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Ending of the Era of Radiation Therapy for Enlarged Thymus

Part 1.   Why Did It Stop?
             Views of Dr. Dewing (1965), Scholar of Radiotherapy

          It is not totally clear why the era of radiation therapy for enlarged thymus ended by about 1960. There have been speculations on this subject. In his very readable 1965 book entitled Radiotherapy of Benign Disease, Dr. Stephen Dewing ventured an interesting opinion on the "coup de grace" for this practice. It is succinct and to the point. We quote from p.149:

          "The Thymus:   Radiotherapy of the thymus in infancy and early childhood is a matter of historical interest only at the present time. Its rationale rested on associating thymic enlargement or "hyperplasia" (as seen in the chest radiograph) with a clinical picture of respiratory stridor. The known sensitivity of lymphoid tissue and the experimentally demonstrable shrinkage of the irradiated thymus permitted use of very low doses. These were usually of the order of 100-300 R total tissue dose, spread over one to three weeks, the clinical response being the chief guide to therapy." And:

          "Nowadays responsible clinicians feel that thymic enlargement is almost never related to tracheal compression, even though theoretically there might be a connection in a rare case. Status lymphaticus, or thymico-lymphaticus, has also diappeared from modern concepts of pathology. The coup de grace [emphasis in original], however, was the recent alarm raised over possible late carcinogenic effects --- particularly thyroid carcinoma. It would take a bold radiologist indeed --- or a very stupid one --- to undertake therapy of an infant mediastinum today no matter how huge the thymus might appear. Furthermore, the `proof of the pudding' is that infants are recovering from croup and stridor just as well now as they did in the days when radiation therapy was most in vogue." And:

          "One could speculate --- idly --- that the therapy acted as much to quell the inflammation of a tracheo-bronchitis as to shrink the thymus. In this area the modern antibiotics are now doing the same job, and possibly much better." We return to Dr. Dewing in our Chapter 36. He was, in 1965, Associate Clinical Professor of Radiology at New York University Postgraduate Medical School.

Pitfalls in the Words "Very Low Dose" ... and in Dose-Comparisons

          Readers may note that Dr. Dewing, in 1965, regarded a dose of 100 to 300 Roentgens as a "very low dose." Today, such doses are commonly referred to as high doses.

          Even though a dose of 300 R is not in the ballpark of the thousands of Roentgens used in cancer therapy for specific targets, a dose of 300 R far exceeds the "kerma" gamma-ray doses received by most of the irradiated survivors of Hiroshima and Nagasaki (details in Gofman 1990, Table 9-B).

          However, whenever readers attempt to compare doses, they must keep at least three distinctions in mind. First is the quality of the radiation --- for instance, bomb radiation versus medical irradiation, which is usually more serious (see Chapter 3). Second is the difference between partial-body exposure and whole-body exposure, which is always more serious per rad. And third is the difference between the entrance dose and the dose which actually reaches a particular part of the body (such as the breasts) or an internal organ. For example, the average internal organ-dose received by the irradiated A-bomb survivors was less than 50 rads of whole-body exposure --- and less than 20 rads for most of them (Gofman 1990, Table 13-A). Expressed as "medical rads" (see Chapter 3), those values would be less than about 25 rads and 10 rads, respectively.

          In 1950, the Fifth Edition of Mitchell-Nelson (the famous textbook of pediatrics edited by Dr. Waldo E. Nelson) emphatically made several assertions to its readers about the thymus story. Its chapter on "The Thymus Gland" was written by Dr. Nelson himself.

Thymus-Size:   Accidental Deaths vs. Unexplained Deaths in Infancy

          At page 1164, Dr. Nelson described the controversy about "normal" and "abnormal" thymus-size. We quote:   "Weight or size of the thymus has been accorded considerable significance in relation both to the production of respiratory obstruction and of sudden death. The data of Hammar and Boyd, in particular, indicate that the weights which had been considered to be those of normal glands have, in actuality, been those of glands reduced in size by inanition and disease. Thymic tissue is extremely sensitive to the general nutritional status of the body. According to Boyd, severe undernutrition or disease (hyperthyroidism and leukemia are exceptions) will reduce the weight of the thymus by one-third within three days. When the weights of the thymus in well-nourished infants dying suddenly from such adequately explained causes as falls from high structures and automobile accidents are compared with those in well-nourished infants dying suddenly from unexplained causes, there are no significant differences."

Difficult Breathing, Sudden Death:   "No Relationship" to the Shadow

          At page 1165, Dr. Nelson expressed a very negative opinion about obstruction of respiration by the thymus gland. We quote:   "Whether the thymus is ever responsible for obstruction of respiration of any significant degree is a controversial point. Once considered as the most frequent cause of laryngeal and tracheal stridor, many clinicians of wide experience now think it is never a factor. It has been shown that laryngeal stridor and attacks of apnea and cyanosis can be explained otherwise in the majority of instances if a careful study is made. The strongest arguments that a thymic enlargement is responsible for respiratory obstruction are the bronchoscopic observations of Jackson and the roentgenologic studies of Pancoast. However, there may well be some doubt that the thymus causes compression of the trachea in any significant number of instances. There is no doubt that the thymus may cause a widening of the upper mediastinal shadow, which may be eliminated by shrinkage of the thymic tissue by roentgen therapy. It is of considerable moment, however, that the size of this shadow bears no relationship to the occurrence of symptoms of respiratory obstruction or to sudden death..."

