Biomedical subjects
Publications and source records attributed to J W Pickren.
In a double-blind, randomized study, 500 premature infants were treated with plasminogen or placebo intravenously within 60 minutes of birth. There was a substantial decrease in severe clinical respiratory distress, death caused by hyaline membrane disease, and total mortality in the plasminogen-treated infants as compared to the controls.
We have reviewed the histopathology of lung cancer patients seen over the past 13 years at RPMI. Assessment of this data indicates that adenocarcinoma is becoming progressively more prevalent as related to the other forms of lung cancer. Factors which in part may account for this increased prevalence are: 1) changes in criteria for reading histopathology of lung cancer, particularly since 1967; 2) the increased incidence of lung cancer among the female population who have a propensity for adenocarcinoma; and 3) occupational and environmental factors. In 1974 adenocarcinoma for the first time became the most prevalent type of lung cancer at RPMI. Whatever the reason, if our data are truly representative of a national trend, adenocarcinoma will soon become the most prevalent type of lung cancer in the United States. This fact may result in an increasing death rate since the present 18-month survival rate for adenocarcinoma is substantially less than for squamous cell carcinoma, which has in the past been the prevalent form of the disease. As the smoking habits of women more closely approximate those of men, we expect that the incidence and mortality of lung cancer will prove to be quite similar in both sexes.
A study to determine the frequency of metastases to the adrenal glands following carcinoma of the colon and rectum was undertaken. Patients with, or without, adrenal spread were compared regarding age, sex, race and survival time. The over-all metastatic pattern was analyzed to determine its usefulness for predicting the presence of metastases to the adrenal glands. Autopsy reports and clinical records of patients with adrenal spread were reviewed regarding the extent of tumor involvement in the glands and possible adrenal insufficiency. Of 457 patients with adenocarcinoma of the colon and rectum who underwent autopsy, 63 or 14% had metastasis to the adrenal glands. Of these, 29 had bilateral involvement. Patients with bilateral metastases had a lower median age than did those without adrenal spread. No correlation was found between adrenal metastatic status and sex or race. Although survival time was found to be shorter for patients with bilateral metastases of the adrenal glands, adrenal insufficiency did not seem to be the reason for this shorter survival time. In retrospect, however, the presence of adrenal insufficiency could not be ruled out in several of these patients. Eight sites were studied with regard to whether or not metastatic involvement in a specific site might indicate a higher risk for simultaneous metastases to the adrenal glands. It was found for all sites that, when involved, there was a higher frequency of metastases to the adrenals than if free of tumor. Metastases especially above the diaphragm indicated a considerable risk for adrenal involvement. Different sites were combined in groups and studied in the same way. It was found that the more sites involved, the higher the relative chance of metastases to the adrenals. It was suggested that the results presented may be useful in predicting the relative chance of adrenal metastases in patients with advanced carcinoma of the colon and rectum.
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An autopsy study was performed on 190 cases with Hodgkin's disease and on 134 cases with reticulum cell sarcomas. It was found that a cascade spread of metastases, as opposed to a random spread, was detectable in patients with Hodgkin's disease, but not in patients with reticulum cell sarcoma. Metastatic key-sites for both lymphomas are defined as those organs whose chance of being seeded by the primary tumor is the highest; these sites are the spleen, liver, bone marrow and lungs. This study could not demonstrate in Hodgkin's cases that metastases in the liver and bone marrow were spleen dependent, but rather it showed that the spleen, liver and bone marrow acted as three independent sources of generalized metastases. Explanations proposed to account for the different metastatic spread in Hodgkin's disease and reticulum cell sarcomas, included different intrinsic cellular characteristics of the two lymphomas. the different location of the primary tumor either because of nodal, or of extra nodal origin, or because the primary tumor was located either in the upper or in the lower torso or in both areas. Malignant cells in the kidney, central nervous system and endocrine system were either released by the spleen via the lungs, or released by the liver and the lungs, or they were bone marrow dependent. The cascade spread of metastases hold true only for Hodgkin's disease. In cases with reticulum cell sarcomas, metastases appeared to spread at random from the primary tumor throughout the body, with rare exceptions such as metastases in the central nervous system, which originated either in the liver or in the spleen, lungs, kidney and bones.
A total of 1,615 patients with a confirmed diagnosis of lung cancer were treated at Roswell Park Memorial Institute between 1963 and 1974. Particular emphasis was given in this review to the 295 patients that underwent surgical resection of their primary lung lesion. Factors such as histology, type of resection, sex, age, staging, and degree of dissemination were considered possible influences on survival. The risks and benefits of intentional reductive or palliative surgery are considered along with the risk related to thoracotomies performed for diagnostic purposes.
