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Thymus Irradiation before Anesthesia and Surgery in Childhood

          We think it is worth repeating the first line of Chapter 9 here.

          "A thymic death is one of the supreme tragedies of surgery..." "Harris P. Mosher, M.D. (1926, p.1)

          Dr. James Tayloe Gwathmey's Anesthesia (1914) leaves no doubt about the anesthetists' level of long-time concern about sudden deaths (see preceding chapter, Part 3). The anesthetists and surgeons were concerned about the sudden deaths associated with anesthesia, with even minor surgery, and with the possibility of all these difficulties being brought on by the mysterious constitutional syndrome, Status Lymphaticus. They worried a lot about this long before Dr. Roentgen discovered the x-ray in 1895. According to Dr. Gwathmey (p.331), a connection between an enlarged thymus and sudden death was suspected for centuries:

          "As early as 1614 attention was called by Felix Plater to the fact that the thymus was enlarged in three cases of sudden death from dyspnea in one family." Even today, with our plethora of statistical studies, one would sit up and take notice of that series of three cases.

          What advice was offered by Dr. Gwathmey in 1914 to his colleagues? He provided tips on how to spot the people who might have difficulty with anesthesia, he advised strongly against use of chloroform in all suspected cases, and he passed along Dr. Henderson's warning against interrupting anesthesia.

          He said nothing about pre-surgical roentgen treatment of the thymus gland. Friedlander (1907) had treated one case of enlarged thymus with x-rays. In 1911, Lange had published his landmark paper about x-ray treatment of four cases (see Chapter 6, Part 3). But Gwathmey did not mention these. Perhaps he was unaware of them, but the more likely explanation is that Lange's focus was not on anesthesia and Status Lymphaticus, but rather was primarily on the symptom-laden syndrome of respiratory distress and "enlarged thymus."

          Although the surgical implications of the 1911 Lange paper appear unrecognized in 1914, the recognition did not take many more years.

          Before the mid-1920's, the era spawned by Dr. Lange had arrived. At last surgeons and pediatricians felt they could do something about this dreaded sudden-death disaster --- namely, use x-rays to shrink the thymus gland. Moreover, the Pancoasts and others were teaching the medical profession how one should do a meaningful roentgenologic examination to ascertain whether thymic enlargement truly existed. It is interesting to speculate on what might have happened without the 1911 paper of Dr. Lange.

          So now the ingredients were in place for a dynamic rise in activity --- and in breast-irradiation. Diagnosis of enlarged thymus and prophylactic shrinkage were introduced as necessary preludes to anesthesia. Surgeons started to refuse to operate unless thymus enlargement had been evaluated. And if thymic enlargement existed, surgery was postponed while x-ray therapy of enlarged thymus was conducted (Part 3).

          We can best pick up the story by listening to Dr. David Husik.

Part 2.   Some Scary Episodes:   Their Effect upon Dr. Husik, 1926

          In 1926, Dr. David N. Husik's paper reported (p.859):

          "It has been my unfortunate and rather sad experience to see three deaths during or immediately following the removal of tonsils and adenoids --- two in children under four years of age whose tonsils were removed under ether anesthesia, and who had apparently recovered from the anesthetic, when they suddenly became cyanotic and died, and the case herein reported under local anesthesia. All three cases were signed out as status lymphaticus, although no necropsy reports were obtained in the two children."

          And, after this experience:

          "It is my custom now to radiograph the chest of all patients who are referred to me for tonsillectomy --- children as well as adults. This, of course, puts the patient to an added expense, which is not necessary in a good many cases, but my experience teaches me it is safer for the patient, and a comfort to the doctor to know the chest is negative before operating."

          Then Dr. Husik relates the following for two leading medical centers:

          "It is now the routine treatment to radiograph all children between one and fourteen years of age booked for tonsil and adenoid operations at the throat department of the Massachusetts General Hospital and the Massachusetts Eye and Ear Infirmary. All children showing a broad superior mediastinum are considered as suspicious cases, and are given four x-ray treatments of a third of an erythema dose [an erythema dose was estimated at 300 Roentgens or more, at the time]. The treatments are repeated at intervals of ten days."

