Poor-Prognosis Patients with Cancer Metastatic to Brain: Implications for Stereotactic Radiosurgery

The risk of brain recurrence after whole-brain radiotherapy for metastatic disease has been infrequently reported, but quoted to be as high as 50%. These values are in the context of autopsy series or clinical trials and thus may not represent experience in routine clinical practice. This retrospective analysis was undertaken: (1) to confirm recursive analysis-based prognostic factors contributing to survival; and (2) to investigate efficacy of Gamma Knife Stereotactic Radiosurgery (GKSRS) in the poorest prognosis population. The records of 85 unselected, consecutive patients receiving whole-brain radiotherapy for brain metastases at Naval Medical Center San Diego were analyzed. Median dose of whole brain radiotherapy was 30 Gy in 10 fractions. These records were categorized by Radiation Therapy Oncology Group (RTOG) categories based on several prognostic factors. Further, analysis of 153 consecutive patients (178 treatments of 396 lesions) receiving GKSRS at the San Diego Gamma Knife Center was made for patients with Karnofsky Performance Status (KPS) < 70 (RTOG class 3). Twenty patients were identified. Median dose of GKSRS was 17.5 Gy at the 61% mean isodose line for all GKSRS patients. Six patients experienced clinical brain recurrences after whole-brain radiotherapy; the actuarial risk of clinical brain recurrence after whole-brain radio therapy approached 30% at 3 years, although few patients survived this long. Survival of patients after whole brain radiotherapy alone by RTOG category mirrored findings of other centers. Patients in class 3 (n = 26) had a median survival in our population of 59 days. For the 20 GKSRS patients with similar performance status and clinical follow-up, the median survival was longer, but not significantly so (162 days; p = 0.467). In the off-protocol setting, clinical brain recurrence of metastatic disease after whole-brain radiotherapy occurs not infrequently in patients with otherwise long survival. The RTOG criteria well describes an extremely poor-prognosis group of patients for whom the single fraction of stereotactic radiosurgery may optimize palliation as well as or better than longer courses of conventional palliative radiotherapy.     

Leksell Frame Fixation Using Zygomatic Bone for Stereotactic Radiosurgery

The present report describes a unique frame fixation technique for -knife radiosurgery that was used on a patient with an arteriovenous malformation (AVM) located in the occipital pole. Because the patient had a relatively long head and the nidus was located near the occipital pole, the nidus was out of the coordinate frame indicator when applied in the routine frontal pin position. Therefore, the anterior pins were placed on the zygomatic bone for frame fixation. Using this frame fixation technique, the target point could be moved anteriorly by 2.0 cm, or slightly more, within the coordinate frame, as compared with the ordinary frontal pin position. Therefore, appropriate -knife treatment could be carried out and treatment was successful; the AVM was confirmed to be completely obliterated on 2-year postradiosurgical angiography. This technique is applicable to all stereotactic procedures using a Leksell frame in patients with conditions such as that of the present case.     

Radiosurgery for Cerebral Arteriovenous Malformations

From September 1991 to May 1997, a total of 59 patients diagnosed with cerebral arteriovenous malformations were treated using radiosurgery. There were 29 men and 30 women, with an age range of 5 to 75 years (mean 36). Of these patients, 39 patients were treated using a LINAC-based system (group 1) and 20 using the Leksell -knife unit (group 2). Tumor volume ranged from 0.38 to 35 cc, and the number of isocenters varied from 1 to 3 in group 1 and from 2 to 15 in group 2. Lesion location was as follows: 14 temporal, 8 basal ganglionic, 8 frontal, 6 parietal, 6 thalamic, 5 intraventricular, 5 cerebellar, 3 brain stem, 3 occipital, and 1 corpus callosal. Seven patients underwent prior embolization and three patients had prior surgery with incomplete resection of their lesions. The marginal radiation dose ranged between 1500 and 2000 cGy with a mean of 1800 cGy. Twelve patients had concomitant embolization done on the morning of radiosurgery. Follow-up ranged from 1 month to 4 years. Thirty-six patients have been followed for more than 1 year. Thirty had an angiography during the follow-up period that showed complete obliteration of the lesion in 28 patients. The rate of obliteration was estimated to be 47.1% at 1 year, 82.3% at 2 years and 88.2% at 3 years.     

