Radon Implants Research Articles

Acquired salivary dysfunction. Drugs and radiation.

When considering the effects of drugs on salivary glands, a distinction should be drawn between the complaint of oral dryness (xerostomia), a symptom, and measurable secretory hypofunction, a sign. In general, the symptom of xerostomia is often not accompanied by objective reductions in salivary output, and xerostomia is not a reliable indicator of secretory hypofunction. Whereas therapeutic pharmaceutical side effects represent the most prominent cause of xerostomia, with over 500 drugs associated with this symptom, only a small number of drugs have been demonstrated to reduce salivary output substantially. There are examples in which drugs with a high prevalence of xerostomia complaints do not affect secretory function. The mechanisms responsible for this discrepancy between subjective and objective findings have not been fully identified. It is hypothesized that alterations in systemic or mucosal hydration may play a role. Of the drugs with true salivary hypofunctional actions, most have direct anticholinergic properties. In almost all cases, the salivary effects of pharmaceuticals are not permanent, and function returns to pretreatment levels when the medication is stopped. By contrast, the effects of irradiation on the salivary glands are permanent when exposures exceed 50 Gy. About 40,000 individuals per year receive irradiation that involves the salivary glands (by external beam or internal sources--radon implants and 1311) for treatment of cancers of the head and neck region. Although these radiation effects have been recognized as a significant clinical problem for more than 80 years, the specific mechanisms responsible for radiation-induced salivary gland dysfunction are still not understood. With the exception of studies documenting the secretory functional deficits following head and neck irradiation, limited studies have been done in humans. The majority of experimental work has been done in rodents. A variety of mechanisms, including mitotic and interphase cell death, direct DNA damage or effects of secondary metabolites, damage to progenitor cells, or altered gene expression, have all been proposed to explain the salivary epithelial cell death observed. Recent experimental studies with models of radiation-induced salivary damage in rats and a human salivary cell line suggest that the small percentage of surviving epithelial cells are capable of performing functions such as signal transduction and ion transport normally. Apoptotic cell death following irradiation has not been a prominent feature in these model systems. The effects of head and neck radiation on the salivary glands and oral cavity continue to present multiple significant clinical problems both during and after radiotherapy. In recent years, there has been some progress in minimizing these effects through more careful shielding and pretreatment planning. Additionally, there are preliminary results from a clinical trial suggesting that the use of a secretagogue, pilocarpine HCl, given during the course of radiotherapy, may reduce the secretory hypofunctional effects. A multicenter trial is now underway to test this hypothesis. There is still a real need to develop more effective treatments for this condition.

Soft X-Ray “Seeds” for Cancer Therapy

The use of soft x-ray-emitting radioisotopes in cancer therapy offers many potential advantages. Sixty-day iodine 125 and 9.7-day cesium 131 are particularly promising because of their “un-contaminated” monoenergetic x-ray emission of approximately 30 keV. Numerous advantages accrue as a result of the ease of shielding the 30 keV x rays, coupled with their useful range in tissue. Soft x-ray “seeds” containing I125 and Cs131 have been fabricated for use in brachytherapy. Dosimetry studies have shown that standard distribution rules normally used for radium or radon implants will apply equally well to implants of these “seeds” with the added advantages of more rapid fall-off beyond the implant. The tissue dose distribution in the first 1.5 cm from such a “seed” was found to be comparable to that from radium, while at distances beyond 5 cm the fall-off was significantly greater due to increased tissue absorption. Experience gained from their use in animal studies has demonstrated their ease of handling and p...

