hyperactivity/enzymology , Nucleotidases/metabolism , 5'-Nucleotidase/metabolism , Adenosine Deaminase/metabolism , Adenosine Kinase/metabolism , Attention Deficit Disorder with Hyperactivity/physiopathology , Cells, Cultured , Child , Child, Preschool , Cytidine Deaminase , DCMP Deaminase/metabolism , Female , Fibroblasts , Humans , Male , Methyltransferases/metabolism , Neurologic Examination , Nucleoside Deaminases/metabolism , Pentosyltransferases/metabolism , Purines/metabolism , Pyrimidines/metabolism , Thymidylate Synthase/metabolism , Uridine Kinase/metabolismABSTRACT
PURPOSE/OBJECTIVE: To evaluate the feasibility, response rates, and toxicity of a Phase II study using targeted supradose cisplatin and concurrent radiation therapy in unresectable Stage III-IV head and neck squamous cell carcinoma. METHODS AND MATERIALS: Sixty patients presenting between 6/93-9/94 were enrolled, 44 (73%) of whom had T4 and/or N2-N3 nodal disease. All patients were treated with rapid targeted superselective intraarterial infusions of cisplatin (150 mg/m2 weekly x 4) and simultaneous sodium thiosulfate intravenously (9 g/m2) for systemic neutralization of cisplatin. Concurrent (day 1) daily radiation therapy was delivered to the primary tumor and overt nodal disease to 66-74 Gy while the uninvolved lower neck received 50 Gy, at 2.0 Gy/fraction. RESULTS: Fifty-one (85%) patients completed the full RADPLAT protocol as planned. Fifty-seven of 60 patients were evaluable for response. Histological (n = 50) or clinical (n = 7) assessment of primary site revealed a complete response (CR) in 52 patients, partial response (PR) in 4, and stable disease (SD) in 1. Of the 40 patients presenting with nodal metastases, pathological (n = 31) or clinical (n = 6) assessment revealed a CR in 25, PR in 11, and SD in 1, while 3 were unevaluable. Overall, for both primary site and nodal disease, CR was attained in 44 (75%), PR in 12 (23%), and SD in 1 (2%) of the 57 evaluable patients. Only 2 (4%) of 57 evaluable patients have recurred above the clavicle, 1 in the primary site and 1 in the regional lymph nodes. Twelve patients (23%) have failed in distant sites. Grade III/VI toxicity has included gastrointestinal in 6, hematologic in 6, mucosal in 12, vascular in 4, and neurological in 4 patients. CONCLUSION: Concurrent radiation therapy and targeted supradose cisplatin (i.e., RADPLAT) can be safely delivered with high response rates and excellent loco-regional control in advanced Stage III/IV head and neck squamous cell carcinoma.
Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Cisplatin/administration & dosage , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Radiation-Sensitizing Agents/administration & dosage , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Combined Modality Therapy , Disease-Free Survival , Feasibility Studies , Female , Head and Neck Neoplasms/pathology , Humans , Male , Middle AgedABSTRACT
PURPOSE: To determine the effects of enucleation, irradiation, and age at diagnosis on bony orbital growth in long-term survivors of retinoblastoma using measurements based on computed tomographic (CT) imaging. PATIENTS AND METHODS: We used CT obtained at a median age of 13 years to measure orbital volume and configuration in 54 patients who had been treated for retinoblastoma a minimum of 5 years previously. RESULTS: Enucleation and high-dose orbital irradiation (> 35 Gy) both independently adversely affected orbital development (P = .014 and P = .022, respectively). Orbital volume differences for children treated when < or = 1 year old were no greater than those for children treated when older than 1 year of age. In children treated for bilateral retinoblastoma, the impact of enucleation on orbital development was not statistically different from that of irradiation (P = .13). Small implants (12 to 14 mm in diameter) were more commonly associated with smaller orbital volumes. Migration of orbital implants was associated with the smaller orbital sphere size in children < or = 1 year of age (P < .035). CONCLUSION: Treatment for retinoblastoma compromises orbital development. Resulting orbital asymmetry seems to be at least partially related to the size of the implant. Detailed imaging-based measurements of orbital volume and configuration may aid the planning for cosmetic and reconstructive surgery in those who develop orbital asymmetry.
