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The association of neoplastic disease and thromboembolic disorders was first recognized by Trousseau in 1865. Abnormalities of blood coagulation tests have been reported in the majority of patients with cancer, including ovarian carcinoma. However, Trousseau's syndrome has rarely been reported in women with ovarian carcinoma.A literature search for cases of Trousseau's syndrome in association with ovarian carcinoma was performed using the MEDLINE database. Case notes of patients with ovarian carcinoma treated at St. George's Hospital were reviewed and cases of Trousseau's syndrome identified.We report a series of 4 cases of Trousseau's syndrome in association with ovarian carcinoma occurring over a 3- to 4-year period, and highlight the particular difficulties associated with the management of these thromboembolic effects.Trousseau's syndrome can impair quality of life in patients with advanced ovarian carcinoma and enhanced anticoagulation regimens may be required for effective palliation.

A 55-year-old woman with total situs inversus viscerum was subjected to total thyroidectomy for a well-differentiated follicular thyroid carcinoma. After surgery the patient remained euthyroid for two months and serum TSH did not rise. A whole body scan with iodine-131 (131I) showed mediastinal uptake. A chest computed tomography visualized a sequestered substernal goiter. Upon the patient's refusal to undergo surgery, she was treated with 150 mCi of 131I. A further dose of 100 mCi of 131I was administered six months later. Ten years after treatment, the patient is still alive and disease-free.

Eosinophilic pustular folliculitis is a rare disorder previously reported predominantly in Japanese people who are otherwise healthy. Recently, the disorder has been noted in patients with acquired immune deficiency syndrome, as has eosinophilic folliculitis, a similar but distinct entity. The authors report a patient with eosinophilic folliculitis who was immunocompromised after high dose chemotherapy and bone marrow autograft for treatment of non-Hodgkin's lymphoma.

To assess the ability of color Doppler flow imaging to help evaluate the response of breast cancer to medical therapy.Thirty-four patients with large or centrally located breast carcinomas were studied. All tumors had been treated medically. Tumor size was assessed at clinical examination, volume at B-mode ultrasound (US), and vascularity at color Doppler flow imaging. The changes seen during the treatment course were cross compared and correlated with final tumor response.In 97 of the 126 treatment cycles (77%), changes in vascularity were concordant with changes in the size of the tumors (reduction in the vascularity with response to therapy and an increase in tumor size with lack of response or progression). Changes seen at color Doppler flow imaging occurred at least 4 weeks before those seen at clinical and B-mode US examination in 40% and 38% of cases, respectively. Changes in vascularity could be assessed in every patient.Color Doppler flow imaging can help assessed and predict the response of breast cancer to medical treatment.

Early diagnosis of postinfarction left ventricular aneurysm is mandatory. We suggest that Tc 99m-albumin radionuclide angiography, Tc 99m-MIBI scintigraphy and magnetic resonance study of the heart as useful non-invasive diagnostic tools.

PURPOSE To evaluate the use of high-dose busulfan (HDB) with autologous bone marrow transplantation (ABMT) in patients with myeloma. PATIENTS AND METHODS Fifteen patients received HDB (16 mg/kg), eight of whom received high-dose melphalan (HDM) but had experienced a short remission or progression-free interval. Two patients had received HDM on two previous occasions, one had no response to low-dose melphalan, and four had impaired renal function (edathamil clearance < 40 mL/min). All patients received induction chemotherapy before HDB. RESULTS Two patients were in complete remission (CR) after induction chemotherapy before HDB. Of the remaining 13 patients, four (31%) achieved CR and two (15%) achieved a partial remission for an overall response rate of 46%. There were three treatment-related deaths, but the toxicity was otherwise predictable and manageable. CONCLUSIONS In heavily pretreated patients, HDB results in a relatively high response rate. It can also be used safely in patients with renal impairment who are not suitable for HDM.

