Three-dimensionnal representation and descriptive geometry of the pure spherical and pure cylindrical profiles of Excimer photoablation

PURPOSE: To analyze the theoretical shape of the lenticules of corneal tissue ablated using Excimer laser for the correction of pure negative and positive spherical and cylindrical refractive errors, and to investigate the possible correlations between their spatial configuration and the clinical outcome for each procedure. METHODS: To obtain a theoretical three-dimensional representation of each ablated lenticule, we used software that performs boolean operations on three-dimensional virtual surfaces (Bryce 3D, Metacreation, Dublin, Ireland). The representation of the theoretical shape of the refractive lenticule etched by a given profile of ablation based on a paraxial model over a circular optical zone was obtained by performing appropriate Boolean operations between different preoperative and postoperative surfaces or elements. These operations were repeated to obtain the representation of the theoretical additional lenticule corresponding to the volume of tissue ablated to blend any abrupt optical zone edges with a constant slope. RESULTS: The lenticule corresponding to the negative spherical treatment had its maximum thickness in its center and no thickness at its edge, thus inducing a natural blend with the peripheral untreated cornea. The lenticule corresponding to the positive spherical treatment had its maximal thickness at the junction between the optical and transition zones, which are both circular. The lenticule corresponding to the negative cylindrical treatment had its maximal thickness along the flatter initial meridian and an elliptical transition zone contour. The lenticule corresponding to the positive cylindrical treatment had its maximal thickness at the edge of the optical zone along the initial flatter meridian, and no thickness at the perpendicular principal meridian. The transition zone is also elliptical. CONCLUSION: The basic characteristics of the lenticule corresponding to the pure negative spherical treatment could explain the lesser degree of postoperative refractive regression than that one occurring after pure positive spherical treatment and pure positive and negative cylindrical treatments. The characteristics of the lenticules corresponding to the negative and positive cylindrical treatments may also account for the substantial spherocylindrical coupling and regression, respectively commonly observed after such treatments. The three-dimensional representation of the lenticules ablated for the correction of pure spherical and cylindrical refractive errors may help to better understand the outcome of these procedures aimed at reshaping the anterior surface of the cornea.     

Endocrine involvement in pediatric-onset Langerhans' cell histiocytosis: a population-based study

OBJECTIVE: To document the frequency and outcome of endocrine involvement in pediatric-onset Langerhans' cell histiocytosis (LCH), and the association with other types of organ involvement. STUDY DESIGN: This retrospective nationwide multicenter study involved 589 patients with pediatric-onset LCH, 148 of whom had endocrine dysfunction. Median follow-up was 11.6 years. RESULTS: Pituitary dysfunction was present in 145 patients, and 141 had diabetes insipidus (DI). The estimated 10-year risks of pituitary involvement were 24.2% +/- 1.8%. GH deficiency occurred in 61 patients. Median age at onset was 2.8 years for LCH, 3.9 years for DI, and 7.7 years for GH deficiency. The risk of cranial involvement; ear, nose, and throat involvement; pneumothorax; and cholangitis was significantly higher in patients with endocrinopathy. The chronology of episodes did not support a causal link between pituitary involvement and involvement of other organs. Systemic treatment of LCH did not prevent pituitary involvement. The most severe complication was a neurodegenerative syndrome, which affected 4.3% and 10.8% of patients, respectively, 5 and 15 years after initial diagnosis, and appeared to be linked to pituitary involvement. CONCLUSION: Patients who develop endocrine LCH disorders are at a high risk of neurodegenerative LCH and require long-term follow-up.     

