[Difference in 201TlCl accumulation mechanism in brain tumors: a comparison of their Na(+)-K+ ATPase activities].

The accumulation levels of 201TlCl and Na(+)-K+ ATPase activity in tumor tissue were compared among glioblastoma, benign glioma and meningioma to study the difference in the mechanism of 201TlCl accumulation. The subjects were 19 cases comprised of 6 glioblastoma, 2 oligodendroglioma, 1 fibrillary astrocytoma, 1 pilocytic astrocytoma and 9 meningioma. Preoperative 201TlCl SPECT was performed in all the cases, and Thallium Index (TL index) was calculated by a ratio of 201TlCl in the tumor area and the contralateral area. In addition, cell membrane was extracted from the tumor tissue collected intraoperatively to determine Na(+)-K+ ATPase activity. No statistically significant difference in TL index was noted between the glioblastoma group (6.97 +/- 2.67) and the meningioma group (5.87 +/- 1.99). This fact showed that there was no difference in the accumulation level of 201TlCl between the two groups. On the other hand, the glioblastoma group indicated a higher value of Na(+)-K+ ATPase activity (49.13 +/- 43.76 mumole/hour/mg protein) than the meningioma group (7.73 +/- 13.84 mumole/hour/mg protein) (p < 0.05, t test). These results suggested the involvement of Na(+)-K+ ATPase activity in 201TlCl accumulation in glioblastoma and the influences of other accumulation mechanism than Na(+)-K+ ATPase activity such as the volume of intratumoral vascular bed in meningioma.

[Radiosurgery for cystic metastatic brain tumor].

Stereotactic radiosurgery (SRS) for brain metastasis results in a high local control rate. But cystic metastatic tumor should have been a contraindication for SRS. Because it is often found that a cyst is too large to be irradiated, the tumor does not exist in the center of the irradiation field. Between 1995 and 1998, 8 consecutive patients underwent linear accelerator-based SRS for cystic brain metastases identified by computed tomography or magnetic resonance image scan. Stereotactic cyst aspiration is carried out after placement of the BRW frame under local anesthesia. All of the patients except one were confirmed to have sufficient reduction of the cysts. 5-7 days after stereotactic cyst aspiration, SRS was performed. The dose range was 25-30 Gy. In follow-up MRI, local recurrences and enlargement of cysts were not noted. Six patients with neurological symptoms recuperated satisfactorily. Median survival was 30 weeks from the date of radiosurgery. All of the patients died and the causes of death were related with the primary lesion. We conclude that our technique, a combination of stereotactic cyst aspiration and SRS is an effective measure which leads to palliation of neurologic symptoms and is a low risk treatment for patients with cystic brain metastasis.

[Contralateral cerebellar infarction after aneurysmal clipping with pterional craniotomy: report of two cases].

A 77-year-old woman underwent right fronto-temporal craniotomy for a right ruptured IC-PC aneurysm (case 1), and a 44-year-old woman underwent right fronto-temporal craniotomy for a right ruptured BA-SCA aneurysm (case 2). They were clipped completely without any troubles during surgery. But postoperative CT scan demonstrated contralateral cerebellar infarction. We recognized left-hand tremor as a neurological deficit caused by cerebellar infarction in case 1. Concerning the mechanism of contralateral cerebellar infarction after pterional craniotomy, we think that it could be; --1) changing of venous blood flow by overdrainage of cerebrospinal fluid, 2) destruction of the bridging vein because of cerebral transformation with rapid decompression, 3) ischemia caused by brain retraction and compression during operation, 4) hypertension or hypoxia during operation, 5) crossed cerebellar diaschosis, and so on. In our 2 cases, we believe that perioperative CSF overdrainage caused the contralateral cerebellar infarction or CCD. To avoid this kind of infarction, we should try to take more protective and careful procedures as well as closer perioperative management.

[Extraneural metastasis of pineal germinoma through a ventriculoperitoneal shunt, following histological change].

