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The middle fossa approach is an excellent technique for removing appropriate vestibular schwannomas in patients with serviceable hearing. Knowledge of the intricate middle fossa anatomy is essential for optimal outcomes. Gross total removal can be achieved with preservation of hearing and facial nerve function, both in the immediate and long-term periods. This article provides an overview of the background and indications for the procedure, a description of the operative protocol, and a summary of the literature on postoperative hearing outcomes.

Between 1977 and 1988, 67 patients underwent surgical removal of residual metastatic deposits following an aggressive chemotherapy regimen (cisplatin, vincristine, methotrexate and bleomycin alternating with etoposide, actinomycin D and cyclophosphamide) for disseminated germ cell tumours of the testis (stage IIB or above). Ninety-one surgical procedures were performed. There were 63 (69 per cent) retroperitoneal lymph node dissections, 16 (18 per cent) thoracotomies, three (3 per cent) hepatic resections, three (3 per cent) craniotomies, five (5 per cent) delayed orchidectomies and one anterolateral decompression of the vertebral column. Nine (13 per cent) patients required a repeat retroperitoneal node dissection and one patient needed a repeat thoracotomy to remove recurrent metastatic deposits during the period of follow-up. Multivisceral resections and vascular reconstruction procedures were required in 20 (30 per cent) patients undergoing retroperitoneal node dissection. Fifty-five (82 per cent) patients remain in complete remission with a mean follow-up period of 49·6 months (range 2–121 months). Nine (13 per cent) patients died with metastatic disease between 2 months to 4 years after operation. There were three deaths in the perioperative period (4 per cent). The histology of the resected metastases revealed undifferentiated active tumour in 20 (30 per cent) patients, differentiated mature teratoma in 29 (43 per cent) patients and fibrosis/necrosis in 18 (27 per cent) patients. Twelve (60 per cent) patients with undifferentiated elements and 15 patients (60 per cent) with raised preoperative tumour markers (poor prognostic categories) are in complete remission. Cytoreductive surgery in patients with metastatic germ cell tumours offers the best chance of remission following chemotherapy even in poor prognostic group categories.

Increasing numbers of commercial assays for the established tumour markers are available which are capable of excellent analytical performance. Whilst all these assays are useful as research tools, their clinical value is more limited and should be appreciated before any decision is taken to offer a tumour marker assay service.Calcitonin (medullary carcinoma of thyroid), alphafetoprotein (hepatoma) and human chorionic gonadotrophin (choriocarcinoma) are the only tumour markers that can be used for screening for malignancy in high risk populations.Hormones, paraproteins, alphafetoprotein, human chorionic gonadotrophin and prostate specific antigen are valuable in establishing the diagnosis of certain tumour types.Alphafetoprotein and human chorionic gonadotrophin concentrations at the time of diagnosis are of value in predicting prognosis in specific tumour types.Although their sensitivity for a particular tumour type may be poor, most tumour markers can be used for monitoring the therapy and follow-up of selected marker positive patients.Optimal clinical results of the management of patients with malignancy are usually obtained by specialist centres, and laboratory tumour marker services should be established so that they are appropriate to local oncology specialities.

Cancer therapy utilising radiolabelled murine monoclonal antibodies frequently leads to the production of Human Anti-Mouse Antibodies (HAMA) in the recipient. HAMA interferes with “sandwich” immunoassays, such as those for tumour markers, rendering results unreliable. Published methods for eliminating HAMA from serum are not suitable for use in a laboratory which is processing a large number of assays using an automated system. We report on the use of Immunoglobulin Inhibiting Reagent (IIR) in CA125 assays from recipients of intraperitoneal radioimmunotherapy who had spuriously elevated results due to HAMA. IIR was found to be comparable to the admixture of mouse serum as a way of eliminating the effect of HAMA. IIR is ideally suited to use with an automated assay process.

Eighty-two patients with small cell lung cancer (SCLC), 32 with limited disease, were treated with alternating chemotherapy. Eight courses were administered at weekly intervals, and responding patients received radiotherapy to sites of bulk disease. Overall response rate was 76.8%. Overall median survival was 265 days, 408 days in patients with limited disease. The median symptom free period after chemotherapy was completed was 123 days. These results are comparable with those in reports of chemotherapy of longer duration and warrant the further investigation of short duration treatment in this disease.

