Pure ovarian choriocarinoma mimicking ectopic pregnancy in true hermaphroditism.

Ovarian choriocarinoma is a rare tumor and has not been described before in a true hermaphrodite condition. A 23-year-old karyotype 46XX parous female was admitted to hospital because of amenorrhea, irregular vaginal bleeding, an adnexal mass, and an increased beta-hCG serum level. Ectopic pregnancy was suspected three times and exploratory laparoscopy done each time removing the right ovarian mass and local pelvic and omental spread. Final pathology revealed a true hermaphrodite state with testicular tissue with distinct tubules, ovarian tissue with follicles, and ovarian choriocarinoma with necrosis and hemorrhage. She received chemotherapy followed by radical pelvic surgery.

Delayed effects of whole brain radiotherapy in germ cell tumor patients with central nervous system metastases.

PURPOSE: Central nervous system (CNS) metastases are uncommon in patients with germ cell tumors, with an incidence of 2-3%. CNS metastases have been managed with whole brain radiotherapy (WBRT) and concomitant cisplatin-based combination chemotherapy. Our previous study did not observe serious CNS toxicity (Int J Radiat Oncol Biol Phys 1991;22:17-22). We now report on 5 patients who developed delayed significant CNS toxicity. PATIENTS AND METHODS: We observed 5 patients with delayed CNS toxicity. The initial diagnosis was between 1981 and 2003. All patients had poor-risk disease according to the International Germ Cell Consensus Collaborative Group criteria. Of the 5 patients, 3 had CNS metastases at diagnosis and 2 developed relapses with CNS metastases. These 5 patients underwent WBRT to 4,000-5,000 cGy in 18-28 fractions concurrently with cisplatin-based chemotherapy. RESULTS: All 5 patients developed delayed symptoms consistent with progressive multifocal leukoencephalopathy. The symptoms included seizures, hemiparesis, cranial neuropathy, headaches, blindness, dementia, and ataxia. The median time from WBRT to CNS symptoms was 72 months (range, 9-228). Head imaging revealed multiple abnormalities consistent with gliosis and diffuse cerebral atrophy. Of the 5 patients, 3 had progressive and 2 stable symptoms. Treatment with surgery and/or steroids had modest benefit. The progressive multifocal leukoencephalopathy resulted in significant debility in all 5 patients, resulting in death (3 patients), loss of work, steroid-induced morbidity, and recurrent hospitalizations. CONCLUSION: Whole brain radiotherapy is not innocuous in young patients with germ cell tumors and can cause late CNS toxicity.

Successful neoadjuvant synchronous chemo- and radiotherapy for disseminated primary intracranial choriocarcinoma: case report.

We report a 17-year-old male with disseminated intracranial choriocarcinoma at the basal ganglia whose consciousness level was very low at diagnosis. He received neoadjuvant therapy (NAT) consisting of combined chemo- and radiotherapy prior to radical excision of the tumor. Postoperatively he was treated with three courses of high-dose chemotherapy (carboplatin (CBDCA), methotrexate (MTX), and etoposide (VP-16)) and peripheral blood stem-cell transplantation. This combination of therapies resulted in tumor regression on MRI and remarkable improvement in his neurological condition. Ours is the first report of the effectiveness of NAT followed by radical surgery in a patient with disseminated primary intracranial choriocarcinoma.

Mixed germinoma and choriocarcinoma in the intramedullary spinal cord: case report and review of the literature.

Primary germinomas in the spinal cord are very rare with only 15 cases published previously. In this case a 22-year-old woman with urinary incontinence, lumbago, and bilateral leg pain and weakness was found to have a solid tumor in the conus medullaris between the L1 and L2 vertebral bodies. Serum HCG was elevated without pregnancy. The pathological diagnosis was mixed germinoma and choriocarcinoma of the intramedullary spinal cord. She received craninospinal irradiation and three courses of chemotherapy and is currently asymptomatic with no evidence of recurrence and metastasis 22 months after surgery. To our knowledge, this is the first case report of a patient with a primary mixed germinoma and choriocarcinoma of the intramedullary spinal cord. The previous 15 cases of primary spinal cord germinoma have been reviewed for comparison.

Radiation therapy for intracranial germ cell tumors.