Phase II study of temozolomide without radiotherapy in newly diagnosed glioblastoma multiforme in an elderly populations

BACKGROUND: Currently, the survival of patients age > 70 years with glioblastoma multiforme (GBM) ranges from 4 months to 6 months, although radiotherapy and/or chemotherapy may prolong survival in certain subgroups. Temozolomide is an oral chemotherapeutic agent with efficacy against malignant gliomas and a favorable safety profile. This open-label, single-center, Phase II study was designed to evaluate the efficacy and safety of temozolomide as first-line chemotherapy and exclusive treatment in elderly patients with newly diagnosed GBM. METHODS: Chemotherapy-na?ve patients (age > 70 years) were treated with temozolomide at a dose of 150-200 mg/m(2) per day for 5 consecutive days of a 28-day cycle until they developed disease progression. No radiation therapy was administered. The primary endpoint was median overall survival (OS); secondary endpoints included progression-free survival (PFS) and toxicity. RESULTS: Thirty-two patients (median age, 75 years; median Karnofsky performance status, 70) experienced a median OS of 6.4 months and a median PFS of 5.0 months. Of 29 patients who were assessed for response, 9 patients (31%) achieved a partial response, 12 patients (41%) maintained stable disease, and 8 patients (28%) developed progressive disease. Adverse events primarily were mild, with NCI CTC Grade 3-4 thrombocytopenia and neutropenia reported to occur in 6% and 9% of patients, respectively. No neurotoxicity was observed. Treatment delays and dose reductions occurred in 13% and 14% of cycles, respectively. CONCLUSIONS: Temozolomide represents a safe, easily administered, and effective therapeutic approach for elderly patients with newly diagnosed GBM.     

Oligodendrogliomas: An update on basic and clinical research

Oligodendrogliomas have been the focus of considerable interest over the past decade, ever since they were recognized as chemosensitive tumors. They were once believed to represent less than 5% of gliomas, but by using expanded criteria, they may well represent up to one third. In fact, morphologic criteria are vague and highly subjective and the histologic diagnosis, therefore, remains highly controversial and unsatisfactory. New oligodendrocytic lineage markers, such as OLIG1/2 gene, will probably help to define the real spectrum of oligodendroglial tumors, which may include a wide variety of tumors with very different prognoses. Recently, genetic markers, and particularly loss of 1p and 19q chromosomes, have been shown to predict both prognosis and response to treatment. There is little doubt that these emerging techniques will be very helpful in clinical practice for refining both classification and therapeutic indications of oligodendroglial tumors.     

Standards, Options and Recommendations 2002 for the management of adult patients with intracranial gliomas (summary report)

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVE: To define clinical practice guidelines for the management of adult patients with intracranial glioma in collaboration with the Association of French-speaking Neuro-oncologists (Anocef) and the French society of neurosurgeons (SNCLF). These recommendations cover diagnosis, classification, treatment and follow-up of patients with these tumors. METHOD: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: This article is a summary version of the full document presenting the clinical practice guidelines with algorithms. The main recommendations concern the place of the surgery, radiotherapy, chemiotherapy, imagery and concomitant medical treatments in the specific treatment strategy of grade III and IV glioma, grade II glioma, gliomatosis cerebri, pilocytic astrocytoma, subependymoma, xanthoastrocytoma, intracranial ependymoma and brain stem glioma.     

Treatment of ocular cicatricial pemphigoid with sulfasalazine

PURPOSE: To assess the outcome of patients with ocular cicatricial pemphigoid (OCP) treated with sulfasalazine as an alternative to dapsone. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Nine patients with biopsy-proven OCP and previous dapsone-related adverse effects (hemolysis and gastrointestinal disturbances) treated with oral sulfasalazine. METHODS: Clinical data were abstracted from patients' medical records. MAIN OUTCOME MEASURES: Patients' symptoms, ocular inflammation, conjunctival scarring, complete blood cell count (including reticulocyte count). RESULTS: At the initiation of sulfasalazine therapy, ocular inflammation was controlled in all patients but one. Mean follow-up was 12 months (range, 2-35 months). Median oral sulfasalazine dosage was 3 g (range, 1-4 g). The disease remained controlled with sulfasalazine alone in four patients (45%). Two patients (22%) required adjunctive oral cyclophosphamide. Adverse effects necessitating drug withdrawal occurred in three patients (33%): hemolysis in two and gastrointestinal disturbances in one. CONCLUSIONS: Sulfasalazine may be useful in OCP patients with previous dapsone-related adverse effects.     

Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse

Background:Recurrent glioblastoma multiforme (GBM) is resistantto most therapeutic endeavors, with low response rates and survival rarelyexceeding six months. There are no clearly established chemotherapeuticregimens and the aim of treatment is palliation with improvement in thequality of life. Patients and methods:We report an open-label, uncontrolled,multicenter phase II trial of temozolomide in 138 patients (intent-to-treat[ITT] population) with glioblastoma multiforme at first relapse and aKarnofsky performance status (KPS) 70. One hundred twenty-eight patientswere histologically confirmed with GBM or gliosarcoma (GS) by independentcentral review. Chemotherapy-naïve patients were treated withtemozolomide 200 mg/m²/day orally for the first five days ofa 28-day cycle. Patients previously treated with nitrosourea-containingadjuvant chemotherapy received 150 mg/m²/day for the first fivedays of a 28-day cycle. In the absence of grade 3 or 4 toxicity, patients onthe 150 mg/m² dose schedule were eligible for a 200mg/m² dose on the next cycle. Results:The primary endpoint was six-month progression-freesurvival assessed with strict radiological and clinical criteria. Secondaryendpoints included radiological response and Health-related Quality of Life(HQL). Progression-free survival at six months was 18% (95%confidence interval (CI): 11%–26%) for theeligible-histology population. Median progression-free survival and medianoverall survival were 2.1 months and 5.4 months, respectively. The six-monthsurvival rate was 46%. The objective response rate (complete responseand partial response) determined by independent central review ofgadolinium-enhanced magnetic resonance imaging (MRI) scans was 8% forboth the ITT and eligible-histology populations, with an additional 43%and 45% of patients, respectively, having stable disease (SD).Objectively assessed response and maintenance of a progression-free statuswere both associated with HQL benefits (characterized by improvements overbaseline in HQL domains). Temozolomide had an acceptable safety profile, withonly 9% of therapy cycles requiring a dose reduction due tothrombocytopenia. There was no evidence of cumulative hematologictoxicity. Conclusions:Temozolomide demonstrated modest clinical efficacy,with an acceptable safety profile and measurable improvement in quality oflife in patients with recurrent GBM. The use of this drug should be exploredfurther in an adjuvant setting and in combination with other agents.     

Treatment of Meningeal Gliomatosis

To evaluate whether vigorous treatment is beneficial for patients with meningeal gliomatosis (MG) we reviewed the case records of 20 consecutive patients treated for a symptomatic MG in our center. All received systemic or intrathecal chemotherapy and six received additional cranial or spinal radiotherapy. Six patients (30%) achieved a partial response (one low-grade astrocytoma, two anaplastic astrocytomas, one anaplastic oligodendroglioma and two glioblastomas). In these cases, clinical improvement was associated with radiological improvement on CT scan or MRI in five and with a major cerebrospinal fluid improvement in three. Three patients (15%) were stable for 3 months or more and 11 (55%) had progressive disease. Median survival was longer for the responding patients (10 months) than for the other patients (2 months). This study suggests that some patients with MG may benefit from a treatment combining radiotherapy to symptomatic areas and chemotherapy with agents that cross the blood–brain barrier or are delivered directly into the CSF.     

Breaks in Descemet's membrane. Association with secondary warts. Histologic and ultrastructural study

We analysed the histological and ultrastructural aspects of corneal buttons obtained by keratoplasty in two patients presenting breaks in Descemet's membrane. The edges of the breaks appear clinically as glassy ridges or ledges and are also called Haab's lines. One patient had a birth trauma and the other had congenital glaucoma. The edges of the breaks coiled anteriorly towards the stroma and were dramatically thickened by a multilaminar Descemet's like membrane that exhibited excrescences within its outer part and that was secreted by regenerated endothelial cells. Only one case was analysed by SEM. Secondary guttuta could not be detected by this technique because it was completely covered by a sheet of newly secreted fibrous tissue that prevented the warts from indenting the endothelial cells. The part of cornea corresponding to the break was also covered by a new thick Descemet's like membrane exhibiting guttate warts. This study is thus a good opportunity to discuss the mechanisms of endothelial and Descemet's membrane regeneration.