Angiographic Follow-up of One-Stage Radiosurgery for Multiple Cerebral Arteriovenous Malformations

Because multiple cerebral arteriovenous malformations (AVMs) are extremely rare, little information is available as to stereotactic radiosurgery for multiple AVMs. We present a patient with three cerebral AVMs who underwent one stage gamma knife radiosurgery for all three nidi. Each nidus was covered with a 90% isodose volume and a central dose of 27.8 Gy was used to obtain a marginal dose of 25 Gy. Angiography that was performed 10 months after irradiation demonstrated complete obliteration in one nidus, remarkable shrinkage in another and no significant changes in the other. The patient has experienced neither bleeding nor complications related to irradiation, to date. We consider one of the major benefits of stereotactic radiosurgery to be that multiple intracranial AVMs, if all nidi are sufficiently small (<3 cm), can be treated with a single procedure.     

Radiosurgery for Intracranial Arteriovenous Malformations in Children

Background: The objective of this retrospective study is to determine the value of radiosurgery in the management of arteriovenous malformations (AVM) in the pediatric age group. Methods: From January 1994 through January 1999, thirty-one children with arteriovenous malformations (AVMs) were treated with radiosurgery. All patients were treated on an outpatient basis at the same institution by the same team. The Leksell Gamma Knife unit was used. Workup included angiography, MRI, and MRA. Follow-up ranged from 7 months to 67 months, with a median of 33 months. Minimum doses of radiation, depending on the size of the lesion, ranged from 20 Gy to 25 Gy. Treatment volumes for all the vascular malformations ranged from 0.6 cc to 17 cc with a mean volume of 4.7 cc. The mean number of isocenters was 4.8. Results: Total obliteration of AVM nidus was obtained in 22 of 31 (71%) patients, while 9 patients had partial obliteration. Stabilization of the benign lesions was obtained in all the patients treated. None had rebleeding after the procedure and, as of this writing, no patient required retreatment. Conclusion: Radiosurgery is an effective noninvasive and safe therapeutic modality for the management of vascular malformations independent of location, size, or grade.     

γ-Knife Radiosurgery for Brainstem Lesions: The Wayne State University Experience

Stereotactic radiosurgery (SRS) is increasingly being used for tumors of the brainstem because it suits the anatomical constraints of this area. We now report on the 2-year experience at Wayne State University using -knife SRS for such lesions, with an emphasis on toxicity and morbidity. From January 1996 to January 1998, sixteen patients (6 males and 10 females) with lesions in the area of the brainstem were treated with SRS. Average age was 53 years (range 19–80). Nine lesions were malignant; 7 were benign. Median Karnofsky performance status (KPS) prior to SRS was 80 (range 50–100). Median follow-up period from initial diagnosis to analysis, and from the date of SRS to analysis, was 24 months (range 11–73) and 15 months (range 4–29), respectively. Results were analyzed for the whole population treated and then stratified by diagnosis: benign versus malignant. At analysis, 10 (62.6%) patients were alive and 6 (37.5%) were dead. No deaths followed SRS. Values for KPS prior to SRS were compared to 3 months post-SRS. No significant change in KPS scores could be observed for those with benign lesions, but 67% of patients with malignant tumors showed a KPS drop 30 points. There was no correlation between the treated volume and survival. At the time of review, no patients had developed new neurological symptoms after SRS. Results for benign lesions indicate that SRS is well tolerated, provides good local control, and does not cause unusual rates of morbidity or mortality. Results for malignant lesions demonstrate that pretreatment performance status influences the post-SRS values. The post-SRS Median Survival (MS) of 10 months for the Malignant Lesions (M) is impressive, in light of the drop of KPS observed; the outcome for such patients is likely determined by the activity of the primary disease process. Our results suggest that SRS in the brainstem is safe, feasible, and merits further study.     

Geometrical Accuracy Test Obtained on the OUR Rotating γ-System

In 1996, a new -ray brain surgical apparatus, the OUR rotating -system (RGS), was developed for stereotactic radiosurgery. The device contains 30 cobalt-60 sources distributed in 5 groups along 6 helical lines in a hemispherical primary collimator body, which rotates during treatment together with the built-in secondary collimator body. By rotating the primary and secondary collimator body together, 30 nonoverlapping, full 360° arcs are formed. The 30 cobalt-60 -radiation sources have approximately 6000 Ci total initial activity with 3 Gy/min initial dose rate at the isocenter. The purpose of this study was to test the geometrical accuracy of this new radiosurgical equipment. The investigations were carried out on Gafchromic Dosimetry Media, Type MD-55 films. Following a pin-prick directed toward the center point of the radiation unit, the films were exposed, and the optical density profiles were analyzed with an automatic densitometer (Molecular Dynamics Personal Densitometer, Model PD SN 50238, Innovative Optical Systems for Biological Research). By measuring the asymmetry of the position of the pin-prick in relation to the density distribution, the geometrical accuracy of the OUR RGS was determined. The calculated difference between the mechanical unit center point and the radiological center point verify the unit of ±0.1054 mm against the generally accepted ±0.5 mm.     

