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Analyze the impact of implementing a structured reporting system for primary brain tumors, the Brain Tumor Reporting and Data System, on attitudes toward radiology reports at a single institution.Following Institutional Review Board approval, an initial 22 question, 5 point (1-worst to 5-best), survey was sent to faculty members, house staff members, and nonphysician providers at our institution who participate in the direct care of brain tumor patients. Results were used to develop a structured reporting strategy for brain tumors which was implemented across an entire neuroradiology section in a staged approach. Nine months following structured reporting implementation, a follow-up 27 question survey was sent to the same group of providers. Keyword search of radiology reports was used to assess usage of Brain Tumor Reporting and Data System over time.Fifty-three brain tumor care providers responded to the initial survey and 38 to the follow-up survey. After implementing BT-RADS, respondents reported improved attitudes across multiple areas including: report consistency (4.3 vs. 3.4; p0.001), report ambiguity (4.2 vs. 3.2, p0.001), radiologist/physician communication (4.5 vs. 3.8; p0.001), facilitation of patient management (4.2 vs. 3.6; p = 0.003), and confidence in reports (4.3 vs. 3.5; p0.001). Providers were more satisfied with the BT-RADS structured reporting system (4.3 vs. 3.7; p = 0.04). Use of the reporting template progressively increased with 81% of brain tumor reports dictated using the new template by 9 months.Implementing a structured template for brain tumor imaging improves perception of radiology reports among radiologists and referring providers involved in the care of brain tumor patients.

BackgroundStudies including our own have shown that the Medullary Visceral Zone (MVZ) can effectively regulate systemic inflammation and immunity through the Cholinergic Anti-inflammatory Pathway (CAP). Sepsis usually causes neuroinflammation in the Central Nervous System (CNS), which will inevitably affect the structure and function in related brain areas such as MVZ, whether the intervention of CAP can affect the structure and function of the MVZ in sepsis needs to be further verified. Methods64 adults, specific pathogens free Sprague-Dawley male rats were used in this study. The septic models were prepared by cecum ligation and puncture (CLP) method, GTS-21 (a selective α7 nicotinic acetylcholine receptor agonist which can mimic CAP’s activation) and MLA (a powerful and selective nicotine acetylcholine receptor antagonist which can mimic CAP’s blocking) were used to interfere CAP. The pathological changes, apoptosis, the expressions of Tyrosine Hydroxylase (TH) and Choline acetyltransferase (CHAT), the expression levels of GAP-43 mRNA, Olig-2 mRNA, VEGF mRNA, GFAP mRNA, MMP-9 mRNA in MVZ were analyzed among different groups. ResultsIn this study, we found that sepsis induced apoptosis and functional suppression of catecholaminergic and cholinergic neurons and gliosis in MVZ, up-regulated key genes’ expressions such as GAP-43 mRNA，GFAP mRNA，VEGF mRNA，MMP-9 mRNA, down-regulated the expression of Olig-2 mRNA. GTS-21, a selective α7 nicotinic acetylcholine receptor agonist, obviously mitigated the above changes; whereas, methyllycaconitine (MLA), a powerful and selective nicotine acetylcholine receptor antagonist, significantly aggravated these changes. ConclusionsOur research shows that activating CAP can effectively mitigate the neural remodeling and neuronal suppression induced by early sepsis in MVZ, the mechanism may involve with its control of systemic and local inflammation. This study reveals that MVZ and CAP may be potential targets to curb the inflammatory storm in early sepsis.