Large-Scale Use of the Practice

          We are always looking for clues to ascertain when such practices began. The next paragraph, quoted from Husik 1926, was read at the "Symposium on the Thymus Gland," Section on Eye, Ear, Nose, and Throat Diseases of the Medical Society of the State of Pennsylvania, Harrisburg Session, October 8, 1925. Husik is citing results from Drs. Mosher, MacMillan, and Motley from the Massachusetts General Hospital and the Massachusetts Eye and Ear Infirmary, as they were published in the November 1924 issue of "The Laryngoscope" (p.900). Mosher points out (in Mosher 1926) that the numbers published in 1924 cover just the first year's work.

          "The total number of children radiographed was 2,344. Of these, 185 (or 7.5 %) showed a positive thymus shadow. Of the 185 positive cases, 110 have been treated [x-ray therapy] and successfully operated on. Ninety per cent of the children treated showed diminution of the broadness of the superior mediastinum."

          The number doubles. In their 1926 paper, Mosher and colleagues state the following (p.3):

          "The present paper adds the figures for the second year and brings the series up to the present. There have been no thymic deaths during the past two years. Two cases which the X-ray showed had an enlarged thymus and which had had the regulation treatment with the usual reduction of the gland to normal size gave trouble --- one during the giving of the anesthetic (ether), and one after the completion of the tonsillectomy. The symptoms in both cases were those of extreme shock. Both patients recovered." And, in their conclusions:

          "A series of near five thousand consecutive (4820) X-rays shows that 7 % of children in the tonsil and adenoid age --- namely 2 years to 16 --- have an enlarged thymus."

Part 3.   Was There a Special Focus on Tonsillectomies?

          Although a great deal of attention was centered on preventing thymic deaths during removal of tonsils (and adenoids), we should make it clear that concern extended to all types of surgery. We will cite a few examples, to which we have added the relevant emphasis:

          o - Mosher (1926, p.1):   "A thymic death is one of the supreme tragedies of surgery. An apparently healthy child dies during the administration of an anesthetic, during or after an uncomplicated tonsil and adenoid operation, or, as recently happened, during a simple circumcision." Gwathmey (1914, p.334) cites Hilliard (1908) about a fatal case of Status Lymphaticus related to anesthesia. The type of operation:   Circumcision.

          o - Perkins (1929, p.261) about practice at the Seaside (New York) Hospital:   "In any case awaiting tonsillectomy or other surgical operation, when there was enlargement, operation was cancelled and roentgen therapy was instituted for the purpose of reducing the gland. When the gland was reduced, operation was performed."

          o - O'Brien (1929, p.271, p.274, p.276) made repeated references to anesthesia or surgical procedures, without mentioning tonsillectomy:   "For some years now, it has been the routine in certain hospitals to examine all children roentgenologically before submitting them to a general anesthetic." And:   "The other group of so-called thymic deaths occurring in older children in an apoplectiform manner without premonitory symptoms is the one responsible for the current hospital practice to which I have referred of roentgenographing all children before anesthesia." And:   "... it would appear not only desirable but requisite, until such time as more exact knowledge or experience shall warrant a contrary opinion, to prescribe radiation therapy for those children presenting roentgen evidence of `broadened mediastinal shadow' without symptoms in whom general anesthesia or surgery is contemplated."

One Million Adenotonsillectomies per Year

          Although concern about thymic death associated with anesthesia and surgery was not limited to tonsillectomies and adenoidectomies, there are reasons that these operations received a great deal of attention. Two reasons.

          First, the tonsils are regarded as some of the lymphatic structures of the alimentary canal, which include the thymus, and all of which were considered to undergo hyperplasia in the "Status Lymphaticus" syndrome.

          Second, tonsillectomy and adenoidectomy were super-favorites for surgical therapy in the earlier years of this century --- wholly aside from and independent of any considerations of enlarged thymus. John F. Bayley, Jr. (1968, p.918) stated the following:

          "Approximately one million children [USA] are subjected to adenotonsillectomy each year. Although this procedure accounts for as high as 44 per cent of all operations in some children's hospitals, no unanimity exists as to the indications."

          It should occasion no surprise that the difficulties with anesthetic deaths would be noted more frequently for the most common operation being performed by surgeons of that era.

