The long-term results of 22 adult cases with craniopharyngioma admitted to our hospital between 1960 and 1978 were studied. Out of 22 cases 12 were treated initially with palliative surgery in combination with irradiation or chemotherapy using bleomycin. Operative deaths were nil in this group. However, 10 cases showed deterioration of clinical signs and symptoms over and over again in spite of repeated treatment and finally died mainly of intracranial hypertension within 11 years after the initial surgery. In the remaining 10 cases radical removal of the tumor was performed initially via the bifrontal approach using an operating microscope. The operative deaths were also nil in this latter group. In the latter radical treatment group, tumors were classified into four principal types according to their locations and modes of extension; intrasellar, subtuberal, tuberal and ventricular types. Among four cases with a tumor of the tuberal type which had been radically resected, two cases showed severe diabetes insipidus and hypopituitarism following the operation and their daily activities were restricted because of postoperative mental disturbances. In three cases out of four cases of the subtuberal type in which craniopharyngioma had arisen in an intermediate position, between the gland below and the 3rd ventricle above, the pituitary stalks were preserved. In these three cases postoperative diabetes insipidus was mild and transient and functions of the anterior pituitary lobe were saved except for TSH secretion. All six cases including four subtuberal types and two intrasellar types returned to full working capacity after the operation.
The results mentioned above suggest that better long-term results can be obtained in the radical treatment group than in the conservative treatment group and therefore attempts should be made to remove craniopharyngioma radically, especially in cases of the subtuberal and the intrasellar types, making efforts to preserve the pituitary stalk if possible.

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FT207 is retained for long periods in tumor tissues and is gradually released as 5FU in an activated form. This 5FU has antitumor effects as an antimetabolite, and also blocks the repair mechanism of DNA by radiation therapy (potentiation). On the other hand, vitamin A has been said to cause lysosome release and cell coat changes of tumor cells, and also activation of immunological responses. Through these subcellular alterations provided by vitamin A treatment, drug affinity or drug sensitivity and radiosensitivity of tumor tissues can be achieved.
For these reasons a new therapeutic method combining FT207, vitamin A and Radiation (FAR therapy) is introduced.
This therapy was applied to 32 brain tumor patients. Four to five hours before daily radiation of 200 rads, 800 to 1, 200 mg of FT207 and 50, 000 to 60, 000 IU of vitamin A were orally administered until total radiation doses of 5, 000 to 6, 000 rads were achieved. Marked improvement was observed in 12 patients out of 32 (37.5%). The total efficacy rate was calculated as 75%. Side effects from this therapy were anorexia in 28%, leucopenia in 25% and slight elevation of transaminase in 9% of the cases.
FT207 uptake by C6 rat experimental brain tumors was investigated. A high concentration of 5FU in brain tumor tissues was maintained until 6 hours after intraperitoneal administration of FT207 and vitamin A. The tendency toward high concentrations of 5FU was much more pronounced in cases of pretreatment with vitamin A.
FT207 uptake by eight brain tumor patients was investigated. Before surgery, 50, 000 to 60, 000 IU of vitamin A and 1, 000 to 1, 200 mg of FT207 were administered orally. At various intervals surgical specimens were obtained under the same anesthetic conditions. Blood loss during the operation was negligible. Generally 4 to 5 hours after administration of these drugs, a high concentration of 5FU in tumor tissues was achieved and maintained.
In our FAR therapy, vitamin A and FT207 were easily and safely administered orally without noticeable side effects and readily indicated for use in children.