Acoustic Neurinoma and Its Treatment Using the Leksell γ-Knife as a Primary or Secondary Treatment

Over 4 years (1992–1996) we have treated 122 patients with unilateral acoustic neurinoma using the Leksell -knife; 121 patients had a follow-up of 2–48 months (median 24 months). Tumor volume was 0.1–17.8 cm³ (median 2.9 cm³); dose to the tumor margin was 10–17.5 Gy (median 12 Gy) delivered on 40–80% isodose (median 50%). A decrease in the tumor volume was observed in 41.3% of patients, the tumor volume was unchanged in 54.6%, and an increase in the tumor despite radio-surgery was observed in 4.1%. Hearing loss was detected in 17.4% of patients, and 3% of patients gained useful hearing after radiosurgery. The overall risk of the method is 4.3% of hearing loss. Weakness of the facial nerve was observed in 1.9% of patients; normalization of the weakness, which was present before radiosurgery, was observed in 6.3% of patients. The overall risk of facial weakness is 1% for -knife radiosurgery. Impairment of trigeminal neuropathy was observed in 5% of patients and improvement in 31%. Impairment of vertigo was observed in 5.8% of patients and improvement in 46%. Leksell -knife radiosurgery was the primary treatment in 97 patients (80.7%); microsurgical resection preceded radiosurgery in 24 patients (19.8%). Hearing loss and neuropathy of facial and trigeminal nerves before -knife radiosurgery were significantly more frequent in the group of patients with previous microsurgical resection than in the group with -knife radiosurgery as the primary treatment. After radiosurgery there was no significant difference in impairment or improvement of hearing, facial and trigeminal nerve neuropathy, and vertigo and imbalance for the groups of patients with previous microsurgery or primary -knife treatment. After -knife radio-surgery neuropathy of facial and trigeminal nerves in the group of patients with previous microsurgery was significantly worse.     

Effect of tumor necrosis factor-α and interferon-γ on the growth of human prostate cancer cell lines

Human recombinant tumor necrosis factor- (rTNF-, 10^-12–10^-8 M) inhibited the proliferation of androgen-dependent LNCaP cells by 32–56%. In contrast, proliferation of androgen-independent PC-3 and JCA-1 cells was only slightly inhibited, or not inhibited at all, respectively. Human recombinant interferon- (rIFN-, 500 U/ml) decreased proliferation of PC-3 and JCA-1 cells by 35% and 53%, respectively, but had no effect on LNCaP cells. Interestingly, the combination of rIFN- and TNF- had greater antiproliferative effects on JCA-1 cells than treatment with either cytokine alone. However, the antiproliferative effects of this combination were similar to those observed for PC-3 or LNCaP cells treated with rIFN- or TNF- alone, respectively. These data suggest that some forms of androgen-independent prostate cancer may benefit from a combination therapy of IFN- and TNF-, while the use of IFN- alone may be more efficacious in others.     

Expression of interferon-γ receptors on bladder cancer cells: does it correlate with biological response?

Summary Previously we have shown a differential biological response of three human bladder cancer cell lines (RT4, RT112 and MGH-U1) to gamma interferon (IFN-). The present study examines the relationship between the biological response and the expression of the interferon- receptor on the tumour cell surface. Using a competitive radioligand binding assay and Scatchard analysis, we measured the number and affinity of the IFN- receptors on each of the above cell lines. Individual cells from each line expressed large numbers (29,100–41,800) of high-affinity receptors (k _d =2.4–3.9×10¹⁰M). There was no statistically significant difference in either of these parameters between the three lines. We therfore conclude that the biological response of these bladder lines to IFN- does not relate to the number or affinity of its receptor on the plasma membrane of these tumour cells.     

