Preoperative routine evaluation of bilateral adrenal glands by endoscopic ultrasound and fine-needle aspiration in patients with potentially resectable lung cancer.

BACKGROUND AND STUDY AIMS: The aim of the current study was to assess the detection rate of the right adrenal gland and the diagnostic ability of endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) for the diagnosis of adrenal metastasis in potentially resectable lung cancer. PATIENTS AND METHODS: This retrospective cohort study included a consecutive series of 150 patients undergoing EUS/EUS - FNA for staging of lung cancer. The detection rate of the right adrenal gland by EUS and the diagnostic accuracies of computed tomography (CT), positron emission tomography-CT (PET-CT), and EUS/EUS - FNA for the diagnosis of adrenal metastasis were evaluated. RESULTS: The right adrenal gland was visualized by EUS in 131 patients (87.3 %); the left adrenal gland was visualized in all patients. Findings suggestive of metastasis in either one of the adrenal glands or in both were observed in 6 patients (4.0 %) by CT, in 5 patients (3.3 %) by PET-CT, and in 11 patients (7.3 %) by EUS. EUS - FNA was performed simultaneously in the 11 patients, and in 4 patients the diagnosis of metastasis was established. The accuracy for the diagnosis of adrenal metastasis was 100 % for EUS/EUS - FNA, 96.0 % for CT, and 97.0 % for PET-CT (P = 0.1146). CONCLUSIONS: As well as the left adrenal gland, the right adrenal gland was also usually visible by EUS. EUS/EUS - FNA provided an accurate diagnosis of adrenal metastasis, although the prevalence of adrenal metastasis was relatively low in these patients with potentially resectable lung cancer.

Combined endobronchial and endoscopic ultrasound-guided fine needle aspiration for mediastinal nodal staging of lung cancer.

BACKGROUND: Recently, transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been evaluated for mediastinal nodal staging (N staging) of lung cancer, as this technique is less invasive than mediastinoscopy and possibly more accurate than 18F-fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT). However, EUS-FNA does not provide access to pretracheal and hilar lymph nodes. More recently, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been introduced as a novel technique for accessing pretracheal and hilar lymph nodes. Although the combined endoscopic approach of EUS-FNA and EBUS-TBNA is presumably more accurate than PET-CT, only a few reports have quantitatively evaluated its diagnostic ability. Therefore, we prospectively assessed the diagnostic yield of this combined endoscopic approach for mediastinal N staging of lung cancer. METHODS: A consecutive series of 120 patients with suspected resectable lung cancer on CT findings underwent PET-CT and combined EUS-FNA/EBUS-TBNA. The accuracy and other diagnostic indices of the combined approach in mediastinal N staging were compared with those of PET-CT. RESULTS: Among the enrolled patients, a final pathological N stage was established in 110 patients. The accuracy of the combined approach using EUS-FNA and EBUS-TBNA was significantly higher than that of PET-CT (90.0 % vs. 73.6 %; P < 0.0001). The sensitivity, specificity, and positive and negative predictive values were respectively 71.8 %, 100 %, 100 %, and 86.6 % for the combined approach vs. 47.4 %, 87.5 %, 66.7 %, and 75.9 % for PET-CT. CONCLUSIONS: The combined endoscopic approach using EUS-FNA and EBUS-TBNA provided excellent diagnostic performance. Therefore, this approach is strongly recommended before surgery or mediastinoscopy to avoid futile thoracotomy and surgical intervention.

Effect of polyamines on mitochondrial F1-ATPase catalyzed reactions.

The effect of polyamines on F1-ATPase catalyzed reactions has been studied through the use of submitochondrial particles and F1-ATPase. ATP degradation catalyzed by submitochondrial particles and F1-ATPase was inhibited by spermine and spermidine. Spermine's inhibition was much greater than spermidine's effect. In contrast, P1-ATP exchange and succinate dependent ATP synthesis catalyzed by submitochondrial particles were both stimulated by spermine. The inhibition of ATPase activity by polyamines probably occurs through polyamine's replacement of Mg2+ on ATP, for the following reasons. (a) The ATPase activity inhibited by spermine was partially recovered when Mg2+ was added. (b) Spermine bound to ATP and phospholipids but not to F1-ATPase; yet spermine inhibited the ATPase reaction catalyzed by F1-ATPase, a protein free of phospholipid. (c) The binding of spermine to ATP was inhibited by Mg2+. The ATP content in polyamine-deficient cells definitely was lower than that in normal cells. On the basis of these results, the possible role of spermine in keeping the ATP concentration at a high level is discussed.

[Immunohistochemical study of S-100 protein in the normal human brain and glioblastoma].

