Evarts A. Graham

Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma.

General Increase.--There is rather general agreement that the incidence of bronchiogenic carcinoma has greatly increased in the last half-century. Statistical studies at the Charity Hospital of New Orleans (Ochsner and DeBakey), (1) the St. Louis City Hospital (Wheeler) (2) and the Veterans Administration Hospital of Hines, Ill. (Avery) (3) have revealed that at these hospitals cancer of the lung is now the most frequent visceral cancer in men. Autopsy statistics throughout the world show a great increase in the incidence of bronchiogenic carcinoma in relation to cancer in general. Kenneway and Kenneway, (4) in a careful statistical study of death certificates in England and Wales from 1928 to 1945, have presented undoubted evidence of a great increase in deaths from cancer of the lung. In this country statistics compiled by the American Cancer Society show a similar trend during the past two decades? Tobacco as a Possible Cause of Increase.--The suggestion that smoking, and in particular cigaret smoking, may be important in the production of bronchiogenic carcinoma has been made by many writers on the subject-even though well controlled and large scale clinical studies are lacking. Adler (6) in 1912 was one of the first to think that tobacco might play some role in this regard. Tylecote, (7) Hoffman, (8) McNally, (9) Lickint, (10) Arkin and Wagner, (11) Roffo (12) and Maier (13) were just a few of the workers who thought that there was some evidence that tobacco was an important factor in the increase of cancer of the lungs. Muller (14) in 1939, from a careful but limited clinical statistical study, offered good evidence that heavy smoking is an important etiologic factor. In 1941 Ochsner and DeBakey (15) called attention to the similarity of the curve of increased sales of cigarets in this country to the greater prevalence of primary cancer of the lung. They emphasized the possible etiologic relationship of cigaret smoking to this condition. In a recent paper Schrek (16) concluded that there is strong circumstantial evidence that cigaret smoking is an etiologic factor in cancer of the respiratory tract and finds that his data are in agreement with the results of a preliminary report presented by Wynder and Graham at the National Cancer Conference in February 1949. (17) Purpose of Study.--The purpose of the present study was to attempt to determine, so far as possible by clinical investigations, statistical methods and experimental studies, the importance of various exogenous factors that might play a role in the induction of bronchiogenic carcinoma. In this regard we intended to learn the relative importance of previous diseases of the lungs, rural and urban distribution of patients, various occupations and hereditary background as well as smoking habits. By obtaining all this information, we hoped to determine whether any of these factors, either singly or in combination, have had an effect in increasing the incidence of bronchiogenic carcinoma. In the present paper the chief emphasis will be placed on our findings in regard to smoking. METHOD OF STUDY The results of this study are based on 684 cases of proved bronchiogenic carcinoma. It should be emphasized that the results in this report have not been obtained from hospital records since we learned at the outset of our study that the routine records did not supply satisfactory answers to our questions. It was therefore decided to seek the desired information by special interviews. Six hundred and thirty-four patients reported on in this paper have been personally interviewed, and in 33 cases we obtained the information by mailing a questionnaire. (18) In the remaining 17 cases information for the questionnaire was obtained from a person who had been intimately acquainted with the patient throughout his adult life. Through the cooperation of many hospitals and physicians throughout all parts of the country who permitted us to interview their patients, it is felt that a fairly good cross section of the entire United States has been obtained. …

Diseases of the gall bladder and bile ducts

I believe that nearly all the diseases of the biliary tract are directly or indirectly due to blood-borne infections, causing cholecystitis with the consequent deposition of gall-stones in the gall-bladder, where the bile becomes so greatly concentrated. It is acknowledged that the gallbladder is the only considerable factory for the formation of gall-stones, which rarely form elsewhere. We have reason to believe that mankind has suffered from cholelithiasis from time immemorial, as is well illustrated by the recent discovery of gall-stones in Egyptian mummies, which can-be seen at the Royal College of Surgeons. It is sad to think of the terrible pain and suffering which -gall-stones have caused men and women throughout the -ages. Medicine had little to offer beyond imperfect relief of pain by sedatives. As late as 1890 a distinguished physician seriously advocated massage as a means of expelling stones through the bile ducts into the duodenum. Nature occasionally succeeded in getting rid of stones, but with a high niortality and long suffering, for Nature is a poor substitute for modern surgery.