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The success of transsphenoidal adenomectomy in 10 patients with Cushing's disease was judged by the residual adenohypophysial function. Surgery was indicated mainly by endocrinological results. Radiologically, the sella turcica was slightly enlarged in three cases, which had all macroadenomas with the diameter of more than 10 mm. The other seven had microadenomas 3-7 mm in diameter with normal-sized sella. In two cases, localized bulging of the floor was confirmed by polytomography. In one case the adenoma was far away from the midline and was completely buried in the It-lateral wing. All the others were located in the center of the adenohypophysis. Complete adenomectomy involving adjacent normal tissue resulted in amazing clinical improvement with hypoadrenocortisolism in all cases except one in which the surgical maneuvers appeared incomplete.
The preoperative basal levels of plasma ACTH were 135.6±27.5 pg/ml (M±S.E.) and responsiveness to insulin hypoglycemia was absent in all cases with a loss of diurnal rhythmicity, whereas conspicuous ACTH responsiveness to 8-lysine vasopressin (LVP) was observed in most cases, as shown by the increase from 107.8±23.8 to 362.5±98.7 pg/ml. The postoperative basal plasma ACTH levels dropped to 24.6±11.3 pg/ml and their responses to LVP became blunted in most cases with a peak value of 57.0±21.4 pg/ml, whereas hypoglycemic responses became positive in most cases, as shown by the peak value of 62.7±12.6 pg/ml. The diurnal rhythmicity of plasma ACTH and cortisol became apparent in all five cases examined 6 months after surgery.
Preoperative plasma GH responses to insulin hypoglycemia were impaired in all cases and the peak value did not exceed 10 ng/ml in any case. Postoperatively, the peak value significantly increased at an average of 7.9±3.9 ng/ml (M±S.D.) and in four cases it exceeded 10 ng/ml. TSH responses to TRH and LH to LH-RH were also significantly improved postoperatively. FSH responses to LH-RH and PRL to TRH did not change significantly.
These results support the concept that ACTH hypersecretion of pituitary adenoma is the primary abnormality in Cushing's disease and hypothalamic CRF activity is suppressed by long-standing hypercortisolism. Furthermore, the hypothalamic-pituitary functions of other anterior pituitary hormones such as GH, TSH and LH are impaired by hypercortisolism and could be returned to normal by selective transsphenoidal adenomectomy. We conclude that this operation is the first choice of treatment of Cushing's disease for clinical and endocrinological improvements.

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Cerebral vasospasms with subsequent infarction have an important effect on the outcome of patients with ruptured intracranial aneurysms. Clinical and experimental studies of intravascular factors in the pathogenesis of cerebral infarctions, with particular regard to platelets and coagulation factors, were performed. In these studies, a systemic hypercoagulable state and platelet hyperactivity were observed, and in the experimental study, crenated red blood cells were seen in the course of vasospasms. These systemic changes in intravascular components are thought to accelerate cerebral ischemia through an increase in blood viscosity, microthrombosis, and reduced deformability of red cells.

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The present study was designed to assess a role of hemoglobin in the genesis of vasospasms following subarachnoid hemorrhages. Isolation of human hemoglobin A₀ was carried out by chromatography using DEAE-Sephadex A50. The in vitro contractile activities of human hemoglobin were analyzed quantitatively in isolated dog arterial segments. The following results were obtained.
1) Human hemoglobin Aa caused dose-related contractions in the basilar arteries. The dose-response curve of hemoglobin A₀ was obtained.
2) The dose-response curve of hemoglobin A₀ was almost identical with that of red blood cell hemolysates. This result indicates that hemoglobin is mainly responsible for contractile activities of red blood cell hemolysates.
3) The maximum contraction induced by hemoglobin A₀ was 70% of that induced by serotonin.
4) The sensitivity of the basilar arteries to hemoglobin was markedly greater than that of the peripheral arteries.
5) Oxyhemoglobin caused greater contraction in the basilar arteries than methemoglobin.
6) Globin, protoporphyrin, hematin, ferrous chloride and ferric chloride did not cause significant contractions in the basilar arteries.
These data suggest that hemoglobin plays an important role in the genesis of vasospasms following rupture of an aneurysm.