The aim of this study was to evaluate the efficacy of high-dose paclitaxel in patients with previously untreated stage IV epithelial ovarian cancer. Paclitaxel was administered intravenously over 3 h at a dose of 225 mg m(-2) on a 21-day cycle for six courses. Thirty-six patients were entered into this study; all 36 were assessed for toxicity and 33 patients were evaluable for response. One patient had a complete response and 12 patients had partial responses (overall response rate 39.4%, 95% CI 23-58%). The overall median duration of response was 9 months (range 3.5-23+ months). The response rate to carboplatin following failure of paclitaxel within 1 year of stopping therapy was 57% (four out of seven patients). The median survival of patients was 17.2 months. The main toxicity encountered was neutropenia which was WHO grade 3 in 11 patients (31%) and WHO grade 4 in seven patients (19%). Granulocyte colony-stimulating factor (GCSF) was not given to any patient during the study. Other toxicities were: grade 3/4 infection (11%) and nausea and vomiting (11%); grade 3 bone pain (22%), fatigue (14%), diarrhoea (3%), myalgia/arthralgia (3%) and dry eyes (3%). Transient peripheral neuropathy occurred in 16 patients (44%), and alopecia was encountered in most patients (grade 2/3, 78%). Paclitaxel given at 225 mg m(-2) to patients with stage IV epithelial ovarian cancer is active, well tolerated and does not require GCSF support.

The purpose of our study was to investigate the efficacy and toxicity of paclitaxel in patients with relapsed or refractory epithelial ovarian cancer in the context of a large multicentre study performed in the UK and Eire. Patients with previously treated epithelial carcinoma of the ovary or fallopian tube who fulfilled the eligibility criteria were entered in the study. Eligibility criteria included: measurable or evaluable disease; Eastern Cooperative Oncology Group (ECOG) performance status 0-2; up to three prior chemotherapy regimens, one of which had to contain a platinum agent; adequate haematological, renal and hepatic function; and no significant cardiac history. Patients received either 175 mg m-2 or 135 mg m-2 paclitaxel. The lower dose was administered to patients who had received more than two prior chemotherapy regimens. Paclitaxel was given by i.v. infusion over 3 h every 21 days. Response was assessed at three-cycle intervals or earlier if required. A total of 155 patients were registered for the study in the UK of whom 140 were eligible for response and toxicity evaluation, and 12 patients were assessed for toxicity only. Hair loss was the most frequently reported toxicity, with 74% (119/152) of patients reporting grade 3 alopecia. The most frequently reported serious toxicity was neutropenia, with 49% (74/152) of patients experiencing neutropenia grade 3 or 4. The response rate was 16% [two complete responders (CR), 20 partial responders (PR)], the median duration of response was 275 days and median survival was 244 days. Paclitaxel is active in relapsed and platinum-resistant epithelial ovarian cancer. It is well tolerated and can be given in an out-patient setting. The UK and Eire experience is very similar to that of US investigators in this group of patients. Further work is required to assess the optimal use of the drug in both first- and second-line therapy.

Open or uncontrolled studies have suggested that providing cancer patients with audiotapes of their clinical interviews can improve information recall and reduce psychological distress. We tested these hypotheses in a 'clinician-blind', prospective, randomised controlled trial. A total of 117 patients newly referred to a medical oncology clinic who were to be given 'bad news' had their consultations audiotaped. Blind to the clinician, patients were randomly allocated to receive a copy of the tape to play at home or not (control group). At 6 months follow-up, tape group patients reported positive attitudes to the audiotape and were shown to recall significantly more information about their illness than did controls. Overall improvement in psychological distress at 1 and 6 months follow-up, as measured with the 30-item General Health Questionnaire and the Hospital Anxiety and Depression Scale was no different in the two groups. However, a second-order interaction suggested that poor-prognosis patients were disadvantaged specifically by access to the audiotape, with less improvement in psychological distress at 6 months follow-up than non-tape controls. Patient access to audiotapes of clinical interviews promotes factual retention but does not reliably reduce psychological distress and may be actively unhelpful in some subgroups of patients.