Purpose Radiation oncologists are frequently involved in providing palliative and supportive care (PSC) for patients with advanced cancers through delivery of palliative radiation. Whether they are confident in their ability to assess and initiate treatments for pain, nonpain, and psychosocial distress is unknown. The American Society for Radiation Oncology surveyed its practicing members in the United States on self-assessment of their primary PSC skills and access to continuing medical education on PSC. Methods We electronically surveyed 4093 practicing radiation oncologists in the United States. The survey consisted of 16-questions in 5 sections 1 : demographics, 2 PSC training, 3 domains of PSC, 4 perceived barriers as a radiation oncologist to initiate advanced care planning, and 5 discussion of prognosis. Results The survey was e-mailed to 4093 American Society for Radiation Oncology members, and 649 responses were received (response rate 16%). The majority (91%) of radiation oncologists surveyed believe PSC is an important competency for radiation oncologists. Most radiation oncologists reported that they are moderately confident in their ability to assess and manage pain and gastrointestinal symptoms, but less confident in their ability to manage anorexia, anxiety, and depression. Despite areas of decreased confidence, a large number (42%) of radiation oncologists do not receive any additional PSC education beyond their residency training. Lastly, a perceived fear of upsetting referring medical oncologists and lack of clinic time are concerns for radiation oncologists who may want to initiate goals of care/advance care planning discussions with patients and their families. Conclusion Radiation oncologists are more confident in their ability to assess and manage pain than in their ability to manage depression, anxiety, anorexia, and fatigue. There is a need for increasing continuing medical educational efforts in PSC for practicing radiation oncologists, and strengthening PSC training in residency programs.

BACKGROUND Stereotactic radiosurgery (SRS) is an increasingly common modality used with surgery for resectable brain metastases (BM). OBJECTIVE To present a multi-institutional retrospective comparison of outcomes and toxicities of preoperative SRS (Pre-SRS) and postoperative SRS (Post-SRS). METHODS We reviewed the records of patients who underwent resection of BM and either Pre-SRS or Post-SRS alone between 2005 and 2013 at 2 institutions. Pre-SRS used a dose-reduction strategy based on tumor size, with planned resection within 48 hours. Cumulative incidence with competing risks was used to determine estimated rates. RESULTS A total of 180 patients underwent surgical resection for 189 BM: 66 (36.7%) underwent Pre-SRS and 114 (63.3%) underwent Post-SRS. Baseline patient characteristics were balanced except for higher rates of performance status 0 (62.1% vs 28.9%, P < .001) and primary breast cancer (27.2% vs 10.5%, P = .010) for Pre-SRS. Pre-SRS had lower median planning target volume margin (0 mm vs 2 mm) and peripheral dose (14.5 Gy vs 18 Gy), but similar gross tumor volume (8.3 mL vs 9.2 mL, P = .85). The median imaging follow-up period was 24.6 months for alive patients. Multivariable analyses revealed no difference between groups for overall survival (P = .1), local recurrence (P = .24), and distant brain recurrence (P = .75). Post-SRS was associated with significantly higher rates of leptomeningeal disease (2 years: 16.6% vs 3.2%, P = .010) and symptomatic radiation necrosis (2 years: 16.4% vs 4.9%, P = .010). CONCLUSION Pre-SRS and Post-SRS for resected BM provide similarly favorable rates of local recurrence, distant brain recurrence, and overall survival, but with significantly lower rates of symptomatic radiation necrosis and leptomeningeal disease in the Pre-SRS cohort. A prospective clinical trial comparing these treatment approaches is warranted. ABBREVIATIONS BM, brain metastasesCI, confidence intervalCTV, clinical target volumeDBR, distant brain recurrenceGTV, gross tumor volumeLC, local controlLMD, leptomeningeal diseaseLR, local recurrenceMVA, multivariable analysisOS, overall survivalPost-SRS, postoperative stereotactic radiosurgeryPre-SRS, preoperative stereotactic radiosurgeryPTV, planning target volumeRN, radiation necrosisSRN, symptomatic radiation necrosisSRS, stereotactic radiosurgeryWBRT, whole-brain radiation therapy.

Preclinical evidence suggests angiotensin blockade therapy (ABT) decreases late radiation toxicities. This study aims to investigate the association between ABT and symptomatic radiation necrosis (SRN) following stereotactic radiosurgery (SRS). Resected brain metastases (rBM) and arteriovenous malformation (AVM) patients treated with SRS from 2002 to 2015 were identified. Patients in the ABT cohort were on therapy during SRS and at 1-month follow up. Kaplan Meier method and cumulative incidence model were used to analyze overall survival (OS) and intracranial outcomes. 228 consecutive patients were treated with SRS: 111 with rBM and 117 with AVM. Overall, 51 (22.4%) patients were in the ABT group: 32 (28.8%) in the rBM and 19 (16.2%) in AVM cohorts. Baseline characteristics were similar, except for higher Graded Prognostic Analysis (3–4) in the rBM (ABT: 25.0% vs. non-ABT: 49.0%, p = 0.033) and median age in the AVM (ABT: 51.4 vs. non-ABT: 35.4, p

