The cellular events associated with regression and progression of murine (Moloney) sarcomas.
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Malignant mesothelioma presenting in the pleura and peritoneum is described in a middle-aged man. The patient lacked significant asbestos exposure which is not unexpected from both the clinical literature and animal inhalation tumor data. Computerized axial tomographic correlation is provided. Partial remission was achieved with the administration of adriamycin and DTIC.
Seven children with malignant mesothelioma have been seen at Memorial Hospital since 1953. In six, the origin was at the pleura and in one at the peritoneum. None of the patients related a history of exposure to asbestos. Two patients lived more than five years. The other five patients died within two years of the diagnosis. Distant metastases were seen in four of the patients, including three who had metastases to brain. Surgery or radiotherapy were not effective in controlling the disease in most of the patients. One patient had a complete response to a combination of Adriamycin, cyclophosphamide, and vincristine and has remained free of disease for 5 1/2 years. The seven cases are reviewed, as are the other 42 cases of malignant mesothelioma in children reported in the literature.
It is established that subtypes of human malignant mesotheliomas (MM) are associated with different survival times. Ninety cases of MM were examined using DNA cytometry and comparative genomic hybridization (CGH), with emphasis on the main histological subtypes; epithelioid, sarcomatoid and biphasic. A comparison by DNA cytometry revealed moderate differences, with the rare subgroup of mesodermomas having the highest and the sarcomatoid group the lowest rate of aneuploidy. Using CGH, 6.2 chromosomal imbalances per case on average could be detected. Losses (4.1/case) were more common than gains of chromosomal material (2.1/case). MM show no single, specific defect, but a typical pattern of genomic defects can be attributed to this tumour entity. Common losses are clustered at the chromosomal regions 9p21 (34%), 22q (32%), 4q31-32 (29%), 4p12-13 (25%), 14q12-24 (23%), 1p21 (21%), 13q13-14 (19%), 3p21, 6q22, 10p13-pter and 17p12-pter (16% each). Common gains are located on 8q22-23 (18%), 1q23/1q32 (16%), 7p14-15 and 15q22-25 (14% each). While differences in the frequencies of the defects between epithelioid and sarcomatoid MM are not as pronounced as are seen with the pleomorphic mesodermomas, several chromosomal locations (3p, 7q, 15q, 17p) show significant variations. The most pronounced distinguishing feature of sarcomatoid MM is a more than fourfold higher number of amplicons. These data indicate that MM has a distinctive tumour biology with a broad spectrum of heterogeneity, as reflected in morphology and also, more subtly, in the patterns of chromosomal imbalances of the subtypes.
A case of a 61-year-old woman who had a serous papillary carcinoma of probable peritoneal or surface ovarian origin, which formed a single tumor mass in the pelvis but did not metastasize throughout the abdominal cavity but only to the pleura and then the hilar lymph nodes over a protracted period lasting more than 7 years, is reported. This unusually behaving tumor was well differentiated and at least partially responded to therapy, as witnessed by its histologic appearance at autopsy. This type of neoplasm usually shows diffuse peritoneal dissemination and no distant metastasis.
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Seventeen patients with malignant mesothelioma were treated in a phase II study with carboplatin, a cisplatin analogue without significant nephrotoxicity or neurotoxicity. The drug was given in a dose of 300-400 mg/m2 by i.v. infusion, repeating at 28-day intervals. One patient achieved a complete clinical and radiological remission of 15 months' duration, and a second patient achieved a partial response of 11 months' duration (overall response rate 12%; overall response rate in previously untreated patients 20%). Four other previously untreated patients achieved symptomatic relief. Treatment was well tolerated without severe side-effects. Carboplatin, like most other cytotoxic drugs, is active only in a small minority of patients with mesothelioma, but its ability to achieve occasional good responses and frequent symptomatic relief, combined with low toxicity, may justify a short therapeutic trial in patients whose tumour is symptomatic.
