SUGGESTIVE FINDINGS REVEALED AT AUTOPSY IN PATIENTS TREATED BY RADIATION *

SUGGESTIVE FINDINGS REVEALED AT AUTOPSY IN PATIENTS TREATED BY RADIATION * A. A. THIBAUDEAU (From the New York State Institute jor the Study of Malignant Disease. Burton T. Simpson, Director) The studies here reported were instigated by the finding in 1925-1926 of a number of cases of pulmonary embolus occurring in cancer patients and revealed at autopsy. Because of the well-known damage to small vessels resulting from radiation the possibility of this factor having an etiological bearing on the production of the emboli was suggested. A review of three hundred autopsies made for the most part on cases of malignancy at the New York State Institute for the Study of Malignant diseases developed several points of interest. PULMONARY EMBOLUS In the total series of cases, eight were found in which a pulmonary embolus was the direct cause of death. Of these seven were cases of malignancy, the eighth being a case of chronic appendicitis in which the patient died thirty days after operation. Four of the eight cases had received radiation treatment at periods of from two days to ten weeks before death and two of these had been subjected to operative interference within a week of the demise. The remaining four cases had received no radiation treatment whatsoever and death had occurred in from five to thirty days following operations. A painstaking histological study of the blood vessels of the radiated areas failed to reveal in any of the cases so treated any evidence of change in the vessel wall, while the findings in radiated and unradiated cases were, in this respect at least, identical. It seems safe to say therefore that radiation treat- * Read at the Annual Meeting of the American Association for Cancer Research, April, 1928. 66

FINDINGB IN PATIENTS TREATED BY RADIATION 67 ment was not responsible for any change in the blood vessel walls which caused thrombosis and the possible subsequent production of pulmonary emboli, while the fact that these emboli occurred with equal regularity in the cases which had no radiation treatment would seem to argue also that this type of therapy cannot be held responsible for changes in the blood, etc., which might indirectly cause the production of such emboli. HYDRONEPHROSIS Hydronephrosis was a fairly common finding in our review. Of these cases we had a total of fifteen, in twelve of which both the ureters and kidneys were involved and three in which a onesided involvement only was recorded. With one exception, all of these were cases of pelvic tumors which at autopsy proved large enough to account mechanically for the obstruction of one or both ureters, with a consequent hydronephrosis. The single exception was a case of treated epithelioma of the cervix which had remained cured for several years and in which no gross nor histological evidence of the original tumor was found at autopsy. In this case both ureters were constricted at the pelvic brim by dense scar tissue, with a resultant dilation of the ureters above this point and as a termination, infection with the production of a pyonephrosis. This patient though cured of her cancer, still died of a septicaemia the result of scar tissue formed on the regression of the carcinomatous process. Though it was at first thought that excessive radiation therapy might indirectly, by the production of a large amount of reactive scar tissue, be responsible for this constriction of the ureter, a careful consideration of all the factors in these cases would seem to indicate that the inflammatory changes consequent upon and accompanying a malignant process in the pelvis might be not less productive of a sufficient amount of scar tissue to produce this condition. This contention would seem to be borne out in one of our cases in which no radiation treatment was given but in which the autopsy revealed a double hydronephrosis with both ureters markedly dilated. As most of these casea were cervix epitheliomas which received intensive

68 A. A. THIBAUDEAU radiation therapy, it is difficult to show comparative findings in radiated and non-radiated cases. It is evident, however, that scar tissue from whatever source can produce this type of constriction and that the inflammation produced by the tumor must be held at fault as well as any possible effect of radiation. At the present time at the Institute we are carefully watching by means of pyelograms, all cases of pelvic tumor for dilation of the ureters. While it is possible that the replacement of malignant tissue destroyed by radiation therapy by scar tissue may be responsible for constriction of the ureter from the outside, the damage can be considered only as a secondary factor. In our cases, with the exception of two cases of malignancy of the prostate in which the ureters were obstructed close to the bladder, the constriction occurred at the level of the pelvic brim. INTRA-PERITONEAL INFECTIONS In the literature several references are found to the possibility of lighting up of old infections in the abdomen by radiation treatment. In our series of three hundred autopsies we recorded seventeen cases of local and general infection of the abdominal cavity. Of these fourteen had received treatment by radium and X-ray for periods of from twenty-four hours to three weeks before death, while three cases fall in the non-radiated group. While it is possible that the effect of radiation in reducing local and general resistance may have some effect in the loosing of a general infection upon a patient, in the majority of the cases studied in this series the presence of necrotizing degenerating masses of tumor tissue and the destructive effect of the tumor upon normal surrounding tissues, thus opening up direct avenues of infection, might be considered as sufficient in itself to account for the invasion of the abdominal cavity. In several cases operative procedures must be definitely blamed for the fatal termination of the case. In one case the surgeon on making a curettage, reported a uterine cavity six inches longin a carcinoma of the body. Autopsy several days later showed a perforation of the uterus through a carcinomatous mass with