Metastatic tumours involving the brain overshadow primary brain neoplasms in frequency and are an important complication in the overall management of many cancers. Importantly, advances are being made in understanding the molecular biology underlying the initial development and eventual proliferation of brain metastases. Surgery and radiation remain the cornerstones of the therapy for symptomatic lesions; however, image-based guidance is improving surgical technique to maximize the preservation of normal tissue, while more sophisticated approaches to radiation therapy are being used to minimize the long-standing concerns over the toxicity of whole-brain radiation protocols used in the past. Furthermore, the burgeoning knowledge of tumour biology has facilitated the entry of systemically administered therapies into the clinic. Responses to these targeted interventions have ranged from substantial toxicity with no control of disease to periods of useful tumour control with no decrement in performance status of the treated individual. This experience enables recognition of the limits of targeted therapy, but has also informed methods to optimize this approach. This Review focuses on the clinically relevant molecular biology of brain metastases, and summarizes the current applications of these data to imaging, surgery, radiation therapy, cytotoxic chemotherapy and targeted therapy.

Sorbic acid (SA) is a PUFA with a conjugated double bond. The conjugated fatty acids, including CLA, are multifunctional bioactive fatty acids with the ability to improve growth performance. The effect of SA on pig growth performance was examined to determine its mechanism of action. The ADG, ADFI, and serum IGF-I concentration were examined, as were IGF-I secretion and IGF system gene expression in hepatocytes. Two hundred forty 21-d-old Duroc × Landrace × Yorkshire weaned piglets (6.86 ± 0.02 kg) were randomly divided into 4 groups, each consisting of 3 pens of 20 piglets (10 female and 10 male). The 4 groups of piglets were kept in a temperature-controlled room (26 to 28 °C), and feed and water were provided to the pigs ad libitum. Weanling piglets were fed diets that included 0, 0.5, 2, or 4 g of SA/kg for 42 d. The diet supplemented with 0.5 g/kg of SA improved (P 0.05; 1 g of SA/kg, P 0.05) IGFBP or PPARγ mRNA expression, in pig primary hepatocytes. These results indicate that SA improves growth performance by regulating IGF system gene expression and hormone secretion.

Malignant gliomas are the most common and deadly brain tumors. Nevertheless, survival for patients with glioblastoma, the most aggressive glioma, although individually variable, has improved from an average of 10 months to 14 months after diagnosis in the last 5 years due to improvements in the standard of care. Radiotherapy has been of key importance to the treatment of these lesions for decades, and the ability to focus the beam and tailor it to the irregular contours of brain tumors and minimize the dose to nearby critical structures with intensity-modulated or image-guided techniques has improved greatly. Temozolomide, an alkylating agent with simple oral administration and a favorable toxicity profile, is used in conjunction with and after radiotherapy. Newer surgical techniques, such as fluorescence-guided resection and neuroendoscopic approaches, have become important in the management of malignant gliomas. Furthermore, new discoveries are being made in basic and translational research, which are likely to improve this situation further in the next 10 years. These include agents that block 1 or more of the disordered tumor proliferation signaling pathways, and that overcome resistance to already existing treatments. Targeted therapies such as antiangiogenic therapy with antivascular endothelial growth factor antibodies (bevacizumab) are finding their way into clinical practice. Large-scale research efforts are ongoing to provide a comprehensive understanding of all the genetic alterations and gene expression changes underlying glioma formation. These have already refined the classification of glioblastoma into 4 distinct molecular entities that may lead to different treatment regimens. The role of cancer stem-like cells is another area of active investigation. There is definite hope that by 2020, new cocktails of drugs will be available to target the key molecular pathways involved in gliomas and reduce their mortality and morbidity, a positive development for patients, their families, and medical professionals alike.

