Gerhard Friehs

Gamma knife for glioma: Selection factors and survival

PURPOSE To determine factors associated with survival differences in patients treated with radiosurgery for glioma. METHODS AND MATERIALS We analyzed 189 patients treated with Gamma Knife radiosurgery for primary or recurrent glioma World Health Organization (WHO) Grades 1-4. RESULTS CONCLUSION The median minimum tumor dose was 16 Gy (8-30 Gy) and the median tumor volume was 5.9 cc (1.3-52 cc). Brachytherapy selection criteria were satisfied in 65% of patients. Median follow-up of all surviving patients was 65 weeks after radiosurgery. For primary glioblastoma patients, median survival from the date of pathologic diagnosis was 86 weeks if brachytherapy criteria were satisfied and 40 weeks if they were not (p = 0.01), indicating that selection factors strongly influence survival. Multivariate analysis showed that increased survival was associated with five variables: lower pathologic grade, younger age, increased Karnofsky performance status (KPS), smaller tumor volume, and unifocal tumor. Survival was not found to be significantly related to radiosurgical technical parameters (dose, number of isocenters, prescription isodose percent, inhomogeneity) or extent of preradiosurgery surgery. We developed a hazard ratio model that is independent of the technical details of radiosurgery and applied it to reported radiosurgery and brachytherapy series, demonstrating a significant correlation between survival and hazard ratio. CONCLUSIONS Survival after radiosurgery for glioma is strongly related to five selection variables. Much of the variation in survival reported in previous series can be attributed to differences in distributions of these variables. These variables should be considered in selecting patients for radiosurgery and in the design of future studies.

Electroencephalographic and evoked potential monitoring in the hyperbaric environment

The purpose of this study was to investigate brain bioelectrical activity during hyperbaric oxygenation by continuous and simultaneous monitoring of electroenccphalographic and bimodal (auditory, somatosensory) evoked potentials. Multivariable recordings (electroencephalogram, brainstem auditory evoked potentials, early somatosensory evoked potentials, heart rate, heart rate variability, and transcutaneous partial pressure of oxygen) were measured with a new technique in 12 healthy male volunteers 26 to 52 years old (mean ± SD, 35.9 ± 9.5 years). Recordings were obtained while the subjects breathed (1) air at normal atmospheric pressure, (2) 100% oxygen at normal atmospheric pressure, (3) air at 2 atm (10 meters sea water [msw]), and (4) 100% oxygen at 2 atm (10 msw). Spontaneous brain electrical activity, somatosensory evoked potentials, and heart rate variability were not significantly affected during hyperbaric oxygénation, whereas the heart rate showed a significant decrease (pairedt test,P < 0.05). Alterations in brainstem auditory evoked potentials were seen under hyperbaric conditions and did not reach statistical significance (increase of the I-V interpeak latency by pairedt test;P < 0.2). All subjects showed insignificant increases in dominant alpha frequency and decreases in delta frequency under hyperbaric situations.

Clinical features and therapy of "typical" and "atypical" bronchial carcinoid tumors (grade 1 and grade 2 neuroendocrine carcinoma).

Between 1971 and 1992, 55 patients with grade 1 (G1) (n = 32) or grade 2 (G2) (n = 23) neuroendocrine bronchial carcinomas (males: 26, females: 29; mean age: 47.7 years, range: 13-77 years) were treated. The sexes were evenly distributed in the two groups. Patients with G1 were significantly younger than those with G2 tumors (43.3 vs 53.7 years; P < 0.05). There were no statistically significant differences between G1 and G2 concerning peripheral or central localization, laterality or maximum tumor diameters. Patients with G1 had a higher incidence of tumor-related symptoms and a longer mean duration of these symptoms (21.8 months) than G2 cases (14 months) but the differences were not statistically significant either. No case displayed any symptoms of hormonal activity. Fifty-two patients underwent resection, one was non-resectable for anatomical, and one for functional, reasons; a third refused an operation. We performed 8 pneumonectomies, 36 lobectomies (8 by using bronchoplasty), 2 bronchotomies and 6 segmental resections. Twelve G2 cases had N1 or N2 lymph node metastases, two intrapulmonary metastases were removed. After a median observation time of 55.7 months the 10-year survival rate for the total collective is 90.6%. For G1 it is 100%, compared with 76.4% for G2 patients, 3 of whom died of the tumor (P < 0.05; significant). In univariate analysis: age over 48 years, lymphatic invasion, and lymph node metastasis were also significantly correlated with a poor survival rate. Multivariate analysis proved lymphatic permeation to be the only independent prognostic factor (the survival rate was 100% where there was no invasion, but only 74% where this had occurred).

