3-D-Conformal Radiation Therapy for Pediatric Giant Cell Tumors of the Skull Base

Background: Giant cell tumors (GCT) of the base of skull are rare neoplasms. This report reviews the treatment of four pediatric patients presenting with aggressive giant cell tumor, using fractionated and combined, conformal proton and photon radiation therapy at Massachusetts General Hospital and Harvard Cyclotron Laboratory. Patients and Methods: Three female patients and one adolescent male, ages 10-15 years, had undergone prior, extensive surgical resection(s) and were treated for either primary (two patients) or recurrent (two patients) disease. Gross residual tumor was evident in three patients and microscopic disease suspected in one patient. Combined proton and photon radiation therapy was based on three-dimensional (3-D) planning, consisting of fractionated treatment, one fraction per day at 1.8 CGE (cobalt-gray equivalent) to total target doses of 57.6, 57.6, 59.4, and 61.2 Gy/CGE. Results: With observation times of 3.1 years, 3.3, 5.3, and 5.8 years, all four patients were alive and well and remained locally controlled without evidence of recurrent disease. Except for one patient with partial pituitary insufficiency following radiotherapy for sellar recurrent disease, thus far no late effects attributable to radiation therapy have been observed. Conclusions: 3-D-conformal radiation therapy offers a realistic chance of tumor control for aggressive giant cell tumor in the skull base, either postoperatively or at time of recurrence. Conformal treatment techniques allow the safe delivery of relatively high radiation doses in the pediatric patient without apparent increase of side effects. Hintergrund: Der Riesenzelltumor der Schädelbasis ist eine seltene neoplastische Erkrankung. Es werden in dieser Studie vier Kinder mit einem aggressiv wachsenden Riesenzelltumor vorgestellt. Die Behandlung erfolgte unter Verwendung einer fraktionierten und kombinierten konformalen Protonen- und Photonentherapie am Massachusetts General Hospital und am Harvard Cyclotron Laboratory. Patienten und Methoden: Drei Mädchen und ein Junge im Alter zwischen 10 und 15 Jahren wurden nach neurochirurgischer Entfernung des Tumors entweder primär (zwei Patienten) oder wegen eines Rezidivs (zwei Patienten) strahlentherapeutisch behandelt. Ein makroskopisch sichtbarer Tumor konnte bei drei Patienten nachgewiesen werden. Wegen des Verdachts auf mikroskopische Tumorreste wurde ein Patient behandelt. Es wurde eine kombinierte Protonen- und Photonentherapie, basierend auf einer dreidimensionalen Bestrahlungsplanung, verwendet. Es erfolgte eine fraktionierte Behandlung mit täglichen Einzeldosen von 1,8 CGE (Cobalt-Gray-Äquivalent) bis zu einer Gesamtdosis von 57,6, 57,6, 59,4 und 61,2 Gy/CGE. Ergebnisse: 3,1, 3,3, 5,3 und 5,8 Jahre nach Therapie sind alle vier Patienten bei guter Gesundheit. Alle vier Patienten sind bezüglich des Riesenzelltumors lokal kontrolliert und zeigen keinen Hinweis auf ein Rezidiv. Bei einem Patienten entwickelte sich nach Rezidivbestrahlung eines sellär gelegenen Tumors eine partielle Insuffizienz der Hirnanhangsdrüse. Weiter Strahlenspäteffekte konnten nicht beobachtet werden. Schlussfolgerungen: Die postoperative oder die zum Zeitpunkt des Rezidivs angewandte dreidimensionale konformale Strahlentherapie ermöglicht eine hohe Kontrollrate des aggressiv wachsenden Riesenzelltumors der Schädelbasis. Mit der konformalen Technik konnten relativ hohe Dosen bei der Behandlung von Kindern sicher verwendet werden. Es kam dabei nicht zu einem Anstieg der Nebenwirkungsraten.     

Das Ambulatorium für Chirurgisch Tuberkulöse

Ohne Zusammenfassung     

Über weibliche Sexualhormone bei einzelligen Tieren

Zusammenfassung Es wurde zum ersten Male bei tierischen Einzellern eine östrogene Substanz sicher nachgewiesen. Ein alkoholischer Auszug aus Protozoen (Colpoda Steini) rief bei kastrierten weiblichen Mäusen nach 30 bis 40 Stunden Vollbrunst (Östrus) hervor. Ob die fraglichen östrogenen Substanzen mit den östrogen wirkenden weiblichen Sexualhormonen der Warmblüter identisch sind, muß erst geklärt werden.Dem bei der Kultur der betreffenden Protozoen verwendeten pflanzlichen Material kam eine östrogene Wirkung nicht zu.Alkoholische Auszüge aus den Protozoen (Colpoda Steini) erwiesen sich bei Versuchen an Mäusen als giftig; sie bewirkten Lähmungserscheinungen.Am isolierten Froschherzen veranlaßten sie Gruppenbildung, Abnahme der Hubhöhe, diastolischen Stillstand und sonstige Erscheinungen, die an die Wirkung von Gallensäuren erinnerten.Auf gewaschene Rinderblutkörperchen wirkten die Extrakte der Protozoen schwach hämolysierend.     