Primary germinoma of the central nervous system carries a good prognosis because of their radiosensitivity. Recurrence is rare and extraneural metastases are even more unusual. We report a unique case of a primary intracranial germinoma exhibiting complete response to radiotherapy, but recurring as an intra-abdominal yolk sac tumor. The presence of a VP shunt is thought to have facilitated metastatic spread of the intracranial neoplasm. An 21-year-old (corrected) male was admitted with headache and consciousness disturbance. Computed tomography (CT) revealed an enhanced tumor of the pineal region and hydrocephalus. A ventriculo-peritoneal shunt was emplaced immediately. No serum tumor markers such as alpha-fetoprotein or human chorionic gonadotropin were detectable. A test dose of radiotherapy (whole brain 20Gy) was given. The tumor size was remarkably decreased. Clinical diagnosis was germinoma. Additional whole brain radiation (total 45Gy) and whole spine radiation (20Gy) were given. The tumor and the hydrocephalus regressed completely and the patient returned to school. Three years later, he experienced a feeling of abdominal fullness. CT and echotomography of the abdomen showed a large peritoneal and intra-hepatic tumor. But MRI revealed no recurrent tumor of the pineal lesion or of the other areas in the central nervous system. Radiological and clinical findings showed no tumors in the testis, the retroperitoneal cavity, or the thymus. Laboratory investigation demonstrated elevated serum AFP (26,550 ng/ml). AFP level regressed after combined chemotherapy. However, the patient died due to pneumonia and multiple organ failure. Only needle necropsy was performed. The microscopic appearance of the peritoneal tumor was confirmed to be an endodermal sinus tumor. It was suspected to be a metastasis of the pineal tumor through the V-P shunt system.

[201T1C1 accumulation dynamics in glioma with different grades of malignancy: an investigation using dynamic SPECT].

Dynamic SPECT was performed using 201TICI in a total of 21 gliomas, 14 cases of glioblastoma multiforme (GM) and 7 cases of anaplastic astrocytoma (AA), to investigate the relationship between test results and malignancy. The accumulation of isotope (counts/pixel) in the tumor was measured every 3 minutes with dynamic SPECT. The initial 3-minute value was reduced from subsequent accumulations (counts/minute) to obtain the time-activity curve (TAC). Thallium index (TL index), the ratio of 15-minute accumulation in the tumor to that in the same region of the contralateral normal brain, was also calculated. TL index was significantly higher (p < 0.05, Mann-Whitney test) in GM (6.25 +/- 1.97) than in AA (4.10 +/- 1.66), although no clear differential value could be determined between the two. TAC in the GM group showed that compared with the initial 3-minute value, accumulation increased significantly (p < 0.05) at every measurement point after isotope injection: 6 minutes, 0.660 +/- 0.671; 9 minutes, 1.322 +/- 1.319; 12 minutes, 1.315 +/- 1.632 and 15 minutes, 1.234 +/- 1.552. The increase in isotope accumulation in the tumor after 6 minutes or later was noted in 11 of the 14 cases in the GM group. In the AA group, however, there were no significant differences between the initial 3-minute value and value after 6 minutes (-0.283 +/- 0.462), 9 minutes (-0.574 +/- 0.681), 12 minutes (-0.690 +/- 0.611) and 15 minutes (-0.707 +/- 0.636) after isotope injection. A decrease in isotope accumulation in the tumor after 6 minutes or later was noted in 6 of the 7 cases in the AA group. Compared with static SPECT, dynamic SPECT, which can be performed easily and quickly, is more useful in clinical settings because of its high ability to differentiate the grade of malignancy of gliomas.

[Usage of intra-operative scalp expansion for primary wound closure in cranio-facial operation].

The size of detects in scalp for which primary wound closure can be applied is limited. Cases with a scalp defect for which primary wound closure is difficult to perform are frequently seen. In these cases, an attempt is made to close the wound by extending the margin of an incision produced by extensive subgaleal undermining or galeal incisions. However, its effectiveness is limited. We performed in such cases intra-operative scalp expansion with a tissue expander for primary wound closure, and this technique has yielded good results. A case with craniosynostosis and five cases with cranioplasty received this procedure. Four of these cases had a previous history of undergoing surgery for carvarial bone defect three to five times from the same incision. The scalp at the carvarial bone defect had a scar and was atrophic with great depression. It was expected that the expansion of cranium resulting from cranioplasty would make it difficult to perform primary wound closure. During the surgery, a tissue expander was placed subgaleally in an osseous area prior to the bone operation, and intermittent air expansion was carried out for 20 to 30 minutes by means of air inflation and deflation to expand the scalp. In all of these cases little tension was generated by the wound closure despite the lapse of time during the bone operation. In consequence, primary wound closure was accomplished easily, and the reliable closure of the galea made it possible to prevent the scar widening. This is a simple and easy technique combining primary wound closure of the scalp with intra-operative scalp expansion. We believe that the technique should be considered for cases for whom primary closure of compression deformity is difficult or in whom there is a wound at the carvarial reconstruction site. The technique and typical cases are reported.

[Changes in metabolism and peritumoral circulation after radiosurgery of metastatic brain tumors: evaluation by three dimensional dual isotope SPECT].

