Gerald Langmann

Gamma knife radiosurgery for uveal melanomas: an 8-year experience

The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.A-60-year-old man with medically intractable left-sided maxillary division trigeminal neuralgia had severe cardiac disease, was dependent on an internal defibrillator and could not undergo magnetic resonance imaging. The patient was successfully treated using computerized tomography (CT) cisternography and gamma knife radiosurgery. The patient was pain free 2 months after GKS. Contrast cisternography with CT scanning is an excellent alternative imaging modality for the treatment of patients with intractable trigeminal neuralgia who are unable to undergo MR imaging.The authors describe acute deterioration in facial and acoustic neuropathies following radiosurgery for acoustic neuromas. In May 1995, a 26-year-old man, who had no evidence of neurofibromatosis Type 2, was treated with gamma knife radiosurgery (GKS; maximum dose 20 Gy and margin dose 14 Gy) for a right-sided intracanalicular acoustic tumor. Two days after the treatment, he developed headache, vomiting, right-sided facial weakness, tinnitus, and right hearing loss. There was a deterioration of facial nerve function and hearing function from pretreatment values. The facial function worsened from House-Brackmann Grade 1 to 3. Hearing deteriorated from Grade 1 to 5. Magnetic resonance (MR) images, obtained at the same time revealed an obvious decrease in contrast enhancement of the tumor without any change in tumor size or peritumoral edema. Facial nerve function improved gradually and increased to House-Brackmann Grade 2 by 8 months post-GKS. The tumor has been unchanged in size for 5 years, and facial nerve function has also been maintained at Grade 2 with unchanged deafness. This is the first detailed report of immediate facial neuropathy after GKS for acoustic neuroma and MR imaging revealing early possibly toxic changes. Potential explanations for this phenomenon are presented.In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume of the lesion are measured. To determine the lesion volume without using stereotactically defined images, the software program VOLUMESERIES has been developed. VOLUMESERIES is a personal computer-based image analysis tool. Acquired DICOM CT scans and MR image series can be visualized. The region of interest is contoured with the help of the mouse, and then the system calculates the volume of the contoured region and the total volume is given in cubic centimeters. The defined volume is also displayed in reconstructed sagittal and coronal slices. In addition, distance measurements can be performed to measure tumor extent. The accuracy of VOLUMESERIES was checked against stereotactically defined images in the Leksell GammaPlan treatment planning program. A discrepancy in target volumes of approximately 8% was observed between the two methods. This discrepancy is of lesser interest because the method is used to determine the course of the target volume over time, rather than the absolute volume. Moreover, it could be shown that the method was more sensitive than the tumor diameter measurements currently in use. VOLUMESERIES appears to be a valuable tool for assessing residual lesion volume on follow-up images after gamma knife radiosurgery while avoiding the need for stereotactic definition.This study was conducted to evaluate the geometric distortion of angiographic images created from a commonly used digital x-ray imaging system and the performance of a commercially available distortion-correction computer program. A 12 x 12 x 12-cm wood phantom was constructed. Lead shots, 2 mm in diameter, were attached to the surfaces of the phantom. The phantom was then placed inside the angiographic localizer. Cut films (frontal and lateral analog films) of the phantom were obtained. The films were analyzed using GammaPlan target series 4.12. The same procedure was repeated with a digital x-ray imaging system equipped with a computer program to correct the geometric distortion. The distortion of the two sets of digital images was evaluated using the coordinates of the lead shots from the cut films as references. The coordinates of all lead shots obtained from digital images and corrected by the computer program coincided within 0.5 mm of those obtained from cut films. The average difference is 0.28 mm with a standard deviation of 0.01 mm. On the other hand, the coordinates obtained from digital images with and without correction can differ by as much as 3.4 mm. The average difference is 1.53 mm, with a standard deviation of 0.67 mm. The investigated computer program can reduce the geometric distortion of digital images from a commonly used x-ray imaging system to less than 0.5 mm. Therefore, they are suitable for the localization of arteriovenous malformations and other vascular targets in gamma knife radiosurgery.