BACKGROUND Because few large studies of pediatric ependymoma treatment are available, the authors believed that a retrospective review of treatment outcomes from a single institution would yield potentially valuable information regarding potential prognostic factors. In this article, they report their 20-year institutional experience with this disease. METHODS Medical records were reviews of patients with intracranial ependymoma who received their initial treatment at the Children's Hospital of Philadelphia (CHOP)/Hospital of the University of Pennsylvania (HUP) between January 1980 and December 2000. Of the 61 patients who were identified, 49 patients underwent primary therapy at CHOP/HUP and formed the basis for the study. Actuarial overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and Cox proportional-hazards models. RESULTS With median follow-up of 110.2 months, the 5-year OS and PFS rates were 66.2% and 40.7%, respectively. Older age and higher radiation dose significantly predicted for improved OS. Anaplastic histology predicted for decreased PFS. Cervical spinal cord extension resulted in decreased OS primarily caused by failures outside the primary site. Patients who had a favorable prognosis (aged ≥3 years, no dissemination or cord extension, complete resection, and radiation dose ≥54 grays [Gy]) had 5-year OS and PFS rates of 83.1% and 60.6%, respectively. CONCLUSIONS In this study of patients with pediatric intracranial ependymoma, OS and PFS rates were concordant with the rates published in other modern series. The finding of a dose response up to 54 Gy supported the current trend toward dose escalation. Tumor extension to the cervical spine was identified as a predictor for failure outside of the primary site. Although the survival rates were encouraging, there is still significant room for improvement in the management of this disease. Cancer 2007. © 2007 American Cancer Society.

BACKGROUND Because few reports on outcome in patients with pediatric malignant gliomas during the magnetic resonance imaging era were available, the authors studied the outcomes of children with these tumors at their institution. METHODS The medical records of 39 patients with nonbrainstem, malignant gliomas who were treated at the Hospital of the University of Pennsylvania/Children's Hospital of Philadelphia between February 1, 1989 and December 31, 2000 were reviewed retrospectively. Magnetic resonance imaging was used to assess tumors at presentation and at follow-up. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan–Meier method. Univariate and multivariate analyses were performed using a Cox proportional hazards model. RESULTS The median follow-up for the 14 surviving patients was 47.6 months. The median PFS for all patients was 12.2 months, and the median OS for all patients was 21.3 months. The extent of surgery was the strongest prognostic factor for predicting outcomes in these patients, with a median survival of 122.2 months in patients who underwent macroscopic total resection compared with 14.1 months in patients who had significant residual disease after surgery. In univariate analyses, other than the extent of surgery, only the absence of visual symptoms at diagnosis significantly predicted improved OS. Local control was improved for patients who underwent better resection and had smaller tumors. In multivariate analyses, although the extent of surgery continued to predict outcomes significantly, histologic grade, which was not significant in the univariate analysis, also was significant. CONCLUSIONS Children with malignant gliomas appeared to fare better than their adult counterparts. Because the extent of resection was one of the strongest predictors of outcome, the authors concluded that the optimal therapy for these patients would include the maximal possible resection. Cancer 2004. © 2004 American Cancer Society.

Isolated sulphite oxidase deficiency (ISOD) is a very rare hereditary metabolic disorder. Imaging findings of the neonatal form of ISOD, including multicystic leukoencephalopathy with brain atrophy, resemble those of severe ischemic changes of the brain. We report the case of a ten-month-old boy who exhibited neonatal seizures on the 24th day after birth. Excessive quantities of sulphite and S-sulphocysteine in the urine and normal blood uric acid were noted. These findings were consistent with those of ISOD. Point mutations were found in two alleles of the sulphite oxidase (SUOX) gene. One of the mutations was a 1029 C > G mutation, which resulted in an amino acid substitution of tyrosine to a stop code (Y343 X); and the other was a 479 G > A mutation, which resulted in an amino acid substitution of arginine to glutamine (R160 Q). Y343 X is a novel SUOX gene mutation. A review of the literature, including data from this report, showed that 3 of 6 cases had typical imaging findings characterized by initial cerebral edema followed by dramatic multicystic leukoencephalopathy. We emphasize that neonatal ISOD should be included in the differential diagnosis of neonates with unexplained hypoxic-ischemic changes on neuroimaging studies.

