Intracranial meningiomas after high-dose irradiation

Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high-dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high-dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with "spontaneous" meningiomas. Similar to the situation with meningiomas after low-dose irradiation, a relatively high proportion of meningiomas induced by high-dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high-dose radiation may play a role in the pathogenesis of meningiomas.     

Primitive neuroectodermal tumors in the central nervous system following cranial irradiation: a report of four cases

BACKGROUND: Radiation induced intracranial neoplasms are uncommon but well described and include gliomas, meningiomas, and sarcomas. The development of primitive neuroectodermal tumors (PNETs) following prophylactic craniospinal irradiation has been infrequently reported previously. The authors present four additional cases of PNETs that developed after previous cranial irradiation. METHODS: Four patients who had previously been irradiated were determined to have PNETs of the central nervous system characterized by histopathologic and immunohistochemical features. The average patient age at diagnosis of the initial tumors and cranial irradiation was 17 years. The PNETs developed 5, 11, 11, and 18 years after completion of radiation. RESULTS: Three patients had posterior fossa tumors, one pilocytic astrocytoma, one low grade astrocytoma, and one malignant ependymoma, which had been diagnosed and treated in childhood. Two of those patients developed supratentorial PNETs and the third a cerebellar hemispheric PNET. The fourth patient developed a posterior fossa PNET following irradiation for a temporal astrocytoma, which was initially diagnosed and resected at 37 years of age. Mean survival was 12 months after diagnosis. CONCLUSIONS: The development of PNETs after cranial irradiation may be more common than thought previously and should be considered in the differential diagnosis of irradiation induced neoplasms. Survival after diagnosis of these radiation induced PNETs was short, and this may reflect an inability to provide standard therapy used for primary PNETs.     

Does retroperitoneal lymph node dissection have a curative role for patients with sex cord-stromal testicular tumors?

BACKGROUND: Sex cord-stromal tumors account for < 5% of all adult testicular tumors, and 10% are malignant. Due to the limited reported experience, there is no agreement on the best management, especially in patients who have tumors with malignant pathologic features or who present with metastatic disease. The authors attempt to evaluate the role of retroperitoneal lymph node dissection (RPLND) in the management of patients with these malignant sex cord-stromal tumors. METHODS: Reviewing the Indiana University testis cancer registry revealed 17 patients who underwent RPLND for sex cord-stromal tumors. Pathology was reviewed for features suggestive of malignancy. The data examined included clinical and pathologic stage, surgical procedure, additional therapy received, and outcome. RESULTS: Pathology included Leydig tumors in six patients, Sertoli tumors in four patients, sex cord-stromal tumors in five patients, a granulosa cell tumor in one patient, and a poorly differentiated non-germ cell tumor in one patient. Nine patients had histologic features suggestive of malignancy. Clinical stage at surgery was Stage I in nine patients and Stage IIA-IIIA in eight patients. Patients underwent modified or bilateral RPLND. Nine patients had pathologic Stage I tumors, and the remaining eight patients and had pathologic Stage IIB-IIIA tumors. Follow-up ranged from 8 months to 11 years. Of the eight patients with Stage II-III disease, six patients eventually died of metastatic disease despite additional radiotherapy and/or chemotherapy. CONCLUSIONS: Sex cord-stromal tumors have a potentially aggressive malignant behavior that is difficult to predict based on clinical and pathologic features. Although the therapeutic role of RPLND in patients with small-volume metastatic retroperitoneal tumors is unclear, RPLND remains an option to be performed immediately after orchiectomy, especially in patients who have tumors with malignant features and/or small-volume metastatic disease.     

Secondary anaplastic oligodendroglioma after cranial irradiation: a case report

Secondary brain tumors rarely arise after cranial irradiation; among them, meningiomas and glioblastomas are the most common and secondary oligodendroglial tumors the most rare. We present a 48-year-old man who developed an oligodendroglial tumor 38 years after receiving 50 Gy of cranial irradiation to a pineal tumor. He underwent gross total removal of a calcified, ring-enhanced mass in the right temporal lobe. The tumor was histologically diagnosed as anaplastic oligodendroglioma. Our review of previously reported secondary oligodendroglial tumors that developed after cranial irradiation revealed that these rare tumors arose after low-dose cranial irradiation or at the margin of a field irradiated with a high dose. We suggest that secondary oligodendroglial tumors arising after cranial irradiation are more aggressive than primary oligodendrogliomas.     