A New Technic for the Radium Treatment of Carcinoma of the Bladder

Treatment of cancer of the urinary bladder entails not only eradication of the primary tumor by methods tolerable to the patient, but also prevention of recurrent and new tumor growths. The high incidence of new growths following local resection, fulguration, or irradiation, and the necessity of relentlessly guarding against recurrence by periodic examination, are evidence of the inadequacy of the present methods of treatment. To meet these problems, a new radium technic was devised and first used at Walter Reed General Hospital on July 18, 1945. Favorable experience with the first 13 cases warrants this preliminary report. The Walter Reed technic entails isoirradiation of the lower two-thirds of the bladder wall with fractionated exposures of penetrative gamma rays from a focal source of radium, radon, or radioactive cobalt fixed at the center of the bladder cavity. With this procedure certain disadvantages of other methods of irradiation are circumvented. Interstitial irradiation with radium needles or radon implants often results in focal radionecrotic ulceration attended by intractable pain, fistula, and fibrosis. Surface application of radium through a cystoscope is inaccurate and ineffective. External irradiation with x-rays, especially supervoltage irradiation, is occasionally effective, but may injure the bladder and adjacent bowel, and is frequently followed by a fibrosed contracted bladder of small capacity. The Walter Reed Technic Preoperative Diagnosis and Delineation of the Tumor: It is first necessary to ascertain as accurately as possible the geometric size, location, and type of the tumor to be treated. This is done by cystoscopy, biopsy, and pyelography and cystography with an opaque medium or air. Radiographic examination should include anteroposterior and postero-anterior as well as lateral and oblique views of the bladder, for occasionally these may yield more information as to infiltration and extravesical extension than direct observation and palpation of the opened organ. Cystotomy: At the time of the first radium insertion, the bladder is opened by suprapubic cystotomy and the tumor carefully inspected and classified. A papillary tumor with a narrow pedicle is totally resected with scissors, and the mucosa is sutured (Fig. 1). A bulky papillary tumor with a pedunculated or broad base is removed by electrosurgery, care being taken to cut down to the base only and not into the bladder wall, leaving a flat, slightly elevated sessile base of partly coagulated tissue about 3 or 4 mm. thick. If coagulation is carried down to the level of or into the bladder wall, secondary infection plus subsequent irradiation will unduly retard healing and result in an indolent ulcer requiring several months to heal, attended by painful cystitis. If the tumor is flat or sessile (Case 8) coagulation is unnecessary.

Cancer of the lip: A study of fifty-six five-year cases

Cancer of the lip is a slowly growing squamous carcinoma, grade I or II, of the exposed surface of the lower lip of aged men. Carcinoma of the upper lip and carcinoma of the lip of a woman are medical curiosities. One lip cancer in four metastasizes to the cervical lymph nodes; visceral metastases are rare. A large cancer or a cancer of high histological grade is more apt to metastasize than a small or low grade cancer, but metastasis of a particular cancer irrespective of size or grade cannot be predicted accurately. Death is caused by uncontrolled neck metastases not by cancer of the lip itself. X-ray, radium or surgery can be used successfully to destroy the cancer of the lip. If the patient is cooperative, any kind of prophylactic treatment of the cervical lymphatics is unnecessary; follow-up examinations are preferable. Movable metastatic nodes are treated, by choice, with block dissection of the cervical lymphatics. Fixation of large submaxillary metastasis from lip cancer is sometimes due to tension of the walls of the submaxillary space rather than the invasion of the mandible or floor of the mouth. This type of fixed metastasis is operable. The cancer cells in lymph nodes can be destroyed by the combined effect of x-radiation and radon implants, rarely if ever by external radiation alone; but the disease in the neck will be cured by combined radiation only if no new metastatic nodes develop in the implanted area of elsewhere in the neck.

FIVE YEAR CONTROL OF BLADDER CANCERS BY RADON IMPLANTS

There is no body cancer which is as well adapted for attack by radon implants as bladder carcinomas. Notwithstanding that these tumors are radioinsensitive, their accessibility to cystoscopic view and suprapubic exposure, their long confinement to the bladder, the flexibility of radon seed implantation and the possibility of early diagnosis all contribute to place bladder cancers in a unique class for control by radon implants. Cystoscopy in a fourth of all cases offers a means of both seeing and implanting the entire tumor. Because of size, position or bleeding, three fourths of all bladder cancers have to be subjected to suprapubic cystotomy, both to view completely and implant accurately the tumor with radon seeds. Such an operation has a relatively low mortality; 5 per cent as top, 3 per cent as low, if cases are carefully worked up. Papillary cancers of the bladder are confined to the bladder for a

The Use of Intravesical Low-Voltage Contact Roentgen Irradiation in Cancer of the Bladder

For many years we have had at our command five methods of dealing with carcinoma of the urinary bladder. These are fulguration, either trans-uretheral or via suprapubic cystotomy; implantation of radium needles or radon seeds; resection of part of the bladder wall; total cystectomy; external x-ray therapy. Each of these methods has its field of usefulness, and all of them will continue to be employed. Transurethral fulguration of small papillomatous growths of low-grade malignancy will yield, in skilled hands, a high percentage of five-year cures. Since bladder tumors tend to metastasize late, and since the bladder has remarkable power to regain its capacity, resection is a satisfactory procedure for the treatment of those tumors to which it is applicable. Although good results have been reported by some workers, the use of radium and radon implants has not been, in general, very satisfactory. External radiation therapy has been reserved, and properly, for advanced cases which have no prospect of cure by ...