Biochemical Investigations of Deer Antler Growth: Part I. Alterations of Deer Blood Chemistry Resulting from Antlerogenesis

A colony of thirteen male and female deer have been studied for seasonal fluctuation of blood calcium phosphorus, albumin, globulin, and alkaline phosphatase. The female animals had stable levels of these parameters of body chemistry throughout all periods of the years. The male animals, beginning i

SUCCESSFUL REMOVAL OF AN ENTIRE LUNG FOR CARCINOMA OF THE BRONCHUS

In a recent extensive review of the lit erature, Carlson and Ballon of the Barnes Hospital have discussed the reported cases in which surgical removal has been accomplished or attempted. In all, there are apparently six cases in the literature in which a patient has the sur gical removal of the carcinoma and has been well at the time of the report, a year or more later. Two of these patients were operated on by Sauerbruch, one by Churchill. two by Tudor Edwards and one by Allen and Smith. In these reported cases only a limited removal of lung tissue has been performed, amount ing, however, in most cases to the re moval of one lobe of the lung. In Chur chills case, the lower and middle lobes of the right lung were removed. There have also been six cases reported in which malignant tumors of the bronchi have been removed by means of the bronchoscope. In practically all the lat ter cases, however, there is no evidence that survival has extended beyond one year. The case about to be reported is ap parently the first one in which an entire lung has been successfully removed for a carcinoma. In fact, it is apparently the first time in which the whole lung has @en deliberately removed at one stage. It is possible that Kummell removed the whole lung for a carcinoma, but the de Carcinoma of the bronchus in recent years has become a problem of major importance. Itisnow known thatpri mary carcinoma of the lung, which al most always arises in a bronchus, consti tutes between five and 10 percent of all carcinomas. In frequency. therefore, it is comparable with carcinoma of the large intestine, and it is much more fre quent than the malignant tumors of some other organs that have received much more comment. The problem of primary carcinoma of the lung is of special im portance, since up to the present time at least the prognosis has been almost uni formly bad because of the complete fu tility of any methods of treatment other than surgical excision. There is no record in the literature of the successful treatment by radiotherapy of a single case in which the pathologic evidence has been incontrovertible and in which a five-year interval without recurrence has elapsed between the treatment and the time of reporting the case, despite the fact that many cases have been treated according to the most modern methods of using both X-ray and radium. It would seem, therefore, that unless some entirely new general principle in the treatment of carcinoma is devised, the only method that at present can offer any

Estimating the Risk of Operations on the Biliary Tract by Testing the Excretory Function of the Liver

IN 1918, observations were published by the writer (1) which indicated that, in every case of cholecystitis, there is an associated hepatitis. The inflammation, which is more marked in the right lobe than elsewhere, seems to be essentially an infection of the lymphatics around the small intrahepatic bile channels. This work has now been corroborated by many others, notably by Heyd (2), by Moynihan (3) and by Flint (4). In those cases in which jaundice is associated with cholecystitis, but without demonstrable obstruction of the common bile duct, it seems probable that the jaundice is due to an obstruction of the intrahepatic bile ducts caused by the type of inflammation which has just been mentioned. The fact that an actual hepatitis can be demonstrated to be practically a constant accompaniment of cholecystitis shows that the possibility of the presence of a damaged liver must always be taken into consideration when dealing with a case of inflammation of the gall bladder. We are just beginning to appreci...

Symposium on Cancer of the Esophagus: Diagnosis and Treatment: LXXIII. III. Surgical Aspects

It is unfortunate that this part of the symposium was not assigned to some surgeon who is more optimistic than we are. In spite of occasional dramatic successful operations. the whole story of the surgical treatment of cancer of the esophagus is a most gloomy one. Apparently the chief difficulties at present with the surgical treatment are not only that in the majority of cases the growth is in a relatively inaccessible portion of the body, but also the fact that most patients who present themselves are late in the respect that they are already suffering from inanition and some degree of cachexia. Early diagnosis seems to be almost impossible now because of a limitation of methods of examination and also because symptoms are not produced, as a rule, until after a considerable involvement of the esophagus has occurred. The most satisfactory methods of examination now in use are the roentgenologic and the esophagoscopic. The latter should be accurate in most cases, but a difficulty which is presented in this method is the inability to recognize with certainty very early lesions. The presence of leukoplakia, which is considered by some as a precancerous lesion, has been shown by Schaerto be perhaps of less significance than ordinarily supposed because in an examination of 200 noncancerous cases at autopsy he found leukoplakia of the esophagus in 60 per cent. Because of the anatomic difficulties associated with a surgical attack upon this organ it is advisable to consider the condition under headings referable to the particular portion of the esopha-