Secondary intracranial meningiomas after high-dose cranial irradiation: report of five cases and review of the literature

PURPOSE: To review cases of secondary intracranial meningiomas following high-dose cranial irradiation (>/= 10 Gy) identified in Slovenia between 1968 and 1998, to determine their histological profile and to review the literature on this topic. METHODS AND MATERIALS: Personal files of patients treated for secondary intracranial meningioma during a 31-year period were reviewed. In cases which met the criteria for radiation-induced tumors, steroid hormone receptor and Ki-67 status were analyzed. For the literature review, computerized database systems and reference lists from respective publications were used. RESULTS: Five patients (2 females, 3 males), 3-11 years old at the time of cranial irradiation, developed secondary meningioma after a latency period of 9.5-31.5 years. Three patients had multiple tumors and 2 developed recurrent disease. Of 9 histologically examined tumors, 5 were graded as benign and 4 as atypical meningiomas, with Ki-67 proliferative index 3.2 +/- 3.6 and 10 +/- 6, respectively. The ratio between positive and negative meningiomas regarding immunostaining for progesterone and estrogen receptors was eight-to-one and six-to-three, respectively. Cumulative actuarial risk of secondary meningioma in a cohort of 445 children 16 years or younger treated with high-dose cranial irradiation between 1968 and 1990 in Slovenia at 10, 20, and 25 years was 0.53%, 1.2%, and 8.18%, respectively. Out of 126 cases of radiation-induced meningiomas reported, 57% were females and 43% were males, with mean age at presentation 33 +/- 17.3 years. The majority (68%) of patients was irradiated during childhood. The latency period was significantly shorter in those who aged 5 years or less at the time of cranial irradiation (p = 0.04), and in those with atypical/anaplastic tumor (p = 0.01). Correlation between radiation dose and latency period could not be found. CONCLUSION: Secondary meningiomas following high-dose cranial irradiation are characterized by younger age at presentation, by higher male-to-female ratio and by biologically more aggressive variants compared to primary spontaneous meningiomas. Latency period correlated with the age at the time of cranial irradiation and with tumor grade but not with irradiation dose. Ki-67 immunoreactivity correlated with histological grade. The progesterone and estrogen receptor immunoreactivity was high. The risk for development of secondary meningioma after high-dose cranial irradiation was increasing with the time of follow-up.     

Pseudoprogression in boron neutron capture therapy for malignant gliomas and meningiomas

Pseudoprogression has been recognized and widely accepted in the treatment of malignant gliomas, as transient increases in the volume of the enhanced area just after chemoradiotherapy, especially using temozolomide. We experienced a similar phenomenon in the treatment of malignant gliomas and meningiomas using boron neutron capture therapy (BNCT), a cell-selective form of particle radiation. Here, we introduce representative cases and analyze the pathogenesis. Fifty-two cases of malignant glioma and 13 cases of malignant meningioma who were treated by BNCT were reviewed retrospectively mainly via MR images. Eleven of 52 malignant gliomas and 3 of 13 malignant meningiomas showed transient increases of enhanced volume in MR images within 3 months after BNCT. Among these cases, five patients with glioma underwent surgery because of suspicion of relapse. In histology, most of the specimens showed necrosis with small amounts of residual tumor cells. Ki-67 labeling showed decreased positivity compared with previous samples from the individuals. Fluoride-labeled boronophenylalanine PET was applied in four and two cases of malignant gliomas and meningiomas, respectively, at the time of transient increase of lesions. These PET scans showed decreased lesion:normal brain ratios in all cases compared with scans obtained prior to BNCT. With or without surgery, all lesions were decreased or stable in size during observation. Transient increases in enhanced volume in malignant gliomas and meningiomas immediately after BNCT seemed to be pseudoprogression. This pathogenesis was considered as treatment-related intratumoral necrosis in the subacute phase after BNCT.     