Subject(s)
Eye Enucleation/adverse effects , Eye Neoplasms/therapy , Orbit/growth & development , Retinoblastoma/therapy , Age Factors , Age of Onset , Child , Child, Preschool , Eye Neoplasms/pathology , Eye Neoplasms/radiotherapy , Eye, Artificial/adverse effects , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/radiotherapy , Neoplasms, Multiple Primary/therapy , Orbit/diagnostic imaging , Orbit/radiation effects , Radiotherapy Dosage , Retinoblastoma/pathology , Retinoblastoma/radiotherapy , Survivors , Tomography, X-Ray ComputedABSTRACT
PURPOSE: Very little objective data has been reported on mastication and swallowing in xerostomic patients, which would substantiate presumed causal relationships between xerostomia and patient complaints. The purpose was to elucidate which components of mastication and swallowing were abnormal, and most directly related to xerostomia, and which appeared unaffected. METHODS AND MATERIALS: A retrospective analysis of timing events in mastication and swallowing was done using videofluoroscopic data for 15 cancer patients with xerostomia, and 20 normal controls. Scintigraphy was also used to determine oropharyngeal residue after a water swallow. Cancer treatment modalities included radiation therapy or chemoradiation therapy. RESULTS: For barium liquid and paste substances, timing measures were equivalent for controls and patients. Xerostomic patients took 46% longer to masticate a shortbread cookie, and timing for the initiation of swallowing was shorter, but duration of swallowing appeared unaffected. Oral and pharyngeal residues following the swallow were greater in the patient group. CONCLUSIONS: Xerostomia primarily affected mastication and oral manipulation of a dry, absorbent food material. Increased oral and pharyngeal residues after a water swallow are ambiguously related to xerostomia. The initiation and duration of the pharyngeal swallow was not abnormal.
Subject(s)
Deglutition/physiology , Mastication/physiology , Xerostomia/physiopathology , Aged , Dentition , Female , Fluoroscopy , Head and Neck Neoplasms/physiopathology , Head and Neck Neoplasms/radiotherapy , Humans , Male , Middle Aged , Radiotherapy/adverse effects , Retrospective Studies , Time Factors , Xerostomia/etiologyABSTRACT
PURPOSE: This research aimed to study the anatomic relationship between the internal jugular vein with the surrounding internal jugular lymph node chain and the underlying bony anatomical structures which are commonly used as landmarks for radiation therapy planning. METHODS AND MATERIALS: Twelve patients with carcinoma of the head and neck region were studied prospectively. Using our three-dimensional planning system, a beam's-eye view of the internal jugular vein was projected onto a lateral and anterior simulation film. Quantitative measurements were made in every case of the anatomic relationship between the internal jugular vein and the posterior border of the cervical vertebrae and sagittal midline. RESULTS: The distance between the posterior border of the internal jugular vein and the posterior border of the cervical vertebrae ranged between 0 and 2.5 cm. The distances between the sagittal midline and the medial border of the internal jugular veins ranged between 2 and 4 cm. CONCLUSION: To ensure adequate irradiation of the internal jugular lymph nodes, the posterior border of the lateral radiation therapy upper-neck fields should be placed at least 1 cm posterior to the posterior aspect of the cervical vertebrae. The midline block used in the lower neck anterior field should not exceed 2 cm in width.
Subject(s)
Cervical Vertebrae , Head and Neck Neoplasms/radiotherapy , Jugular Veins , Lymph Nodes , Radiotherapy Planning, Computer-Assisted/methods , Cervical Vertebrae/anatomy & histology , Cervical Vertebrae/diagnostic imaging , Head and Neck Neoplasms/diagnostic imaging , Humans , Jugular Veins/anatomy & histology , Jugular Veins/diagnostic imaging , Lymph Nodes/anatomy & histology , Lymph Nodes/diagnostic imaging , Prospective Studies , RadiographyABSTRACT
Management of retinoblastoma is highly individualized and depends heavily on grouping or staging. In view of evolving methods of imaging and treating retinoblastoma, we have developed and evaluated a revised staging scheme. We analyzed the survival data of 73 patients treated at St. Jude Children's Research Hospital to compare the ability of the Reese-Ellsworth grouping system, the original St. Jude, and the modified St. Jude staging schemes to predict progression-free survival. None of the staging schemes significantly correlated with progression-free survival. This modified staging scheme provides an instrument for assessing the natural history of retinoblastoma based on ophthalmolgic, other clinical, and imaging findings. Because it can identify patients at higher risk, the modified St. Jude scheme may be useful in selecting appropriate therapy regimens for children with retinoblastoma.
ABSTRACT
From January 1992 to November 1996, 17 patients with the diagnosis of intracranial meningioma underwent radiosurgical treatment. Of these, 7 patients were treated using a Linac-based system (group 1), and 10 using the Leksell Gamma Knife unit (group 2). The follow-up ranged between 12 and 48 (median 33) months for group 1 and between 1 and 11 (median 5) months for group 2, consisting of clinical and MRI assessments every 3 months during the first year, and every 6 months thereafter. There were 14 women and 3 men. The mean age was 42 years. Prior to radiosurgery, 15 patients underwent surgical procedures. Histological diagnosis was consistent with benign meningioma, except in 2 patients (malignant meningioma). In 15 patients with benign meningiomas there was no evidence of tumor growth as demonstrated by clinical and radiological evaluation, in 2 patients with a malignant histological type there was tumor progression.