The Nerve Pathways in the Vomiting of Peritonitis

Summary The experiments here reported show that the vomiting of peritonitis is the result of the stimulation of afferent nerve endings located in the peritoneum. The emetic impulse thus initiated passes to the medullary center by way of sensory nerve fibers which are included in both the vagal and sympathetic trunks. Section of these trunks prevents the occurrence of vomiting in peritonitis although phrenic and other cerebrospinal nerve paths are left undisturbed. Since, by sympathectomy alone or by vagotomy alone, vomiting in peritonitis is not abolished, the afferent emetic impulse evidently traverses either path with equal facility.

Influence of Hypophysectomy on Epithelization of Wounds and on Fibroplasia

In the present studies, attempts are made to determine what effects the removal of the hormones of the pituitary and of those glands under its control has upon the ability of an animal to exert reparative epithelial growth or reparative fibroplasia. Rats of the Wisconsin strain, obtained from the local Anheuser-Busch laboratories were used. At the age of approximately 14 weeks they were hypophysectomized, and then used 7-10 weeks later, at which time they showed a 10-20% loss of weight, loose thin skin, emaciation, appearance of fine silky hair, atrophy of testes, and atrophy of the adrenals, gonads and thyroid at postmortem. In the first part of the experiment an area of 2 sq cm was resected from the right flank of 19 normal and 18 hypophysectomized animals under nembutal-ether anesthesia. This area was measured on the first and every other subsequent day by tracing on cellophane and measuring with a planimeter. The reduction in wound areas for the hypophysectomized animals is identical with that of the controls. The wounds in the normals were slightly larger than those in the experimentals for the first 4 days. This is probably due to a greater amount of elastic tissue and less stretching of the normal skin before the area was demarcated, for in the normals the skin is more tightly bound down by the subcutaneous tissue that is strikingly lacking in the hypophysectomized animals. In the second part, we attempted to test the rate of fibroplasia. Harvey had shown that fibroplasia is proportional to the return of strength in wounds of the stomach. Using his technic, incisions 1 cm long were made in the stomachs of 29 normals and 18 hypophysectomized rats.

THE 9-9-9 PLAN FOR INTERNSHIPS AND RESIDENCIES

To the Editor:— The medical services of the Army and Navy are justly proud of the superb health record of our armed forces and of the even more remarkably low mortality rate in wounded soldiers and sailors. Part of this magnificent performance is due, of course, to the efficient organization of the medical services of the armed forces. A large share has resulted from the advances in medical knowledge of the past twenty-five years. It seems probable, however, that the major element in the achievements of the military medical services is the high standard of medical education in this country during the past quarter century. The doctors now serving the nation in a military capacity are almost all graduates of modern schools and many have had excellent opportunities for postgraduate education. Unless the men coming into active service know the fundamental principles of medicine, have been taught to keep abreast

Effect of Phrenicectomy upon the Efficiency of Cough and upon Elimination of Lipiodol from Lungs

The removal of a phrenic nerve to paralyze one-half of the diaphragm is now extensively performed in certain cases of pulmonary tuberculosis and in other conditions. Although the literature contains many statements to the effect that cough and expectoration are facilitated by phrenicectomy we have been unable to find any recorded experimental work dealing with such a result. Our experiments show that on the contrary the operation actually interferes with cough and diminishes the elimination from the lung of lipiodol injected into it. The efficiency of the cough mechanism was measured by the elimination of lipiodol from the lungs before and after phrenicectomy. The rate of disappearance of the oil was determined by means of fluoroscopy and serial roentgen-ray films. Experiments were performed upon 10 dogs. In 2 dogs the time required for the complete disappearance of the oil from the lung was determined. In these 2 dogs a unilateral phrenicectomy was performed after all the oil had disappeared. After they had recovered from their operations the rate of disappearance of lipiodol was again determined and the effect of phrenicectomy upon this rate noted. In 8 dogs unilateral phrenicectomy was performed first and then equal amounts of lipiodol were injected into the right and left lower lobes. Following the phrenicectomy it was noted under the fluoroscope that some of the oil injected into the lung on the side of the normal diaphragm was coughed up either during the injection or immediately thereafter. Fluoroscopic observations indicated that the cough mechanism was interfered with on the side of the paralyzed diaphragm.