Antibodies Against Hypothalamus and Pituitary Gland in Childhood-Onset Brain Tumors and Pituitary Dysfunction.

Purpose: To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction. Methods: We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls. Results: Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA (P = 0.001) and their titers (P = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA (P = 0.002) and their titers (P = 0.012). In addition, we found a significant association between radiotherapy and APA (P = 0.03). Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic-pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.

Use of 11C-methionine positron emission tomography in basal germinoma: assessment of treatment response and residual tumor.

INTRODUCTION: Prognosis of germinoma arising in the basal ganglia or thalamus is worse compared to that in the pineal or suprasellar region. One of the reasons for poor prognosis is the difficulty in evaluating the efficacy of treatment by conventional neuroimaging tools. PET STUDIES: The usefulness of (11)C-methionine (MET) positron emission tomography (PET) in monitoring the biological nature of brain tumors has been proved in glioma patients. CASE REPORTS: Herein, we describe MET-PET findings in three cases of germinomas in the basal ganglia or thalamus and discuss the use of MET-PET in the assessment of treatment response and residual tumor for the next treatment strategy. The patients showed transient increase of MET uptake in the lesions after the initial treatment. Although we did not perform histological verification, MET- PET findings suggested that active tumor cells were still alive in the lesions after the initial treatment. MET uptake gradually decreased during the course of intensive therapy in these patients. MET-PET also revealed germinoma invasion in the brain before discernible signal abnormality or mass lesion in conventional magnetic resonance images in two patients. DISCUSSION: Further studies including histological verification and long-term follow-up might validate the use of MET-PET in monitoring the treatment efficacy and evaluation of active residual tumor after the treatment. CONCLUSION: Until we understand what MET uptake truly represents, treatment strategy based on MET uptake must be carefully designed to prevent overtreatment and resultant complications.

[Case report of germinoma with synchronous lesions in the thalamus and para lateral ventricle].

A 25-year-old man presented with headache and consciousness disturbance. MRI revealed well enhanced mass lesions using gadolinium at bilateral thalamus and right para lateral ventricle with mild perifocal edema. Obstructive hydrocephalus was observed. On neuroendoscopic observation, the tumor was not appeared on the surface of the ventricle, therefore biopsy of the lesion was not sufficient to make a definitive pathological diagnosis. Third ventriculostomy was successful and the patient's consciousness improved. One week later, a stereotactic biopsy for right para lateral ventricle lesion made possible the histological diagnosis of typical germinoma. Post operative course was uneventful. Chemotherapy (CDDP and etoposide) following 30 Gy whole ventricle irradiation resulted in the complete response of the lesion. Four years later, he has no neurological deficit except for mild disturbance in his eye movement. Our experience suggests that a synchronous lesion at thalamus and para lateral ventricle seems to be due to subependymal infiltration other than CSF dissemination.

The germinomas arising from the basal ganglia and thalamus.

OBJECTIVE: To introduce the features of germinomas arising from the basal ganglia (BG) and thalamus. METHOD: Retrospective analysis was done with the clinical cases of germinomas in BG and thalamus from 1996 to 2000. The data included the symptoms, signs, neuroimaging findings, treatment, and outcomes. RESULT: Fourteen cases were included, only one female was included. The main symptoms are disorder of numbness and weakness in limbs. Neuroimaging showed no or mild peritumor high signal in T2 weighted imaging of magnetic resonance, accompanied with cyst, calcification or bleeding. Total gross resection was obtained in nine cases, subtotal resection in four. Follow-up data were available in 11 cases with average of 56 months. Eight cases underwent only postoperative radiotherapy, one underwent only chemotherapy, and two underwent both. One case died of complication 6 months after chemotherapy, the rest lived good life. CONCLUSION: Germinoma in BG and thalamus predominate in a boy. The neuroimaging features are very informative for diagnosis. Surgical resection should not be the first choice although it is has lesser complications. The long-term outcome is favorable.

An approach for cure: PEI-chemotherapy and regional deep hyperthermia in children and adolescents with unresectable malignant tumors.