Gliomas following low-dose irradiation to the head report of three cases

Three patients developed cerebral gliomas decades after exposure to low-dose x-ray irradiation in childhood for the treatment of tinea capitis. One of the patients had a glioblastoma multiforme concomitant with multiple intracranial meningiomas, a condition highly correlated with previous irradiation. The other tumors were malignant cerebellar astrocytoma and a diffuse cerebral astrocytoma. We review the evidence suggesting that low-dose irradiation is involved in the pathogenesis of gliomas.     

胃肠道间质瘤的血管造影诊断

目的探讨胃肠道间质瘤（GIST）的血管造影表现,评价血管造影对该肿瘤的诊断价值。方法采用PUCK和DSA方法,对12例GIST患者术前1周行血管造影检查,分析病灶的部位、大小、形态及血管造影表现。结果肿瘤发生于胃区2例,空肠8例,回肠2例。良性者7例,恶性者5例。肿瘤供血动脉明显增粗者8例,静脉提前显影者3例。GIST的血管造影改变主要有两种类型：（1）肿瘤血管紊乱呈卷发状,部分血管边缘毛糙、模糊。（2）肿瘤血管呈抱球状,肿瘤染色均匀一致。结论血管造影检查对于GIST的定位、定性诊断有很大的帮助,可以明确肿瘤的大小、范围及部位,尤其是对于不明原因的黑便患者更有价值。     

Soft tissue sarcoma. Integration of brachytherapy, resection, and external irradiation

Between December 1981 and August 1988, 63 patients with clinically localized nonretroperitoneal soft tissue sarcomas underwent 65 brachytherapy procedures in conjunction with conservative resection with (61 tumors) or without (four tumors) external beam irradiation. Implant doses of 1500 to 2000 cGy were combined with 4500 to 5000 cGy of external irradiation. External irradiation was given preoperatively for larger lesions near bone or neurovascular structures, whereas it was used postoperatively for smaller, more resectable lesions or those that had previously been inadequately excised. There were 47 high-grade tumors, 34 tumors greater than 5 cm, and nine patients with recurrent lesions (five with previous irradiation). With mean follow-up of 20 months, conclusions on local control are tentative, but only two of 56 tumors (4%) with brachytherapy as part of initial management had recurred locally and three of nine recurrent tumors had re-recurred locally. Only one of five local recurrences was within the implanted volume. Only two of 40 implantations (5%) performed at initial resection followed by postoperative external irradiation led to wound complications, whereas four of 16 implantations (25%) performed at resection after preoperative external irradiation were associated with wound problems. This technique does not increase local morbidity and may enhance local tumor control in comparison with either external radiation or brachytherapy alone as an adjuvant to conservative resection.     

Radiation induced meningioma with a short latent period following high dose cranial irradiation – Case report and literature review

Radiation induced meningiomas (RIM) are rare late complications in patients who have received high dose irradiation for brain tumors. The mean latency period for induction of RIM in most of the series is 18.7+/-10.2 years. There are only 9 reported cases of RIM following high dose cranial irradiation with unusually short latency periods of less than 5 years. Herein, we report a child diagnosed with RIM with an unusually short latency period of 14 months. An 11-year old male child underwent gross total resection of medulloblastoma. Following surgery he received high dose craniospinal irradiation. Postoperative computed tomography scan (CT scan) after 1 month did not show features of any residual tumor, recurrence or tumor at a new site. The child was asymptomatic for 14 months and then presented with complaints of headache and vomiting. CT scan head showed multiple solid homogenously enhancing lesions in bilateral basifrontal and right basitemporal region. Histopathology of the lesions turned out to be atypical meningioma.     

Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.

Since 1984, we have treated 26 patients with malignant ovarian germ cell tumors with a combination of bleomycin, etoposide (VP-16), and cisplatin (BEP) at The University of Texas MD Anderson Cancer Center (UTMDACC). The median age of the patients was 19 years (range, 8 to 32). All patients underwent initial surgery (unilateral salpingo-oophorectomy in 14, unilateral salpingo-oophorectomy plus abdominal hysterectomy in one, and bilateral salpingo-oophorectomy with or without hysterectomy in 11 patients). Twenty patients had no residual disease, three had less than or equal to 2 cm (one each, dysgerminoma, mixed, and immature teratoma), and three had more than 2 cm lesions (two dysgerminomas, one endodermal sinus tumor). Fourteen patients had pure dysgerminoma (five, stage I; one, stage II; six, stage III; and two, recurrent), and 12 had nondysgerminomatous tumors (five, stage I; two, stage II; three, stage III; and two, recurrent). All four patients with clinically measurable disease had a complete response. All four patients who underwent second-look laparotomy had negative findings. Twenty-five patients (96%) remain in sustained remission 10.4 to 54.4 months from the start of chemotherapy. One patient died of progressive disease 14 months after beginning chemotherapy. We conclude that the BEP regimen has excellent activity and acceptable toxicity in patients with malignant ovarian germ cell tumors.     