Incidence of radiation retinopathy after high-dosage single-fraction gamma knife radiosurgery for choroidal melanoma

OBJECTIVE To investigate the incidence and clinical findings of radiation retinopathy after single-fraction high-dose gamma knife radiosurgery for choroidal melanoma. DESIGN Retrospective noncomparative interventional case series. PARTICIPANTS Thirty-two patients with choroidal melanoma. METHODS Review of charts, color fundus photographs, and fluorescein angiograms of 32 choroidal melanoma patients after radiosurgery. All patients were treated with the Leksell gamma knife in one fraction with a marginal dose between 40 and 80 Gy (median, 50 Gy) and were followed for at least 24 months (or until enucleation because of complications secondary to radiation). MAIN OUTCOME MEASURES Any clinical feature of radiation retinopathy and neovascular glaucoma. RESULTS During a mean follow-up of 38 months (range, 6-81 months) we found radiation retinopathy in 84% of our patients. The most common findings in these patients were intraretinal hemorrhages with an incidence of 70%, macular edema and capillary nonperfusion in 63%, and hard exudates in 52% of the patients. Less common were microaneurysms in 30% and retinal neovascularization in 22%. The time of onset of the various radiation-associated retinal findings ranged between 1 and 22 months. Forty-seven percent of all patients developed neovascular glaucoma. In our study there was no correlation between radiation dosage applied and clinical findings. CONCLUSIONS Single-fraction high-dose Leksell gamma knife radiosurgery of choroidal melanomas with a median marginal dose of 50 Gy is highly associated with early radiation retinopathy and with neovascular glaucoma.

Radiation Sensitivity of Visual and Oculomotor Pathways

Adverse effects of stereotactic radiosurgery on cranial nerves, especially the optic nerve and its pathways, are not yet sufficiently understood. 29 patients who underwent Gamma Knife radiosurgery for benign skull base tumors were reviewed. In all of them, parts of the visual pathways and/or other cranial nerves in the middle cranial fossa received significant doses of radiation. The dose given was correlated with neuro-ophthalmological findings during a follow-up period of 6-24 months. Cranial nerves III, IV and VI within the cavernous sinus, exposed to a dose from 4.5 to 30 Gy, did not develop signs of a neuropathy. Neither did the trigeminal nerve which received between 5 and 20 Gy. In patients with normal neuro-ophthalmological findings prior to radiosurgery, the visual pathways tolerated a dose between 7.5 to 15 Gy. However, in a group of patients with visual deficits before treatment and where the visual fibers received between 6 and 16.6 Gy, 31% deteriorated afterwards. These results indicate that the visual pathways are more at risk for radiation damage than the other cranial nerves in the region and that they may be even more vulnerable to radiation if prior to radiosurgery their function has been compromised by tumor or previous surgery.

Ocular melanoma: Epidemiology, clinical presentation and relationship with dysplastic nevi

Purpose: Ocular melanoma is a rare entity compared to cutaneous malignant melanoma. We examined the frequency of the tumor in a defined geographic region, its clinical presentation and its relationship with dysplastic nevi in 136 patients. Methods: 136 patients (64 men and 72 women; mean age 61.7 years, range 20–92 years) with ocular melanoma were treated at the University Hospital of Graz between June 1996 and December 2001. 129 had primary uveal melanoma in one eye (117 choroidal melanomas, 11 melanomas of the ciliary body and 1 of the iris), 2 patients had uveal melanoma in both eyes, 4 patients had conjunctival melanoma and 1 patient had a melanoma of the lacrimal sac. Epidemiology, history, potential risk factors, clinical presentation and relationship with dysplastic (= atypical) nevi were documented. Results: 48 patients (35.3%) showed more than five dysplastic nevi, compared to only 1.2% in the general population (χ2 test: p < 0.001). 5 (3.7%) had additional cutaneous melanoma and 7 (5.1%) had a family history of melanoma. The lifelong risk for the occurrence of an additional primary cutaneous melanoma was 2.9%, which is significantly higher than the usual estimate of 1% for the general population. Conclusions: Patients with primary ocular melanoma have an increased risk to develop cutaneous melanoma and should therefore be examined regularly by dermatologists.

Adverse side effects with perfluorohexyloctane as a long-term tamponade agent in complicated vitreoretinal surgery.