PURPOSE: To review the combined experiences of University of California, San Francisco, and Stanford University Medical Center in the treatment of intracranial germ cell tumors (GCT) and to assess the impact of craniospinal radiation (CSI) on patterns of relapse, progression-free survival (PFS), and overall survival (OS). PATIENTS AND METHODS: Ninety-three patients received radiation for newly diagnosed intracranial GCTs, including 49 germinomas, 16 nongerminomatous GCTs (NGGCT), and 28 with no biopsy. Median follow-up for surviving patients was 4.5 years (range 0.25-34). Tests for variables correlating with OS and PFS were conducted using Cox proportional hazards model. RESULTS: Five-year PFS and OS rates were 60% +/- 15% and 68% +/- 14% for patients with NGGCT and 88% +/- 5% and 93% +/- 4% for those with germinoma. Of 6 patients with localized NGGCT who did not receive CSI, 1 experienced an isolated spinal recurrence but was salvaged. Of 41 patients with localized germinoma, 6 who received CSI and 35 who did not, no isolated spinal cord relapses occurred. Twenty-one patients with localized germinoma received neither CSI nor whole brain radiation. Of these, none of 18 with ventricular radiation relapsed. One of 3 patients with primary tumor radiation relapsed intracranially but had only received 11 Gy at initial treatment. On multivariate analysis, germinoma histology but not CSI correlated with improved PFS and OS. CONCLUSION: CSI is not indicated in the treatment of localized germinomas. For patients with localized germinomas treated with radiation alone, we recommend ventricular irradiation followed by primary tumor boost to a total of 45-50 Gy.

[Cerebral metastasis in choriocarcinoma a case report]. / Zerebrale Metastasen beim Chorionkarzinom: ein Fallbericht.

Choriocarcinoma are malignant neoplastic tumors from the trophoblastic tissue with a tendency to early metastases. Beside pulmonary metastases there are often cerebral metastases, leading to intracerebral hemorrhage often responsible for the first clinical symptoms. In young women, symptoms like vaginal or pulmonary bleeding or neurologic disturbances shortly after a hydatiform mole or a normal pregnancy, accompanied by high levels of HCG in serum and CSF, choriocarcinoma should be considered. Choriocarcinoma are very sensitive to chemotherapy, which consists--depending on the stage of the disease--of a mono- or polychemotherapy. Cure rates are high, even in extended stages with cerebral metastases--as in the case described. Brain metastases with or without oncotic aneurysms can be rapidly controlled by immediate whole brain irradiation. Surgical interventions may be necessary in the case of life threatening bleedings. Levels of HCG in serum and cerebrospinal fluid are good markers to control the effect of therapy. But--as shown in this patient--levels of HCG in CSF may decrease protracted without affecting prognosis. Oncotic aneurysms are rarely reported and mostly detected post mortem. The presented case leads to a more optimistic attitude and demonstrates efficacy of immediately started radio- and chemotherapy.

[Role of radiotherapy in the combined treatment of uterine choriocarcinoma with brain metastasis]. / Rol' luchevoi terapii v kombinirovannom lechenii bol'nykh khoriokartsinomoi matki s metastazami v golovnoi mozg.

A retrospective analysis of data on 27 patients with uterine choriocarcinoma metastatic to the brain and other distant sites treated at the Center's Clinic (1980-1996) has been undertaken. Advantages offered by combined treatment (irradiation of the brain + combination chemotherapy) of 15 patients are discussed and practical advice is given.

Radiation therapy for primary intracranial germ-cell tumors.

PURPOSE: To evaluate the diagnosis, therapy, and survival of patients with intracranial germ-cell tumors. To define the role of prophylactic craniospinal irradiation and chemotherapy necessary to impact on survival. METHODS AND MATERIALS: Forty-eight patients with surgically confirmed or suspected primary intracranial germ-cell tumors treated at UCSF between 1968-1990 were reviewed. Thirty-four patients had a pathologic diagnosis, including 24 germinomas, 3 malignant teratomas, 2 choriocarcinomas, 1 embryonal carcinoma, 1 endodermal sinus tumor, and 3 mixed tumors. Information obtained included histology, location, cerebrospinal fluid (CSF) cytology, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (B-HCG), metastatic evaluation, radiation details, survival, and sites of failure. Minimum follow-up time was 2 years and ranged to a maximum of 24 years, with a median of 8 years. RESULTS: Median age at diagnosis was 16 years with 36 males and 12 females. Ten of 32 patients had elevated B-HCG at diagnosis; 6 of 29 had elevations of AFP. Cerebrospinal fluid cytology was negative in 35 of 36 patients evaluated; myelography or spinal MRI was positive in only 1 of 31 patients studied. Five-year actuarial disease-free survival after irradiation was 91% for germinomas, 63% for unbiopsied tumors, and 60% for nongerminoma germ-cell tumors with doses of 50-54 Gy to the local tumor site with or without whole-brain or whole-ventricular irradiation. Routine prophylactic cranio-spinal axis irradiation was not given with a spinal only failure rate of 2%. Eleven of 48 patients have expired, with an actuarial 5-year survival rate of 100% for germinomas, 79% for nonbiopsied tumors, and 80% for nongerminoma germ-cell tumors. CONCLUSION: With complete diagnostic craniospinal evaluation, spinal irradiation is not necessary. Cure rates for germinomas are excellent with irradiation alone. Multidrug chemotherapy is necessary with irradiation for nongerminoma germ-cell tumors. Histology is the most important prognostic factor; therefore, all patients should have surgical conformation of their diagnosis so that appropriate treatment can be given.

