The Hirntumorstudien (HIT)-LGG-1996 protocol offered a comprehensive treatment strategy for pediatric patients with low-grade glioma (LGG), ie, observation, surgery, adjuvant radiotherapy, and chemotherapy to defer the start of irradiation in young children. In this current study, we sought to determine clinical factors for progression and survival. Between October 1, 1996 and March 31, 2004, 1031 patients were prospectively recruited into an observation arm (n = 668) and a nonsurgical arm stratifying 12 months of vincristine-carboplatin chemotherapy (n = 216) and conventional radiotherapy/brachytherapy (n = 147) in an age-dependent manner. Median patient age was 6.9 years; 28 patients had diencephalic syndrome, 44 had dissemination, and 108 had neurofibromatosis type 1(NF-1). Main tumor location was the supratentorial midline (40.4%), and the main histology was pilocytic astrocytoma (67.9%). Following a median observation of 9.3 years, 10-year overall survival (OS) was 0.94 and 10-year event-free survival (EFS) was 0.47. Ten-year progression-free survival was 0.62 following radiotherapy and 0.44 following chemotherapy. Sixty-one of 216 chemotherapy patients received radiotherapy 0.3-8.7 years after initial diagnosis. By multivariate analysis, diencephalic syndrome and incomplete resection were found to be unfavorable factors for OS and EFS, age ≥11 years for OS, and supratentorial midline location for EFS. Dissemination, age <1 year, and nonpilocytic histology were unfavorable factors for progression following radiotherapy (138 patients); and diencephalic syndrome, dissemination, and age ≥11 years were unfavorable factors following chemotherapy (210 patients). NF-1 patients and boys experienced prolonged tumor stabilization with chemotherapy. A nationwide multimodal treatment strategy is feasible for pediatric LGG. Extended follow-up yielded results comparable to single-institution series for the treatment groups. Three-quarters of surviving chemotherapy patients have not yet received radiation therapy. Infants with or without diencephalic syndrome and dissemination bear the highest risk for death and progression following diagnosis or treatment.
This study was conducted to assess the coincidence of mucosal hyperplasia in the maxillary sinus and related clinical diagnoses of posterior maxillary teeth found in cone beam computed tomography (CBCT) scans. A total of 204 patients who underwent CBCT examinations between 2006 and 2008 were evaluated retrospectively. Clinical and CBCT findings were correlated using patient records. Absolute frequencies, odds ratios (OR), and 95% confidence intervals (95% CI) were calculated for statistical evaluations. There was a pronounced association between periodontitis and radiological signs of sinusitis. Basal mucosal wall thickening was more likely in patients with decayed and non-vital teeth compared to patients with sound teeth (OR = 5.2; 95% CI = 1.2-23.1). Basal mucosal wall thickening was also more likely than total mucosal thickening (OR = 10.4; 95% CI = 2.6-42.2). Patients with decayed and endodontically treated teeth were more likely to exhibit involvement of the basal wall (OR = 9.2; 95% CI = 3.3-25.2) than were patients with healthy teeth. CBCT examinations revealed a correlation between basal mucosal thickening in the maxillary sinus and decayed posterior maxillary teeth or periodontitis. Chronic symptoms involving the sinuses are one of the most common reasons for patients to consult physicians. One reason for chronic orofacial pain is the prevalence of undiagnosed sinus conditions.
Complete MRI scan should be a standard diagnostic procedure in young children with hypothalamic-chiasmatic tumors especially if presenting with diencephalic syndrome. Dissemination in childhood LGG relates to impaired PFS. CT delays progression for responders. Multicenter studies have to evaluate the efficacy of extended treatment strategies in DLGG to improve outcome.
