Comparison of Brain Glucose Metabolism and Monoamine Oxidase B (MAO B) in Traumatic Brain Injury

OBJECTIVE: Positron emission tomography (PET) studies in patients with temporal lobe epilepsy have reported that hypometabolism in temporal regions is associated with elevated monoamine oxidase B (MAO B) probably reflecting gliosis. The purpose of this study was to examine a group of head trauma patients suffering from seizures and memory loss to determine whether hypometabolic regions show correspondingly elevated MAO B.METHODS: Seven patients with traumatic brain injury received PET scans with (18)FDG and [(11)C]L-deprenyl-D2 to measure regional glucose metabolism (LCMRglu) and MAO B respectively. Results were compared to a group of nine age-matched healthy controls. Hypometabolic regions were identified and MAO B values corresponding to these brain regions were determined. Averaged brain images for temporal regions for LCMRglu and MAO were also compared.RESULTS: LCMRglu values for temporal regions were reduced in patients relative to normal subjects. Of the 13 hypometabolic brain regions, 6 (46%) showed a corresponding elevation in MAO B. There was a trend for a significant inverse relationship between normalized LCMRglu and normalized MAO B values for medial temporal cortex. Glucose metabolism was significantly higher in lateral than medial temporal regions whereas the pattern was reversed for MAO B.CONCLUSION: MAO B images provide a markedly better delineation of the medial temporal regions than LCMRglu. There was not a consistent inverse relationship between metabolism and MAO B as had been reported in PET studies of epileptogenic temporal lobes with [(11)C]L-deprenyl-D2 and (18)FDG indicating that prospective studies are needed to determine the pathophysiology of hypometabolic lesions in head trauma.     

The mechanisms underlying MMR deficiency in immunodeficiency‐related non‐Hodgkin lymphomas are different from those in other sporadic microsatellite instable neoplasms

The spectrum of tumors showing microsatellite instability (MSI) has recently been enlarged to sporadic neoplasms whose incidence is favored in the context of chronic immunosuppression. We investigated the biological, therapeutic and clinical features associated with MSI in immunodeficiency‐related non‐Hodgkin lymphomas (ID‐RL). MSI screening was performed in 275 ID‐RL. MSI ID‐RL were further analyzed for MMR gene expression and for BRAF/KRAS mutations since these genes are frequently altered in MSI cancers. We also assessed the expression of O⁶‐methylguanine‐DNA methyltransferase (MGMT), an enzyme whose inactivation has been reported in lymphomas and may help in the selection of MMR deficient clones. Unlike other sporadic MSI neoplasms, MSI ID‐RL (N = 17) presented with heterogeneous MMR defects and no MLH1 promoter methylation. About one third of these tumors presented with normal expression of MLH1, MSH2, MSH6 and PMS2. They accumulated BRAF activating mutations (33%). Unlike other ID‐RL, MSI ID‐RL were primarily EBV‐negative NHL of T‐cell origin, and arose after long‐term immunosuppression in patients who received azathioprine as part of their immunosuppressive regimen (p = 0.05) and/or who exhibited methylation‐induced loss of expression of MGMT in tumor cells (p= 0.02). Overall, these results highlight that, in the context of deficient immune status, some MSI neoplasms arise through alternative mechanism when compared to other sporadic MSI neoplasms. They give the exact way how to make the diagnosis of MSI in these tumors and may help to define biological and clinicalrisk factors associated with their emergence in such a clinicalcontext. © 2009 UICC     

Excellent local control rates and distinctive patterns of failure in myxoid liposarcoma treated with conservation surgery and radiotherapy

PURPOSE: To evaluate the local control rates and patterns of metastatic relapse in patients with localized myxoid liposarcoma treated with conservation surgery and radiotherapy (RT). PATIENTS AND METHODS: Between 1960 and 2003, 127 patients with non-metastatic myxoid liposarcoma were treated with conservation surgery and RT at our institution. The median patient age was 39 years (range, 14-79 years). Of the 127 patients, 46% underwent preoperative RT (median dose, 50 Gy) and 54% underwent postoperative RT (median dose, 60 Gy). Also, 28% received doxorubicin-based chemotherapy as a part of their treatment. RESULTS: The median follow-up was 9.1 years. The overall survival rate at 5 and 10 years was 87% and 79%, respectively. The corresponding disease-free survival rates were 81% and 73%. The local control rate at > or =5 years was 97%. The actuarial rate of distant metastases at 5 and 10 years was 15% and 24%, respectively. Of the 27 patients who developed distant metastases, 48% did so in the retroperitoneum, 22% in other extrapulmonary soft tissues, 22% in the lung, 15% in bone, and 4% in the liver. CONCLUSION: The results of our study have shown that RT and conservation surgery for localized myxoid liposarcoma provide excellent local control. Distant metastatic relapse tended to occur in the retroperitoneum and other nonpulmonary soft tissues. Therefore, staging and surveillance imaging should include the abdomen and pelvis, as well as the thorax, for patients with localized myxoid liposarcoma.     