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The authors previously reported the sequential morphological changes at the site of carotid endarterectomy (CE) in cats using light and scanning electron microscopy (SEM). The following problems remain unsolved; a) at the stage of restoration after CE, why do thrombi not increase at the site and why does cerebral embolism never occur? b) what is the nature of the amorphous material covering the CE site? c) what is the origin of new endothelial cells growing like islands far away from both ends of the CE? The present study was conducted to obtain some insight into these unsolved problems. The ultrastructural healing process of the endarterectomized carotid arterial wall was observed with a transmission electron microscopy (TEM). The authors found that the amorphous material covering the naked surface in the acute phase of CE consisted mainly of platelets. The platelets were loosely arranged on the luminal surface but were closely packed together in the deeper layer. In reparative phase, two kinds of cells could be recognized on the luminal surface of CE, namely, ovoid and flattened cells. Some of the ovoid cells were isolated from other cells. Most of the ovoid cells maintained contact with other cells by the cell membrane but without definite junctional structures. The rough endoplasmic reticulum (rERs) of these cells was remarkably enlarged and occupied most of the cell. There were many cells in the subendothelial space which resembled ovoid type cells but collagen fibrils were seldom recognized. In the third week after CE, the vessel surface was lined by two different cells as in the second week. However, the difference of intercellular organelles between the two types became minimal. In the deeper layer, there were many cells with myofilaments, dense bodies and basement membrane which had an appearance of modified smooth muscle cells, and the rER of the cells in the deeper layer developed more markedly than that of cells in the superficial one. In the mature phase, the luminal surface was covered with only flattened type cells. These cells satisfied a criterion of endothelial cells and had tight junctions. Beneath these cell layers, several layers of smooth muscle cell were seen although no elastic laminae was present. There were particular cells in the deeper layer of these muscle cells which possessed dense bodies and basement membrane but no intercellular filament. No collagen existed around these cells. These particular cells were neither fibroblasts nor smooth muscle cells and are more actually undifferentiated type cells. These findings suggested that undifferentiated cells, originating in the media (medial multipotential mesenchymal cells) became ovoid type cells during migration to the luminal surface, then differentiated to flattened type cells and finally matured to new endothelial cells.

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A new method of nonsuture microvascular anastomosis using magnet rings and cogwheel-shaped hollow metal instruments with six spurs or oval hollow instruments was developed. With this method, both end to end and end to side anastomosis are possible.
End to end anastomosis in experimental animals was possible for small vessels with outer diameters of up to 1 mm with an average patency rate of 900, requiring 8.0 minutes on average. In cases of end to side anastomosis, the patency rate was 84%, requiring 8.4 minutes on average.
In end to end anastomosis, electromagnetic flowmeter measurement showed that there was no difference in blood flow and blood flow patterns between control and operated vessels, even 40 days after anastomosis. In end to side anastomosis-, blood flow at the donor vessel and the total blood flow at the recipient vessel were same even after 40 days in cases of artery-to-artery anastomosis, and also after 60 minutes in cases of artery-to-vein anastomosis. No change in blood flow pattern was recognized.
Histological examination in experimental animals 20 days after anastomosis revealed a continuity of the media and the intima. After 180 days, no marked abnormal findings were recognized. In a scanning electron microscope study, no disruption and flattening of longitudinal endothelial folds on the inner surface of the vessels were observed. Histological examinations showed that magnetic power did not have any effect on blood vessel walls and surrounding tissues.

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The frequency of determination of cryptic AVM largely depends on the method of search during surgery. We introduced our method here together with a discussion of the microscopic and electron microscopic views. Generally, cryptic AVM is rarely found by angiography, and the key to its discovery is a skillful and thorough search for it during surgery rubbing all under a surgical microscope, the wall of the hematoma cavity is rubbed all over with a piece of cotton soaked with physiological saline solution, and a histological specimen is obtained from the easily-bleeding portion. We have performed patho-histological examinations on these specimens.
In the last six years, we had 16 cases of histologically confirmed cryptic AVM, among them 12 cases were in the subcortex, and four in the brain stem. We suspected cryptic AVM in 15 cases having no histories of hypertension or blood diseases. Among these we found small nidi and achieved histological confirmations in 12. Of these 12, only seven had been found to have cryptic AVM by pre-operative angiography.
They were found most frequently in the frontal lobe (8 cases), followed by the temporal lobe. In almost all, onset of cryptic AVM was relatively slow in spite of the presence of hematoma. Consciousness was clear and the outcome was generally good. Most of them were found in younger age groups, but we did find a few in older groups. In the four cases of cryptic AVM in the brain stem, there had been no particular indications of it before the operation.
We are of the opinion that conventional histological classification of cryptic AVM is not adequate in view of the actual status.

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