“Adjuvant” external radiation of the mediastinum in radically resected non-small cell lung cancer

OBJECTIVE The effect of postoperative external beam radiation in MO non-small cell lung cancer resected with curative intention was evaluated in a randomized trial. METHODS In 155 patients (121 males, 34 females; mean age: 59 years) 105 lobectomies, 12 bilobectomies and 38 pneumonectomies with radical lymph node dissection to the contralateral side were carried out. Histology revealed squamous cell (n = 68), adeno- (n = 53), large cell (n = 21), adenosquamous (n = 6) or bronchioloalveolar type (n = 7) carcinomas. The pathologic stages T1 (n = 38), T2 (n = 89), T3 (n = 28); NO (n = 39), N1 (n = 67), and N2 (n = 49) were evenly distributed between the two treatment groups: group A (72 patients) had no further oncologic treatment, while group B (83 patients) had external beam radiation to the mediastinum (50-56 Gy, 8 or 23 MeV photons, 2 Gy/day, 5 days a week) beginning 4 weeks after the operation. RESULTS The overall 5-year survival rate of the whole collective was 24.1% without any significant difference between the radiotherapy group B (29.7%) and the control group A (20.4%) (log-rank test: P > 0.05). The overall 5-year recurrence-free survival rate was 20.1%, with no difference between groups B and A (radiotherapy: 22.7, controls: 15.6%, long-rank test: P > 0.05). There was no difference in the incidence of distant metastases (external beam radiation: n = 32; controls: n = 38). The rate of local recurrences at the bronchial stump or in the mediastinum, however, was significantly reduced in the radiotherapy group (n = 5) compared with 17 in the controls (P < 0.01 chi-square test). A multivariate analysis confirmed the independent influence of postoperative radiotherapy on the incidence of local recurrence. CONCLUSIONS External radiation of the mediastinum in radically resected non-small cell lung cancer reduces the risk of local recurrence, but has no influence on distant metastastic spread and overall survival.

Life-saving muscle flaps in tracheobronchial dehiscence following resection or trauma

OBJECTIVE In the presence of acute inflammation and necrosis of the wall, tracheo-bronchial defects are difficult to manage. The absence of adequate vascularization and the contaminated area prevent successful direct re-suturing. METHODS In order to restore a sufficient blood supply we used a pedicled latissimus dorsi or a pectoralis major flap that was entered into the thorax after a 10-cm resection of the second rib. A portion of the muscle was fitted into the tracheo/bronchial defect by reinforced sutures. The remaining muscle was sutured to the tissue surrounding the defect. This method was applied in various septic conditions: Bronchial defects; complete dehiscence of the right (n = 6) or left (n = 1) main bronchus at the carinal level following resection for lung cancer (n = 4) or for tuberculous (n = 2) on nontuberculous pleuropneumonia (n = 1). Tracheal defects; (1) destruction of one third of the tracheal circumference involving the cricoid down to the fourth ring following tracheotomy in presence of a septic sternum after intrathoracic goiter and Bechterews disease; (2) 30% dehiscence of the anastomosis and septic sternum following tracheal resection; (3) Mediastinitis involving tracheal and esophageal wall following a 7 cm long iatrogenous laceration of the intrathoracic trachea. RESULTS In one case the latissimus dorsi developed venous stasis on day 2 and was replaced by the pectoralis major muscle which showed uneventful healing. In all other patients the muscle flap resulted in an uneventful closure of the defect and recovery. CONCLUSIONS Large, well vascularized, pedicled muscle flaps ensure a safe closure of tracheo-bronchial defects or dehiscences even in presence of gross necrosis and sepsis.

Intraoperative radiation therapy combined with external irradiation in nonresectable non-small-cell lung cancer: Preliminary report

Twenty-one patients with nonresectable non-small-cell lung cancer (15 squamous-cell, 4 adeno, 2 large-cell; T1-T3, N0-N2, all M0) underwent lymph node dissection and intraoperative irradiation of the tumor (IORT) with doses between 10 and 20 Gy (energies: 7 to 20 MeV electron beam). Postoperatively, 46-56 Gy external beam irradiation (8 or 23 MeV photon beam) were delivered to the mediastinum and 46 Gy to the tumor bearing area. Fifteen patients were available for follow-up investigations. The CT-scan tumor volumetry 4 weeks postoperatively showed a significant overall decrease (Wilcoxon test: p less than 0.05) with eight minor responses (MR) (tumor regressions between 4 and 45%) and six partial responses (PR) (between 50 and 84%). One case was not evaluable. A second volumetry after external irradiation was done in 14 patients, 18 weeks after IORT, showing 3 complete responses, 10 partial responses (62 to 84%), and 1 minor response (28%). The recent volumetries (10 patients) between 4.5 and 16.5 months after IORT showed 7 complete responses and 3 partial responses (63 to 94%). One patient died from intrabronchial hemorrhage at 7 weeks. Three others died from unrelated causes, 6, 12 and 14 months, respectively, after IORT and in one further case the cause of death at 15 months was local tumor regrowth. Within the median time elapsed since IORT (12 months) only this one case of local regrowth and one further case of distant spread were observed.

Open-window thoracostomy in pleural empyema.