19F Magnetic resonance spectroscopy (MRS) has been used to monitor the metabolism of the chemothgrapeutic drug 5-fluorouracil (5FU) in patients with hepatic metastatic disease (Wolf et al. 1987; Glaholm et al. 1990; Semmler et al. 1990). Glaholm et al. compared the time course of 5FU metabolism following intravenous and intraperitoneal administration, noting the build-up and decay of 5FU and its major catabolites in the liver. Semmler et al. reported intra-arterial administration of 5FU, observing in one case the presence of fluoronucleotides. In all of these studies 5FU metabolism was observed following bolus administration or rapid infusion of approximately 1 g 5FU.

We describe a case of histologically confirmed malignant melanoma of the nipple. The rare occurrence of these lesions accounts for the relative lack of criteria for standard surgical treatment. After a conventional workup including mammography, chest X ray, bone scan, liver ultrasonography and cytologic smear of the lesion, we used specific radiolabeled monoclonal antibody and external photoscanning to differentiate melanoma from Paget's disease. The patient underwent wide local excision of the lesion and axillary node dissection, and tumor control is optimal since she has no evidence of disease after 5 years of follow-up.

This paper reports the clinical features of 2 patients affected by mixed transcortical aphasia. Both of them had extensive damage of the left hemisphere. Cerebral blood flow measurement showed a marked decrease in left-hemisphere flow. In particular, speech areas were found to be morphologically and functionally damaged. The present findings, together with a critical review of the literature, served as a starting point for a discussion of linguistic features, diagnostic criteria and classical neuroanatomical interpretation of mixed transcortical aphasia. The possible contribution of the right hemisphere in determining this aphasic syndrome is suggested.

Using an antiserum to epithelial membrane antigen we have screened multiple bone marrow aspirates from 350 patients with primary breast cancer taken at the time of initial surgery. 89 (25%) patients were found to have micrometastases and their presence was related to pathological size (P less than 0.01), the presence of peritumoral vascular invasion (P less than 0.001), and positive lymph nodes (P less than 0.005) but not menopausal status. At a median follow-up of 76 months (range 34-108) 107 patients had relapsed with distant metastases. 48% (43 of 89) of these patients had micrometastases initially compared with 25% (64 of 261) who did not (P less than 0.005). The test predicts for relapse in bone (P less than 0.01) and other distant sites excluding bone (P less than 0.001) and is associated with a shorter overall survival (P less than 0.005). We conclude that the detection of micrometastases signals a high likelihood of early relapse and decreased survival in breast cancer.

We investigated the effects of the antimycotic agent amphotericin B (AmB) on the phagocytic activity of the isolated perfused rat liver. At a concentration of 5 microM, the drug markedly reduced the clearance of latex beads by the liver as compared to control preparations. Scanning electron microscopy observations showed that latex beads were attached only to Kupffer cells. A liver scan performed infusing 99Tc-colloidal albumin showed that AmB depressed the uptake of the colloid in all hepatic lobes, with no focal defects. Both in control and AmB experiments no trypan blue uptake occurred. The pretreatment of the perfused liver with the calcium antagonist nifedipine prevented the decrease in phagocytosis induced by AmB. In addition, AmB had no effect on livers perfused with a Ca2(+)-free medium. A decrease in the phagocytic capacity of the perfused liver was also observed after the administration of the Ca2(+)-ionophore A23187. The observations suggest that AmB may exert an intrinsic toxicity on the Kupffer cells, which is, at least in part, responsible for the decrease in phagocytosis induced by the drug. This effect may be of relevance to clinical situations and deserves careful consideration.

The case histories of 15 patients with endometrial stromal sarcoma attending the Royal Marsden Hospital between 1973 and 1987 were reviewed. Eight patients were classified as having low-grade and seven as high-grade tumors using specific histological criteria. Those patients with low-grade tumors had a long relapse-free and overall survival in the absence of receiving specific therapy after initial surgery. Five are alive and disease free, one has shown a partial response to hormonal manipulation, and one is alive with disease on no therapy. Only one patient has died and this occurred 111 months postdiagnosis. Conversely, all seven patients with high-grade tumors relapsed with local disease and three have died. Thus, after surgical resection patients with low-grade tumors probably do not require treatment until relapse, whereas adjuvant radiotherapy should be given to those patients with high-grade tumors. On relapse, hormone therapy should be the treatment of first choice for patients with low-grade tumors, whereas chemotherapy is more appropriate for patients with high-grade tumors.