The present study describes cause-specific mortality of asbestos cement workers in the Emilia Romagna region of Italy. The cohort included workers in ten factories, most of which started operating between 1955 and 1965. Asbestos, mainly chrysotile, constituted 10%-20% of the dry component of the mixture. Crocidolite range between 5% and 50% of total asbestos. Asbestos concentrations up to 44 ff/cc were reported prior to 1975, while in recent years they have usually been below 0-1 ff/cc. The cohort included 3341 workers who had at some time been employed in the ten factories under study. Their mortality experience was compared with that of the population resident in Emilia Romagna. Vital status was ascertained at 1989. Seventy-three subjects were lost to follow-up (2.2%). Mortality from all causes and from all types of cancer was increased in the cohort. Malignant neoplasms of the respiratory tract showed a significant increase (SMR: 134; 90% confidence interval: 101-175; 40 observed) due to lung cancer (SMR: 124; 90% confidence interval: 91-166; 33 observed) and neoplasms of the pleura, mediastinum, and other parts of the respiratory tract (SMR: 602; 90% confidence interval 237-1267; 5 observed). The discrepancy between observed and expected mortality mainly concerned subjects with at least 20 years of employment in the factories. Five more cases of histologically confirmed mesothelioma occurred after the end of follow-up.
In 1972, a procedure was introduced by the Industrial Injuries Insurance Institutes (Berufsgenossenschaften) of the Federal Republic of Germany, which is to be used by the special occupational health service for employees exposed to asbestos dust. Since 1 January 1972, occupational health examinations are performed when exposure to asbestos dust has been of at least 3 years' duration. On 1 January 1977, a prospective cohort study was started with employees formerly exposed to asbestos dust whilst working for companies manufacturing or using asbestos. Data on these persons are collected in the Central Register of Employees Exposed to Asbestos Dust of the Industrial Injuries Insurance Institutes. A total of 3,070 male and female employees in whom asbestos exposure terminated after 1 January 1972 formed subcohort I of the study. For comparison, 665 persons whose exposure terminated before 1 January 1972 served as subcohort II. In addition to several other inclusion criteria, each individual's permission was required before personal data could be evaluated. Of the subjects in the two subcohorts, 185 and 71, respectively, had died by 31 December 1982. Tumours were more frequently than this cause of death is expected in the general population. In addition to a high incidence of mesothelioma, the standard mortality rate was especially increased for lung cancer. The proportional mortality rates of about 40% for tumours of all sites (with about 17% lung cancer and 8% mesothelioma) especially in subcohort II, seemed to be comparable to the international figures for epidemiological mortality.
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Expression of mdr1 gene has been evaluated in 34 tumor samples obtained from breast cancer patients who were classified according to their treatment, and clinical follow-up. No gene amplification was found. mdr1-RNA was never detected in 29 primary breast tumors including 5 samples from patients previously treated by 6 courses of 5-fluorouracil, epirubicin, cyclophosphamide (FEC). On the other hand, mdr1-RNA expression was detected in 1 local recurrence and 2 out of 3 metastases, all of them being treated and exhibiting a poor evolution. A second, untreated local recurrence remained negative. Clinical follow-up for 7 to 48 months in patients receiving chemotherapy showed that absence of mdr1-RNA could not be an accurate factor of satisfactory response to chemotherapy. But, all the patients with detectable mdr1-RNA exhibited a poor evolution and response to treatment. In conclusion, evaluation of mdr1-RNA seemed to be of little interest in primary breast tumors. However, the concomitant presence of an mdr1-RNA and a metastatic phenotype could give a new insight into the relationship between invasive and resistance properties of cancer cells. Such situations would need to be analyzed very carefully for a better utilization of chemotherapy.