A total of 24 patients who were receiving combination chemotherapy (POMB) including cisplatin at a dose of 100–120 mg/m2 were treated with the 5HT3 antagonist GR38032F (GR) as an anti-emetic prophylaxis. GR was given as a 15-min laoding infusion followed by a 24-h infusion at three escalating dose levels of 1, 2 and 4 mg/h. In the first 24 h after commencing treatment, six patients had complete control of nausea and vomiting (CR), two had 1–2 emetic episodes (MR) and five had 3–5 emetic episodes (mR). The major response rate (CR+MR) was thus 35%. Eight responding patients (CR or MR) went on to receive oral GR at 8 or 12 mg t.i.d. for 5 days. In this group there was one CR, one MR, two mRs and four failures (F). There was no evidence of an improved therapeutic effect with increasing dose in either the infusion or the oral section of the study, although numbers were limited in the latter part of the trial. Toxicity was mild, with low-grade headache affecting 25% of patients being the most frequent side effect. Pharmacokinetic data was obtained in six patients at each dose level. There was a progressive rise in clearance with increasing dose, indicating that the kinetics are non-linear. However, there was no evidence of an association between high plasma levels and therapeutic efficacy. GR38032F is well tolerated and has promising single-agent activity in preventing vomiting induced by high-dose cisplatin.

A Phase 2 trial was conducted using intramuscular lymphoblastoid interferon (IFN, Wellcome Research Laboratories), 4 MU per day, in 10 patients with chemotherapy-resistant teratomas. There was stabilisation of disease in 2 patients both of whom were in retrospect considered to have had differentiated teratoma at the time of IFN administration. There was progression of presumed active anaplastic germ cell tumour in 8 patients. One of these patients, a 15-year-old boy with biopsy proven differentiated teratoma has received 2 courses of lymphoblastoid IFN and 1 course of recombinant leukocyte A IFN (Roche Products Ltd.) lasting 5 1/2, 8 and 8+ months respectively. He has had a mixed response in his differentiated tumour which on each occasion has been maintained for the duration that he received IFN. Rising HCG levels during his second course of interferon required additional cytotoxic chemotherapy. Lymphoblastoid IFN does not appear to be active against anaplastic germ cell tumours but both lymphoblastoid and recombinant leukocyte A IFN may be useful in the treatment of unresectable differentiated teratoma.

Between 1977 and November 1979 we have treated 53 patients with malignant teratomas (43 males, 10 females). Thirty (70%) out of the 43 male patients had advanced and bulky disease at the time of presentation. Using different drug combinations in a sequential manner as described below, results are as follows: of the initial 33 male patients, 22 (67%) have discontinued treatment (mean 9.5 months). Nineteen have responded completely and 3 have static computed tomography (CT) nodules. Life-table analysis projects a survival of 66% (analysis at 1 December 1979). Nine out of 10 ovarian teratoma patients are alive. Adverse prognostic factors at the start of treatment were recognized in 9/10 male patients and the 1 female patient who have died. Although the survival of patients with malignant teratomas has improved dramatically, there are still problems with drug resistance in patients with very advanced disease. Patients with these tumours should continue to be treated in centres specializing in managing what has now become a potentially curable disease in most cases.

Using electron microscope cytochemistry and cells separated on Ficoll-Hypaque, Mg2+-dependent ATPase, ADPase and 5′-nucleotidase were predominantly localized as ectoenzymes on normal human granulocytes. Large deposits of ATPase final reaction product and more finely granular deposits of 5′-nucleotidase final reaction product were firmly attached to the outer surface of cell plasma membranes. The final reaction product from ecto-ADPase was, however, only loosely associated with the plasma membrane. In addition, finer deposits of ADPase final reaction product were seen in specific granules and in background cytoplasm. No nucleotidase phosphatase activity was localized to the alkaline phosphatase-containing granules (phosphasomes) recently described by Rustinet al. In granulocytes from patients with chronic granulocytic leukaemia, ecto-ATPase had a patchy distribution on the plasma membranes. There was considerable heterogeneity between cells with regard to ADPase and 5′-nucleotidase localization. In some cells, ADPase was seen only as an ectoenzyme and in a few it was present in specific granules, but in others it was seen at both sites, while in some cells no activity was detected. 5′-Nucleotidase localization was normal in some cells but lacking from many. No correlation was found between enzyme heterogeneity and the degree of morphological cell maturity.