The various etiological factors of “hard capsule” formation in breast augmentations

The use of Silastic implants in breast augmentation has been one of the greatest advances in aesthetic plastic surgery during the past 20 years. This article deals specifically with one of the most important complications, namely, the formation of the hard capsule surrounding the prosthesis. The specific use of a saline-filled Silastic prosthesis with the intra-luminal use of methylprednisolone acetate suspension is discussed, based on experience with 133 patients. Illustrative case histories and photos are shown. The etiology, prevention, and/or total definitive treatment is explained and the conclusion reached is that this management leads to permanent, satisfactory results.     

Laparoscopic splenectomy

We have now used a new patient position for laparoscopic splenectomy: The patient is placed in right lateral supine position on a bean bag positioning apparatus and the left arm is elevated. The operator is located on the right of the patient; the first assistant is on the same side and the second is on the left.We have a very good view of the spleen which is hung on the diaphragm by the peritoneal attachments, and we can sever successively inferior polar splenic vessels, short gastric vessels, and hilus splenic vessels. With this patient position, it is our opinion that laparoscopic splenectomy is feasible and safe if the spleen volume is not too large. To date, we have performed thirteen splenectomies with this procedure. We have had twelve good results and one conversion to laparotomy.     

“T”-osteotomy of the calcaneum

Summary The relative length and height of the lateral and medial walls of the calcaneum probably govern the production and persistence of structural hindfoot deformity, forefoot supination and adduction, and pronation and abduction. Anatomical restoration of the proportions of the calcaneal walls forms the basis of the T-osteotomy of the calcaneum. We have undertaken this operation on 72 feet in 60 patients for cavovarus deformity with forefoot adduction. The calcaneum is approached from the lateral side and the T-shaped osteotomy is performed through the body, the vertical limb being 1 to 1.5 cm behind and parallel to the calcaneo-cuboid joint. The horizontal limb starts from the centre of the vertical cut and ends above the attachment of the tendo achillis. The postero-inferior segment is pushed out correcting the heel varus and at the same time broadening the heel. The forefoot is manipulated downwards and outwards to correct the residual cavus and the adduction and supination of the forefoot. The over-all results, with an average follow-up of 3.7 years, have been satisfactory.Paper presented at Kyoto, Japan, during the XIVth World Congress of SICOT on October 17, 1978     

Vitamin K-induced changes in markers for osteoblast activity and urinary calcium loss

Summary The objective of this study was to identify subjects in whom vitamin K has an effect on markers for calcium and bone metabolism and to detect hitherto-unnoticed correlations between vitamin K-induced changes in these markers. Participants in our studies were apparently healthy women, in whom we measured serum-immunoreactive osteocalcin (irOC) before and after adsorption to hydroxylapatite; total serum alkaline phosphatase (T-AP) and bonespecific alkaline phosphatase (B-AP); and fasting urinary calcium and creatinine. We describe a trial among 145 women who were treated with vitamin K (1 mg/day) for 2 weeks, and a prospective placebo-controlled trial among two groups each of 70 postmenopausal women with a treatment period of 3 months. It turned out that in elderly women vitamin K induced increased levels of serum irOC with a high affinity for hydroxylapatite (irOC_bound), whereas that with low affinity (irOC_free) remained unaffected. In placebo-treated women the ratio irOC_free/irOC_bound shifted from 0.38 to 0.65 around the 50th year of age. This shift was not found in vitamin K-treated women. After 3 months of treatment the vitamin K-induced changes in irOC_bound were correlated with changes in B-AP, whereas irOC_free was correlated to urinary calcium excretion. In fast losers of urinary calcium vitamin K induced a 30% decrease of calcium excretion. The hypothesis is put forward that irOC_bound may be a marker for bone formation, that serum irOC_free may be a marker for bone resorption, and that the serum irOC_free/irOC_bound ratio may become a marker for skeletal remodeling. It is concluded that vitamin K administration may help to reduce urinary calcium loss in postmenopausal women, notably in the fast losers of calcium. The ratio irOC_free/irOC_bound provides more information than total irOC and may become a practical marker for bone metabolism.     