A case report on radiotherapy in choriocarcinoma: a life saving procedure.

Radiation therapy was tried to control hemorrhage from uterine cavity in a case of choriocarcinoma in which surgery was not practically possible due to the presence of a large nodule extending from suburethral region up to anterior fornix involving the entire anterior vaginal wall and patient being in a very critical condition. Radiotherapy was found to be successful and life saving.

Prognosis of intracranial germ cell tumours: effectiveness of chemotherapy with cisplatin and etoposide (CDDP and VP-16).

A co-operative study for patients with intracranial germ cell tumours was performed to analyze their prognosis and the effectiveness of Cisplatin/Etoposide (CDDP/VP-16) chemotherapy. A total of 46 patients; 30 primary and 16 recurrent cases were registered from 15 participating neurosurgical institutions in Japan. Based on histological criteria and tumour markers, they were classified into three groups; germinoma, germinoma with syncytiotrophoblastic giant cell (STGC), and non-germinomatous malignant tumour. Sixteen patients were treated with CDDP/VP-16 chemotherapy alone and the other 30 patients were treated by a combination of surgery and/or radiation in addition to chemotherapy. Eleven out of 13 patients (85%) with germinoma showed a complete (n = 10) or partial (n = 1) response to CDDP/VP-16 chemotherapy even if their tumours were recurrent and there was evidence of CSF dissemination. For the germinoma with STGC and non-germinomatous malignant tumour, a high response rate; 100% for the former and 78% for the latter, could also be achieved in both the primary and the recurrent cases except in those cases of immature teratoma. Their survival times were still different between them. Two-year survival was 50% in germinoma with STGC and 48% in non-germinoma, while it was 88% in germinoma cases.

Optimum management of pineal germ cell tumours.

Non-seminomatous pineal region germ cell tumours have a poor prognosis when treated with radiation alone but little is known of the results of treatment with modern chemotherapy. Between 1983 and 1990 five pineal region germ cell tumours presented to the Charing Cross Hospital, London. All five patients received the EpPlt/OMB chemotherapy schedule with escalated dose systemic methotrexate and intra-CSF methotrexate. Two patients had had prior radiotherapy. Four patients (80%) remain well and disease-free 6 months--5 years after completing therapy. Chemotherapy is an effective modality for the treatment of pineal germ cell tumours and should be used when non-seminomatous elements are present or when the placement of ventriculo-peritoneal shunt in the presence of malignant cells in the CSF presents a risk of dissemination.

Tissue dose estimates following the selective uptake of 125IUdR and other radiolabelled thymidine precursors in resistant tumours.

For the purposes of evaluation of the therapeutic potential of the radiohalogenated thymidine analogue 125IUdR, estimation of the radiation dose to the tumour cells and normal tissues is important. To determine the dose to any tissue from the radionuclide 125I is not simple, since the major emissions are very short-range Auger electrons. The cytotoxicity of 125I is strongly dependent on the position of the decay relative to the DNA, the principal target for cell sterilization. Estimates of the cytotoxicity of 125I based on the traditional MIRD recommended formulation (ICRU Report 32, 1979) may produce gross underestimates if it is incorporated into the DNA via the thymidine precursor 125IUdR. In this work, tissue count and autoradiography (ARG) data from studies by Bagshawe et al were used to estimate tissue doses following the administration of 125IUdR to LS174/T (a colorectal carcinoma) and CC3 (a choriocarcinoma) tumour-bearing animals, after a hydroxyurea block of the normal tissue turnover. The tumour cell toxicity is estimated from ARG data on the degree of 125I incorporation into the cell nucleus. Major drawbacks with 125I for this type of therapy are the long 60-day half-life, leading to radiological and waste disposal problems and the extreme short range of the radiotoxic effects. Possible alternative radiohalogens, 13I, 77Br, 131I and 211At, are suggested in place of 125I in the thymidine analog iododeoxyuridine. Dose calculations are performed and cytotoxicities estimated on the assumption that their biological retention characteristics are the same as for 125IUdR.