The intracellular localization of alkaline phosphatase was determined in human neutrophils by electron microscope cytochemistry. In normal individuals, the largest and most intense deposits of reaction product were seen in a unique cytoplasmic granule population termed ‘phosphasomes’. Lighter deposits were seen on nuclear membranes, some intracytoplasmic membranes lining vacuoles and granules and occasionally in focal patches on the internal surface of the plasma membrane. In cell isolated from women in the third trimester of pregnancy, activity was found in the same intracellular sites but there were, on average, more alkaline phosphatase-containing granules per cell than in the cells from non-pregnant individuals. Neutrophils from pregnant women were also characterized by the presence of large deposits of reaction product on the external surface of the plasma membrane (extramembranous). This activity had properties characteristic of the placental isoenzyme of alkaline phosphatase, found in serum during pregnancy. Neutrophils from patients with chronic granulocytic leukaemia, showing normal mature morphology, contained significant amounts of granule reaction product but there were fewer phosphasomes per cell than in normal individuals. In morphologically immature cells, reaction product was present in nuclear membrane, endoplasmic reticulum and large granules. These results were in agreement with previous biochemical data confirming a quantitative lack of alkaline phosphatase in chronic granulocytic leukaemia.

Resistance of tumour cells to methylating and monochloroethylating agents in vitro and in vivo has been linked to levels of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). In a clinical trial of temozolomide in advanced malignant melanoma, the relationship between pretreatment MGMT levels in biopsies of cutaneous tumours and involved lymph nodes and clinical response to the drug has been studied. Among 50 evaluable patients, there were three complete responses (CR), four partial responses (PR), six with stable disease (SD) and 37 with progressive disease (PD), with an overall response rate of 14%. In 33 patients in whom MGMT level and clinical response could be evaluated, the tumour MGMT levels (fmol mg(-1) protein) were: CR, 158 +/- 119; PR, 607 +/- 481; NC, 171 +/- 101; PD, 185 +/- 42.3. Thus, measurements of pretreatment levels of MGMT in melanoma did not predict for response to temozolomide.

Twenty patients with advanced testicular teratoma and 1 with advanced seminoma have undergone abdominal surgery for the removal of residual disease following treatment by sequential chemotherapy (1). Fourteen out of the 21 patients (66 per cent) have achieved complete remission with a follow-up period of 6–41 months. In 12 patients (57 per cent) the tumour had undergone histological maturation or necrosis following chemotherapy, those patients in whom the tumour remained histologically active having a worse prognosis. Raised preoperative serum levels of the tumour markers human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) indicating active disease, forecast a particularly poor prognosis, 5 out of 9 such patients (55 per cent) having died. Computerized tomography gave false negative results in 3 patients (14 per cent). Postoperative complications were few, and only 2 patients (9 per cent) suffered with failure of ejaculation. At present our policy is surgical removal of any residual mass after chemotherapy to determine the histology, and, wherever possible, to achieve complete clinical and biochemical remission. Six patients with an apparently poor prognosis have benefited directly from surgery and remain in long term remission. The selection of patients who benefit most from surgery can only be determined by more experience and longer follow up.

Flavone acetic acid (FAA), 8.6 gm-2 has been administered by 6h intravenous infusion to 19 patients with advanced colorectal carcinoma and 15 patients with advanced malignant melanoma. The drug associated toxicity was generally mild and as predicted from the phase I study. No responses were seen in either disease.

TO THE EDITOR. —Choriocarcinoma is a trophoblastic tumor that is usually of placental origin. Metastatic lesions are common, and therefore this diagnosis should be considered in a young woman with metastatic cancer.1 Metastases to the choroid are extremely rare. To our knowledge, this is the first reported case of choroidal metastases of choriocarcinoma responding to systemic chemotherapy. REPORT OF A CASE. —The patient, a 32-year-old woman, was referred to Moorfields Eye Hospital, London, England, with a 33-day history of blurred vision in her left eye. She denied any previous ocular episodes, medical problems, or constitutional symptoms. She stated that her menses had been irregular for the past 2 months, but denied that she could be pregnant. Her last pregnancy was 4 years earlier.Pinhole acuities were 6/6 OD and 6/12 OS on visual testing. Pupillary responses and ocular movements were normal. The slit-lamp examination findings were normal. Dilated