儿童颅内幕上胚胎性肿瘤的治疗及预后分析

  目的  对儿童颅内幕上胚胎性肿瘤的治疗及预后进行分析，提高对儿童颅内幕上胚胎性肿瘤的认识。  方法  回顾性分析首都医科大学附属北京世纪坛医院放疗科2011年5月至2018年12月间收治的27例年龄18岁以下行术后放疗的儿童颅内幕上胚胎性肿瘤的患儿资料，对其临床特点和治疗效果以及预后进行分析。  结果  27例患儿均完成术后全脑全脊髓放疗。全脑全脊髓放疗剂量为27.0~30.6 Gy，瘤床区加量照射至55.8~60.0 Gy。22例患儿放疗结束后行化疗，化疗方案为伊立替康+长春新碱+依托泊苷+奈达铂。中位随访时间22（4~93）个月，27例患儿死亡18例，9例生存。1、3、5年生存率分别为79.4%、50.2%、36.5%。死亡患儿中颅内播散8例，脊髓播散10例。  结论  儿童颅内幕上胚胎性肿瘤是临床少见的高度恶性神经系统肿瘤，治疗上应采取手术、术后辅助放化疗的综合治疗手段，预后较差。      

Immunohistochemical study of MRP5 expression in meningiomas

Purpose

Meningiomas are the most common benign intracranial tumor, accounting for 30 % of all primary intracranial tumors. Although benign meningiomas rarely recur after a complete resection, anaplastic tumors are associated with high recurrence rate and unfavorable outcome. In the current study, we investigated the expression of the multidrug resistance protein 5 (MRP5) in patients with meningiomas.

Methods

We retrospectively studied twenty patients with meningiomas that were treated surgically in our institute over a 3-year period. MRP5 protein expression was determined immunohistochemically.

Results

The immunohistochemical expression of MRP5 was observed only in anaplastic meningiomas. No MRP5 expression was detected in benign or atypical meningiomas. No significant correlation was found between MRP5 expression and Ki-67 index. After a mean follow-up period of 23 months, there were 4 cases of tumor recurrence. No correlation was found between extent of resection and tumor recurrence.

Conclusion

Immunohistochemical MRP5 protein expression was observed only in anaplastic meningiomas. Further research is needed to clarify whether MRP5 is indicative of malignant pathological features in meningiomas and whether possible therapeutic implications exist.     

Radio-induced malignancies of the scalp about 98 patients with 150 lesions and literature review.

InTRODUCTION: - The induction of malignant diseases is one of the most concerning late effects of ionizing radiation. The topic of this study deals with skin tumors developed in the irradiated areas in children given X-ray therapy for tinea capitis. MATERIAL AND METHODS: - All patients with malignant tumors of the scalp referred to Salah Azaiz Institute between 1970 and 2001 have been questioned in order to determine if there had been a prior X-ray irradiation for tinea capitis, its modality, and its consequences. The first scalp irradiation goes back to 1922 and the last was performed in 1963. RESULTS: - Ninety-eight patients with 150 radio-induced cancers of the scalp following irradiation for tinea capitis are reported (1.5 lesion per patient). The patients were irradiated in various hospitals and dispensaries throughout the country. Eighty-one patients (82%) had only one session of radiation. The average age at irradiation was 12 (+/-6) years, the latent period for radiation-induced skin cancers was 36 (+/-14) years. In 61 patients (62%), the scalp appeared normal and in 38% radiodermatitis was noted. Patient age at diagnosis of malignancy varied from 20 to 83 years with an average of 47 years. Basal cell carcinomas (125 cases) and spinocellular carcinomas (16 cases) were the most common, three other cases of annexial tumors, two malignant non-Hodgkin's lymphomas and four melanoma lesions are also present. Radiotherapy was used for the treatment of 74 patients (alone in 42 and associated with surgery in 32 patients); 14 patients had exclusive surgical excision. CONCLUSIONS: - Basal cell carcinomas are the most frequent tumors arising on chronic radiodermatitis. In spite of the long latency period, patients' young age at irradiation explained the occurrence of these cancers at a relatively young age. Literature review is suggesting recessive mutation of tumor-suppressor genes as the characteristic abnormality in radio-induced cancer.     