The Measurement of Radium Emanation Implants

A rapid method of measuring sources of ionization is described. The ionizing agent is moved relative to the ionization chamber and the change in the ionization current is treated as if it were half a wave of an alternating current. This wave is amplified by means of an a.c. thermionic amplifier. The sensitivity of the apparatus is of the order of 10−12 amp./mm and it is capable of measuring radon implants at the rate of three a minute.

The Effect of Radiation from Filtered Radon Implants on the Growth of Carcinoma and Sarcoma in Animals

It is only within comparatively recent years that the therapeutic value of radium and x-rays in the treatment of malignant neoplasms has been definitely established. Numerous clinical studies have shown that in certain types of tumors irradiation has been of little benefit because of the exceptional resistance of these tumors to radiation or because their location was such that in order to deliver a lethal dose to the tumor, the adjacent normal tissue must be over-irradiated. The authors have made a study of the effect of radiation from filtered radon implants on the growth of carcinoma and sarcoma in animals, in order to determine the minimal lethal closes for these tumors. Materials and Methods The Flexner-Jobling rat carcinoma and the Sugiura rat sarcoma were selected for the preliminary study. The behavior of these tumors in the hosts has been reported elsewhere. It may be of interest, however, to summarize their manner of development, since this may have a bearing upon the present investigation. The grafts of Flexner-Jobling rat carcinoma grew progressively and rapidly. Many of them reached the size of a walnut before ulceration. The transplants took in about 80 per cent of all cases. They showed only occasional spontaneous absorption, such cases representing about 20 per cent of the positive transplants.1 As the tumors grew larger, they became soft, due to central degeneration and necrosis. Later they ulcerated, usually about seven weeks after the implantation, though sometimes as early as the fourth week, and subsequently caused the death of the animals from toxemia, septicemia, and nutritional failure. About 10 per cent of the animals showed metastases ninety days after tumor implantation.

The Effect of Radon Implants on the Cytology of the Liver of the Albino Rat

RADIOTHERAPISTS, since the early days, have depended for therapeutic results on selectivity of their radioactive agent for certain cells of the organism. Since mature or fully differentiated tissue possesses increased resistance to irradiation, particularly to the hard beta and gamma rays of radium, the stages of cellular retrogression after exposure to these rays no doubt transpire more slowly in the adult, and thereby afford adequate time for a more accurate and comprehensive study of the consequent cellular changes. This experimental study was undertaken to determine the cellular changes which occur in the liver, a specialized parenchymatous organ, subjected to the influence of radium as contained in gold-filtered radon seeds. The white rat was selected for the experiments because large numbers are available, and because the rat is well adapted to operative procedure and laboratory confinement. In 1898, three years after the discovery of the roentgen ray, Curie submitted her thesis regarding the new el...

An Apparatus for Collecting Radium Emanation

Introduction Radium emanation has a definite place in the treatment of cancer. Its chief advantage over the radium element is that it can be put into small enough containers and is of such nature that, once inserted into a tumor, it need never be removed. A second advantage is that while radon can be used for every treatment for which the radium element can be used, radon implants contain no radium. If they are mislaid, carried away on a patient, or lost in any other way, the loss is negligible. However, good radium emanation plants are of necessity sufficiently complicated to make them costly to install and to maintain. By the adoption of modern scientific methods it was hoped to develop a plant of low initial and maintenance costs which would be practical for both small and large amounts of radium. The requisites of a good emanation plant are: 1. The apparatus must be efficient; that is, as much as possible of the emanation formed must be collected in the container in which it is to be used, and it mus...

