Biomedical subjects
Publications and source records attributed to E J Beattie.
Metastatic tumors to the esophagus have been described as having the imaging characteristics of benign mural tumors such as leiomyomata, but application of enucleation in treating such tumors has not been described. Our report describes long esophageal myotomy and enucleation of tumor for palliation of dysphagia due to a mural tumor originating from a lung primary.
Fourteen primary human lung tumor DNAs from smokers were analyzed for transforming activity by two DNA transfection assays. Activated protooncogenes were detected in 3 of 11 tumor DNAs by the NIH 3T3 focus assay, whereas activated protooncogenes were detected in 11 of 13 tumor DNAs by the NIH 3T3 cotransfection-nude mouse tumorigenicity assay. K- or NRAS genes activated by point mutation at codons 12 or 61 were detected in a large cell carcinoma, a squamous cell carcinoma, and 5 adenocarcinomas. An HRAS oncogene activated by a different mechanism was detected in an epidermoid carcinoma. One adenocarcinoma was found to contain an activated RAF gene. Two unidentified transforming genes were detected in a squamous cell carcinoma DNA and two adenocarcinoma DNAs. Eight of 10 lung adenocarcinomas that had formed metastases at the time of surgery were found to contain RAS oncogenes. No significant increase in metastasis was observed in the lung adenocarcinomas that contained one or more 6-kilobase EcoRI alleles of the LMYC gene. Overall, 12 of 14 (86%) of the lung tumor DNAs from smokers were found to contain activated protooncogenes. RAS oncogenes appear to play a role in the development of metastases in lung adenocarcinomas.
A 20-year follow-up of children who had complete resection of pulmonary metastases from osteogenic sarcoma of the extremities was undertaken. Four of six 10-year survivors survived more than 19 years even with multiple metastases and as many as nine thoracotomies. Fifty percent of the 10-year survivors developed second primary cancers during the second decade of follow-up.
AIDS is a syndrome caused by HIV. The virus is spread by homosexual or heterosexual transmission and by infected blood or certain body fluids. Respiratory infections are the commonest cause of death, and diagnosis may be difficult. The fiberoptic bronchoscope (FOB) plays an essential role in diagnosing respiratory infections in AIDS and is important in minimizing the need for open lung biopsies. Various problems require thoracic surgical consultation and treatment. We do not consider it ethical to deny these patients help. There can be no "double standard" in the care of patients in the hospital or in the operating room since any of our patients may have HIV without our knowledge.
Glutathione transferase are divided into three classes: Alpha, Mu and Pi. Isoenzyme(s) from one of these classes, class Mu, is dominantly inherited and can be determined by activity measurements directed towards the substrate trans-stilbene oxide. The frequency of this phenotype has been measured in patients with bronchial carcinoma and in control subjects matched for age and smoking history. After combining an earlier study from our laboratory (Carcinogenesis, 7, 751-753, 1986) with the additional material presented here (control smokers, n = 114, lung cancers, n = 125) non-cancer smokers had an increased number of subjects who expressed class Mu isoenzymes (58.3% of total n = 192) compared with lung cancer patients (36.6% of total n = 191; P less than 0.0001). The pathology of lung tumors related to the lack of class Mu isoenzymes which occurred most frequently in patients with adenocarcinomas. It is concluded that the gene expressing class Mu isoenzymes may be a host determinant of genetic susceptibility to lung cancer among smokers.
Primary choriocarcinomas of the lung are extremely rare. Like choriocarcinomas elsewhere, they possess rapid growth ability and a high propensity to metastasize. There is minimal information available on the treatment of lung choriocarcinoma. In the case reported herein, neoadjuvant chemotherapy with 5-fluorouracil (5-FU) infusion, etoposide, and cisplatin induced a partial response permitting complete excision of a massive tumor of the right upper lobe involving the chest wall and superior vena cava. The patient relapsed with a metastasis to the brain that was surgically excised. Contralateral lung metastases were soon noted and responded well to systemic chemotherapy; yet the patient died of a new brain metastasis. To our knowledge, this is the first example of a primary choriocarcinoma of the lung treated with intensive multimodality therapy. The latter seems to offer a potential benefit if certain guidelines are followed.
