5-aminolevulinic acid induced protoporphyrin IX fluorescence in high-grade glioma surgery: a one-year experience at a single institutuion.

OBJECTIVE: Among the factors determining prognosis in patients with malignant glioma, the extent of resection has long been controversial. However, recent data have shown that patients derive a survival benefit from extensive tumour resection. 5-aminolaevulinic acid (5-ALA)-induced fluorescence renders more complete resection possible in malignant glioma. We report on the feasibility of the method in daily clinical practice, the benefits for patients and surgeons, the technical limitations and the methods we have devised of overcoming these limitations. METHODS: We describe our initial experience in 74 cases undergoing gross total resection, partial resection and biopsy. Fluorescence intensity and histological data are analysed, specificity and sensitivity are calculated according to fluorescence intensity, and the pitfalls and limitations are defined. The fluorescence signal was quantified via digital video data and by single photon count. RESULTS: Solid fluorescence signals define tumours with a sensitivity of 0.98 and a specificity of 1.0. Vague fluorescence reduces sensitivity to 0.76 and specificity to 0.85. Limitations of 5-ALAassisted surgery are apparent within the inter-observer interpretation of solid or vague fluorescence, heterogeneity of gliomas, invasion beyond the resection cavity and intercell heterogeneity of porphyrin IX fluorescence. CONCLUSION: 5-ALA-induced PIX fluorescence improves the results in high-grade glioma surgery for gross total resection. Specificity and sensitivity in regions of solid fluorescence are very high. Quantitative analysis of fluorescence intensity corrects the reduced reliability of the method in areas of vague fluorescence and renders gross total resection more feasible without additional risk to the patient. PIX fluorescence is easy to implement in daily neurosurgical practice and side effects are very few. Heterogeneous tumours with lower grade elements and satellite lesions cannot be reliably resected using fluorescence-assisted surgery alone. In these cases the additional use of intra-operatively updated imaging-based neuronavigational methods (MR, ultrasound) is needed.

Age at diagnosis and loss of heterozygosity on chromosome 1p and 19q in oligodendroglial tumors.

The age distribution and incidence of loss of heterozygosity (LOH) of 1p and 19q was analyzed in 85 oligodendroglial tumors WHO II and III. The peak of tumor manifestation was in the age group of 35 to 55 years. There was no association between age at diagnosis and LOH incidence. We conclude that the prognostic effect of age on survival is not mediated by LOH 1p/19q.

The pituitary in klinefelter syndrome.

BACKGROUND: Klinefelter syndrome is a genetically determined primary gonadal defect characterized by the XXY karyotype. The testes are small, blood testosterone levels are low, and blood gonadotropin levels are elevated. Pituitary changes in patients with Klinefelter syndrome have not been evaluated in detail. DESIGN: The first patient, a 76-yr-old man, was operated for a large sellar mass. The second and third patients, a 62- and a 52-yr-old man, respectively, died of cardiac failure. Both the latter pituitaries were normal-sized and removed at autopsy. The diagnosis of Klinefelter syndrome was confirmed by genetic testing in all three cases. The formalin-fixed and paraffin-embedded pituitaries of three patients were evaluated for adenohypophysial hormone immunoreactivity. For immunohistochemistry, the streptavidin- biotin-peroxidase (ABC) complex method was applied. RESULTS: In case 1, histology and immunohistochemistry revealed an oncocytic gonadotroph macroadenoma immunoreactive for FSH and alpha subunit. No pituitary gland was evident. The pituitary of case 2 featured hyperplasia of gonadotrophs, some with features of "gonadal deficiency cells," and a microadenoma immunoreactive for GH. The pituitary of case 3 similarly showed hyperplasia of gonadotrophs and the formation of gonadal deficiency cells. CONCLUSION: Protracted stimulation of gonadotrophs due to lack of androgen feedback might have been a factor in the formation of the gonadotroph adenoma in case 1 and in the development of gonadotroph hyperplasia in cases 2 and 3. The clinically silent GH microadenoma of case 2 was regarded as an incidental finding.