Characteristics of malignant tumors in young people, with particular emphasis on carcinomas and sarcomas.

The aims of the study are to investigate the characteristic patterns related to different aged subgroups of young Chinese patients with malignant tumors. The subjects were young Chinese patients (defined as age > 1 and < 40 years) who underwent autopsy for malignant tumors in a teaching hospital in Hong Kong from 1970 to 1999. They were divided into four age groups: 1 to 9 years, 10 to 19 years, 20 to 29 years, and 30 to 39 years. The malignant tumors were classified into subgroups according to the pathological classification. The clinicopathologic features of patients with carcinomas and sarcomas were reviewed in depth. Four hundred sixty-three (22%) of 2,080 young patients had malignant tumors detected at autopsies. The male-to-female ratio was 1.5. The two most common malignant tumors were malignant lymphoid tumors and carcinomas, accounting for 49.9% and 29.8%, respectively, of all malignant tumors. In children (ages 1-9 years), 78.9% of malignant tumors found were malignant lymphoid tumors and neuroendocrine tumors. In teenagers (ages 10-19 years), malignant lymphoid tumors were the most important group of malignant tumor, accounting for 69% of malignant tumors in this age group. Carcinomas and malignant lymphoid tumors were seen in more than 80% of malignancies in young adults (ages 20-39). Overall, carcinomas and sarcomas were noted in 29.8% and 4.1%, respectively, of young patients with malignant tumors. The common primary sites of carcinomas were liver, stomach, lung, and nasopharynx. Sarcomas were more common in females (11 females, seven males), and rhabdomyosarcoma was the most common sarcoma found. Compared with other malignant tumors, carcinomas were less often diagnosed before death. In conclusion, malignant tumor is a common cause of death in young patients. Different types of malignant tumors were seen in various groups of young patients.     

The value of radiation therapy as an adjuvant to surgery in intracranial meningiomas

Our experience with benign and malignant intracranial meningiomas between 1970 and 1983 is reported. Fourteen cases were treated after surgery, 10 benign and four malignant, following complete or incomplete resection or recurrence after resection. Two of 10 benign meningiomas have recurred and one of the two has been controlled by reoperation. None of the malignant meningiomas have been cured, but disease-free intervals up to 4 years were noted. The mean radiation dose was 5,400 rad, given with complex fields and shrinking field technique with no major complications. Adjuvant radiation after resection of meningiomas results in frequent cure of benign meningioma and may extend the interval of recurrence in malignant variants.     

Epigenetic subclassification of meningiomas based on genome-wide DNA methylation analyses

Meningiomas are among the most common intracranial tumors and are mostly curable by surgical resection. However, some populations of meningiomas with benign histological profiles show malignant behavior. The reasons for this inconsistency are yet to be ascertained, and novel diagnostic criteria other than the histological one are urgently needed. The aim of the present study is to subclassify meningiomas from the viewpoint of gene methylation and to determine the subgroup with malignant characteristics. Thirty meningiomas were analyzed using microarrays for 6157 genes and were classified into three clusters on the basis of their methylation status; these were found to be independent of the histological grading. One of the clusters showed a high frequency of recurrence, with a marked accumulation of methylation in a subset of genes. We hypothesized that the aggressive meningiomas universally share characteristic methylation in certain genes; therefore, we chose the genes that strongly contributed to cluster formation. The quantified methylation values of five chosen genes (HOXA6, HOXA9, PENK, UPK3A and IGF2BP1) agreed well with microarray findings, and a scoring system consisting of the five genes significantly correlated with a high frequency of recurrence in an additional validation set of 32 patients. Of particular note is that three cases with malignant transformation already showed hypermethylation at histologically benign stage. In conclusion, a subgroup of meningiomas is characterized by aberrant hypermethylation of the subset of genes in the early stage of tumorigenesis, and our findings highlight the possibility of speculating potential malignancy of meningiomas by assessing methylation status.     