Cerebellar Bottom-of-Fissure Dysplasia—a Novel Cerebellar Gray Matter Neuroimaging Pattern

We report on seven patients with a novel neuroimaging finding that involves exclusively the cerebellar gray matter at the bottom of several fissures of both hemispheres but spares the vermis. The abnormal fissures were predominantly located in the lower and lateral parts of the cerebellar hemispheres. The affected cerebellar cortex was hypointense on T1-weighted and hyperintense on T2-weighted and fluid attenuation inversion recovery sequences. In some patients, the involved cerebellar gray matter was mildly thickened and the affected fissures slightly widened. In three of seven patients, the neuroimaging findings were unchanged on follow-up studies up to 6 years. The seven patients had various indications for the brain magnetic resonance imaging studies, and none of them had cerebellar dysfunction. Based on the similarity of the neuroimaging pattern with the cerebral “bottom-of-sulcus dysplasia,” we coined the term “cerebellar bottom-of-fissure dysplasia” to refer to this novel neuroimaging finding. The neuroimaging characteristic as well as the unchanged findings on follow-up favors a stable “developmental” (malformative) nature. The lack of cerebellar dysfunction in the affected patients suggests that cerebellar bottom-of-fissure dysplasia represents most likely an incidental finding that does not require specific diagnostic investigation but allows a reassuring attitude.     

Pre- and Postnatal Neuroimaging of Congenital Cerebellar Abnormalities

The human cerebellum has a protracted development that makes it vulnerable to a broad spectrum of developmental disorders including malformations and disruptions. Starting from 19 to 20 weeks of gestation, prenatal magnetic resonance imaging (MRI) can reliably study the developing cerebellum. Pre- and postnatal neuroimaging plays a key role in the diagnostic work-up of congenital cerebellar abnormalities. Diagnostic criteria for cerebellar malformations and disruptions are based mostly on neuroimaging findings. The diagnosis of a Dandy-Walker malformation is based on the presence of hypoplasia, elevation, and counterclockwise upward rotation of the cerebellar vermis and cystic dilatation of the fourth ventricle, which extends posteriorly filling out the posterior fossa. For the diagnosis of Joubert syndrome, the presence of the molar tooth sign (thickened, elongated, and horizontally orientated superior cerebellar peduncles and an abnormally deep interpeduncular fossa) is needed. The diagnostic criteria of rhombencephalosynapsis include a complete or partial absence of the cerebellar vermis and continuity of the cerebellar hemispheres across the midline. Unilateral cerebellar hypoplasia is defined by the complete aplasia or hypoplasia of one cerebellar hemisphere. Familiarity with these diagnostic criteria as well as the broad spectrum of additional neuroimaging findings is important for a correct pre- and postnatal diagnosis. A correct diagnosis is essential for management, prognosis, and counseling of the affected children and their family.     

Testing patients during seizures: A European consensus procedure developed by a joint taskforce of the ILAE – Commission on European Affairs and the European Epilepsy Monitoring Unit Association

There is currently no international consensus procedure for performing comprehensive periictal testing of patients in the epilepsy monitoring units (EMUs). Our primary goal was to develop a standardized procedure for managing and testing patients during and after seizures in EMUs. The secondary goal was to assess whether it could be implemented in clinical practice (feasibility). A taskforce was appointed by the International League Against Epilepsy (ILAE)—Commission on European Affairs and the European Epilepsy Monitoring Unit Association, to develop a standardized ictal testing battery (ITB) based on expert opinion and experience with various local testing protocols. ITB contains a comprehensive set of 10 items that evidence the clinically relevant semiologic features, and it is adaptive to the dynamics of the individual seizures. The feasibility of the ITB was prospectively evaluated on 250 seizures from 152 consecutive patients in 10 centers. ITB was successfully implemented in clinical practice in all 10 participating centers and was considered feasible in 93% of the tested seizures. ITB was not feasible for testing seizures of very short duration.     

Force Majeure: Therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease

Gaucher disease is the first lysosomal disorder for which clinically effective enzyme replacement therapy has been introduced. Lifelong treatment with imiglucerase, the recombinant glucocerebrosidase manufactured by the Genzyme Corporation (MA, USA), is administered intravenously — usually at biweekly intervals. An acute shortage of imiglucerase (to 20% of prior global supply) has occurred as a result of viral contamination of the production facility; production was halted, and a full supply of imiglucerase is not anticipated until January 2010. An urgent meeting of physicians, researchers, and patients was convened through the agency of the European Working Group for Gaucher Disease; this was instigated by patients internationally represented by the European Gaucher Alliance. Here we present a position statement based on the findings of the group, with key recommendations about identification and monitoring of at-risk patients threatened by the abrupt withdrawal of treatment, the equitable distribution of residual imiglucerase — and access to alternative treatments including those that have completed phase III clinical trials but have not yet been licensed.