FINDINGS IN PATIENTS TREATED BY RADIATION 69 general peritonitis. Two cases of gall bladder carcinoma in which operations were performed are recorded, the one having received radiation treatment one week before operation, the other with no application of radium nor the X-ray, but with identical terminal results-general peritonitis. In another case a rupture of intestine was found well above a carcinoma which caused complete obstruction of the large bowel, while in a colostomy of the sigmoid with complete removal of an adenocarcinoma, without radiation, the peritonitis followed a failure of the sutures to hold the bowel to the abdominal wall. In a series of cases previously reported by Dr. Schreiner, the possibility of the lighting up of old infections in the Fallopian tube and a subsequent peritonitis by means of radiation therapy was definitely shown. It is probable that even this result is due to mechanical means, being caused by the manipulation of the patient in the insertion of radium seeds or appliances, the contents of the tube being forced into the abdominal cavity through its fimbriated end. In the case of external radiation alone the resultant hyperemia and edema in a tube partially occluded at its uterine end might well produce the same results. In a series of five cases which had received deep X-ray treatments at periods before death varying from twenty-four hours to three weeks, specimens of liver, stomach, and intestine at different levels were taken for histological examination. Careful histological studies failed in these cases to reveal any constant or characteristic findings when comparison was made with similar material from non-radiated cases. We have been interested to note in our series, four invasions of the meninges and brain by metastatic processes arising from malignant tumors elsewhere. All of these occurred in females, two in cases of breast carcinomas, one in a thyroid cancer, and one in an epithelioma of the cervix uteri. Four invasions of heart muscle by metastatic carcinomata are also recorded. Two of these occurred in cases of extensive metastatic processes from breast carcinomas; one from a carcinoma arising in the region of the eye and the fourth secondary to an oesophagus epi thelioma.

70 A. A. TRIBAUDH1AU A statistical survey of our cases shows one hundred forty-nine malignancies in the male and one hundred twelve in the female, while thirty-nine cases showed no evidence of malignant tumor. These latter include several cases of cured malignancy, several aneurysms in which a satisfactory differential diagnosis had not been made before death, as well as a number of cases in which the diagnosis of a malignancy was only tentative. Of the two hundred seventy-one actual malignancies, one hundred fortyfour occurred in the age period of from forty-one to sixty years. While the greatest actual number of deaths resulting from one type of tumor was accorded to carcinoma of the uterus with forty-five-just forty per cent of all cases of malignancy in the female-no malignancies of the lip or tongue were recorded in females while the males showed twelve such tumors. Carcinoma of the breast in the female showed a total of twenty-five with none in the male, but as against forty malignancies in the neck and oesophagus in the male we find but four in the female. We have also eight cases of primary carcinoma in the lung in the male with but two in the female. Bladder tumors were about evenly divided-four in the male, five in the female. One epithelioma of the vulva is balanced by an epithelioma of the scrotum in an old man of ninety-five years-the oldest in this series. Nine malignant tumors of the testicle are found as against three ovarian malignancies. In carcinoma of stomach and intestines we find eighteen in the male as against eleven in the female, the proportion being about even when the total of malignancies in each group are considered. All types of sarcoma are much more frequent in the male-fifteen cases as against four in the female. This is further borne out by the comparison of pathological conditions in the lymph glands in the two aexes. From tumors of the lymph glands, including such conditions as lymphosarcoma, Hodgkin s disease, and leukemia, we have twenty-two deaths in the male against six in the female. Tables showing the sources of malignant neoplasms together with their age-incidenoe in males and females are as follows:

~ FINDINGS IN PATIENTS TREATED BY RADIATION 71 Aae Over Total 10-20 21-30 31-MI 41-.5o 51-60 fil-70 71-80 RIJ - ~ - _ ~ ~ ~ - - _ Lip... Tongue and Mouth... Neck.... Lung... Prostate.... Bladder... TestJicle Penis..... Stomach Intestine.... Sarcoma.... Leukemia Hodgkin s..... Abdominal Organs.... 1 4 5 4 2 1 7 2 9 6 3 20 1 2 3 1 1 8 2 9 8 1 20 1 1 2 7 1 1 1 3 1 1 2 4 2 2 2 2 1 I 10 1 4 7 6 18 3 2 3 1 5 1 15 6 5 3 4 2 1 1 22 2 1 3 1 7 Breast.... Uterus..... Bladder... Ovary... Vulva.... Esophagus.... Stomach Intestine.... Sarcoma..... Leukemia Hoclgkin s..... Ahdominal Organs.... A PP 10-20 21-30 31-40 -I-l-RO 51-60 61-70 71-80 $rr ~ ~ ~ ~ - 2 2 1 2 3 I 3 8 7 3 2 1 25 1 1 2 1 2 7 24 8 1 2 45 1 2 2 5 1 1 1 3 1 1 1 1 3 7 1 11 1 3 4 1 3 1 1 6 4 1 1 2 Pulnionary embolus....... Toxaemia (cachexia).... 157, Intest,inal o1)struction.... 2% Meningitis... 2fh Oedenia of glottis.... 4(y0 Malnutrition in Oesophagus carcinoma... 5% Hemorrhage....... 12% Pnenrnonia... 14(% 3 (XI Infection...... 43(% 100% 5

72 A. A. THIBAUDEAU CONCLUSIONS 1. 1tadi:ition therapy cannot be said to have any causal relation in the production of pulmonary embolus. 2. Hydronephrosis is a very common complication of msligrinncies in the pelvis. It occurs in bot>h radiated and nonradiated cases. 3. Li st:ttistical resume is made on three hundred aut]opsies in cases of malignancy. I