Comparison of Various Sources of Interstitial Radiation

THE importance of interstitial radiation in cancer therapy is constantly being emphasized. It is now recognized that it is impossible to deal adequately with some types of lesion by external irradiation alone, but that many of these can be controlled by the judicious use of radium or radon needles, or radon seeds. Up to the present time the dosage for these buried sources has been largely developed empirically by each radiologist for himself, except in the case of the gold radon seeds. For these, on a basis of experimental data, a practical system of dosage has been developed which is very satisfactory for lesions up to several centimeters in diameter (1, 2). For various types of implants there has been so far very little basis for comparison. Dosages employed in one clinic could not be related to those in others using somewhat different types of sources. It has thus been difficult to duplicate treatments in different clinics, unless the implants employed happened to be the same size and strength. Some time ago a preliminary paper was published correlating the effects of weak (1–4 mc.) radon seeds, permanent or removable, and certain 1 mg. radium needles, in bleaching butter (3). This work has now been extended to certain 5 and 10 mg. needles and seeds up to 11 mc., of various lengths. In addition to the use of the butter medium, the production of tissue necrosis in the dorsal muscles of rabbits has been employed. The purpose of the present paper is to present the results of these experiments and some conclusions drawn from them. There is considerable variation among the types of implant in use. Most of the filtered permanent radon implants (gold seeds) have a filter of from 0.25 to 0.35 mm. gold, and a length of 4 or 5 millimeters. The removable radon implants have a filter of from 0.25 to 0.3 mm. platinum, and are 5 or 6 mm. long. The strengths of either of these may range from a fraction of a millicurie to four or five millicuries—seldom more. Such small differences in filtration and length may easily be corrected for, or neglected for a first approximation. On the other hand, the needles may have filtrations varying from 0.25 mm. steel or monel metal to 0.5 mm. or more of platinum, and may range in length from a few millimeters to several centimeters. Obviously this part of the problem is much more difficult. It is impracticable to cover the whole range experimentally, but a good deal of information can be obtained from a detailed study of relations between a few types of implants. The sources of radiation used in the present study were gold seeds and platinum radium needles. Detailed specifications are given in Table I. The two reactions used, as already stated, were the bleaching of butter and the formation of tissue necrosis. The bleaching of butter has been used in a great deal of work regarding dosage from both gold and glass seeds, and its use has been discussed in previous papers (4, 5).

Radium and X-ray Therapy as Palliative Measures in the Treatment of Rectal Cancer

EXCLUSIVE of the stomach and oral cavity, approximately 60 per cent of the remaining intestinal cancers are indigenous to the rectum. Rectal cancers are notoriously difficult to cure because 40 to 50 per cent are inoperable when first seen by the surgeon; the rectum is in daily use; the tumor mass is not easily accessible; the degree of dissemination cannot be estimated by physical examination; the complete removal of all cancer-bearing tissue is a difficult operative feat accompanied by a high immediate mortality. The Pathology of Rectal Carcinomas Epithelioma or squamous-cell carcinoma of the anus is uncommon, aggregating only 3 to 4 per cent of all rectal cancers. Its site of predilection is at the mucocutaneous junction in the mid-line, anteriorly. It forms a nodular, warty, flattened growth which tends to ulcerate and involve the rectum proper. Its radiosensitivity corresponds with that of the lip and the buccal mucosa; the most satisfactory plan of treatment is irradiation by the interstitial deposition of small metal-filtered radon implants, known as gold or platinum seeds. The remaining cancers of this region are adenocarcinomas, which are also the most frequent tumors. The symptomatology, growth tendencies, and pathology of these differ according to their location in the rectal canal. At the rectosigmoidal junction the tumor early encircles the bowel to form an annular stricture. The majority of carcinomas of the rectal ampulla begin on the posterior wall. The four common types of adenocarcinomas of this region are: (1) The papillary carcinoma. (2) The malignant adenoma, or adenoma destruens. (3) The colloid, or gelatinous carcinoma. (4) The scirrhus or fibrocarcinoma. The papilliferous, or papillomatous, carcinoma resembles the benign papilloma somewhat, except for the invasive nature of its base. This tumor may be frankly malignant from its onset, or it may be a malignant degeneracy of the benign papilloma. Its growth energy is expended largely by evertent or surface proliferation, producing a bulky exuberant tumor, before the bowel wall is infiltrated. This cancer is readily amenable to surgical extirpation; when radium therapy is to be employed, the papilliferous fronds are removed by surgical endothermy and gold or platinum filtered radon seeds are implanted into the base of the cancer. The scirrhus or fibrocarcinoma is a peculiar type of rectal carcinoma, exhibiting desmoplastic tendencies, in which the atypical cancer cells are growing diffusely and are nestled away among wide strands of new connective tissue. This cancer is markedly radioresistant. The colloid or gelatinous carcinoma is a degenerative type of adenocarcinoma. It usually forms a bulky, massive growth in which gelatinous or mucoid material replaces the tumor tissue. It likewise does not respond well to radiation therapy. Adenoma destruens is the most common type of cancer of the rectum.