Forty three patients with histologically confirmed malignant mesothelioma were entered onto an Eastern Cooperative Oncology Group phase II study of ifosfamide given with mesna. Eligibility criteria included adequate performance status, hemogram and renal functions. Ifosfamide was given at 1.5 g/m2 in 200 ml of normal saline over 30 minutes by intravenous infusion on days 1 to 5 of each 21 day cycle. Mesna was given at 300 mg/m2 on each day of ifosfamide at 0, 4 and 8 hours. Two patients were cancelled and one patient was ineligible. The most common toxicity was haematologic. More than 50% of the patients had at least one episode of severe or life threatening toxicity and 2 patients had lethal toxicity (1 renal and 1 pulmonary oedema attributed to treatment), and an additional 4 patients died while on study (2 of cardiac and 2 of cerebral vascular disease not considered directly related to treatment). Of the 40 eligible patients one was unevaluable for response, and one patient had a partial response lasting 6.3 months. Twenty four patients had a no change status with a median duration of 5 months. The median time to treatment failure for all eligible patients was 2.5 months. The median overall survival time (from registration) for all eligible patients was 6.9 months. In multi variable models, factors that predicted for a statistically significant poorer survival were age > or = 62, stage > or = 3, performance status poorer than 0 to 1 and prior surgery (i.e.: more than biopsy).(ABSTRACT TRUNCATED AT 250 WORDS)
In 25 patients, who received repeated doses of cis-DDP, we determined iodo-131-hippurate-clearance, creatinine clearance and serum creatinine to assess the nephrotoxic effect induced by cis-DDP. A highly significant decrease in the iodo-131-hippurate-clearance was found between the first and the following cycles. There was no significant change in serum creatinine and creatinine clearance however. The radio-hippurate-clearance showed a clinically not important reduction during several cytotoxic courses in 15/25 patients (60%). A clinically relevant impairment of the radio-hippurate-clearance occurred in 8/25 patients (32%), mainly before the third and fifth cytotoxic cycle. In two patients this clearance did not alter or was even rising. In 12 cases a diminuation of the iodo-131-hippurate-clearance was observed, which in only 5 cases correlated to a decreased creatinine clearance and in only two cases to an elevated serum creatinine. Therefore, we consider neither creatinine nor creatinine clearance nor the combination of both parameters to be appropriate to assess tubular nephropathy induced by cis-DDP. Radio-hippurate-clearance should play a superior role deciding on treatment stop or dose reduction of cis-DDP. The regression of cis-DDP-induced nephropathy was not evaluated.
Percutaneous fine-needle aspiration biopsy is a relatively simple invasive procedure with good patient acceptance, low morbidity, and almost negligible mortality. It provides a diagnosis of pulmonary, hilar, and mediastinal masses quickly and accurately, thus eliminating many laboratory tests, saving hospital days, and thereby saving time and money. Percutaneous fine-needle aspiration biopsy should be performed early in the investigation of many types of intrathoracic lesions.
The occurrence and coexpression of the cytoskeletal proteins vimentin and cytokeratins were studied in malignant mesotheliomas and pulmonary carcinomas. For this purpose a double immunoenzyme staining with monoclonal antibodies was developed which made it possible to visualize vimentin and cytokeratins simultaneously within the same cell. A clear distinction between stromal cells (vimentin only) and tumour cells was also obtained. A total of 12 mesotheliomas (six mixed type and six epithelioid type) and 13 carcinomas (eight adenocarcinomas and five large cell undifferentiated carcinomas) were studied. The results revealed a clear difference between mesotheliomas and adenocarcinomas: 11 of 12 mesotheliomas showed coexpression of vimentin and cytokeratins in at least 50% of the tumour cells, while in seven of the eight adenocarcinomas none or only a few cells could be seen with this coexpression. In the undifferentiated large cell carcinomas three of five expressed both components, but in less than 25% of the cells. It is concluded that a reliable double immunoenzyme staining of vimentin and cytokeratins can be used as an additional means to distinguish malignant mesothelioma from pulmonary adenocarcinoma.
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We report a patient with pleuropulmonary blastoma who had a benign teratoma as a second primary tumor. The radiology, clinical course, and the biological importance of this rare neoplasm are discussed.
The purpose of this study was to determine the feasibility of dynamic contrast-enhanced perfusion CT (CTP) in evaluating the hemodynamic response of tumors in the chest and abdomen treated with a combination of AZD2171 and gefitinib. Thirteen patients were examined just before and every 4-6 weeks after starting therapy. Following intravenous injection of a contrast agent, dynamic image acquisition was obtained at the level of a selected tumor location. To calculate perfusion, the maximum-slope method was used. Pre-treatment average perfusion for extra-hepatic masses was 84 ml/min/100 g, for liver masses arterial perfusion was 25 ml/min/100 g, and a portal perfusion of 30 ml/min/100 g was found. After the administration of AZD2171 and gefitinib, in extra-hepatic masses an initial decrease in perfusion of 18% was followed by a plateau and in liver masses an initial decrease of 39% within the lesions and of 36% within a rim region surrounding the lesions was followed by a tendency to recovery of hepatic artery flow. In conclusion, CTP is feasible in showing changes of perfusion induced by anti-angiogenic therapy.