Chordoid meningioma: a clinicopathologic study of 11 cases at a single institution

Chordoid meningioma is an uncommon variant of meningioma, which histologically bears a great resemblance to chordoma and often follows an aggressive clinical course. We examine clinicopathologic features of 11 cases of this rare tumor to further elucidate its behavior. Thirteen specimens of chordoid meningioma belonging to 11 patients were obtained at a single institution from 1995 to 2009. Correlations of histologic parameters, immunohistochemical study, and clinical features were assessed. This series included six men and five women with a mean age of 60.8 years at first surgery. Aside from one patient (case 5) who died of disease immediately after the first operation, the mean postoperative follow-up period for the other 10 patients was 41.4 months. Two patients each had a local tumor recurrence. The mean time to recurrence was 10.4 years. No systemic manifestations of Castleman syndrome, such as iron-refractory hypochromic/microcytic anemia and dysgammaglobulinemia, were found. Six tumors (46%) were classified as benign (grade I) and seven tumors (54%) atypical (grade II), if based solely on histologic grading irrespective of chordoid or clear cell components in our cases. Lymphoplasmacytic infiltrate was moderate in one tumor (7%), mild in eight tumors (62%), and absent in four tumors (31%). The inflammatory cells were predominantly T cells (CD3+), with only scarce B cells (CD20+). There was a wide range of MIB-1 labeling indices (0.3–25.8%, mean 7.5%), which increased following tumor recurrence. Our study demonstrates that chordoid meningiomas are not always associated with Castleman’s Syndrome, and that this histologic category can be seen in the elderly as opposed to only in younger age groups.     

Effects of Roentgen Irradiation on Human Melanoma Metastases in the Skin

Skin metastases of malignant melanomas in 17 patients were irradiated with three different levels of total dose (40 Gy, 60 Gy and 80 Gy), using a constant fraction size of 5 Gy five times a week. The tumors were removed 10 to 14 days after the last irradiation. The morphologic alterations of the tumor tissue correlated with the total dose. More extensive destruction was seen only after 80 Gy, but even at this level and with this fraction size viable appearing tumor cells remained in all cases. The tumors of one patient exhibited exceptional radiosensitivity. No completely resistant tumor was seen.     

Study on postoperative local chemotherapy of malignant brain tumors using ACNU and PSK

There have been many attempts to treat patients with malignant brain tumors represented by glioblastomas using nitrosourea (NU) derivatives such as BCNU and CCNU but the clinical results are not so remarkable compared with previous reports concerning experimental studies. The reason for an efficacy of NU derivatives in brain tumors is considered to be its higher lipid solubility which makes the drug crossing the BBB easily. On the other hand, there is some evidence that higher lipid solubility did not guarantee NU to reach always to all portions of solid tumor after systemic administration. We have performed a chemotherapy of malignant brain tumors using ACNU for five years. This drug is not only lipid but also water-soluble in some grade; therefore, the drug is administrated intravascularly and locally with ease. Nine cases of malignant gliomas were treated with local chemotherapy employing ACNU and two cases of glioblastomas are surviving now over five years and about four years, respectively. From the anatomical standpoint of view, it is considered to be necessary for local chemotherapy of brain tumors to possess some pathognomonic characters such as cyst formations, central necrosis and localized cortico-meningeal adhesions, which are rather frequently found in malignant gliomas and are suspected also easily by CT examination preoperatively. A local chemotherapy in the present study has been performed using 10 to 50 mg of ACNU through an indwelling catheter inserted during operation. No general toxicity occurred in all patients except one, who experienced purulent meningitis after long-term drainage. In our study on concentration of ACNU, intracarotid injection resulted in higher concentration in brain tumor tissue than intravenous injection, but these concentration considered to be not high enough to suppress the tumor cell growth. On the other hand, the intracavitary concentration of ACNU at 24 hr after drug administration was high enough to suppress the tumor cell growth.