Pulmonary arterio-venous fistula is a rare congenital lesion of the pulmonary vasculature, causing cyanosis in children. The lesion can be solitary or multiple, usually involves the lower lobes and is often associated with the Rendu-Osler-Weber syndrome. The case of a 9-year-old boy is reported in whom diagnosis was made on pulmonary angiophotoscintigraphy and confirmed at angiography. The usual treatment of choice of these lesions is lobectomy which promptly relieves the symptoms.

To evaluate alterations induced by injectedmurine radiolabelled F(ab’)2fragments of the anti HMW-MAA MoAb 225.28S on the principal haemato-immunological parameters, 32 patients with advanced malignant melanoma were studied. No statistically significant change was found after MoAb administration, but monocytes (3h after injection) and granular eosinophils (24 h after) were reduced and circulating immune complexes increased (3 h after). No toxic effect or adverse reaction was observed.Therefore, the controlled administration of purified MoAb fragments for diagnostic purposes seems to involve only a very low risk of immediate adverse reactions

In 141 postmenopausal node-positive patients with primary breast cancer, routine biochemical markers (alkaline phosphatase, gamma-glutamyl transpeptidase, carcinoembryonic antigen), and chest x-ray, in combination with history and clinical examination, have been performed at 3 monthly intervals for at least 2 years. Sixty one patients relapsed at a median time of 14 months. The recurrence was detected at routine follow-up in 40 (66%) patients. Of these 40 patients, 26 (65%) presented with symptoms, 11 (28%) were asymptomatic but were found to have relapsed on clinical examination, and only 3 (8%) had their relapse diagnosed on the basis of an abnormal chest x-ray. The remaining 21 patients presented early with symptoms. Therefore symptoms and clinical examination accounted for the detection of relapse in 58 of the 61 (95%) patients. Of the patients who had relapsed, 49% (30 of 61) had one or more abnormal markers/chest x-rays prior to relapse, rising to 79% (48 of 61) at the time of relapse. Of 80 patients with no evidence of recurrence, 36% (29) had no marker abnormality recorded, whereas in 64% (51) one or more abnormalities were found. These results suggest that history and examination are the important procedures in follow-up, and that abnormal markers are not always due to metastatic disease and may be misleading.

Over 150 cases of central nervous system tumors have been studied with positron emission tomography using fluorine-18-labeled fluorodeoxyglucose (18FDG) as a tracer. From this material 100 consecutive cases of cerebral glioma have been reviewed and analyzed. The results show a strong correlation of tumor grade with glycolytic rate, with visual "hot spots" present in all high-grade neoplasms and in only four low-grade tumors. The quantitative accuracy is limited by three basic factors. First, the measurement of tissue uptake, as compared with the parent technique, autoradiography, is more difficult because detection must be done outside the body. Effects such as scattered radiation and self-attenuation introduce errors unless properly corrected. A more serious problem when measuring small structures, such as a rim-shaped high-grade glioma, is the limited spatial resolution. The most advanced scanner, the Neuro-PET, has a resolution of 6 to 7 mm. Second, corrections are needed for backflow, including free tracer at the time of the scan that will return to the blood and "trapped" tracer that will backflow because of the presence of phosphatase. These corrections are calculated from the blood activity using nominal rate constants for 18FDG. Our study found no significant alteration in rate constants between normal and tumoral tissue. Finally, a lumped constant is needed to correct for kinetic differences between 18FDG and glucose. If there is a change in the mechanism of either membrane transport or the hexokinase reaction, the lumped constant may change. However, measurements of actual glucose utilization in tissue culture lines from six patients support the 18FDG results.