[Radiotherapy for brain metastasis of malignant trophoblastic tumor].

From 1982 to 1985, 26 patients with malignant trophoblastic tumor were treated. Of them, 8 patients developed brain metastasis. Seven out of these 8 patients were treated with 60Co whole brain radiotherapy. The total dose on the longitudinal mid-plane of brain was 3300 cGy/2-3 weeks. Four patients were cured, 3 of them have survived without recurrence or sequelae for 6.5, 6 and 4.5 years, respectively; the other one died of liver metastasis 1 year after radiotherapy. Radiotherapy is an effective method in the combined treatment for brain metastasis of malignant trophoblastic tumors.

Brain metastasis from nonseminomatous germ cell tumors of the testis: case report and review of the role of surgery.

The prognosis for patients with nonseminomatous germ cell tumor of the testis is good, even when extensive metastatic disease is present, because this tumor is very sensitive to chemotherapy with cisplatin, vinblastine, and bleomycin (PVB). If a metastasis occurs in the brain, however, the prognosis is poor because the blood-brain barrier limits the entrance of these drugs into the brain and creates a sanctuary for tumor. The current treatment for a brain metastasis is either standard PVB chemotherapy plus whole brain radiation therapy or a rigorous chemotheraputic regimen that penetrates the blood-brain barrier better than PVB. Surgery is seldom used for brain metastasis, largely because of the poor results with surgical debulking in noncentral nervous system disease. This is the report of a patient with disseminated nonseminomatous germ cell tumor and multiple large brain metastases, who was treated with surgery, PVB, and whole brain radiation therapy and cured. Evidence is presented to support a role for surgical debulking in patients with large brain metastasis.

[Causes of death after the first sessions of irradiation of the brain in metastatic involvement]. / Prichiny smerti posle pervykh fraktsii pri obluchenii golovnogo mozga pri ego metastaticheskom porazhenii.

Of 240 patients irradiated for metastatic brain tumors 4 died 4.5-60 h after the first session of irradiation at doses of 1.7-6 Gy. A clinicomorphological analysis showed that the main cause of death was acute microcirculatory disturbance in cerebral tissues with the formation of new hemorrhagic microfoci associated with severe disorders of cerebral tissues as a result of their involvement by far-advanced tumors.

[Recent advances in the treatment of choriocarcinoma].

Recent advances in intensive care procedures have improved the therapeutic results of choriocarcinoma treatment. The mortality of patients with choriocarcinoma, which was 100% in 1958, has gradually decreased, and finally fell to about 10% in 1983. These favorable results have been mainly due to the progress made in chemotherapy, including combined administration of methotrexate and actinomycin-D. However, recent progress has been chiefly dependent on intensive care procedures, involving so-called multidisciplinary treatment, including surgical treatment for pulmonary or intracranial metastatic foci and whole-brain irradiation. When the treatment results for choriocarcinoma were compared between metastatic and non-metastatic cases, the mortality, which had decreased for both groups with time, had already reached 0% in non-metastatic cases, although it was still about 20% in metastatic cases. These results have made it clear that the most important aspect is how to treat choriocarcinoma metastatic foci. With the goal of finding some form of treatment that will help to attain complete cure of choriocarcinoma, we present here details of recent progress made in choriocarcinoma treatment.

Role of surgical therapy and radiotherapy in gestational trophoblastic disease.

Surgical procedures and radiotherapy continue to play a significant role in the management of gestational trophoblastic disease (GTD) despite continuing advances in chemotherapy. Suction curettage and hysterectomy are preferred techniques for evacuation of hydatidiform mole. Although primary chemotherapy alone is usually successful in women with nonmetastatic or good-prognosis metastatic GTD, hysterectomy is useful in selected patients to decrease the amount of chemotherapy required to produce remission or as salvage therapy in patients who have failed primary chemotherapy. Even among patients with poor-prognosis metastatic GTD, such adjunctive surgical procedures as hysterectomy, thoracotomy and craniotomy may be useful. Whole brain and liver irradiation is employed as adjuvant therapy to reduce hemorrhagic complications of brain and liver metastases.