Background: To report long-term intraocular tolerance of perfluorohexyloctane (F6H8). Methods: F6H8 was used as an endotamponade in 18 patients (9 male and 9 female) with a median age of 65 years (range, 14–82 years) and complicated pathologic conditions of the inferior fundus: rhegmatogenous retinal detachment (17 patients) and tractional retinal detachment owing to proliferative diabetic retinopathy (1 patient). In six eyes, additional proliferative vitreoretinopathy was present. The use of F6H8 was primary in 2 patients, and 16 patients had had previous retinal detachment surgery (median number, 2). F6H8 was left in the eye for a median duration of 8 weeks (range, 2–14 weeks). Results: The median follow-up period was 6 months (range, 3–18 months). Permanent reattachment was achieved in 10 (56%) eyes after removal of F6H8. In 8 (44%) of 18 eyes, a redetachment occurred. Two eyes became phthisic. Adverse side effects included photophobia in two patients, pain in two, hypotony in four, early emulsification in one, corneal lesion in one, fibrinous membranes in five, posterior lens opacification in one, and retinal scar formation in one. Conclusion: Perfluorohexyloctane provides good support to the inferior retina. Because of numerous adverse side effects, it should be considered carefully when used as a long-term tamponade. Early removal may reduce the number of side effects.

Die radiochirurgische Therapie mit der Leksell Gamma Einheit in der Behandlung von Aderhautmelanomen

ZusammenfassungDie Radiochirurgie mit der Gamma Einheit, vom Schweden Lars Leksell für die Behandlung von Hirntumoren eingeführt, scheint auf Grund ihrer physikalischen Eigenschaften (Emission einer hohen Dosis in einer Sitzung mit scharfem Dosisabfall gegenüber gesundem Gewebe) für die Behandlung von Aderhautmelanomen geeignet.Durch erste positive Erfahrungen von Chinela, Zambrano und Bunge ermutigt, haben wir die neurochirurgische Therapie für die Behandlung von Aderhautmelanomen adaptiert.Die Therapie mit der Leksell Gamma Einheit wird in Anlehnung an ein multizentrisches Protokoll durchgeführt:1.Fixation des Auges in Retrobulbäranästhesie2.Stereotaktische Lokalisation des Tumors mittels CT3.Therapieplanung4.Radiochirurgische Behandlung Zwischen Juni 1992 und Februar 1993 wurden 6 Aderhautmelanome an der Grazer Leksell Gamma Einheit in interdisziplinärer Zusammenarbeit mit der Universitätsklinik für Neurochirurgie und der Abteilung für Strahlentherapie radiochirurgisch behandelt. In 5 Fällen blieb die Prominenz der Tumoren über einen Beobachtungszeitraum von maximal 8 Monaten unverändert, bei 1 Patientin mit einem juxtapapillären Melanom kam es zur Reduktion der Tumorhöhe von 8 auf 4 mm, als frühe Nebenwirkungen wurden bei letzterer Patientin Blutungen im Tumorareal sowie eine seröse Netzhaut- und Aderhautabhebung mit spontaner Rückbildung verzeichnet.Unsere ersten Erfahrungen weisen die Gamma Knife Therapie als vielversprechende alternative Therapie großer Melanome, makulärer und juxtapapillärer Melanome aus, die endgültige Beurteilung bezüglich der Effizienz dieser neuen Therapieform bedarf jedoch großer Fallzahlen über einen längeren Beobachtungszeitraum.SummaryGamma Knife radiosurgery, developed by Lars Leksell for treatment of brain tumors, is useful for treatment of uveal melanomas due to its unique physical features. It allows the delivery of a high single dose with minimum involvement of the surrounding tissue.Encouraged by first positive results by Chinela, Zambrano and Bunge we adopted the procedure for treatment of uveal melanomas.Regarding to a multicentric trial Gamma Knife procedure is performed in 4 steps1.Fixation of the globe with retrobulbar anaestetic block2.Stereotactic location of the tumor by CT3.Calculation of the isodoses4.Radiosurgical procedure Between June 1992 and February 1993 we treated 6 uveal melanomas with the Leksell Gamma Kife together with the Department of Neurosurgery and the Institute of Radiotherapy. In 5 out of 6 cases Gamma Knife therapy could stop further tumor growth. In one case of a juxtapapillary melanoma a reduction of tumor hight from 8 to 4 mm could be achieved; early side effects like serous retinal detachment resolving spontaneously after 4 months and hemorrhage at the base of the tumor were remarkable in this patient.According to our first encouraging results treatment with the Leksell Gamma Knife seems to be an alternative therapeutic modality in larger tumorus or those located at the posterior pole but definite conclusions about the efficiency of this new therapeutic procedure have to be made in a larger number of patients after a longer follow up period.