"A Wise Precaution" for Those with Responsibility and Liability

          Dr. Mosher and co-authors make it very clear why the practice of checking and treating thymus enlargement reigned for decades (1926, p.6):

          "Since an enlarged thymus is the only available hint that a generalized enlargement of the lymphatic structures of the alimentary tract may exist as well, since this is the only pathological finding at autopsy in status lymphaticus, since deaths from status lymphaticus are more commonly associated with the tonsil and adenoid operation because it is the most common operation in children, it seems a wise precaution owing to our present lack of knowledge of this condition which can express itself so tragically, to learn the size of the thymus and if it is enlarged to reduce it to normal size by the therapeutic use of X-ray before undertaking the tonsil and adenoid operation, in fact before performing any surgical operation on infants and children" (emphasis added). And:

          "As one of those held finally responsible when a status lymphaticus death occurs in our hospital, I shall continue to act on the older theory and advise the continuance of the routine X-ray of the chests of children and the X-ray treatment of an enlarged thymus when found."

Part 4.   Quantitative Analysis for the Master Table, Column D

          Here, we will develop the entries for our Master Table, Column D. The information we use here does not lend itself to all the same steps used in the two prior chapters. However, the principles are the same, and that will become evident as we proceed with the calculation of breast-doses for the Master Table.

          o - Item 1:   What was the place of study? The entire United States. From the outset, we are going to deal with the entire population instead of a specific locale, such as Rochester or Boston.

          o - Item 2:   Can we regard the list of participants as truly representative? Since we are going to begin with data for the entire U.S. Population, the issue of "representativeness" disappears.

          o - Item 3:   How many persons were treated? We shall broaden this question to ask, "How many persons had diagnostic radiation and how many had therapeutic doses to the thymus?" Our final estimate is reached in Items 5 and 11. First we must estimate the annual number of tonsillectomies, in females, for our 1920-1960 period.

          Bayley 1968, cited in Part 3, suggests that in some children's hospitals, as many as 44 per hundred of all surgical cases were (in the 1960s) for adenotonsillectomy. Since Bayley infers 44% as an upper limit, we will approximate that 30 % of pediatric surgical cases were for adenotonsillectomy during the 1920-1960 period.

          Next we need to know how many adenotonsillectomies were conducted on female children per average year during that period.

          Francis H. Williams presented some data in the year 1928. His data show that 514,240 tonsillectomies occurred per year for a population of 46,750,000 persons (male + female), based on the data for cities with over 10,000 population. We can presume that essentially all of these tonsillectomies occurred in the "tonsil" age-years, 2 through 15.

          In 1940, the mid-year of our 1920-1960 period, the population of the United States was 131,670,000 persons (male + female). We shall therefore scale up the number of tonsillectomies reported by Williams, by using the population ratio. So:

          (514,240) x (131,670,000 / 46,750,000) = 1,448,341 tonsillectomies during the 1940 year (midpoint of our 1920-1960 period).

          We need to eliminate the male cases, so we divide (1,448,341 / 2), and obtain 724,171 tonsillectomies annually in females of ages 2 through 15.

          o - Item 4:   Does the ratio of tonsillectomies to all surgeries make any difference in our analysis? It makes a big difference. We have shown in Part 3 that pre-surgical evaluation of the thymus was recommended for all pediatric surgeries, not just tonsillectomies. If 30 % of all pediatric surgeries were for tonsillectomies (Item 3), how many total surgeries must there have been in females?

We let x = the total number of pediatric surgeries in 1940, in females.
Percent of all pediatric surgeries which are tonsillectomies = 30 %.
Then:   0.3x = 724,171 tonsillectomies in females.

          Therefore, x, the number of surgeries in toto (including tonsillectomies) will be (724,171 / 0.3), or 2,413,903 surgeries in toto (for females).

The Breast-Dose from Diagnostic Irradiation

          o - Item 5:   Are we suggesting that all the females in this surgical group are tested by x-ray for thymic enlargement? No, we do not think that everyone was so tested, but it is eminently reasonable, in view of the fear-factor in the general population and also in the medical-surgical population, to estimate that 60 % of the cases were tested by x-ray, nationwide. So:

          o - Item 6:   What is the estimate of radiation dose received by the breasts from the screening procedure?