Concurrent use of two different isotopes, 201T1C1 and 123I-IMP, in SPECT is useful in separative evaluation of tumor metabolism and peritumoral circulation. Three dimensional SPECT employed in our study has an obvious advantage over two dimensional SPECT for its accurate imaging of tumors and peritumoural areas. Changes of tumor metabolism and regional circulation in peritumoral edematous tissues were investigated by fused 3-D SPECT images using 201T1C1 and 123I-IMP. In this study, the volume of isotope accumulative and isotope defective regions were measured. Fusion of SPECT images was performed by the use of panning visualization software; Application Visualization System Medical View (K.G.T.). The threshold of 3-D rendering was determined by conforming the volume of the hemisphere and of the tumor estimated on CT to the volume of 123I-IMP and 201T1C1 accumulating area respectively. Accumulative volume of 201T1C1 in the tumor decreased remarkably at 7 days after radiosurgery (p < 0.01). Defective volume of peritumoral hypoperfusion was measured on 3-D SPECT. The average volume was 80.5 + 32.5cm3 before radiosurgery. It decreased by approximately 60% at 7 days after radiosurgery (p < 0.05). Analysis of 3-D SPECT images using two different isotope tracers is reliable and useful to evaluate early the changes of metabolism and peritumoral circulation in or around intracerebral tumors.

[High uptake of N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) demonstrated by dynamic SPECT in some cases of glioma].

Selective high uptake of N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) in the brain tumors is not common, the mechanism of uptake in the brain tumor is not yet clearly understood. Among 26 cases of gliomas investigated by dynamic SPECT, 4 cases including 2 cases of anaplastic astrocytoma and 2 cases of oligodendroglioma, showed high uptake of 123I-IMP. New three detector type camera which enables us to investigate rapid successive scanning, was used in our study. In dynamic SPECT, 15 successive scans of 2 minutes interval were made for 30 minutes after administration of 123I-IMP. In addition, quick dynamic SPECT was tried in 2 cases, in which 10 quick successive scans of 24 seconds interval were investigated for initial 4 minutes immediately after administration of 123I-IMP. Radioactivity in the region of interest inside the tumor (T) and radioactivity of the corresponding site in the contralateral hemisphere (C) was measured respectively, and T/C ratio was calculated. Time course change of radioactivity (time activity curve: TAC) was analyzed in all cases. Radioactivity was always higher in the tumor and the average T/C ratio was 1.40. TAC showed rapid increase of 123I-IMP in the tumor during initial 2 minutes after administration and keeping its high plateau level for 30 minutes. Angiography in these cases revealed a remarkable tumor stain. On the other hand, these gliomas showed no or slight enhancement effect in CT or MRI. These findings are interpretable as that early high uptake of 123I-IMP in some gliomas is attributable to an increased vascular bed and blood flow with no or minimal derangement of blood brain barrier in these tumors.

Intra-operative scalp expansion for wound closure without tension in craniosynostosis operation--technical innovation.

Primary scalp wound closure using intra-operative scalp expansion in a craniosynostosis operation is described. Since this method enables easy scalp expansion, it is considered to be a useful adjunctive technique which should be taken into account when closing scalp wounds in craniosynostosis surgery, where the risk exists of cranial expansion-induced compression and deformity of the remodelled bone flaps after bone fixation.

[The use of TM HAKEN plate in craniofacial surgery].

Rigid internal fixation using mini/micro plate has become a frequent application in cranio-maxillo-facial surgery. In order to make plate fixation easier and reduce operative time, the TM HAKEN plate, a kind of micro plate, was devised which has a thorny HAKEN like an ice pick and applied to cranio-facial surgery. The plate is made of titanium, and th HAKEN and screw are made of titanium alloy. These allow contoured engagement in all three dimensions due to the flexibility of titanium, and firm fixation due to the physical strength of titanium alloy, resulting in minimized artifact on CT scan and MRI images. The fixation is accomplished by just driving in the plate with a hammer, and using screws. In the case of wide operative field, the plate is driven in directly, while in the case of small field, the plate is driven in with an impactor. TM HAKEN plate has been used for osteosynthesis in 39 cases of craniofacial surgery at the Department of Plastic and Reconstructive Surgery of Toho University Hospital between September 1992 and September 1994. Of the 39 cases, 19 were cranioplasty using frozen preserved auto-carvarial bone, 9 were midface fractures, 6 were fixation of free bone grafting, and 5 were fixation of artificial bone (hydroxyapatite-tricalcium phosphate composite ceramics) grafting. Satisfactory results were obtained in all cases without any difficult complications such as infection, exposure or migration. In addition, reliable post-operative evaluations and follow-ups were possible with reduced artifact on CT scan and MRI images.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrinological and histological changes after treatment of uterine leiomyomas with danazol or buserelin.