This research was performed on 66 autopsy reports of kidney cancers and 58 autopsy reports of prostate cancers. Two alternative hypotheses were tested, i.e. whether metastases spread at random from the primary tumor throughout the body or whether the metastatic spread occurs in steps, referred to as a cascade spread, requiring one or more disseminating sites. It was found that in cancer of the prostate two disseminating sites exist, i.e. bones and lungs. Metastases from the primary tumor appear first in the skeleton and then in the lungs, not vice versa. In cancer of the kidney, the lungs are the major disseminating site. The lymphatic areas did not seem to play a major role in the dissemination of both cancers; on the contrary, the presence of metastases in the lymph nodes seem to depend on the presence of carcinomatous cells in key sites, i.e. the skeleton and the lungs. These results, however, should be interpreted with caution, as explained in the text. Considerations were proposed for future research.
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One hundred ninety-five patients with disseminated bronchogenic carcinoma were treated with 10 different dosage schedules of methotrexate. Patient response to methotrexate therapy varied with the type of treatment, but overall, 18% of the patients treated responded to a measurable degree. Survival was not increased in any of the treatment categories when compared to a placebo group; however, the survival of patients that responded to therapy was greater than the survival of patients that did not respond to therapy. Methotrexate will find its greatest potential use in combination with other drugs proven to be effective in treating bronchogenic carcinoma.
This paper investigates the question of whether different types of histology at the same site can affect the spread of metastases - that is, producing a greater or fewer number of metastases depending on the histological diagnosis. Autopsy records were the source of the data analyzed in this paper. The metastases were subdivided into four categories - central nervous metastases, endocrine metastases, metastases at various lymphatic areas, and a miscellaneous group of metastases called the "remainder" group. It was found that adenocarcinoma and oat-cell carcinoma of the lungs are more aggressive in their metastatic spread than squamous cell carcinoma at the same site. Adenocarcinoma of the cervix uteri had more widespread metastases than squamous cell carcinoma at the same site. No difference at all was detectable in the number of metastases, in men or in women, between transitional cell carcinoma and adenocarcinoma of the bladder and kidney. Cystadenocarcinoma of the ovaries appeared to be less widespread than adenocarcinoma (not otherwise specified) of the same site.
This investigation was based on the analysis of 580 autopsy records of patients with plasma cell myeloma or any type of leukemia. The data were collected by the Department of Pathology at Roswell Park Memorial Institute between 1956 and 1965. The primary purpose of this paper was to elucidate the metastatic process in myelomas and different types of leukemia. Two mutually exclusive hypotheses were tested, i.e. whether the spread of a cancer from the primary tumor throughout the body was due to a simple diffusion or if a cascade process took place. The basic definition of the "cascade or multistep" diffusion of cancer is that it takes place in steps; that is, at least one intermediate step is usually required for the disease to progress from the primary tumor to generalized dissemination throughout the body. It appeared that either the liver or spleen are the two major diffusing sites; that is, no generalized metastasis occurs unless the spleen and/or liver are seeded first.
One hundred fifty-five adult patients with "operable" soft part sarcomas including rhabdomyosarcoma, liposarcoma, leiomyosarcoma and fibrosarcoma of the trunk and extremities are reviewed. Local recurrences of 93% and 60% occurred after local and wide excisions of the primary tumor. In this series of patients, amputation was the most efficient procedure for controlling the primary site. The absolute 5 and 10-year survival rates for all groups of tumors were 50% and 26%. Development of a second primary tumor of a different cell type occurred in 9% of the patients. Local recurrence, single distant metastasis, and/or second primary tumors should be considered potentially curable and appropriate surgical and/or radiation therapy carried out.
Causes of death in the year 1970 were analyzed retrospectively on the basis of clinical and pathologic reports of 506 cases in the Roswell Park Memorial Institute and Hospital. The single major cause of death was infection (36%), which was also a contributory factor in an additional 68% of the cases. Other important causes of death were hemorrhagic and thromboembolic phenomena (18%), which also were contributory factors in an additional 43%. Organ invasion by neoplastic cells including hepatic failure was the major cause of death in 10% and was a contributory factor in 5%. Cachexia was reported as major cause of death in 1% and as contributory factor in 0.4%. Respiratory failure due to various causes (including aspiration) was the main mechanism of death in 19% and a contributory factor in 3%. Cardiovascular insufficiency was the major cause of death in 7% and a contributory factor in 3%.
Clinicopatholigic findings in 8 patients with Paget's disease of the vulva are presented with a discussion if its pathogenesis. In 7 cases the disease was intraepithelial, and in 1 it was accompanied by underlying adenocarcinoma. The treatment of choice is surgical. The importance of early diagnosis, adequate excision, and close followup is emphasized. In 2 cases, the disease was associated with carcinoma of the breast and in 1 case with carcinoma of the liver.
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Autopsy records based on 647 primary carcinomata of the breast provided the data to describe a few possible routes of dissemination of cancer of the breast. Calculations were made to test whether the hypothesis of a multistep dissemination of the tumour from the primary site was likely. A multistep dissemination means that the presence of metastases at peripheral sites is influenced by the presence of the tumour in 3 organs, i.e. lungs, liver and bones, very often seeded by the primary cancer.Several interpretations are discussed, with emphasis on those findings which could be explained in terms of a haematic route of dissemination or in terms of an anatomical proximity.