Comparative Notes on Radon Implants

THE present trend of radium therapy shows a divergence into two widely separated lines of endeavor. The first is the skillfully prepared and ingeniously contained radium implants, making possible the accurate introduction of a definite amount of radium emanation or radon into or in contact with an active neoplastic area. The second is the collection of radium salts in quantities large enough to permit of long range radiation similar to but productive of more gamma radiation than that of the present high voltage X-ray generator. The purpose of this paper is to consider some of the problems which confront the radiologist in his routine work, as well as the conditions which call forth the first-named type, the radium “seed,” or implant. The primary requirement is that one should be cognizant of the fact that he is in control of a very small but exceedingly potent agent which necessitates not only a comprehensive knowledge of radiology but also that skill which a well-balanced medical man must possess in all branches which enter into the successful diagnosis and treatment of neoplastic disease. This statement appears superfluous, but when one realizes that these potent radium seeds can be purchased by anyone, and that they not infrequently fall into the hands of those not qualified either by experience or training to use them, the need for caution is apparent. In this manner an agent which is extremely valuable to the trained radiologist may occasion much abuse and adverse criticism, if permitted to run amuck without proper supervision. Glass radon implants have been used for several years with remarkable success in many cases, and with disastrous results in others. Since the advent of platinum and gold filtered points, it is doubtful if the demand for glass tubes will continue much longer. The writers have entirely discontinued the use of glass implants, although in the past many good results have been obtained from the use of them in their clinic. This is especially true in tongue malignancy, where the blood supply is good and the tissue repair of the necrotic primary beta radiation effects more prompt and certain. Probably the great advantage of the filtered implant is due to the fact that a sufficient amount of radium is used to radiate thoroughly the periphery of the lesion, and at the same time serious local necrosis is avoided by the metallic nitration. Correct estimation of the size of the growth is undoubtedly the most important factor in the consideration of the use of radon implants. The work of Quick, Failla, Quimby, Cutler and others, at the Memorial Hospital, has practically solved the dosage problem. Reference to their charts and hypothetical models will guide the operator so that he may remain well within the safety zone of dosage. The previous or older method of using one millicurie per cubic centimeter of malignant tissue, and spacing the tubes one centimeter apart, often caused either overdosage or underdosage.

The Intensity of Radiation in the Vicinity of Filtered Radon Implants

In the development of filtered radon implants, a great deal of work was necessary before they were used clinically. Much of this has already been reported (1), (2). Since these papers were written, additional data have been accumulated. It is the purpose of this paper to correlate the available information, and to show that it may be represented by a single curve, which is directly applicable to dosage problems. Three distinctly different reactions have been used in obtaining these data: (a) tissue necrosis; (b) butter decoloration; (c) skin erythema. The first two are used in the papers referred to above, and are fully discussed there. The work will be summarized briefly here, and the experimental data taken directly from those papers. (a).-Tissue Necrosis. From the clinical aspect, one of the most important considerations in the use of buried radon is the relation between the strength of the tube and the volume of necrosis produced. This was investigated experimentally by burying tubes of varying radon ...

Radium Radiation from a General Utility Standpoint

The introduction of radium into general therapeutic use has been accomplished by much discussion and also considerable unjustifiable criticism. In the light of past achievements, however, we are in duty bound to review our work with radium and continue in its scientific application, secure in the knowledge that in certain phases of cancer it has demonstrated therapeutic results as yet unequalled by any other medical or surgical measure known. Outside of the comparatively few institutions where radium is supplied in the form of emanation, the bulk of independent radium therapy is carried on by means of elemental radium in the various glass and metallic containers with which we are all acquainted. With the advent of the aerial mail service, even the remotely located radiologist can have placed at his disposal, upon telegraphic request, a suitable quantity of radon or radium emanation of exact measurement and known content. This service is invaluable to those who have not the facilities of an emanation apparatus. According to the experience of the writer, the field where the best results have been obtained from radon implants or seeds is the oral cavity, particularly the tongue. In no other location has this form of therapy seemed to us so surely the best, unless it be in such nodules or tumor masses of the rectum, vagina or cervix uteri as will not react so as to injure seriously a functionating mucous membrane. In early cancerous lesions of the tongue, our experience with radon seeds has been gratifying. In the bladder, prostate and rectum, we have not been so fortunate. In the majority of malignancies, we have noted that outside of a very few favorable cases where a metallic needle imbedded for a limited time gave the desired result, we accomplish a great deal more with much less pain and discomfort to the patient by the screened applicator method. Similarly, our use of the metallic needles imbedded in tongue or throat lesions have given way, either to the radon seeds or to screened topical application. In tissues which are hyperplastic and free from adjacent sensitive structures, as, for example, polypi or small fibroids of the cervix uteri, judicious employment of metallic needles will yield more satisfactory end-results than any other method of eradication. On the other hand, in cancerous nodules elsewhere located, the response with needles has not measured up to what should theoretically be expected from such treatment. Many of us at one time advocated the use of needles imbedded in the various cancer nodules of the breast. We have, in our Clinic, discontinued this procedure for several reasons, the chief one being the severe reaction and sloughing, with a long, tedious healing period which sorely tries the patience of both the operator and his charge. When we have reverted to the older technic of screened external applications, we have secured equally good end-results with no such serious sequelæ.