Total iodide organification defect (TIOD), where the iodide in the thyroid gland cannot be oxidized and/or bound to the protein, is caused by a defect in the thyroid peroxidase (TPO) gene. Single strand conformation polymorphism analysis was used to screen for mutations in the TPO gene from five unrelated TIOD patients in Taiwan, and five novel mutations were detected. Three of these were frameshift mutations: a single T insertion between nucleotide position 2268 and 2269 (c.2268-2269 insT) in exon 13 and two single C deletions at nucleotide positions 843 (c.843 delC) and 2413 (c.2413 delC) in exon 8 and 14 respectively. The other two were single nucleotide substitutions (c.G1477>A and c.G2386>T) located in exons 9 and 13 respectively. While the former would result in amino acid substitution (Gly493Ser) in the highly conserved region of the TPO polypeptide, the latter would result in either amino acid substitution (Asp796Tyr) or alternative splicing. Of those identified TPO mutations, c.2268-2269 insT was most prevalent and was detected as heterozygous in all but one TIOD patients. All five TIOD patients investigated in this study were compound heterozygous. The method presented in this study could be used for carrier assessment and mutation analysis of newly identified TIOD patients.

Objectives. To report the toxicity profile of patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) receiving doses of 82 Gy or more to portions of their prostate. Methods. Forty-four patients treated with radiation therapy for prostate cancer between June 1992 and August 1998 at the University of California, San Francisco received a maximal dose within the target volume (Dmax) of 82 Gy or more. Eighteen patients were boosted selectively to a limited portion of their prostate using IMRT, whereas 26 patients were treated with 3D-CRT and had unselected “hot spots” within their prostate. The Radiation Therapy Oncology Group (RTOG) acute and late toxicity scales were used to score gastrointestinal (GI) and genitourinary (GU) morbidity. Results. Median follow-up and Dmax were 23.1 months (range 10.0 to 84.7) and 84.5 Gy (range 82.0 to 96.7), respectively. Of the patients, 59.1% and 34.1% developed some level of acute GU and GI toxicity, respectively. One patient experienced grade 3 acute GI toxicity. No other grade 3 or greater acute toxicity was observed. The 2-year actuarial rates for freedom from late GI and GU morbidity were 77.1% (95% confidence interval [CI] 60.4% to 87.5%) and 79.5% (95% CI 62.7% to 89.3%), respectively. Although no grade 3 or greater late GU morbidity has been observed to date, 3 patients experienced grade 3 late GI morbidity. However, these cases involved rectal bleeding and were effectively managed with laser coagulation/fulguration. Conclusions. Doses of 82 Gy or more to a portion of the prostate gland can be tolerated with acceptable morbidity. This observation supports the continued investigation of IMRT as a means for improving disease control in prostate cancer.

The development of brain metastases from any primary cancer generally portends a very limited life expectancy. Without treatment, the median length of survival of patients with neurologic symptoms is about 1 month. 36 Although pharmacologic therapies aimed at reducing cerebral edema often improve symptoms, these interventions have little impact on patient survival. 24,46 The mainstay of treatment for patients with brain metastases has been fractionated radiation therapy since the first reports of its effectiveness. 11,13 In the early 1970s, the Radiation Therapy Oncology Group (RTOG) conducted randomized trials that helped define optimal dose fractionation schemes for whole-brain radiation therapy (WBRT). 4,5,31 Although WBRT can alleviate neurologic symptoms, its impact on survival remains modest: Median survival is typically 12 to 24 weeks 4,34,38 and may approach 30 weeks. 18 Other forms of therapy for patients with brain metastases include chemotherapy, which has not been shown to improve patient survival, 23,42 and surgery. The latter has been evaluated in clinical trials in highly selected patients with a single brain metastasis. In one randomized trial, Patchell et al 38 observed significantly improved median survival (40 weeks versus 15 weeks) and local control (18/25 patients versus 11/23 patients) with resection followed by WBRT as opposed to WBRT alone. In a similar randomized trial, Noordijk et al 37 observed a median survival of 10 months in patients treated with resection followed by WBRT versus 6 months in patients treated with WBRT alone. Although patients with multiple brain metastases usually do not have surgery for each separate gross tumor focus in the brain, Bindal et al 3 showed that survival in such surgically treated patients was similar to that of patients with a solitary brain metastasis that was surgically resected. Nonetheless, most patients are not good candidates for gross total resection, either because of tumor location in the brain or because of concomitant medical problems. In addition, patients with recurrent brain metastases who have failed previous WBRT may be ineligible for further fractionated radiation therapy. In all these patients, as well as in patients who may have undergone subtotal resection, radiosurgery has often been recommended, both because it is a noninvasive procedure that requires minimal hospitalization and because retrospective reports have shown improved survival and local control compared with historical results of conventional fractionated radiation therapy. 1,14,15,19,20,21,30,32,33,36 However, no randomized studies have sorted out the relative efficacy of WBRT, radiosurgery, and surgery or combinations of these therapies. The existing studies specifically involving melanoma brain metastases are listed in Table 1. Although the role of radiosurgery for melanoma brain metastases has not been defined, it may provide local control rates comparable to those of conventional surgery. This is supported by a small retrospective series by Samoza et al, 44 in which 23 patients with melanoma metastases to the brain were treated with WBRT and adjuvant Gamma Knife (Elekta Instruments S.A., Geneva, Switzerland) radiosurgery. They observed a median survival of 28 weeks after radiosurgery and a 97% local tumor control rate. In this article we review patients with single or multiple intracranial melanoma metastases treated at the University of California, San Francisco (UCSF), with Gamma Knife radiosurgery.