Prostate cancer screening: results of a prospective trial in Canton Aargau, Switzerland.

INTRODUCTION: Prostate cancer is the most commonly diagnosed cancer in Swiss men and the second leading cause of cancer related death among them (e.g. CH: 1,267 in year 1998). With the population at risk constantly growing these absolute numbers are expected to further increase. While there is no question that aggressive treatment of localised tumour is required for definitive cure of prostate cancer, the application of screening for early stage disease remains controversial. Since 1998 the Clinic of Urology in Kantonsspital Aarau has participated in the ERSPC (European Randomised Study of Screening for Prostate Cancer) study, which is designed to provide data on prostate cancer screening within a prospective randomised controlled setting. METHODS: Men aged between 55 and 70 years were enrolled in the study. From n = 18,361 men invited by a letter to participate, 7,124 (38.8%) agreed and gave their informed consent to be randomised in either a PSA measurement (n = 3,562, group 1) or a control group (n = 3,562, group 2). Men in group 1 with a PSA level ?3.0 ng/ml, n = 372 (10.5%) then underwent ultrasound guided transrectal sextant biopsy of the prostate. RESULTS: Prostate cancer was detected at presentation in every fourth man biopsied (n = 89). Neither the free-to-total PSA ratio nor the PSA density could significantly spare biopsies while sustaining a high sensitivity level. The overall cancer detection rate amounted to 2.5% in PSA tested men. In 7% (n = 5) distant disease was already present. 93% of men with clinically organ confined disease underwent prostatectomy (n = 59) or radiotherapy (n = 22), whilst only (n = 3) chose to follow a policy of watchful waiting. In 92% the histology of the prostatectomy specimens revealed aggressive cancer characteristics according to the criteria of Epstein et al. CONCLUSIONS: Although the clinically relevant tumour characteristics and the relatively low cancer detection rate of 2.5% (less than the lifetime mortality risk of 3% and the morbidity risk of 8%) seem to justify screening in terms of adequate diagnosis and treatment, follow-up until 2008 is needed to prove the benefit in mortality for the prostate cancer screening group over the control group. Furthermore, information from the ongoing ERSPC study is needed in order to assess uncertainties i.e. the degree of overdiagnosis caused by repeated screening and the quality of life adjusted gain in life years. For daily practice a "PSA grey zone" of 4-10 ng/ml can no longer be postulated as only 70% of men in this range presented with organ confined disease. Once the PSA level exceeds 4.0 ng/ml. prostate biopsy should be performed immediately.

Lipomatous meningioma: a clinicopathologic study of 18 cases with special reference to the issue of metaplasia.

We report 18 cases of lipomatous meningioma occurring in patients aged 14 to 79, most being females (72%). Sixteen were supratentorial and 2 involved the spinal meninges. Follow-up ranged from 1 to 120 months. Fifteen patients were cured with surgery alone and 3 (17%) experienced a recurrence at 7, 8 and 24 months. Of these, one died with disease 4 years after resection of the primary lesion. Histologically, 12 tumors were meningothelial, 3 transitional, 2 showed myxoid stromal changes and 1 was microcystic. The 2 spinal tumors were atypical. The proportion of fatty cells ranged from 10 to 90%. These resembled mature adipocytes or less commonly lipoblasts. Xanthomatous meningothelial cells were also noted in 6 tumors (30%). Both conventional meningothelial as well as lipid-laden cells exhibited epithelial membrane antigen immunoreactivity. In addition, occasional cells resembling mature adipocytes showed reactivity for S-100 protein. Ultrastructurally, lipidization of neoplastic cells varied from intracytoplasmic lipid droplets to a single massive globule. Moreover, lipid-laden meningothelial cells featured interdigitating cell membranes and well-formed desmosomes. Lipid droplets were not membrane-bound. In that metaplasia denotes differentiation of one mature cell type to another, lipid accumulation in meningiomas cannot be considered true metaplasia since their lipid-laden cells retain the immunophenotype and ultrastructural features of meningothelium. We suggest that this distinctive subset of meningiomas be termed "lipidized meningiomas" rather than being included in the metaplastic category.