Fifty-four patients with supratentorial tumor and one with brainstem tumor were examined with positron emission tomography (PET) using [18F]fluoro-deoxyglucose (FDG). Twenty-one of these cases had satisfactory studies of the cerebellum. Of these, 12 showed significant metabolic asymmetry between the two cerebellar hemispheres, with the rate of glucose utilization in the hemisphere contralateral to the cerebral tumor being 8-34% lower than on the ipsilateral side, as compared with a right-left asymmetry of only--1.6% +/- 2.1% standard deviation for a group of 5 normal subjects. In these 12 cases the tumor involved the sensorimotor cortex and/or the thalamus with varying degrees of hemiparesis being present. For the remaining 9 patients with no significant cerebellar metabolic asymmetry, the tumor involved regions other than the sensorimotor cortex, and unilateral motor dysfunction was not a prominent clinical feature. The correlation between cerebellar metabolic suppression and unilateral motor dysfunction observed in our cases appears to be due to impairment or interruption of the cortico-thalamo-ponto-olivo-cerebellar circuitry by either the tumor itself or by edema. These results illustrate the ability of FDG-PET scans to detect metabolic changes, not apparent on CT scans, in areas of the brain remote from the primary lesion.

The pathologic features of the primary tumors in 285 patients with breast cancer at the time of initial presentation, and with no clinical evidence of distant metastases, have been analyzed. The results have been compared with the detection of tumor cells in the bone marrow by use of an immunocytochemical method using antisera raised against the epithelial membrane antigen (EMA). The authors found EMA-positive cells (i.e., tumor cells) in the bone marrow of 77 (27%) patients and a significant association between the presence of such EMA-positive cells in the bone marrow and tumor size (P = 0.006) and peritumoral vascular invasion (P = less than 0.001). A possible relationship with estrogen receptor negativity (P = 0.06) also was noted.

Forty-nine patients in whom clomiphene citrate failed to induce ovulation were treated for 177 cycles with a fixed low dosage of menotropin. Among these 49 patients, there were 24 pregnancies. Among these pregnancies were two that were multiple and three spontaneous abortions. In only one treatment cycle was there a hyperstimulation syndrome. These patients were divided into three clinical groups: the secondary amenorrheic patient, the oligo-amenorrheic patient, and the patient with poor corpus luteum function. There was no statistically significant difference in the pregnancy rate per month among all groups during the first three treatment cycles (average value, 0.07). However, there was a statistically significant improvement in the pregnancy rate per month in the group with secondary amenorrhea and the group with poor corpus luteum in the last three treatment cycles, as compared with the first three treatment cycles (P = 0.05; average value, 0.75). The oligo-amenorrheic patients, on the other hand, during the last 3 months of treatment, had no statistically significant increase in the pregnancy rate per month. These data suggest that menotropin therapy may have a priming effect. These data do not fit the currently accepted model of a constant pregnancy rate per month for all patients. The data suggest that caution should be exercised before combining patient groups when evaluating the results of menotropin therapy.

The authors report a patient with disseminated malignant teratoma who has survived for 3.5 years after discontinuation of treatment despite a persistent and nonprogressive elevation of his serum alpha-fetoprotein level. Potential sources of the marker in his case are discussed and the possibility of a chemotherapeutically induced evolution of his tumor considered.

Several decades ago, diethylstilbestrol (DES) was prescribed to support the pregnancy of women who were diabetic, who had had consecutive abortions, or who were threatening to abort. The use of this estrogen substitute to support human gestation had ceased by the 1960s. In 1971, the first report was published in which DES exposure was linked with clear cell carcinoma of the vagina and cervix. Since then, many other documentations have been published on upper genital tract anomalies, poor reproductive performance, and the high incidence of fetal wastage in DES-exposed women. The author describes a case of clear cell carcinoma of the kidney in an 18-year-old pregnant woman with a prior history of vaginal adenosis who had been exposed to DES in utero.