The following results were obtained from our investigations performed to compare the effects of danazol (400 mg/day orally for 4 to 6 months, n = 164) with those of buserelin (900 micrograms/day intranasally for 4 to 6 months, n = 83) on patients with uterine myomas. The effectiveness of buserelin (76.1%) in shrinking uterine myomas was better than that of danazol (56.7%). The serum-estradiol and progesterone levels were lower in the buserelin group than in the danazol group. The estrogen and progesterone receptors in a hysterectomied uterus were positively stained even at the end of those therapies. The degree and frequency of hyaline degeneration were higher in the buserelin group than in the danazol group. Thus, the shrinking of uterine myomas and the degree of hyaline degeneration might be caused by the lowering of uterine-tissue hormones, particularly of estradiol levels.

Conservative therapy for microinvasive carcinoma of the uterine cervix.

The purpose of this study was to evaluate conservative therapy for microinvasive carcinoma (MIC) of the cervix. Large contact Nd-YAG laser conization (laser cone) with contact vaporization using contact probes was performed on 90 cases of MIC and 21 cases of early invasive carcinoma (early IC), with long-term postoperative follow-up for patients at Osaka Medical College, Osaka, Japan. The cure rates of MIC and early IC were 96.7 and 80.9%, respectively. The rates of incomplete excision and true residuation in cases with MIC were 17.8 and 10.0% and those in cases with early IC were 76.2 and 19.0%. Therefore, the spontaneous cure rate following incomplete excision of MIC and early IC was 43.7 and 75.0%. Hysterectomy was performed, for various indications, after cone in 5 patients (5.6%) with MIC, none of the patients with IC of less than 3 mm, 2 (22.2%) of the patients with IC of 3.1 to 5 mm, and 7 patients (87.5%) whose IC was 5.1 mm or more in depth. Combining the data from our department and those in the literature collected an incidence of lymph node metastasis of 0.15% for MIC and of 1.13% of IC of less than 5 mm. In conclusion, conservative therapy is indicated for MIC, and the contact laser cone with contact vaporization is considered to be an excellent therapeutic conservative method.

[In vitro study on the effect of sex steroid and growth factor on growth and laminin, collagen IV, and tissue plasminogen activator production of normal endometrial cells and endometrial cancer cells in culture].

The mechanism of the invasion and proliferation of endometrial cancer is closely related to interactions between the endometrial glands and stroma. In this study, we examined the biological role of sex steroids (estradiol; E2, progesterone; P) and growth factors (epidermal growth factor; EGF, transforming growth factor-beta; TGF-beta) on cell growth and laminin, collagen IV and tissue plasminogen activator (t-PA) production of normal endometrial cells and endometrial cancer cells in culture. Normal endometrial gland cells and stromal cells, and endometrial cancer cell lines (Ishikawa, OMC-2) were used. E2, P, EGF and TGF-beta were added to the culture in physiological concentrations. The growth of normal endometrial gland cells was promoted by E2 and EGF, whereas that of Ishikawa cells and OMC-2 cells was promoted by EGF. E2 enhanced the effects of EGF in normal endometrial gland cells. The growth of normal endometrial stromal cells was not affected by them. OMC-2 was inhibited by anti-EGF receptor antibody. On the other hand, the production of laminin and collagen IV of these cultured cells was inhibited by EGF and promoted by TGF-beta, whereas that of t-PA was promoted by EGF and inhibited by TGF-beta. These results suggest that the growth of normal endometrial gland cells with estrogen receptor (ER) is controlled by both E2 and EGF, whereas that of endometrial cancer cells is affected only by EGF, and those cells without ER depend particularly on the autocrine growth mechanism of EGF.(ABSTRACT TRUNCATED AT 250 WORDS)

[Study on the management of dysplasia of the uterine cervix].

In this study, we investigated problems on the management of dysplasia on the basis of our clinical data obtained in the past ten years. In addition, we also examined the biological significance of protooncogene expression and human papilloma virus (HPV) infection in the initiation and promotion of dysplasia. Among 540 cases of dysplasia we have managed, 48.8% of the cases of mild, moderate and severe dysplasia which we followed up for more than 6 months regressed, and 24.1% of the cases progressed. The cure rate for laser therapy based on the follow up for 6 to 96 months was significantly high (97.9%) in 342 cases treated by the cone method, and low (89.5%) in 38 cases treated by the vaporization method. Preoperative histological findings confirmed 60.5% of postoperative findings, and several early cervical carcinomas were found in preoperative cases of dysplasia by laser conization. Among 28 cases (8.2%) of incomplete excision, 24 cases (85.7%) regressed spontaneously. On the other hand, the positive rate of immunostaining of epidermal growth factor receptor (EGF-R) and c-myc oncogene product (c-myc protein) increased from mild or moderate to severe dysplasia, and the positive rate for EGF-R was significantly high (80.0%) in the progressive group. The positive rate for HPV genome was quite low (16.0%) in dysplasia. Among them, EGF-R was most associated with the prognosis of dysplasia. These results suggest that laser conization should be performed for many cases of dysplasia because of the preoperative possibility of the existence of early cancer, and EGF-R is also useful in determining the necessity for therapy for dysplasia.