          We have to presume that examination of the thymus was taken seriously. Although we assigned no dose from screening in Chapter 9, Item 10, we believe it would be a big mistake to ignore it here. A pre-surgical situation is quite special in the estimation of parents and physicians.

          Considering the level of concern about sudden death, considering the very serious admonitions that a fluoroscopic exam should accompany every chest examination, and knowing that even pediatricians (but not all) were routinely performing fluoroscopy on children (see Chapter 31), we think it would be absurd for us to assume no use of pre-surgical fluoroscopy. So we will assume some use of fluoroscopy, and we will suggest a breast-dose of 1 rad on the average for the individuals examined nationally. This modest estimate, of course, allows for much non-compliance with the Pancoast "imperative" described in Chapter 7, Part 1.

          Dr. Pancoast was not alone in urging fluoroscopy to make a meaningful search for enlarged thymus glands. For example, Dr. C.K. Hasley (1933) concurred vigorously with the Pancoast recommendation. We quote (Hasley 1933, p.477-478):

          "This paper is by no means a final analysis of so complex a subject as thymic hyperplasia, but is offered to stimulate a definite routine in the examination, and to encourage --- yes, to urge --- the use of the fluoroscope in making the study. An examination of an infant's or a child's chest should never be considered complete without thorough fluoroscopic study in both the anteroposterior and lateral positions."

          o - Item 7:   How do we calculate the total person-rads from the diagnostic process?

We have assigned 1.0 rad as the average dose to the breast-pair.
We have estimated 1,448,341 pre-surgical females, ages 2 through 15.
Person-rads = (1,448,341 persons) x (1.0 rads) = 1,448,341 person-rads.

          o - Item 8:   There are 14 separate age-years in the range of 2 through 15 years. For the Master Table, we need the person-rads separately for each of these age-groups. Therefore, we divide 1,448,341 person-rads by 14, and get 103,453 person-rads per age-year.

          o - Item 9:   We wish to have the population dose for each of the age-years. We shall show this in a tabular manner at the end of the chapter. Here, we shall illustrate how the tabulation was calculated by dealing with the entry for age-2.

          o - Item 10:   Does this analysis apply for the entire 1920-1960 period?

          We have shown that the practice of pre-surgical examination by x-ray was well underway by about 1924-1925 (Parts 2 and 3). Regarding the latter part of the 1920-1960 period, there is some difference of opinion. In the next chapter, we report the opinion of Waldo Nelson (1950), who was not at all friendly to the idea that enlarged thymus was a problem. He estimated that the enlarged thymus "story" was over by 1950. Carr (1945) and Conti-Patton (1948) were certainly not suggesting that it could be over by 1950.

          We shall use the estimate that the annual breast-dose from testing, 0.116 rads, applies for only 25 years of the 40-year period, and that the dose was zero for the other 15 years. So the adjustment is:

          ((25 x 0.116 rads) + (15 x zero rads )) / 40 = 0.0725 rads, overall. This value is found in Column E of the tabulation at the chapter's end.

The Breast-Dose from Therapeutic Irradiation

          o - Item 11:   We now need to consider the dose received in the course of therapy for the cases of enlarged thymus which were found.

          Mosher (1926) reported that in the first 2,344 cases studied, there were 185 positive thymus cases, and of these, 110 received therapy with radiation (see Part 2). We have no reason to suggest that any other studied group during those years would lead to a different result. And 110 / 2344 = 0.047, so 4.7 % of those who were studied diagnostically received radiation therapy. This means 0.047 x 1,448,341 (from Item 5), or about 68,072 female children per year.

          o - Item 12:   What was the individual average breast-dose from the therapy?

          The external dose was intended to be at least 400 Roentgens per child (see Husik, in Part 2) --- an exposure which may have been even higher than in the Hildreth Study (Chapter 8). But we can not be sure.

          What matters is the absorbed dose (rads) reaching the breast-tissue. What fraction of the breast received irradiation is a determination which Rosenstein was able to make for the Hildreth Study by using phantoms. For this chapter on pre-surgical therapy, we have fourteen different age-groups (and body-sizes) to worry about for the fraction of breast irradiated. The fraction may be the same as for the Hildreth Study, but it may not. Following our policy of providing a credible lower limit on breast-dose, we will subtract almost 25 % from the dose used in Chapter 8. That dose was 32.6 medical rads, after adjustment downward for supra-linearity of dose-response. For the calculation here, we will reduce it to 25 medical rads.

          o - Item 13:   What was the annual average population dose from such therapy?

