The use of the monoclonal antibody Ki-67 in the identification of proliferating cells: application to surgical neuropathology

In order to test its potential application to surgical neuropathology, the monoclonal antibody Ki-67 was used to demonstrate immunohistochemically the proliferating cells in 40 neoplasms of the nervous system. The antibody, which reacts with a nuclear protein expressed in the G1, G2, S, and M phases of the cell cycle, was demonstrated in frozen sections of all lesions. The highest incidence of stained nuclei was found in a metastatic carcinoma (57%). The percentage of stained cells in gliomas was in general agreement with the histologic grade and known biologic behavior of the lesions, ranging from 0.6% in a pilocytic astrocytoma to 12.4% in a glioblastoma multiforme. In the fibrillary astrocytic neoplasms of low cellularity, there were good correlations between the percentages of stained cells and the degrees of nuclear pleomorphism and chromatin density. In meningiomas, schwannomas, and a cerebellar hemangioblastoma, the fractions of labeled nuclei were less than 1%. The percentage of stained cells in pituitary adenomas showed considerable variation among the four cases (0.2-1.5%), the biologic significance of which is unknown. In four of the above cases, Ki-67 staining was performed on air-dried squash preparations with excellent visualization of immunoreactive nuclei. In one case, a hemangioblastoma, no stained nuclei were seen. The results confirm that Ki-67 staining is technically suitable as a diagnostic method, with good correlations between frozen sections and smear preparations. Determination of the replicating cell fraction could become an important additional criterion to predict the biologic behavior of nervous system neoplasms.     

Impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas: a single-institution retrospective study.

Neuronavigation has become an effective therapeutic modality and is used routinely for intra-axial tumor removal. This retrospective study was conducted to evaluate the clinical impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas. Between 1990 and 2002, 76 adult patients with pathologically confirmed malignant astrocytomas underwent craniotomy and removal of the tumors at the Toyama Medical and Pharmaceutical University Hospital. Of these 76 patients, 42 were treated using neuronavigation with conventional microneurosurgery and the other 34 were treated with conventional microneurosurgery alone. Postoperative early MRI with contrast enhancement was done, and gross total resection was defined as the complete absence of residual tumor. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. In univariate analysis, age (< 65), grade 3, preoperative KPS (>/= 80), use of neuronavigation, and gross total resection were significantly associated with longer survival. However, when the data were submitted to multivariate analysis, grade 3, preoperative KPS (>/= 80), and gross total resection were independent prognostic factors. The median survival periods of patients receiving gross total resection (vs. partial resection) and neuronavigation (vs. no neuronavigation) were 16 (vs. 9) months and 16 (vs. 10) months, respectively. The percentage of a gross total resection was significantly higher in the neuronavigation group compared to that in the no-navigation group (64.3 % vs. 38.2 %, p < 0.05). Neurological deterioration occurred in 4 of 42 (9.5 %) and in 6 of 34 (17.6 %) patients after surgery with neuronavigation and surgery without neuronavigation, respectively, although this difference was not statistically significant. Our results showed that neuronavigation increases the radicality in the resection of malignant astrocytomas and is objectively useful for improving survival time.     

Heart rate elevation precedes the development of metabolic syndrome in Japanese men: a prospective study.

This observational study of Japanese men without metabolic syndrome (MetS) (age: 41+/-8 years) was conducted to clarify whether or not heart rate elevation precedes the development of full-blown MetS. MetS was defined based on two modifications of the criteria of the Japanese Expert Committee on the Diagnosis and Classification of Metabolic Syndrome. Premetabolic syndrome subjects were defined as those having one component of MetS with increased body mass index (BMI). Among the subjects without MetS (n=1,859 when the BMI criterion was >or=25 and n=2,020 when the BMI criterion was >or=27.5), the incidence of progression to full-blown MetS by the time of the second examination at the end of the 3-year study period was higher in the subjects with premetabolic syndrome than in those without it. The receiver-operator characteristic curve analysis and binary logistic regression analysis revealed that the odds ratio (OR) of a heart rate >or=69 beats/min at the first examination for progression to full-blown MetS by the time of the second examination was significant in subjects with premetabolic syndrome (BMI>or=25: OR=3.64 [1.22-10.88]; BMI>or=27.5: OR=3.67 [1.28-10.55]; p<0.05). Thus, heart rate elevation appears to precede the development of full-blown MetS in subjects with premetabolic syndrome. Heart rate seems to be a simple and useful marker for predicting the progression to full-blown MetS of middle-aged Japanese men with premetabolic syndrome.     

Ultrastructure of capillary permeability in human brain tumor: primary meningeal malignant melanoma

The tumor vessels of a primary meningeal malignant melanoma were studied by electron microscopy. There were numerous endothelial fenestrae and basal lamina abnormalities in the intrinsic tumor capillaries. They resembled the tumor vessels found in nonglial tumors, but were distinctly different from those seen in glial tumors with nonfenestrated capillaries. These findings were anticipated because leptomeninges have fenestrated capillaries.     