Clinical evaluation of contact Nd.YAG laser conization for cervical intraepithelial neoplasia of the uterus.

Contact Nd.YAG laser conization (laser cone) was performed in 500 patients with preoperatively diagnosed cervical intraepithelial neoplasia (CIN) since September 1983. The patients treated were followed for 12 to 96 months (39.2 months on average). Average operation time was 11.4 minutes. A cure with laser cone (single treatment) was achieved in 98.6%, including cases with microinvasive and invasive carcinoma, post-operatively. There were only 7 (1.4%) true residual cases of 47 cases (9.4% of total cases) with incomplete excision. High spontaneous cure rates (85.1%) in cases with incomplete excision are considered to be a characteristic of laser cone treatment. The contact laser cone method also got good specimens for histologic examinations. They gave a large amount of information for our follow-up. The results indicate that contact Nd.YAG laser conization for CIN is an excellent conservative therapy from the point of cure rate, safety, indication, operation time and cone specimen, even compared with CO2 laser conization.

[In vitro studies on the expression of c-myc oncogene product in gynecological cultured cancer cells].

In this study, immunocytochemical and biochemical detection of c-myc protein in gynecological cultured cancer cells were performed together with gene expression of the cells. OMC-1 (cervical squamous carcinoma cell line), OMC-2 (endometrial adenocarcinoma cell line), OMC-3 (ovarian mucinous adenocarcinoma cell line) and OMC-4 (cervical adenocarcinoma cell line) were used. Immunocytochemically, c-myc protein was detected in both nuclei and cytoplasms of cultured cells when they were fixed in 95% ethanol, 10% formalin and 4% paraformaldehyde (PFA) including 10mM NaCl. However, it was detected in the nuclei of almost all of the cells in nuclei of the cells when they were fixed in 4% PFA including 1,000mM NaCl. Western blotting against a nuclear fraction of the cells demonstrated 66Kd protein in OMC-1 and 62Kd protein in OMC-2,3,4, respectively. They were completely absorbed by c-myc synthetic peptide. However, there was no reaction against the cytoplasmic fraction of the cells. Slot blot hybridization against the DNA of the cells demonstrated 15 times and 5 times c-myc gene amplification in OMC-2 and OMC-4, respectively. These results suggest that OMC-1,2,3,4 can be used as positive controls for the immunocyto- and histochemical detection of c-myc protein in clinical materials. However, it must be noted that the redistribution of c-myc nuclear protein into the cytoplasm may occur in the fixation process.

Pharmacokinetic study of selective continuous internal carotid CDDP infusion in malignant brain tumors.

Cis-diamminedichloroplatinum (CDDP) was administered by selective continuous internal carotid infusion to nine patients with malignant brain tumors, including five glioblastomas, one mixed glioma, and three metastatic tumors. CDDP was infused through a catheter in the internal carotid artery at 100 mg/hr in all cases, except one glioblastoma case in which the lower rate of 10 mg/hr was used. The results of CDDP concentration measurements were: 1) CDDP in the blood peaked at termination of CDDP infusion and then decreased slowly, 2) CDDP infiltrated intratumoral cysts and accumulated there, 3) CDDP in the cerebrospinal fluid peaked 6-18 hours after infusion, and 4) the tumor/plasma CDDP ratio varied from 2 to 8. The size of tumors decreased moderately in three of the nine cases, but no complete response was achieved. The histological changes due to CDDP were observed in the tumor tissue and were absent in the normal brain parenchyma.

[Super conductive MR imaging of small acoustic tumor].

Eight patients with acoustic tumor were studied with a superconductive MR imaging. T1-weighted images with Gd-DTPA most accurately showed the margin of the seventh and eighth nerves in the internal auditory canal and were most sensitive in detecting small tumors. T2-weighted images were inferior to T1-weighted images, that could fail to detect small tumors. High resolution, thin slice, MR imaging using surface coil is particularly useful for small acoustic tumor because of its higher specificity compared with air-CT, cisternography.