Pre-Surgical Thymus-Evaluation:   "Not Indicated" in Asymptomatic Cases

          At page 1165, Dr. Nelson asserted:   "The routine roentgenographic examination of infants and small children for evidence of an enlarged thymus as a preliminary to a surgical procedure is now rarely practiced and is not indicated. When there are symptoms of laryngeal stridor, apnea, or cyanosis, a complete examination including laryngoscopy, bronchoscopy, and roentgenologic study of the chest should be obtained. In the majority of instances some condition other than an enlarged thymus, such as a laryngeal or tracheal lesion, congenital heart lesion, valvular ring, chronic pneumonic infection, or tetany will be found to be the causative mechanism ... Though one cannot say that there are no instances in which an enlarged thymus is the causative factor, it is obvious that it is rarely so, and the instances in which roentgen treatment is indicated are exceedingly rare."

Unexplained Deaths:   "Incrimination of the Thymus" Not Justified

          Also at page 1165, Dr. Nelson stated:   "Lymphatism as a cause of sudden unexpected death is discussed on page 374. It may be stated here that the evidence available does not justify incrimination of the thymus as a cause of sudden unexpected and otherwise unexplained death. The term `status thymicolymphaticus' and its implication of thymic death should be discontinued because of its inhibiting effect on a more exhaustive search for the real cause of death."

A Lack of Consensus to the Bitter End

          At about the same time --- just a few years apart in a fifty-year controversy --- Professor Jesse Carr (1945) was lobbing shells in the general direction of Dr. Waldo Nelson's position in these matters. (See Chapter 7, Part 5.)

Part 3.   Is Some Useful Knowledge Buried in an Avalanche of Criticism?

          As a life-long researcher in medicine, I feel unsatisfied by the many writers on this entire thymus story.

          Let us not rush to judgment on an earlier era. We are profoundly aware of the danger of self-deception which we as physicians can create when medical studies are conducted without double-blinding and the other safeguards integral to the rules of research. And without doubt, much self-delusion goes on right now concerning some problems in medicine, so we can hardly be too judgmental about the period of 50 to 100 years ago.

          Also, we note that many of the statements made by Dr. Nelson in 1950 had already been made, over and over again, during the height of the controversy in the 1920s, 1930s, and 1940s. How did the physicians who believed in roentgen therapy maintain their faith, if there were no real benefits at all? The enigma endures, we said at the end of Chapter 7.

          Dr. Nelson acknowledged that the change in thymus-size as a result of irradiation was a reality --- he just questioned its medical significance. Dr. Nelson said at page 1165, "There is no doubt that the thymus may cause a widening of the upper mediastinal shadow, which may be eliminated by shrinkage of the thymic tissue by roentgen therapy." That is an admission of a central feature of all that has been claimed by the proponents. Then Dr. Nelson assured us, "It is of considerable moment, however, that the size of this shadow bears no relationship to the occurrence of symptoms of respiratory obstruction or to sudden death."

          I simply do not think that Dr. Nelson --- or anyone else whose writings I have read --- really has a basis for the sweep implied by the Nelson statement. I have not seen it reconciled with equally emphatic reports, such as the two below from earlier chapters. How did the following statements, for instance, come to be made?

          o - Drs. Kerley and Graves, in their Third Edition (1924) of Practice of Pediatrics, stated at page 471:

          "It is well proved by a long series of cases, carefully studied by competent observers, that the condition known as status lymphaticus is an entity and is characterized clinically by a lowered vitality or an unstable equilibrium of the vital forces, so that accidents or disturbances, otherwise unimportant, such as some slight injury or a light anesthesia, may precipitate failure of the heart and respiration."

          o - Dr. George Pfahler, one of the early and great roentgenologists, wrote a paper on this subject in 1924 in which he made the following statement concerning roentgen therapy of enlarged thymus (Pfahler 1924, p.44):

          "There is probably nothing in radiotherapy that gives such uniformly brilliant results. The younger the child, the more prompt are the results."

"Sleeping Dogs" and "Baby's Bath-Water"

          Perhaps it is right for everyone to "let sleeping dogs lie" --- on a story that is long ago dismissed. After all, no one would think of resuming such uses of roentgen therapy today. The health price would be enormous. However, resumption is not the issue we are raising. The issue is "throwing out the baby with the bath-water!"

          We are warning that some items of knowledge which might be useful may well be buried in the avalanche of criticism of the "enlarged thymus episode" in medical history.

          The thymus story is a fascinating one --- as a piece of major medical history. What it teaches us, once again, is that ideas have consequences, actions have consequences which are often unintended, and everything is connected to everything else in medicine, as in ecology in general.

An idea developed that the thymus gland might be enlarged and cause respiratory difficulty, even sudden death of infants ---

Roentgen's discovery of x-rays made it possible for the idea to be tested both as to diagnosis and treatment ---

The idea is now long dead, with many saying the marvelous results seen by physicians were never really seen ---

Many thousands of women, whose breasts intercepted some of the x-rays used in this idea's lifetime, are now dead of breast-cancer, others are dying, and more will still die --- unintended consequences of an idea.

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