The authors investigated the immunohistochemical localization of S-100 protein in normal human brain and glioblastoma tissues by the peroxidase anti-peroxidase method of Sternberger. In normal human brain the positive immunoperoxidase reaction for S-100 protein was observed in astrocytes, oligodendrocytes, ependymal cells, Bergmann's glial cells and epithelial cells of choroid plexus. No positive staining was revealed in any cortical neurons. Immunoelectron-microscopically, the electron dense positive reaction for S-100 protein was seen throughout the cytoplasm, nucleoplasm and cell processes of astrocyte as well as oligodendrocyte. The positive reaction for S-100 protein was demonstrated occasionally in association with cytoplasmic membrane or the membrane constituting cell organelles. We suspect that this observation indicates the existence of membrane-bound form of S-100 protein. In glioblastoma cells, the positive reaction for S-100 protein was relatively weak in intensity as compared with astrocytes, and the degree of positive staining varied from cell to cell. Subcellular localization of S-100 protein in glioblastoma seemed to be essentially similar to that of normal astrocyte. There are some recent reports concerning immunohistochemical localization of alpha and beta subunits of S-100 protein. As compared with these reports, the present immunohistochemical results indicate that the rabbit anti-S-100 antibody embloyed in the present study is mainly against beta subunit of S-100 protein. Although there have been many reports concerning immunohistochemical localization of S-100 protein, the biological role of S-100 protein is still speculative. Some hypotheses are advocated in connection with the possible biological role of S-100 protein. For example, the modulation of synaptic transmission by S-100 protein, the participation of S-100 protein in hormonal secretion and in transport of cations through lipid membrane, the activation of protein kinase and the promotion of disassembly of microtubules by S-100 protein are postulated. It is hard to assume the biological role of S-100 protein based on the immunohistochemical results alone. The present study clearly indicates that S-100 protein exists widely in the cytoplasm, nucleoplasm, cytoplasmic membrane, outer membranes of cell organelles and cell processes of glial cells as well as glioblastoma cells. From these results we assume that S-100 protein plays an important role of intracellular transport of cations as one of the calcium binding proteins.

Methylglyoxal bis(guanylhydrazone) elimination of polyamine effects on protein synthesis.

The effect of methylglyoxal bis(guanylhydrazone) (MGBG), a structural analog of polyamines, on protein synthesis has been studied in the presence and absence of spermidine. The spermidine stimulation of polyphenylalanine- and MS2 RNA-directed RNA replicase synthesis in an Escherichia coli cell-free system and of globin synthesis in a rabbit reticulocyte cell-free system disappeared with the addition of MGBG. The spermidine reduction of misincorporation of leucine during polyphenylalanine synthesis in both E. coli and wheat germ cell-free systems was also disturbed by MGBG. MGBG noncompetitively interfered with polyamine stimulation of polyphenylalanine and globin synthesis, suggesting that MGBG could bind to both RNA and the complex of RNA and polyamine. MGBG was preferentially bound to ribosomal RNA among ribosomal RNA, poly(U), and calf thymus DNA, and strongly inhibited the amount of polyamine bound to ribosomal RNA. These results suggest that MGBG elimination of polyamine effects on protein synthesis may occur through the disturbance of polyamine binding to ribosomal RNA.

Primary central nervous system lymphoma.

A retrospective analysis of 21 cases of primary central nervous system (CNS) lymphoma is reported. All patients presented with a solitary mass in the supratentorial region. None had previously received immunosuppressive therapy. Neuroradiological studies included technetium-99m-pertechnetate brain scanning in eight cases, cerebral arteriography in all 21 cases, and computerized tomography (CT) in 14 cases. The characteristic features were increased uptake in brain scans, mass effect in arteriograms, and marked contrast enhancement on CT scans. Abnormal tumor vessels were occasionally seen on arteriography, and subtraction films were usually required to appreciate tumor stain. All patients underwent craniotomy, and histological studies of the tumors showed a diffuse type of lymphoma in all cases. Immunoglobulin testing was performed in 19 cases and a monoclonal spike was verified in 10, suggesting a B cell origin. All patients were followed until their death except one who was still alive 12 months from onset of symptoms. Therapy included subtotal resection in all 21 cases, whole-brain irradiation in six cases, chemotherapy in two cases, and a combination of whole-brain irradiation and chemotherapy in nine cases. Three different forms of chemotherapy were used. The results suggest that chemotherapy is an important addition to subtotal resection and whole-brain irradiation in the treatment of primary CNS lymphoma.

[Changes of the DNA synthesis and the amount of S-100 protein associated with the morphological differentiation of cultured glioma cells].