A new high resolution positron emission scanner (Neuro-PET) has made possible clear visualization and quantitation of glucose metabolism in the brain stem and upper cervical cord (above C4) using 18F-2-deoxyglucose. The following mean measurements of the glucose utilization rate are based on studies of 34 normal volunteers and patients with no apparent pathology in the brain stem or cord: 5.0 +/- 1.0 (SD) mg Glu/100 g/min for the mesencephalon-upper pons, 3.2 +/- 1.0 for the pons-medulla, and 1.7 +/- 0.6 for the upper cervical cord. (The first value also includes studies done with the ECAT-II scanner.) Resolution of white-gray matter within these structures was not possible. Whenever possible, a correlation was made with autoradiographic data in monkeys, and good agreement was found. The glucose utilization in cases showing brain stem and cord pathology was altered, with marked elevation (as high as 8.2 mg/100 g/min) in cases of high-grade gliomas, and reduction in cases of low-grade gliomas and one pontine hematoma.

Local cerebral glucose metabolism and psychometric function were compared in 17 patients with Alzheimer's disease and 5 healthy age-matched controls. Performance on tests of global intellectual function averaged 30 to 45% lower in the Alzheimer's group. Mean cortical glucose metabolism, as determined by positron emission tomography following fluorine-18-labeled fluorodeoxyglucose administration, was reduced by 30% in the Alzheimer's group. There was a significant positive correlation between the degree of overall dementia and the amount of metabolic reduction. The distribution of cortical hypometabolism was not uniform: the posterior parietal lobes and contiguous portions of the posterior temporal and anterior occipital lobes were most severely involved. The frontal cortex was relatively spared. These findings are compatible with the major clinical deficits found in patients with Alzheimer's disease and may help focus future biochemical probes into the pathophysiology of this disease.

Using an immunocytochemical technique, micrometastases have been found in the bone marrow of approximately 26% of patients with primary breast cancer at the time of initial surgery. To determine the fate of these cells, both in patients receiving and not receiving adjuvant therapy, multiple bone marrow aspirates were repeated in 82 patients at a median time of 18 months after surgery but prior to overt relapse. In both treated and untreated patients micrometastases were only found in one of 45 (2%) and one of 37 (3%) patients, respectively. However, when multiple marrow aspirates were taken from patients with local recurrence the incidence of micrometastases was 19% (three of 16), and this increased to 30% (three of ten) in patients with disease at distant sites other than bone, and 100% (ten of ten) in patients with radiologically proven bony disease. Three of 11 (27%) patients in whom the primary tumor remained in situ while receiving adjuvant therapy before definitive surgery had micrometastases at the time of diagnosis and at follow-up 3 months later. These results suggest that many of the micrometastases from breast cancer patients are the result of "shedding" of cells from the primary carcinoma and that a proportion are not viable. The technique is currently insufficiently sensitive to accurately monitor adjuvant therapy in breast cancer patients.

Ninety-five percent of patients presenting with breast cancer will have local disease only on staging by conventional methods. However, 40 percent of these patients will relapse and die within five years of diagnosis. It is widely accepted that a proportion of patients have disseminated disease at presentation which has failed to be detected using the currently available methods.

A multicenter study was performed to analyze the efficacy of 99mTc- and 111In-labeled F(ab')2 fragments of monoclonal antibody (MoAb) 225.28S (reactive with a high molecular weight melanoma associated antigen) to radioimage malignant lesions in patients with melanoma. A total of 254 melanoma patients, carrying 412 documented melanoma lesions, were studied in 10 nuclear medicine departments. A total of 377 lesions were visualized in 206 patients; in particular (a) 250 of 412 known lesions were visualized in 159 of 191 patients known to carry melanoma lesions; (b) 95 occult lesions were visualized in 61 patients of the same group; and (c) 32 lesions were visualized in 15 of 63 patients without diagnosed lesions. The melanomic nature of 101 of 127 radioimaged occult lesions was confirmed by clinical criteria and/or by additional laboratory investigations. These results indicate that immunoscintigraphy with radiolabeled F(ab')2 fragments of MoAb 225.28S can provide clinically useful information. Analysis of the variables influencing the outcome of immunoscintigraphy with 99mTc- and 111In-labeled F(ab')2 fragments of MoAb 225.28S confirmed the role of size, anatomic site, and level of high molecular weight melanoma associated antigen in melanoma lesions. Such analysis also showed, for the first time, the influence (a) of the isotope used to radiolabel the antibody fragments and (b) of the clinical stage of the patients. The present study has shown good agreement in the results obtained by the 10 nuclear medicine departments, suggesting that immunoscintigraphy with radiolabeled F(ab')2 fragments of MoAb 225.28S is a reliable procedure.