Most patients with intracranial germinomas will be cured and become long-term survivors. Physicians caring for these patients should recognize that these patients may be at risk for disease-related and/or treatment-related late sequelae. We report the case of a 27-year-old man who developed testicular seminoma 16 years after treatment for intracranial germinoma. Like their testicular cancer counterparts, long-term survivors of intracranial germinomas may have a susceptibility to develop a subsequent germ cell tumor. These patients require lifelong medical follow-up and should be encouraged to perform testicular self-examination at the appropriate age.

The BC-3600 Auto Hematology Analyzer (hereinafter call BC-3600) is a quantitative, automated hematology analyzer and leukocyte differential counter for In Vitro Diagnostic Use in clinical laboratories.The analyzer was evaluated and compared with the Mindray BC-3200 3-part differential (BC-3200) and Sysmex XE-2100 5-part differential (XE-2100) Hematology Analyzer in the hematology laboratory of a university hospital. The BC-3600 was evaluated according to guidelines published by Clinical and Laboratory Standards Institute (CLSI), the International Committee for Standardization in Hematology (ICSH), and Department of Food and Drug Administration (FDA).There were no background, minimal carryover (0.5%), and excellent linearity for white blood cell (WBC), hemoglobin (Hb) level, red blood cell (RBC), and platelet (PLT) counts (r 0.999). Precision was good at all levels for the routine cell blood count (CBC) parameters: CV% being ≤2.0, except for platelet count (PLT) at the low level with CV% of ≤5.0% and WBC at the low level with CV% of3.0%. Correlation between the BC-3600 and BC-3200, XE-2100 were excellent (r 0.99) for all major CBC parameters.It is concluded that the overall performance of the BC-3600 is excellent and compares well with that of BC-3200 and XE-2100.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

Purpose The optimal treatment for intracranial germinomas remains controversial. We report on our 25-year experience using craniospinal irradiation (CSI) for this disease. Methods and materials Between September 1976 and May 2001, 39 patients with biopsy-proven intracranial germinomas seen at the Children's Hospital of Philadelphia/Hospital of the University of Pennsylvania received CSI. Thirteen of 36 patients (36%) had evidence of spinal dissemination. Median doses to the whole brain, primary site, and spine were 36 Gy (range, 18–44.2 Gy), 50.4 Gy (range, 44–55.8 Gy), and 30.6 Gy (range, 18–40 Gy), respectively. Results With a median follow-up of 7.1 years (range: 1.5–20.2 years), there have been no documented relapses. This includes 5 patients without spinal dissemination who received 18–19.8 Gy to the craniospinal axis; for these patients, the median length of follow-up was 5.5 years (range, 1.3–6.8 years). One patient, who had no evidence of disease 12.9 years after CSI, died of unknown causes 4 months later. Conclusions Our treatment of intracranial germinomas with CSI has yielded outstanding results with no known relapses during a long follow-up period. These results must be considered when evaluating other approaches, such as chemotherapy only or local field irradiation.