Recent advances in pleural malignant mesothelioma include the sequential use of palliative surgery, perioperative radiation therapy, and systemic chemotherapy. Radical treatments may not only palliate but also improve survival in some patients. The latter may be associated with the appearance of metastases in unusual sites including the central nervous system. In malignant mesothelioma, brain metastases were previously reported in 19 patients at autopsy and in only 1 patient antemortem. We detail the clinical presentation in the second patient with pleural malignant mesothelioma thus far reported to develop brain metastases. The difficulties in diagnosis, the role of immunoperoxidase stains in malignant mesothelioma, excellent tolerance of different modalities of treatment, and a review of the literature of brain metastases in mesothelioma are discussed. Based on our report, the possibility of brain metastases should be investigated by careful clinical examination prior to a radical treatment in patients with progressive refractory mesothelioma.
Large defects of the chest wall require stabilization of the remaining thorax to prevent paradoxical movement. A technique of fixation using rib grafts and compression plates is presented.
Lung cancer remains the greatest killing cancer in the United States with 149,000 new cases expected in 1987. The present expected mortality rate is 87 per cent. More women in the United States died of lung cancer than breast cancer in 1986. Asymptomatic, early and curable lung cancer in high risk individuals is usually found by routine chest X-ray. So-called Stage I lung cancer was reported to have a 83 per cent survival rate at three years by Martini and Beattie in 1977 and 70 per cent five year survival rate subsequently. When the more than 30,000 volunteer males were enrolled in the National Cancer Institute, national lung program for screening, 223 unsuspected lung cancers were found. 47 per cent were Stage I with a survival rate at five years of over 76 per cent. The PMI-Strang/Memorial Sloan Kettering Cancer Center study found 53 cancers in its first screen and 235 lung cancers over the next eight years of the study. Forty per cent were Stage I with a five year survival rate of 70 per cent. Sputum cytology as compared to chest X-ray was of little additional value. Studies (Martini) of Nl lung cancer was found to have a 49 per cent survival rate following resection. The N2 group of lung cancers where the mediastinal tumor was surgically removable and followed by external radiation therapy had a 27 per cent survival rate at five years. Those tumors with solitary brain metastases where the solitary brain metastasis could be resected and the primary tumor controlled, gave a 27 per cent survival rate at six years. The group of advanced N2 disease where the mediastinum could not be completely cleared were a serious group of cancers. A study of 100 patients treated from 1977 to 1980 with surgery plus internal radiotherapy followed by external radiotherapy had an overall 22 per cent survival rate for four to eight years with most of the deaths occurring because of metastases outside the chest. More recently chemotherapy has been used pre-operatively for those individuals with advanced lung cancer in the chest then followed by a combination of surgery, internal radiotherapy, external radiotherapy and more chemotherapy, if chemotherapy sensitive. This is the so-called multidisciplinary approach. In our present early studies it seems that those so treated who are chemotherapy sensitive have a 44 per cent, two year survival rate in a group of patients considered to have extremely poor prognosis.
Twenty-eight patients with metastatic and/or recurrent non-small-cell lung cancer were treated with a new sequential combination of escalating doses of cisplatin (50, 75, and 100 mg/m2 IV X 1) followed by 5-FU infusion (40 mg/m2/hour X 72) and etoposide (80 mg/m2/day X 3). Three patients received concurrent external radiation therapy. Eleven of the 28 (39%) had a partial response to chemotherapy. Four others had a minor response. One partial responder became a complete responder by surgical excision of residual cancer. Median time to response was 6 weeks followed by a median response duration of 4 months. In responders, chemotherapy was discontinued at the time of maximal response. Median survival was 7 months. Chemotherapy was well tolerated with absence of leucopenia, thrombocytopenia, and nausea and vomiting in a majority of courses. The common toxicities were alopecia (100%), leucopenia (35%), nausea and vomiting (30%), and electrolyte imbalances (27%). Reversible nephrotoxicity, thrombocytopenia, anemia, mucositis, and diarrhea were infrequent. The response rate in stage IV was less than in stage III. The combination of moderate doses of cisplatin, 5-FU infusion, and etoposide provides a new palliative chemotherapy that is well tolerated with concurrent/sequential radiation therapy and may be useful in the multimodality treatment of non-small-cell lung cancer.