We used a mixture of antisera to prostatic specific acid phosphatase, prostatic specific antigen, epithelial membrane antigen and cytokeratin to examine multiple marrow aspirates from patients with local (15) and metastatic prostatic carcinoma (15), and benign prostatic hypertrophy (10). We found moderate to large numbers of tumor cells in the bone marrow of 11 of 15 (73 per cent) patients with known metastatic disease and small numbers of abnormal cells in 2 of 15 (13 per cent) patients with apparently local disease. No tumor cells were found in patients with benign prostatic hypertrophy, and only 2 patients with metastatic disease had tumor cells in the bone marrow when conventional hematomorphological preparations were examined.These findings suggest that immunocytochemistry can increase the detection rate of metastatic prostatic carcinoma cells. Further followup of larger numbers of patients with local carcinoma will reveal whether the presence of micrometastases denotes a poor prognosis.

In recent years the development of monoclonal antibodies has revolutionized our understanding of the fundamental nature of human tumors. Not only have they provided the pathologist with probes to study functional and structural properties of tissue, but they have also provided the clinician with further prognostic information on which to base management decisions, and more recently have been used therapeutically as modulators for drug targeting.

The authors report a patient with disseminated malignant teratoma who has survived for 3.5 years after discontinuation of treatment despite a persistent and nonprogressive elevation of his serum alpha-fetoprotein level. Potential sources of the marker in his case are discussed and the possibility of a chemotherapeutically induced evolution of his tumor considered.

We previously reported generalized cerebral glucose hypometabolism in amyotrophic lateral sclerosis (ALS) patients with upper motor neuron disease, using positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose. The present article presents a more detailed regional analysis of the hypometabolism, including measurements of the motor-sensory cortex at higher levels than used earlier. The analysis is based on 19 PET studies of 12 patients with ALS, four of whom had only lower motor neuron involvement, and 11 studies of age-matched control subjects. A brain size correction was included to eliminate differences in metabolism related to brain size but not to pathology. The eight ALS patients with both upper and lower motor neuron disease showed generalized hypometabolism, compared with the normal control subjects, that was greatest in the motor-sensory cortex and putamen. The motor-sensory deficit was strongly correlated with length of disease, and a marked sequential reduction was seen in repeat studies on four of the patients. There was also significant right-left asymmetry in these scans. No cerebral hypometabolism was seen in the four ALS patients without upper motor neuron involvement. Although the observed motor-sensory deficit in ALS is consistent with histopathological findings, the more generalized hypometabolism and the asymmetry suggest more widespread effects.

Fifty-four patients with advanced soft tissue sarcoma were treated with a combination of ifosfamide (5 g/m2) and adriamycin (40-60 mg/m2) at 3 weekly intervals. Of the 50 evaluable patients a response was seen in 11 (22%) patients (3 complete and 8 partial responses), stabilization of disease occurred in 17 patients and the remaining 22 patients progressed whilst on treatment. Of the 22 patients receiving adriamycin 60 mg/m2 12 (55%) required a dose reduction due to toxicity compared to 11 (39%) of the 28 patients who received 40 mg/m2. For the patients who had a response the median relapse-free interval was 7 months (range 2-17+) and the overall median survival was 12 months (range 5-29+). The combination does not appear to show an advantage over either drug used as a single agent.