BACKGROUND: Elevated temperatures of 40 - 44 degrees C increase the actions of various anticancer drugs including N-lost derivatives, cytotoxic antibiotics and platinum analoga. In clinical usage thermochemotherapy (TCH) should facilitate surgical resection and ameliorate local tumor control. PATIENTS AND METHODS: From 07/1993 to 12/2002 a total of 39 patients have been enrolled onto a phase-II study (female = 24, male = 15, age 1 - 37.5 years, median 5.2). Among these, 24 patients had extracranial non-testicular germ cell tumors and 15 patients soft tissue or chondrosarcomas. INDICATION: locoregional relapse (n = 29) or unresectable tumor after neoadjuvant chemotherapy (n = 10). Among these two groups, there were ten patients with poor response or progressive disease under primary or relapse chemotherapy. Ten out of the 29 relapse patients had more than one relapse. Tumor site: pelvis (30), abdomen (4), head and neck (2), proximal leg (2) and lumbar spine (1). Thermochemotherapy (TCH): 1800 - 2000 mg ifosfamide/m (2) and 100 mg etoposide/m (2) on days 1 - 4 and 40 mg cisplatin/m (2) on days 1 + 4 combined with regional deep hyperthermia (42 - 44 degrees C, 1 h) on days 1 + 4. RESULTS: In 39 protocol patients a total of 166 TCH courses (332 heat sessions) were applied. 20 patients achieved complete response, and 10 patients achieved partial response. TCH was followed by surgical tumor resection in 28/39 patients and/or radiotherapy in 13/39 patients. At a median follow-up of 27 months, outcome in this high-risk patient population was 22 NED, 3 AWD, 12 DOD, 2 DOC. Five year event free (EFS) and overall survival (OS) for the whole study cohort was 0.39 +/- 0.11 (20/39 patients) and 0.52 +/- 0.11 (25/39 patients), respectively. CONCLUSION: TCH shows substantial therapeutic efficacy and facilitates complete tumor resection in 14 out of 28 operated patients. Multimodal treatment including TCH, surgical resection and/or radiotherapy leads to sustained remission in the majority of patients with locoregional tumor recurrence. The therapeutic effect is most pronounced, if TCH is administered at first relapse. Due to the clinical and histologic heterogeneity the number of patients eligible for TCH is limited. Therefore, a more valid assessment of treatment efficacy can only be made by a matched-pair comparison in cooperation with the clinical registers.

Recommendations of follow-up after treatment of germ cell tumors.

Patients diagnosed with germ cell tumors (GCT) are relatively young, and most are rendered disease-free by primary treatment. Also, second-line therapies in nearly all instances are potentially curative. Therefore, the schedule and modalities of follow-up testing are important issues in detecting recurrence of GCT and for detecting secondary malignancies and complications of therapy. Follow-up is usually based on the pattern and probability of recurrence following primary therapy according to stage and histology. The National Comprehensive Cancer Network has outlined guidelines (www.nccn.org/physician_gls/index.html). There is a paucity of randomized data regarding the follow-up regimens most effective in identifying relapsed disease. Optimal means of imaging and frequency of physician visits and serum marker level measurements need to be further addressed.

Anaesthesiological experiences with whole body hyperthermia.

OBJECTIVE: In order to investigate the safety of whole body hyperthermia (WBH) within the context of systemic Cancer Multistep Therapy (sCMT) in patients with disseminated malignancies, cardiopulmonary changes and various organ functions were examined. METHODS AND PROCEDURES: Fifty-seven sCMT treatments were performed in 22 patients. WBH with a plateau phase of 1 h at 41.8 degrees C was induced by an IRATHERM 2000 device. Cardiopulmonary parameters were measured at 37, 40, 41.8 and 39 degrees C by use of a pulmonary artery catheter, femoral oxymetry and a radial artery catheter. Organ functions of the liver, kidney, cardiovascular and central nervous system were evaluated before and after treatment. RESULTS: Compared with the initial values, significant alterations were found of most cardiopulmonary parameters in the sense of hypercirculation at 41.8 degrees C. With the exception of extra vascular lung water index, all parameters showed a clear tendency towards the pre-treatment levels at 39 degrees C. In eight out of 57 sCMT treatments, reversible organ dysfunctions were observed. Comparison of radial and femoral arterial blood pressure showed significantly different values at 40 and 41.8 degrees C. CONCLUSIONS: WBH induces cardiovascular stress, but by careful selection of patients and appropriate anaesthesiological monitoring it can be performed safely using general anaesthesia. This enables further evaluation of WBH in multimodal treatment concepts.

Advanced non-seminomatous germ cell cancer of the testis with brain metastases: feasibility of additional brain irradiation and whole body hyperthermia plus chemotherapy.

Patients with brain metastases in disseminated non-seminomatous germ cell cancer of the testis are treated by combined modality, e.g., cisplatin-containing chemotherapy, whole brain irradiation and/or surgical excision. However, cure rates of patients refractory to that standard treatment are low (5-year survival rate <30%). Preclinical data on the use of hyperthermia combined with selected cytotoxic drugs clearly show increased tumor cell killing compared to chemotherapy alone with no increase in toxicity to normal tissue. These results are consistent with the concept that whole body hyperthermia (WBH) at 41.8 degrees C is non-myelosuppressive and can potentiate the tumoricidal effects of specific chemotherapeutic agents, thus improving the therapeutic index. We report on a patient with embryonal testicular cancer presenting with lung, liver and brain metastases who initially underwent orchiectomy, whole brain irradiation and cisplatin-containing chemotherapy. Restaging revealed minor regression of brain and lung metastases and no change of liver metastases. However, beta-HCG values dropped from initial 400000 mIU/ml to 12 mIU/ml with a normal alpha-fetoprotein all the time. Then, two cycles of whole body hyperthermia (WBH) plus chemotherapy were performed, followed by one cycle of chemotherapy without WBH. Radiotherapy, WBH and chemotherapy were well tolerated, especially no neurologic sequelae occurred. After more than 5 years of follow-up, the patient is still alive and disease-free. WBH plus chemotherapy seems to be feasible and may contribute to long-term survival in patients with advanced stages of non-seminomatous germ cell cancer refractory to standard treatment.