Zur Prüfung der Cholerese nach Gallenwegsoperationen

Zusammenfassung Es wird eine Methode beschrieben, die nach Eingriffen am Ductus choledochus Aufschluß über die Abflußverhältnisse an der Papille gibt. Durch Messung der Gallensäurenkonzentrationen und der wiedergefundenen Menge einer intravenös verabreichten, leberspezifischen Testsubstanz —Indocyaningrün — läßt sich der Verzweigungsquotient der Galle an der T-Drainage und an Fisteln bestimmen. Die statistische Auswertung von 26 Untersuchungen mit Darstellung von 5 Einzelbeispielen erläutern die klinische Nutzanwendung dieser Methode. Bei einem dieser Patienten ergibt sich die dringende Notwendigkeit zur Revision einer Gallenfistel, da entgegen den Vermutungen 90% der Galle nach außen sezerniert. In einem anderen Fall sichert die Probe nach Papillotomie eine ausschließliche Refluxsituation aus dem Duodenum in den Choledochus bei fehlendem Galleabfluß ins Duodenum. Intermittierende Verschlußphasen, die durch ein Restkonkrement verursacht werden, können exakt nachgewiesen werden. Die Verminderung des Durchflußvolumens bei einer Papillenstenose kann je nach dem Grad der Stenosierung gemessen werden. In Ergänzung zum direkten Cholangiogramm liefert die Methode wertvolle Hinweise bei unklaren postoperativen Verläufen nach Choledochotomien.

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An investigation of bile flow after common duct surgery

Summary A method is described for determination of the flow through the papilla Vater after operative treatment of the common duct. By measurement of the concentration of bile acids and the amount of Cardiogreen (Indocyanin) — an hepatospecific agent -, which was previously given intravenously, it is possible to estimate the percent distribution of the total bile flow to the duodenum and to the T-tube drain or eventual fistula.Among 26 patients the clinical benefit of this method has been demonstrated at 5 patients. In one of these patients an indication for revision of the fistula was established, when it was shown, that 90 % of bile was discharged by way of the fistula. In another case after papillotomy it was possible to prove complete reflux from the duodenum into the common duct. No bile was reaching the duodenum. In cases of stenosis of the papilla the decrease of the bile flow and therefore the severity of the stenosis can be measured. In addition to direct cholangiography this method yields significant information regarding the nature and severity of complications following common duct surgery.

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Erklärung der Abkürzungen Prozentanteil der drainierten Galle an der Gesamtgallenmenge - V_G Gesamtgallenmenge - V_D Drainierte Gallenmenge - V_u In den Darm abfließende Gallenmenge - I_G Menge der zugeführten Testsubstanz - i Konzentration der Testsubstanz in der Einheit des Volumens - I_D Wiedergefundene Menge an Testsubstanz     

Comparison of Readout Between a New Diode Laser Scanner and a Helium-Neon Laser Densitometer for GafChromic MD-55 Films

GafChromic MD-55 films were irradiated by the Vienna -knife unit with a 14 and 8 mm collimator helmet (spherical field of close to 11 mm diameter) at the same isocenter to compare the dose cross-profiles along the x and z directions with different scanning systems. Dose-response curves for GafChromic MD-55 film (Nuclear Associates Model No. 37-041) were measured using two different densitometer systems: a commercial He-Ne laser densitometer (PTW FIPS Plus, Freiburg, Germany) and a newly developed analog diode laser densitometer. For this purpose, we chose the diode laser as the light source, emitting at 675.2 nm with a single-mode surface, measured with a Lock-In Amplifier by a solar cell. The highest uniformity was seen in the change of absorption ranging from 4% to 6%, depending on the polarizing direction of the light with the new scanning system. The reproducibility of the reading method increases from 0.14% in the region of 2 Gy to 0.18% near 16 Gy. Measurements of the dose cross-profiles of the 11 mm collimator with the 675.2 nm laser scanner generally show good agreement with the values of the dose planning program. Reference studies with the He-Ne laser reveal a general tendency between 1.5 and 2.2 mm in diameter as compared to computer-simulated dose profiles and the 675.2 nm laser densitometer values.     

238. Die glattmuskuläre Sphincterplastik

Zusammenfassung Histologische, elektronenmikroskopische, perfusionsmanometrische, mikroangiographische und elektronenmikroskopische Untersuchungen haben die Eignung der glatten Darmmuskulatur zum Schließmuskelersatz bewiesen. Der Film zeigt die Operationstechnik am Beispiel einer kontinenten Colostomie. Zwischenzeitlich ist ein überblick über 509 Patienten mit einer kontinenten Colostomie möglich. Die postoperativen funktionellen Ergebnisse waren günstig und die Komplikationsrate gering, so daß die Autoren die Verwendung von glatter Muskulatur zur Erzielung eines Schließmuskelersatzes i. B. einer Colostomie empfehlen können.