Leukocyte isozyme(s) of glutathione transferase (GT-tSBO) has been shown to be dominantly inherited. The frequency of the phenotypes of this isozyme in bronchial carcinoma and control patients matched for age and smoking history is reported here. Control smokers showed an increased likelihood of having GT-tSBO (59%) compared with lung cancer patients (35%). The lack of GT-tSBO was related to the extent of smoking by the lung cancer patients but not to the pathology of the lung tumor. It was concluded that the gene expressing this isozyme(s) may be a host genetic determinant of susceptibility to lung cancer in smokers.
Juvenile papillomatosis (JP) is a breast tumor of young women featuring atypical papillary duct hyperplasia and numerous cysts, first described as a clinicopathologic entity in 1980. The disease is of interest because of the youth of these patients and the fact that the pathologic elements resemble those considered to be precancerous in older women. This report summarizes the findings in 180 patients enrolled in the Juvenile Papillomatosis Registry. The mean age at diagnosis was 23 years (range, 12-48 years; median, 21 years; mode, 18 years). No relationship was found with parity, age of menarche, or use of birth control pills. Fifty patients (28%) reported that one or more relatives had had breast cancer. Twelve (7%) patients reported a first degree relative (mother, 10; sister, 2), whereas in 38 (21%) breast cancer was limited to one or more secondary relatives, most often maternal (23/39 or 59%). Persistent (or recurrent) JP was found in 25 patients who had a subsequent biopsy, and 8 patients had bilateral JP. Pathologic analysis revealed focal epithelial necrosis, a feature often associated with carcinoma, in 30 (17%) cases predominantly in those with the most severe cytologic atypia of hyperplastic duct lesions (77%). Positive family history was reported by 33% (10/30) of women with epithelial necrosis and 27% (40/150) without this finding. Seven patients (4%) had breast carcinoma diagnosed concurrent with JP (ipsilateral, 5 cases; contralateral, 2 cases). A previously unreported finding is the diagnosis of carcinoma subsequent to JP in two cases (contralateral intraductal and ipsilateral microinvasive duct, respectively) with intervals of 8 and 9 years, respectively. The nine patients with carcinoma and JP tended to be slightly older at the time JP was diagnosed (mean, 27 years) and had a higher frequency of positive family history (56%) than those without breast cancer (mean age, 23 years; positive family history, 26%). These findings confirm earlier evidence that JP is a marker for families at risk and now indicate that the patient with JP may herself be in jeopardy of developing breast cancer coincidentally or at a later date. Wide local excision is adequate to control the lesion in most cases. Careful clinical surveillance is indicated for any woman who has juvenile papillomatosis and for her female relatives. The early age of onset of this unusually florid proliferative disease, and family history association, suggest there may be an underlying hormonal disturbance or genetic abnormality.
A case is discussed in which the patient presented with a primary extradural sacrococcygeal ependymoma and synchronous pulmonary metastasis. The clinical course has been characterized by recurrent pulmonary metastases. Management has consisted of repeated surgical resections of the pulmonary metastases and the tumor at the primary site; and the use of a wide spectrum of chemotherapeutic agents. Transplantation of this tumor into nude mice initially resulted in rapid growth but there was spontaneous regression in the second transplants. A general discussion of the management of such lesions is presented, and the literature pertaining to this tumor is discussed.
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Reports of the rapidly increasing proportion of persons aged 65 years and more in Canada and the resultant need for changes in the country's health care system prompted experimental changes in the operation and training procedures at St. Mary's of the Lake Hospital, Kingston, Ont. Aimed at better patient care and at better education of medical house staff in geriatrics and long-term care, the revised program is permeated with the philosophy of rehabilitation. It includes full-time staff, a geriatric outpatient clinic, a day hospital, a team approach to patient care (with regular team audits), problem-oriented medical records, a formal physical medicine section with a district inpatient unit, and an intensive inservice education program. After the first year of the program patient outcome had improved and more efficient use was being made of continuing care beds because of larger numbers of patinets being discharged home after shorter stays. This may be one avenue for deceleration of our country's dismal rate of institutionalization.