[Large Brunner's adenoma of the duodenal bulb--a case report]. / Grosses Brunner'sches Adenom im Bulbus duodeni--Ein Fallbericht.

Benign proliferative changes of the Brunner's glands account for about 10% of neoplasias of the duodenal bulb. Since the first description by Cruveilhier in 1835 about 120 cases have been reported in the English literature. The authors present a case of adenoma of Brunner's gland of unusual dimensions (10 x 5.5 x 2.8 cm). Clinical presentation was by melena, anemia and vague epigastric discomfort. Treatment was by laparotomy with duodenotomy and surgical polypectomy. Proliferative changes of Brunner's glands may manifest as diffuse or localized nodular hyperplasia and Brunner's adenoma. They are localized in the submucosa and small superficial endoscopic biopsies may fail to confirm the diagnosis. Malignancy seems to occur only very rarely with only 14 cases reported in the literature. As the majority of Brunner's adenomas are quite small, endoscopic polypectomy will confirm the diagnosis and cure the condition in most instances. Large symptomatic adenomas may require surgical resection.

Morphometric analysis of fetal rat lung development.

Applying the zone concept described previously, we quantitatively analyzed fetal rat lung development. The zone concept allowed us to coherently define reference spaces in the developing lung, a prerequisite for morphometric analysis. The peripheral zone I corresponds to a zone of growth of yet undifferentiated tissues; zone II arises from zone I and represents a region of structural and cellular differentiation; zones III and IV comprise the conducting airways and vessels. Lungs of fetal rats aged 17-23 days and 20 hours postnatal were fixed with OsO4 and glutaraldehyde and processed for light and electron microscopic morphometry implemented by point and intersection counting. Fetal lung volume grew in proportion to body weight. Zone II being the largest compartment, its volume changes largely determined lung growth rates. Zone II increased in mass owing to differentiation processes at the interface to zone I where the proximal portions of zone I were continuously shifted into zone II by differentiation. New tissue was generated within zone I. Due to these combined processes zone I changed little in volume until it disappeared at the end of the canalicular stage. The presence in the pseudoglandular stage of half of the parenchymal epithelial mass available around birth indicated that parenchymal development started earlier than assumed so far. While the endothelial surface increased most at birth, the epithelial surface grew by more than 600% at day 21, reflecting the onset of canalisation. The study confirmed the usefulness of the zone concept for morphometry and provided some new insights into lung development.

Structural analysis of fetal rat lung development.

The primary aim of this morphological investigation was to elaborate a concept allowing us to coherently define reference spaces for morphometric analysis of fetal lung development. Beyond this quantitative goal, morphological analysis of cell types, definition of compartments, and reflection about the prospective fate of their constituents provided per se new insights into the developmental processes. Lungs of rat fetuses aged 17-23 days and newborns aged 20 hours were fixed with an osmium tetroxide and glutaraldehyde mixture and their volume determined. Left lungs were embedded in Epon and investigated by light and electron microscopy. The right lung of one animal per group was embedded in methacrylate and step sections obtained to precisely locate the airways within the mesenchyme. The various cell types, their topographical relationships, and their morphological alterations with ongoing development were analyzed with regard to their prospective potentials of differentiation. The developing lung could be partitioned into four zones further subdivided into defined compartments. Zone I forms a superficial mantle around the lobes and the future acini. Consisting of primitive mesenchymal cells, it represents a zone of growth which disappears with the onset of the saccular stage. Zone II is mainly a zone of differentiation. Its interstitium stains intensely due to a dense population of dark cells. Up to gestational day 19, zone II contains future conductive airways with their vessels. After day 21, it comprises the whole prospective gas exchange region. Zones III and IV contain the elements of the airway tree and vascular system, zone IV corresponding to the most proximal generations with an adventitial layer. For all differentiation processes, a centrifugal directionality is manifested.