S-100 protein is a highly acidic protein unique to the nervous system and exists predominantly in the cytoplasm of glial cells in a water-soluble form. The exact biological function is still unknown in spite of its well-known biochemical properties. Some investigators have reported that the amount of S-100 protein in developing brains increased in proportion to the brain's development and differentiation. In order to clarify the relationship between S-100 protein and differentiation of glial cells the changes of DNA synthesis and the amount of the water-soluble S-100 protein were investigated on cultured rat glioma (C-6) cells in the course of the morphological differentiation induced by dibutyryl cyclic AMP (dbc-AMP). C-6 cells were cultured in Eagle's minimum essential medium supplemented with 10% fetal calf serum and incubated in a humidified atmosphere of 5% CO2-95% room air at 37 degrees C. Dbc-AMP was added to the media at the concentration of 1 mM, and the media were changed every 48 hrs. A flow cytometric analysis of DNA histogram patterns was performed to investigate the changes of DNA synthesis using a Cytofluorograf FC 4800 A-50 (Bio/Physics). The changes of the amount of S-100 protein were examined by micro-complement fixation assay as described by Levine using rabbit antisera against bovine S-100 protein. Dbc-AMP inhibited the growth of C-6 cells remarkably and induced morphological changes resembling normal astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of ACNU, a water-soluble nitrosourea, on cell cycle of cultured glioma cells--flow cytometric analysis].

Cytotoxic and cytokinetic effects of 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl) 3-nitrosourea hydrochloride (ACNU) on cultured rat and human glioma cells (C-6 and KC) were studied in vitro. Exponentially growing culture cells were exposed to ACNU at the final concentrations of 5 micrograms/ml, 20 micrograms/ml, and 80 micrograms/ml, respectively. The cytotoxic effect was evaluated by inhibition of cell growth and the cytokinetic effect was analyzed by DNA histogram using a flow cytometer. Inhibition of cell growth was dose-dependent in ACNU and C-6 cells were more resistant than KC cells. The growth of C-6 and KC cells were not inhibited at all by low concentrations of ACNU (5 micrograms/ml, 20 micrograms/ml), however, at these concentrations a marked accumulation of treated cells in S and G2+ M phases was evident. The accumulation in S and G2+M phases was dose-dependent and it was more prominent in KC than C-6 cells. ACNU-treated cells accumulated initially in S phase and then in G2+M phase. After maximum accumulation in G2+M phase, the cells seemed to be released into G1 or G0 phase. These results indicate that the cytokinetic effect of ACNU (5 micrograms/ml, 20 micrograms/ml) is more conspicuous than the cytotoxic effect on C-6 and KC cells.

Quick gas chromatographic method for measuring the water content of brain tissue: with reference to age-related changes of rat neocortex.

A quick and accurate method for estimating tissue water content by gas chromatography was developed. Age-related changes in tissue water content in the neocortex of rat brain were easily determined by this method.

S-100 protein in human glial tumours. Qualitative and quantitative studies.

The authors studied a total of 48 human glial tumours for S-100 protein, an extremely acidic, protein specific to the nervous system, by immunohistochemistry and by micro-complement fixation assay in order to evaluate S-100 protein as an index for malignancy of glial tumours. All of 48 glial tumours analyzed in the present study demonstrated variable amounts of S-100 protein which might serve as a biochemical cell marker for glial tumours. The mean value of S-100 protein content in 3 ependymomas is higher than those of 19 low-grade (grades I, II) astrocytomas and 26 high-grade (grades III, IV) astrocytomas, being lowest in the latter. A statistically significant (P less than 0.001) difference in S-100 protein levels between low- and high-grade astrocytomas is observed, but not for ependymoma. At present, however, no correlation can be found between S-100 protein content of a tumor and the patient's survival time. Immunoperoxidase staining for S-100 protein in high-grade astrocytomas is generally weak in intensity and heterogeneous throughout the section, whereas that in low-grade astrocytomas and ependymomas is relatively strong and homogeneous, indicating that high-grade astrocytomas consist of a more heterogeneous population of tumour cells in terms of S-100 protein. These results show that the investigation of S-100 protein in a glial tumor is valuable to a certain extent in assessing the degree of differentiation or malignancy of the tumour.

Endoscopic retrograde pancreatic parenchymography.

Endoscopic retrograde pancreatic parenchymography was performed using the technique of endoscopic retrograde cholangiopancreatography. Contrast material was prepared from a nonionic surfactant combined with either sodium iothalamate or sodium and meglumine diatrizoate. With this method, a smooth contour of the pancreas and homogeneous pattern of the parenchyma were shown in the normal pancreas, while an irregular contour of the pancreas, unhomogeneous pattern of the parenchyma, and diminution of the area of the pancreas were found in chronic pancreatitis. In pancreatic carcinoma, a filling defect of the pancreatic field was seen. In the 186 cases studied, the only complication observed was a transient rise in serum amylase level.