Background: The ultraviolet (UV) erythema test is one of the most frequently used methods to investigate the anti-inflammatory potency of topical dermatological preparations in vivo. Methods: The following questions were addressed in four separate studies with healthy persons (skin types 2 and 3): (1) the optimal localization was determined by comparing light scales on the back, buttocks and volar forearms; (2) the optimal UV-B dose was determined by comparing the 1-fold, 1.5-fold and 2-fold minimal erythema doses (MEDs); (3) hydrocortisone and prednicarbate were evaluated as positive controls, and a sample size calculation was performed, and (4) betamethasone valerate and pimecrolimus were tested as further positive controls in the optimized study model. Results: The back proved to be the best localization for the UV erythema test. It showed a good correlation between the light scale and the test areas. The 1.5-fold MED was the best irradiation dose. In contrast to prednicarbate and betamethasone valerate, hydrocortisone was a rather weak positive control. However, when the sample size was ≧40 subjects, significant results were also obtained with hydrocortisone. Pimecrolimus was not effective in the UV erythema test. Conclusions: The UV erythema test should be performed on the back with at least 40 subjects using the 1.5-fold MED. It may be useful to include a potent corticosteroid, such as prednicarbate or betamethasone valerate, in addition to hydrocortisone. The UV erythema test seems to be suitable only for substances with corticosteroid-like effects, since in this test model the calcineurin inhibitor pimecrolimus was not effective.
Children <1 year at diagnosis have a conspicuously impaired survival with current treatment approaches. Age <6 months, diencephalic syndrome and dissemination constitute risk factors for even lower PFS and OS. Treatment adaptations are needed to improve outcome and molecular genetics may explain tumor aggressiveness.
Pediatric neurofibromatosis type 1 (NF-1) patients are prone to developing low-grade glioma (LGG). The HIT-LGG study 1996 aimed to observe the natural history of pediatric LGG and to postpone irradiation in younger children by using carboplatinum and vincristine in case non-surgical treatment was required. A total of 109 of 1,044 (10.4%) protocol patients had a genetic NF-1 trait [57 female patients; median age 5.1 years (range 1-15.4 years)]. Eighty-three patients (76%) suffered from an optic pathway tumor. Neuroimaging only allowed diagnosis in 67 patients. Histology revealed pilocytic astrocytoma WHO grade I in 38 of 42 biopsied patients. Sixty-five (60%) patients received non-surgical treatment, either chemotherapy (n = 55) or irradiation (n = 10). The overall survival rate of 96% after a median observation time of 5.25 years contrasts with an event free survival rate (EFS) of 0.24 at 5 years. Progressive LGG were observed even in children older than 11 years. Chiasmatic/postchiasmatic localization was a univariate risk factor for progressive disease. In the chemotherapy group, we observed a 5-year progression-free survival (PFS) rate of 0.73. Similarly, the PFS rate in the irradiation group was 0.78. Multivariate analysis revealed surgical intervention and localization within the optic pathway as factors that increased the risk of tumor progression. In this large prospective multinational study, LGG in NF-1 patients did progress in 75% of patients. Chemotherapy yielded acceptable PFS. The biological factors determining progression remain poorly understood.
The leaves of sage (Salvia officinalis L., Lamiaceae) contain high amounts of phenolic diterpenes such as carnosol and carnosic acid. These compounds display antioxidant and anti-inflammatory effects in vitro. Here, we have investigated the anti-inflammatory potency of a sage extract (SE) rich in phenolic diterpenes in vivo using the ultraviolet (UV) erythema test. In a prospective randomised double-blind placebo-controlled study, test areas on the backs of 40 healthy volunteers were irradiated with the 1.5-fold minimal erythema dose. Subsequently, the test areas were treated occlusively with 2% SE in a hydrophilic ointment, compared to 1% hydrocortisone and 0.1% betamethasone as positive controls, and the vehicle alone as placebo. Erythema values were measured photometrically prior to irradiation and after 48 hours. Compared to placebo, SE significantly reduced the ultraviolet-induced erythema, to a similar extent as hydrocortisone. These data suggest that SE might be useful in the topical treatment of inflammatory skin diseases.
disseminated pilocytic astrocytomas showed genetic features similar to classic pilocytic astrocytoma, including a similar incidence of KIAA1549-BRAF fusions, BRAF mutations and a stable genetic profile. Given common activation of the MAPK pathway, the use of specific inhibitors can be hypothesized for the treatment of disseminated pilocytic astrocytomas, along with standard chemo- and/or radiotherapy.
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