Open-window thoracostomy (OWT) was performed in 21 cases of empyema. The indications were postpneumonectomy empyema with (n = 6) or without (n = 1) fistula, early recurrent empyema after decortication (n = 6), chronical empyema in ill elderly patients with (n = 5) or without fistula (n = 2), and total unilateral lung gangrene with a large fistula of the main bronchus after radiotherapy and chemotherapy (n = 1). All cases presented with severe sepsis, eight of them with acute septic shock, and six with signs of multiorgan failure. Three to five ribs were resected, the muscles and skin were sutured to the ribs confining the window located at the lowest point of the empyema cavity, while the intercostal muscles of the resected ribs were used to close fistulae. The cavity was packed with dressings every day. In all cases, the sepsis subsided immediately after OWT. With the exception of one patient with postpneumonectomy empyema, who died of contralateral pneumonia on day 36, no surgery-related complications were seen. Four further patients died of unrelated causes 2, 4, 5, and 7 months, respectively, after OWT. In one of them, the OWT had been closed. Up to this time, obliteration and closure of the cavity has been carried out in 7 cases by using thoracoplasty (n = 2) or predicted muscle flaps (n = 5) either in the early course or after a delay of 11 to 23 months, with fair functional and cosmetic results. In one further case, operative closure has been planned. In seven of the eight remaining patients, four of whom declined further operations, the cavities closed spontaneously, despite their initial size after intervals of between 11 and 21 months.

Radiosurgery with the first Austrian cobalt-60 gamma-unit : a one-year experience

SummaryDuring the period of one year, from the 21. 4. 1992 to 21. 4. 1993, a total of 201 radiosurgical sessions on 181 patients were performed with the first Austrian Gamma-unit in Graz. 42% of radiosurgical sessions were undertaken for malignomas, 20% for meningiomas, 11.5% for vascular malformations, 9% for neurinomas, 8.5% for low grade astrocytomas and glomus jugulare tumours, 5% for sellar and suprasellar lesions, and 4% for functional disorders. Dose plan data for all the lesions treated are shown. Clinical and imaging data of the first year which are available for 120 patients (66%) are presented and discussed.

Pitfalls in intraoperative frozen section histology of mediastinal neoplasms.

We evaluated the reliability of intraoperative frozen section histology in 149 mediastinal tumours of which 106 lesions were localized in the anterior, 18 in the central and 25 in the posterior mediastinum. Gross non-resectability was ruled out by preoperative imaging. No preoperative cytological or histological diagnosis was obtained in any case. At thoracotomy, 3 biopsies from 3 different sites of the tumour were processed for frozen section as well as for paraffin histology and immunohistochemistry. In 67 of 73 benign lesions (91%), the intraoperative diagnosis was correct, 5 cases could not be classified by frozen section and 1 case had to be revised. Only 28 of 76 malignant lesions (36.8%) were diagnosed correctly by intraoperative frozen section. In 27 cases (35.5%), no intraoperative classification was possible and in 21 patients (27.6%), the diagnosis was wrong with the consequence of surgical overtreatment for lymphoma misinterpreted as thymic cancer in 3 cases. In patients in whom preoperative investigations suggest borderline resectability, a staged procedure to obtain histology prior to definitive surgery could prevent overtreatment.

Evaluating intraoperative radiation therapy (IORT) and external beam radiation therapy (EBRT) in non-small cell lung cancer (NSCLC). Five years experience.

A pilot study on intraoperative radiation therapy (IORT) combined with external beam radiation therapy (EBRT) in nonresectable non-small cell lung cancer (NSCLC) was performed in 31 patients (mean age: 66.2 years, range: 51-80; 10 anatomically and functionally, 21 functionally, nonresectable; 20 squamous-cell, 11 adenocarcinoma). The tumor was exposed by lateral thoracotomy and a staging lymph node dissection was performed (final staging 7 T1, 16 T2, 8 T3; 11 nodal positive). Ten to 20 Gy IORT (energy: 7-20 MeV electrons) were delivered to the tumor. Unilateral continuous positive airway pressure ventilation of the diseased lung was used to reduce the amount of healthy lung tissue in the IORT port and to minimize the ventilatory movement. Secondary collimation and direct shielding of radio-sensitive structures within the IORT port by aluminium sheets were used to further reduce collateral damage. Four weeks after IORT, 46 Gy EBRT (2 Gy/day 5 times a week; 8-23 MeV photons) were administered to the mediastinum and to the tumor-bearing area on an outpatient basis. In nodal positive cases the mediastinal dose was increased to 56 Gy. Twenty-three patients were evaluable. In 13 complete, in 8 partial (50-97% regression) and in 2 minor response has been achieved. Five patients experienced a recurrence (local only: 2; local and distant: 1; distant only: 2). Twelve patients died of underlying cardio-respiratory disorders within 6 to 25 months after IORT; 7 died of cancer. The overall 5-year survival rate including the incidental deaths is 14.7%. The recurrence-free survival rate is 53.2%.