Pneumonectomy after chemoradiation: the Dana-Farber Cancer Institute/Brigham and Women's Hospital experience

BACKGROUND: The current study was conducted to examine the outcomes of pneumonectomy after induction chemoradiotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC). METHODS: All patients undergoing pneumonectomy after induction therapy at the Brigham and Women's Hospital were retrospectively evaluated for 30-day and 100-day mortality and treatment-related complications with Institutional Review Board approval. Multivariate and univariate analyses for clinical factors correlating with toxicity and/or survival were calculated. RESULTS: Between 1995 and 2005, 73 patients underwent pneumonectomy for NSCLC after induction therapy. All patients received radiation (median dose of 54 gray [Gy]) and 69 patients (95%) received concurrent chemotherapy. The median age was 62 years and 43 patients (59%) were male; Thirty-seven patients (51%) had American Joint Committee on Cancer stage IIIA NSCLC, 27 (37%) had stage IIIB, 6 had stage IIB, and 4 had stage IV NSCLC because of a resected solitary brain metastasis. A majority (44; 60%) of patients received the combination of carboplatin and paclitaxel, whereas 15 (21%) received the combination of cisplatin and etoposide. Forty-five patients (62%) underwent left pneumonectomy. With a median follow-up of 28 months, the 1-year and 2-year overall survival rates were 70% and 49%, respectively. The 30-day and 100-day mortality rates were 6% and 10%, respectively. Only 4 of 73 patients (6%) died of acute respiratory distress syndrome. The rate of nonfatal treatment-related morbidity was 11%. On univariate analysis, right-sided pneumonectomy was associated with a higher risk of treatment-related mortality (P = .099). CONCLUSIONS: With an acceptable mortality rate, a single-institutional series demonstrated that trimodality therapy including pneumonectomy can be safely accomplished in patients with advanced NSCLC.     

Lymphadenectomy for isolated lymph node metastasis from extremity soft-tissue sarcomas

BACKGROUND: Previous studies have suggested that the prognosis in patients with extremity soft-tissue sarcomas (ESTS) with isolated lymph node (LN) metastases (stage IV) is comparable to that of patients with high-risk ESTS without metastases (stage III). This study was performed to determine the outcomes of patients who underwent aggressive therapy, including lymphadenectomy in patients with LN metastasis from ESTS. METHODS: Demographic details, pathology of the primary disease, timing of LN metastasis, and details of the multimodality treatment were obtained from the medical records of 35 patients with nodal metastasis from ESTS who were treated between 1981 and 2003. Survival after the diagnosis of primary disease and LN metastasis was compared with established historical outcomes for patients with American Joint Commission on Cancer (AJCC) stages III and IV ESTS. RESULTS: Epithelioid sarcomas (23%) and malignant fibrous histiocytomas (23%) were the most common primary histologic types. Twenty (57%) patients presented with synchronous nodal metastasis. Median follow-up from the time of diagnosis of lymph node metastasis was 48.5 months. The 1-year, 2-year, and 5-year actuarial survival rates in patients with synchronous nodal metastasis after lymphadenectomy and additional therapy were 79%, 62%, and 52%, respectively. In comparison, the 1-year, 2-year, and 5-year actuarial survival rates in patients with metachronous nodal metastasis after lymphadenectomy and additional therapy were 100%, 95%, and 66%, respectively. CONCLUSIONS: Patients with isolated regional lymph node metastases who are treated with aggressive approaches, including regional LN dissection, may experience prolonged survival similar to that which more closely approximates the survival seen in patients with stage III disease (5-year survival rate, 50%) rather than the survival seen in patients with stage IV disease (5-year survival rate, 25%). These data lend support for reconsideration of the current AJCC staging system for ESTS.     

Mortality after cure of soft-tissue sarcoma treated with conservation surgery and radiotherapy

BACKGROUND: The objective of the current study was to analyze the potential treatment-related mortality in long-term survivors of soft-tissue sarcoma (STS) treated with radiotherapy (RT) and conservation surgery. METHODS: Between 1960 and 2000, 629 of 1089 patients treated with conservation surgery and RT for nonmetastatic STS at the University of Texas M. D. Anderson Cancer Center never developed disease recurrence. Long-term survival and causes of death were evaluated using the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for death from all causes, cancer, and cardiac disease using standard U.S. data. RESULTS: The median follow-up was 13.2 years. The 10-year, 20-year, and 30-year actuarial survival rates were 88%, 69%, and 52%, respectively. The overall all-case mortality was 1.14 (95% confidence interval [95% CI], 0.98-1.33). The all-cause mortality exceeded that expected for female patients with an SMR of 1.48 (95% CI, 1.15-1.88), patients aged 相似文献   

Genetic aberrations of gastrointestinal stromal tumors

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm in the gastrointestinal tract and is associated with mutations of the KIT or PDGFRA gene. In addition, other genetic events are believed to be involved in GIST tumorigenesis. Cytogenetic aberrations associated with these tumors thus far described include loss of 1p, 13q, 14q, or 15q, loss of heterozygosity of 22q, numeric chromosomal imbalances, and nuclear/mitochondrial microsatellite instability. Molecular genetic aberrations include loss of heterozygosity of p16(INK4A) and p14(ARF), methylation of p15(INK4B), homozygous loss of the Hox11L1 gene, and amplification of C-MYC, MDM2, EGFR1, and CCND1. GISTs in patients with neurofibromatosis type 1 appear to lack the KIT and PDGFRA mutations characteristic of GISTs and may have a different pathogenetic mechanism. Gene mutations of KIT or PDGFRA are critical in GISTs, because the aberrant versions not only are correlated with the specific cell morphology, histologic phenotype, metastasis, and prognosis, but also are the targets of therapy with imatinib and other agents. Furthermore, specific mutations in KIT and PDGFR appear to lead to differential drug sensitivity and may in the future guide selection of tyrosine kinase inhibitors. Activation of the receptor tyrosine kinases involves a signal transduction pathway whose components (mitogen-activated protein kinase, AKT, phosphoinositide 3-kinase, mammalian target of rapamycin, and RAS) are also possible targets of inhibition. A new paradigm of classification, integrating the standard clinical and pathological criteria with molecular aberrations, may permit personalized prognosis and treatment.