Five-year results of prognostic value of tyrosinase in peripheral blood of uveal melanoma patients.

Tyrosinase-based reverse transcriptase-polymerase chain reaction (RT-PCR) is a method for the detection of circulating melanoma cells in peripheral blood. To our knowledge, no long-term studies on the prognostic impact of tyrosinase PCR in uveal melanoma have yet been reported. In this prospective, non-randomized, observational cohort study, we included 41 patients with uveal malignant melanoma. RT-PCR for tyrosinase was performed in each patient before and after treatment. A clinical follow-up was performed for each patient for at least 5 years, including chest X-ray, serum liver enzyme determination, ultrasound of the liver and bone scintigraphy. The PCR results, age of the patients, tumour size, tumour location, tumour therapy, internal reflectivity, histology, development of distant metastasis and survival rate during follow-up were analysed. At the time of diagnosis, tyrosinase messenger RNA (mRNA) in peripheral blood, suggesting the presence of circulating melanoma cells, was detected in 16 of the 41 patients. Sixty-nine percent of the PCR samples with a positive result prior to therapy revealed a negative result after therapy. The internal reflectivity of the tumour (P=0.021) and the 5-year survival (P=0.023) showed a statistically significant association with positive PCR. It can be concluded that tyrosinase RT-PCR is a sensitive method for the detection of melanoma cells in peripheral blood. This study indicates that the presence of tumour cells in peripheral blood correlates with 5-year survival. Our results suggest a prognostic value of this method. Nevertheless, prospective analysis of a larger cohort is needed to determine the ultimate value of RT-PCR for tyrosinase in blood testing.

Calculated tumour volume as a prognostic parameter for survival in choroidal melanomas

AbstractPurpose Tumour diameter, tumour height, and tumour volume are considered important prognostic indicators of survival in choroidal melanomas. In this study, we investigated the prognostic impact on survival of the easily calculated volume estimate based on the assumption of a half-rotation ellipsoid.Methods The largest tumour diameter and tumour height were measured by ultrasound A- and B-scan in 93 patients with choroidal melanoma. Tumour volume was calculated by the half volume of a rotation ellipsoid formula, rotated around the y-axis, and compared to tumour diameter and tumour height. All parameters were correlated to the clinical outcome of the patients.Results At the time of diagnosis, the mean diameter was 10.4 mm (range 4.1–18.9 mm), and the mean height was 5.7 mm (range 1.74–14.9 mm). The range of the calculated tumour volume was between 11 and 628 mm3 (mean volume 190 mm3). Among all patients, distant metastases occurred in 10 patients (10.8%). In a univariate approach using Mantel–Haenszel log-rank test, the calculated tumour volume at the time of diagnosis was the best prognostic indicator of survival followed by tumour diameter and tumour height (P=0.028). When tumour volume, horizontal and vertical tumour diameter, age, sex, and primary tumour therapy were considered in a multivariate approach using Cox proportional Hazard model, only tumour volume turned out as a significant prognostic parameter (P=0.001).Conclusions Calculated tumour volume is a better prognostic indicator of survival of patients with choroidal melanomas than the largest tumour diameter and tumour height, and might be established in daily routine.

