5-Aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging.

BACKGROUND: 5-Aminolevulinic acid is used for fluorescence-guided resections. During resection, different macroscopic fluorescence qualities ("strong," "weak") can be distinguished that help guide resections. OBJECTIVE: This prospective study was designed to assess the reliability of visible fluorescence qualities by spectrometry, pathology, and imaging. METHODS: Thirty-three patients with malignant gliomas received 5-aminolevulinic acid (20 mg/kg). After debulking surgery, standardized biopsies were obtained from tissues with "weak" and "strong" fluorescence and from nonfluorescing near and distant brain for blinded assessment of cell density and tissue type (necrosis, solid or infiltrating tumor, normal tissue). The positive predictive value was calculated. Unresected fluorescing tissue was navigated for blinded correlation to postoperative magnetic resonance imaging (MRI). Receiver operating characteristic curves were generated for assessing the classification efficiency of spectrometry. RESULTS: "Strong" fluorescence corresponded to greater spectrometric fluorescence, solidly proliferating tumor, and high cell densities, whereas "weak" fluorescence corresponded to lower spectrometric fluorescence, infiltrating tumor, and medium cell densities. The positive predictive value was 100% in strongly fluorescing tissue and 95% in weakly fluorescing tissue. Spectrometric fluorescence was detected in marginal tissue without macroscopic fluorescence. Depending on the threshold, spectrometry displayed greater sensitivity but lower specificity (accuracy 88.4%). Residual MRI enhancement in the tumor bed was detected in 15 of 23 (65%) patients with residual fluorescence, but in none of the patients without residual fluorescence. CONCLUSION: Macroscopic fluorescence qualities predict solid and infiltrating tumor, providing useful information during resection. Fluorescence appears superior to contrast enhancement on MRI for indicating residual tumor. Spectrometry, on the other hand, is more sensitive but less specific, depending on threshold definition. ABBREVIATIONS: 5-ALA, 5-aminolevulinic acidCI, confidence intervalgamma-GT, gamma-glutamyl transpeptidaseGBM, glioblastoma multiformeNPV, negative predictive valuePPIX, protoporphyrin IXPPV, positive predictive valueSD, standard deviationWHO, World Health Organization.

Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery--a feasibility study.

OBJECTIVE: In glioma surgery, the extent of resection (EOR) is one important predictor of progression-free survival. In 2006, fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) was shown to improve the EOR in malignant gliomas. However, the use of 5-ALA is complex and causes certain side effects. Sodium fluorescein (FL) is a fluorescent dye that is used for angiography in ophthalmic surgery. FL accumulates in areas of the disturbed blood-brain barrier and can be visualized under a 560-nm wavelength fluorescent light source (YELLOW 560 nm, Carl Zeiss Meditec, Oberkochen, Germany). Here, we present the first experiences with low-dose FL and YELLOW 560 nm in 35 patients with malignant brain tumors. PATIENTS AND METHOD: A total of 200 mg of FL (3-4 mg/kg bodyweight) was administered in 35 patients during craniotomy as an off-label use between May and August 2012. We retrospectively analyzed the histology, pre-treatment, clinical parameters pre- and postoperatively and occurrence of any adverse effects. The feasibility and efficacy ('helpful,' 'not helpful') of FL under YELLOW 560 nm (demarcation of the tumor margin) was assessed by the responsible neurosurgeon (n = 5) for each surgical procedure. RESULTS: Twenty-six patients had gliomas (1 WHO grade I, 3 WHO grade II, 5 WHO grade III, 17 WHO grade IV), 5 patients had cerebral metastases, 2 had non-malignant astrogliosis and 2 had post-radiation necrosis. The fluorescence signal was detected in all patients immediately after the FL administration. FL application was classified as 'helpful' in 28 patients, implying improved visualization of the tumor margins. The intensity of the fluorescence signal seemed to be correlated to the histology and was strongly dependent on the pre-treatment status. We did not record any allergic reactions or any other adverse effects. CONCLUSION: The use of FL for the resection of brain tumors is safe and feasible. Presumably, the visualization of the tumor margin depends on the histopathology and on the pre-treatment status. A randomized evaluation of FL under the YELLOW 560 nm filter is planned to prospectively analyze the extent of resection in patients with malignant brain tumors.

Recurrent brain metastases from lung cancer: the impact of reoperation.

OBJECTIVE: The best treatment for solitary brain metastases from lung cancer is surgical resection followed by adjuvant treatment. However, about 50% of these patients develop recurrent brain metastases. There is no established treatment standard for this patient group. We therefore analyzed the survival, neurological function, and overall performance status of patients with recurrent solitary brain metastases from lung cancer after second microsurgical resection. MATERIALS AND METHODS: Treatment outcome was analyzed in 25 patients (19 men, 6 women) with a mean age of 55.8 years (range, 38-78 years) who received a resection of recurrent solitary brain metastases. Eighty-four percent of all patients had non-small-cell lung cancer and 16% small cell lung cancer (SCLC). Eighty percent of the lesions were located supratentorially, 20% infratentorially. RESULTS: The median overall survival after initial diagnosis was 26.9 months, 13.6 months after the first and 8.3 months after the second brain surgery, respectively. The median Karnofsky index improved significantly from 80 to 100 after the second brain surgery; 66.6% of all patients presenting with neurological impairment improved, and 50% regained normal function. No surgery-related morbidity or mortality was noted. Multivariate analysis indicated that the interval until first brain metastasis and between first and recurrent metastases was significantly predictive of survival. CONCLUSIONS: The majority of patients in our study group showed significant functional benefit from surgical resection of recurrent brain metastases. This contributes to a better quality of life in this patient group showing a short overall survival time.

[Reversible metabolic syndrome]. / Reversibles metabolisches Syndrom hormoneller Ursache.

A 52-year-old male patient was admitted to the emergency department with dyspnea and hypertensive urgency. During the previous 6 months, the patient had noticed leg edema, weight gain (particularly in the face and abdomen), and impotence. 1.5 years ago, he was diagnosed with hypertension resistant to medication. After an accident at work 1 year ago, osteoporosis was diagnosed with vertebral and rib fractures. Measurement of sleeping midnight salivary cortisol levels together with 24-h urine free cortisol excretion and an overnight low-dose 1-mg dexamethasone suppression test proved overt hypercortisolism. The high-dose 8-mg dexamethasone suppression suggested an adrenal or ectopic source of hypercortisolism. By contrast, elevated adreno-corticotropic hormone (ACTH) levels and a corticotropin-releasing hormone stimulation test gave evidence for a pituitary source of hypercortisolism. However, pituitary magnetic resonance imaging failed to reveal a pituitary adenoma. Moreover, computed tomography scans of thorax and abdomen were negative. In this situation, an inferior petrosal vein sampling was performed and revealed an ACTH gradient (central-systemic) >3 with lateralization to the right side. The patient underwent a selective, partial, transsphenoidal resection and was cured from clinical signs and symptoms caused by hypercortisolism. Subsequent hormonal replacement therapy of postoperative pituitary insufficiency was necessary.