Purpose The optimal management of craniopharyngiomas remains controversial, especially in children and young adults. This study reports a single institution's experience with such patients. Methods and materials Between 1974 and 2001, 76 patients were treated for craniopharyngioma at the Children's Hospital of Philadelphia and the Hospital of University of Pennsylvania (HUP). Of these, 75 patients (97%) were evaluable with long-term follow-up. Although all patients underwent attempted gross total resection, 27 had documentation of less than total resection with 18 of these patients receiving immediate postoperative radiotherapy (RT). An additional 22 patients received RT at HUP after failing surgery alone. Results Median follow-up for all patients was 7.6 years. The 10-year actuarial overall survival, relapse-free survival, and local control (LC) rates for all patients were 85%, 48%, and 53%, respectively. When comparing the 57 patients treated with surgery alone to the 18 treated with subtotal resection (STR) followed by RT, a significant difference in LC rates at 10 years (42% vs. 84%, respectively; p = 0.004) was noted. However, no statistically significant difference in overall survival was found between the two groups, because RT was highly effective as salvage therapy. Twenty-two patients at HUP treated with RT after relapse had a 10-year ultimate LC rate comparable to that of patients who received RT immediately after STR. Conclusion RT given either immediately after STR or at relapse is effective in controlling craniopharyngiomas.

The CTLA4 (cytotoxic T lymphocyte associated antigen-4) gene encodes the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. C-T polymorphism is present at position -318 from the ATG start codon in the promoter region of the gene. We report a study on the polymorphism in 347 unrelated children with type 1 diabetes mellitus (DM) (age at diagnosis 7.2+/-3.8 years) and their 260 healthy siblings as controls. Genotype C/C conferred a risk of type 1 DM (RR = 2.02, 95% CI 1.32-3.10, pc = 0.0033). The gene frequency of the C allele was higher in patients (RR = 1.91, 95% CI 1.28-2.84, pc = 0.0026). The gene frequency and phenotype frequency of the T allele were negatively associated with type 1 DM (RR = 0.52, 95% CI 0.35-0.78, pc = 0.0026 and RR = 0.49, 95% CI 0.32-0.76, pc = 0.0022, respectively). The frequency of genotype C/T was lower in patients (RR = 0.50, 95% CI 0.32-0.78, pc = 0.0051). This study demonstrates that nucleotide -318 C-T polymorphism of the CTLA4 gene is associated with type 1 DM. The promoter allele -318 C confers a risk of type 1 DM but allele -318 T confers protection against this disease.

Objectives: We performed a retrospective review of the efficacy and morbidity of radical pleurectomy/decortication and intraoperative radiotherapy followed by external beam radiation therapy with or without chemotherapy for diffuse malignant pleural mesothelioma. Methods: A total of 32 patients with diffuse malignant pleural mesothelioma were initially evaluated between January 1995 and September 2000. Three patients were excluded from analysis because of unresectable disease. Two patients died postoperatively, and one patient had recurrent disease previously treated at an outside institution. Of the remaining 26 patients included in the analysis, 24 received intraoperative radiotherapy. External beam radiation therapy was generally started 1 to 2 months after resection and delivered by means of 3-dimensional conformal radiation therapy or with inverse treatment planning intensity-modulated radiation therapy. When given, chemotherapy consisted of 2 to 3 cycles of cyclophosphamide, doxorubicin (Adriamycin), and cisplatin initiated 1 to 2 months after completion of radiation. Results: At the time of data analysis, 5 of 26 patients were alive. The median follow-up was 9.7 months (range, 2-67.6 months). The median overall survival and progression-free interval from the time of the operation were 18.1 and 12.2 months, respectively. The Kaplan-Meier estimates of overall survival and freedom from progression at 1 year were 64% and 50%, respectively. The site of failure was mostly locoregional. However, there were 4 abdominal failures and 1 contralateral lung failure. Conclusions: Radical pleurectomy/decortication with aggressive radiotherapy with or without chemotherapy might offer an alternative treatment option to those who cannot tolerate extrapleural pneumonectomy. J Thorac Cardiovasc Surg 2002;124:1183-9