Echographic findings in uveal melanomas treated with the Leksell gamma knife

BACKGROUND/AIMS Between June 1992 and July 1995, 29 uveal melanomas were treated radiosurgically with the Leksell gamma unit at the University of Graz. The aim of this retrospective study was to examine the pattern of regression and the extent and time period of the decrease in tumour size. METHODS The Leksell gamma knife, model B, was used. Patients were divided into three groups according to marginal dose: group 1: eight patients with a marginal dose >50 Gy, group 2: 15 patients with a marginal dose = 50 Gy, and group 3: six patients with a marginal dose = 45 Gy. For the retrospective study two groups were examined: group A, tumours <5 mm and group B, tumours ⩾5 mm. RESULTS No significant correlation was found between tumour regression and the marginal dose. Tumour shrinkage depends on the pretreatment height. In the group of eight patients with an initial tumour prominence of less than 5 mm, no prominence was found after therapy. In the group of patients with an original tumour prominence of 5 mm and more, only two tumours formed a flat scar while a residual prominence was found in 18 patients. Increase in reflectivity combined with a decrease in size appears to be a good criterion for the effectiveness of the treatment. In five patients with tumours showing low reflectivity, over a longer period of time metastases were found. An enucleation was performed in two patients because of uncertain tumour regression and in one patient as a result of an increase in tumour size. CONCLUSION The pattern of echographic reflectivity and decrease in size is similar to brachytherapy and is one of the most important diagnostic variables for evaluation of tumour regression. An increase in reflectivity as well as a decrease in tumour size in the first 6-8 months can be considered a therapeutic success.

Lymph node metastases arising from uveal melanoma

SummarySince the eye lacks lymphatic vessels, uveal melanomas primarily metastasize hematogenously. Here we report the case of a patient with ciliary body ring melanoma who developed lymph node metastases after a fistulating glaucoma operation. A 40-year-old female Caucasian patient presented with unilateral pigment dispersion. Pigment dispersion glaucoma was diagnosed and since the intraocular pressure could not be managed with topical medication, transscleral cyclophotocoagulation and two trabeculectomies had to be performed. Due to enlargement of the pigmented iris mass and cell deposits in the chamber angle, a ciliary body ring melanoma was presumed and the eye enucleated. Histology confirmed the diagnosis of “ciliary body ring melanoma”. Six months after enucleation the patient presented multiple metastases including ipsilateral preauricular and submandibular lymph node metastases. The patient died two months later. Lymph node metastases arising from ciliary body melanomas are very rare. Tumor seeding through the trabeculectomy site into the bleb and then via conjunctival lymphatic vessels might be the crucial factor for this pathway of metastases. Therefore, in cases of unilateral pigment dispersion, malignancy should be excluded before fistulating operations are performed.ZusammenfassungUveale Melanome metastasieren primär hämatogen, da das Auge keine Lymphgefäße besitzt. In diesem Fall berichten wir über eine Patientin, welche aufgrund eines Ziliarkörpermelanoms nach fistulierender Operation einseitig Lymphknotenmetastasen entwickelte. Eine 40-jährige Patientin mit der Verdachtsdiagnose „einseitiges Pigmentdispersionsglaukom“ wurde zuerst einer transskleralen Zyklophotokoagulation und dann zweimal einer fistulierenden Glaukomoperation unterzogen, nachdem der intraokulare Druck medikamentös nicht mehr beherrschbar war. Da es in weiterer Folge zu einer Zunahme der Pigmentausschwemmung und zu morphologischen Veränderung der Irisstrukturen kam, wurde eine maligne Ätiologie vermutet und das Auge enukleiert. Die histologische Aufarbeitung bestätigte die Verdachtsdiagnose „Ziliarkörperringmelanom“. Sechs Monate später entwickelte die Patientin multiple Leber- und Milzmetastasen und einseitige Lymphknotenmetastasen. Die Patientin verstarb zwei Monate später. Lymphknotenmetastasen eines uvealen Melanoms sind sehr selten. Die Tumoraussaat über die operative Fistel aus der Vorderkammer in das Sickerkissen und dann über die Lymphgefäße in die zervikalen Lymphknoten könnte den Weg der Metastasierung erklären. Bei Patienten mit der Verdachtsdiagnose „einseitiges Pigmentdispersionsglaukom“ sollte eine maligne Erkrankung vor einer fistulierenden Operation unbedingt ausgeschlossen werden. Außerdem sollte bei diesen Patienten auch die Möglichkeit einer lymphogenen Metastasierung in Betracht gezogen werden.