          First we calculate the person-rads, which will be the same for every age-year. There were an estimated 103,453 persons per age-group who were tested (Item 8). And if 4.7 % of them were treated for "enlarged thymus" (Item 11), then the number of persons treated in each age-year per calendar-year was (0.047 x 103,453), or 4,862.3 persons. So:

          Person-rads = (4,862.3 persons) x (25 medical rads) = 121,558 person-rads.

          Average Population Dose = Person-Rads / Total Population.

          We obtain population-size from the Master Table, Column A --- or from the tabulation at the end of this chapter (Column B). For age-2:

          Average Population Dose = 121,558 person-rads / 892,097 persons = 0.1363 rads per year from the pre-surgical therapy of enlarged thymus. This value goes into the first row of the tabulation (Column G).

          o - Item 14:   We need to adjust this radiation-source for duration. We assume that the practice lasted only 25 years out of the 40-year period (see Item 10). So we multiply the per-year population dose of 0.1363 rads by (25 / 40), and enter 0.0852 rads into the first row of the tabulation, Column H. All the other lines of the tabulation are handled similarly.

Combined Population Dose per Year, Diagnosis + Therapy

          o - Item 15:   The final tabulation-step, before making entries in our Master Table, is to combine the population-dose from diagnosis and from therapy. For the age-2 group, Total Dose = 0.0725 + 0.0852 = 0.1577 breast-rads per year. This value, entered in Column Eye of the tabulation, is ready for transfer to the Master Table, Column D, for the 2-year-olds. All the other lines of the tabulation are handled similarly, and each line provides an entry for the Master Table, Column D.

          The pre-surgical application of Dr. Lange's therapy for "enlarged thymus" caused a big increment of breast-irradiation during the typical year of the 1920-1960 period, as indicated by Column Eye of the following tabulation.

 * - Annual Population-Dose from Pre-Surgical Thymus Exams + Therapy.
|Col.A  Col.B   Col.C    Col.D    Col.E    Col.F    Col.G    Col.H    Col. Eye|
|       Number  Person-  Average  Average  Person-  Average  Average  Total   |
|       of      Rads     Dose in  Dose     Rads     Dose     Dose     Average |
|       Females Total    Medical  Adjusted Total    in Med.  Adjusted Dose    |
|Age-   in      for      Rads per for      for      Rads per for      Exam +  |
|Year   Group   Exams    Exam     Duration Therapy  Therapy  Duration Therapy |
|                                                                             |
|  2    892097  103,453  0.1160   0.0725   121,558  0.1363   0.0852   0.1577  |
|  3    891518  103,453  0.1160   0.0725   121,558  0.1363   0.0852   0.1577  |
|  4    891047  103,453  0.1161   0.0726   121,558  0.1364   0.0853   0.1579  |
|  5    890657  103,453  0.1162   0.0726   121,558  0.1365   0.0853   0.1579  |
|  6    890332  103,453  0.1162   0.0726   121,558  0.1365   0.0853   0.1579  |
|  7    890051  103,453  0.1162   0.0726   121,558  0.1366   0.0854   0.1580  |
|  8    889806  103,453  0.1163   0.0727   121,558  0.1366   0.0854   0.1581  |
|  9    889589  103,453  0.1163   0.0727   121,558  0.1366   0.0854   0.1581  |
| 10    889390  103,453  0.1163   0.0727   121,558  0.1367   0.0854   0.1581  |
| 11    889209  103,453  0.1163   0.0727   121,558  0.1367   0.0854   0.1581  |
| 12    889028  103,453  0.1164   0.0727   121,558  0.1367   0.0855   0.1582  |
| 13    888829  103,453  0.1164   0.0727   121,558  0.1368   0.0855   0.1582  |
| 14    888585  103,453  0.1164   0.0728   121,558  0.1368   0.0855   0.1583  |
| 15    888277  103,453  0.1165   0.0728   121,558  0.1368   0.0855   0.1583  |

Notes for these tabulations

Part 4 of the text explains the development of this tabulation.

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