Factor VIII lability, protein C and other vitamin K-dependent proteins

The stability of factor VIII was studied in plasmas from patients on long-term warfarin therapy. The percent residual factor VIII activity (F.VIII:C) after incubation at 37 degrees C for 4 hr was higher in warfarinized patients than in normal subjects; 76.9 +/- 10.8% (mean +/- SD) of the initial F.VIII:C in the patients versus 61.6 +/- 5.8% in normal subjects (p less than 0.001). On the whole, neither protein C nor vitamin K-dependent coagulation factors except factor VII activity (F.VII:C) correlated with the residual F.VIII:C. There was a negative and weak correlation between the residual F.VIII:C at 4 hr and either the initial F.VIII:C or F.VII:C. Another experiment using protein C depleted plasma showed a relatively enhanced stability of F.VIII:C in the protein C deficiency. These results indicate that factor VIII is more stable in warfarinized plasma, and that protein C and vitamin K-dependent coagulation factors are not the sole, main factor responsible for such a phenomenon.     

Comparative promoting activities of phosphate salts on rat two-stage bladder carcinogenesis under conditions of equivalent urinary Na+ or K+ levels.

Promoting effects of Na or K phosphate salts on rat two-stage bladder carcinogenesis were compared. Animals were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks and thereafter received 1.4% Na3PO4, 2.0% NaH2PO4, 1.0% K3PO4, or 2.5% KH2PO4, these dietary concentrations being selected because they result in approximately equal levels of Na+ and K+ in the urine, equivalent to moderate natriuresis or kaluresis in comparison with our previous data. Treatment with Na3PO4 or K3PO4 induced significant increase in urinary pH compared with control values, whereas urinary pH in the NaH2PO4 and KH2PO4 groups was comparable to control values. With regard to preneoplastic lesion development, both incidences and multiplicity were significantly increased in the groups given Na3PO4 or K3PO4 compared with both controls and NaH2PO4 or KH2PO4 groups, respectively. Furthermore, treatment with Na3PO4 significantly increased multiplicity of papillomas, accompanied by a tendency to increased incidence. No statistically significant difference in promoting potential between Na3PO4 and K3PO4 groups was evident. The present results thus suggest that tumor promotion under conditions of moderate natriuresis or kaluresis depends primarily on high urinary pH.     

Long-term results of open reduction for residual subluxation in congenital dislocation of the hip: A new open reduction method involving 360° circumferential capsulotomy

We report satisfactory results with a new operative treatment, conducted via an extensive anterolateral approach, involving 360 degree circumferential capsulotomy, for residual subluxation in congenital dislocation of the hip (CDH). Long-term radiographic results of this procedure (group A) were compared retrospectively with the results of partial capsulotomy (group B), which preserved the posteroinferior joint capsule. The mean center edge angle in group A (22.5°) was greater than that in group B (16.0°). Satisfactory results were achieved in 11 of 15 hips (73%) (Severin class I or II) in group A, and in 5 of 12 hips (42%) in group B. These results suggest that whole circumferential capsulotomy can remove obstacles to complete reduction, and that acetabular development can be expected in hips reduced by the procedure, without the performance of innominate osteotomy. We believe that our technique is a useful alternative for the treatment of residual subluxation in CDH.     

Evaluation of preoperative chemoembolization using ethiodized oil, cisplatin and gelatin sponge (sandwich therapy) for hepatocellular carcinoma

The significance of preoperative chemoembolization using ethiodized oil, cisplatin and gelatin sponge (Sandwich therapy) for resectable hepatocellular carcinoma (HCC) was evaluated. One hundred and thirteen patients with solitary and less than 10 cm sized HCC who underwent radical hepatic resection were chosen for this study. Fifty-three patients received Sandwich therapy before surgery (Group A), and the remaining 60 patients under-went surgery without any preoperative treatments (Group B). Any background factors between two groups were not significantly different. The anticancer effects of this therapy were evaluated by histologic examination in 31 patients who had preoperative Sandwich therapy. In 22 of 31 patients (71%), the main nodules were completely necrotic. The ratios of patients with complete necrosis in daughter nodules were 7/12 (58%), in portal vein tumor emboli, 7/10 (70%), in intracapsular invasions, 11/21 (52%), in extracapsular invasions, 4/11 (36%). The 4-year disease-free survival rates in Group A and Group B were 56% and 27% respectively, and the rate of the former was significantly higher than that of the latter (p less than 0.05). The 4-year survival rates in Group A and Group B were 83% and 53% respectively. The rate of Group A was also significantly higher than that of Group B (p less than 0.01). We concluded that preoperative Sandwich therapy was very significant to obtain successful long-term disease-free survival and survival in regard to relatively early stage HCC.     

Hemorrhagic cystitis after bone marrow transplantation: importance of a thin sectioning technique on urinary sediments for diagnosis.

We used a thin-sectioning technique for the electron microscopic detection of viral particles within the cells of urinary sediments in three recipients who developed hemorrhagic cystitis after allogeneic bone marrow transplantation. Results of viral cultures of urine and electron microscopic (EM) observations on urinary sediments were consistent in only one recipient. In this recipient, EM observations revealed many viral particles within the cells of urinary sediments with diameter of about 80 nm corresponding to adenovirus, of which type 11 was produced in viral cultures. In one of the other two recipients many viral particles with a mean diameter of 41.6 nm corresponding to papovavirus were observed, but viral cultures using conventional cells were negative. Re-cultures using HEK cells produced polyomavirus BK. EM observation was a clue to the correct diagnosis. In the remaining recipient, no viral particles were observed within the cells of urinary sediments, suggesting the hemorrhagic cystitis to be of non-viral origin, despite a positive result of viral culture. These results suggest that a thin-sectioning technique on the cells of urinary sediments is important for the differential diagnosis between a viral-induced and non-viral hemorrhagic cystitis.