- Email: [email protected]
A Contribution TO THE STUDY OF THE TREATMENT OF EPITHELIOMA OF THE TONGUE BY RADIUM.
FEBRUARY 1ST, 1930.
A Contribution TO THE STUDY OF THE
TREATMENT OF EPITHELIOMA OF THE TONGUE BY RADIUM.
That is to say, there was a survival-rate of 17’ 1 per cent. (It is interesting to note in passing that if the period of observation had been continued for longer than five years the percentage of so-called " cures " would be still further diminished, for of the patients noted above as remaining well for five years three showed recurrences at the close of six years, and two at the end of seven years.) Mr. R. F. Phillips, Luther Holden Scholar, who is now working on the end-results of patients suffering from buccal carcinoma (including carcinoma of
Being a Hunterian Lecture delivered before the Royal tongue, floor of mouth, cheek, lip, tonsils, and palate), College of Surgeons of England on Jan. 29th, 1930, has supplied the following interesting figures which BY G. E. GASK, C.M.G., D.S.O., F.R.C.S. ENG., may later throw some light on the problem being PROFESSOR OF SURGERY IN THE UNIVERSITY OF LONDON.
studied.
degrees
He holds that buccal carcinomata show grades of malignancy, which may be
or
IN presenting this study I wish to say that it is really a contribution from the members of the Surgical Unit of St. Bartholomew’s Hospital, of which
I am the mouthpiece. We feel that the time has come to consider, more in detail than was previously possible, the relative value of treatment of carcinoma of the tongue by the old-established method of surgical excision and the new, much hoped for, rather spectacular, and not yet fully established treatment by radium. The amount of information at our disposal is still too small to arrive at definite conclusions, but it is important to consider what there is, seeing that in a short time the amount of radium in the country will be considerably increased. Following the Thanksgiving Fund for His Majesty’s recovery and the foundation of the Radium Commission, a number of national radium centres are about to be started in the University medical teaching centres of England, Scotland, and Wales, so that in a short time we may expect a great stimulus to the radium treatment of patients suffering from cancer, and among these there are sure to be many suffering from cancer of the tongue. It seems to us, therefore, an opportune moment to take stock of the knowledge which is now available, to table the results obtained by surgery, and to scrutinise with care and without fear or favour the results and methods of radium treatment. RESULTS OF SURGERY. We have tried first to reach the approximate figure of the cures of cancer of the tongue obtained by surgery, so as to have a fixed point for comparison between surgery and radium therapy. Operations for removal of the tongue have been performed by surgeons now for many years, and we ought to be able to give accurate detailed figures for the results of surgery in all the different phases of the disease. Unfortunately, the medical profession has appeared unbusinesslike in the matter of compiling statistics, and slow in adopting follow-up schemes, with the result that it is difficult to find a large number of conclusive figures. Statistics are cold, heartless, things, which do not recommend themselves to optimists, but it is necessary to inflict some of them on
you.
Statistics
of St. Bartholomew’s Hospital. follow-up department was started at this hospital for the purpose of tracing the end- ’! results of all patients suffering from cancer of the tongue. The results are shown on the accompanying graph. Included in this series are all those patients who were deemed operable, and were, in fact, operated on in one way or another by the various surgeons attached to the hospital. The results of the varying types of operations are not differentiated, as it was thought that the figures wanted were those that In 1922
a
showed the value of surgery
as
a
whole.
Three
years is not a long enough period to judge of any form of treatment of cancer, so only those patients have been included in this review who might have survived five years from the date of their original operation. Of these there were 70, of which only 12 remained aliveand well and free from recurrence at the end of five years from the date of their operation. 5553
Epithelioma of tongue. Five-year survival-rate of 70 patients operated on at St. Bartholomew’s Hospital.
measured and foretold by their histology. Following Broders’sl work, Mr. Phillips has examined the histology of the tumours from a large number of patients who have been treated at St. Bartholomew’s Hospital between the years 1924 to 1927. These are divided into four grades, according as they show cells approaching the normal tissues or differing greatly from the normal1 and approaching the embryonic type. Thus, Grade 1 contains those cases which show much cell-nest formation and few mitoses, and Grade 4 those cases which show no cell-nest formation and much mitosis : whereas Grades 2 and 3 are intermediate. The 159 patients observed fell into the following
grades :-
1 Broders, A. C.: Grading of Carcinoma and Practical Application, Minn. Med., 1925, viii., 736; and Epithelioma of Cavities and Internal Organs of Head and Neck, Arch. Surg., Chicago, 1925, xi., 1.
E
224
Thus, it will be seen that the largest number falls into Grade 2 and the smallest into Grade 4, the most malignant category. Mr. Phillips next worked out what happened to the patients in these various grades and tabled the survival-rate in each. He believes that the prognosis or chance of survival is definitely related to the type of growth. Thus, he finds that the survival-rate in
are told that epithelioma of the tongue can be cured by radium. Had I been asked my opinion on this question a month ago, I should have said that, although two or three people in different parts of the world have claimed this power for radium, the general belief is that rodent ulcer is the only variety of malignant disease which radium is competent to cure. And I should have added that the only case of epithelioma of the mouth in my own practice to which radium had been applied (by the most skilful man with the best material) had ended disastrously. But I have, Per cent. within the last few days, seen a case in which a typical Grade 1 is 36-4 2 is at the end of three years. epithelioma of the inside of the cheek is so much better, 3 is 8.0 under the application of radium, at the end of four months, 4 is 0 (all dead). that it looks as if it would be quite cured. And this had Number of patients followed, 90. apparently been accomplished without inflammation or sloughing or profound ulceration of the disease. I understand that radium in this case was applied by means of It should be interesting to find out whether any the disc. the As this epithelioma was about It inches in of these grades are more or less susceptible or sensitive diameter and ulcerated all over, when I saw it four months to radium. There is some evidence to support the view ’, ago, there seems no reason to doubt that small epitheliomata that the cases falling into the first group-namely, of the tongue may be removed by radium, probably with those showing marked cell-nest formation with little a better scar than would be left by any other efficient agent. But, having said this, it must not be forgotten that the mitosis, are less sensitive to radium than those highly removal of the primary disease is only part of the cure of is in 4. More work malignant types required, epithelioma. Group Even the smallest, the youngest, and as however, before this can be stated proved. apparently the most insignificant epithelioma of the tongue is capable of affecting the lymphatic glands, as the cases I have related show. So that, unless radium is discovered Selection from Published Sources. to possess a far-reaching influence, spreading from the seat The results of surgery obtained by us at St. of the primary disease to the associated lymphatic glands, Bartholomew’s Hospital are so bad that it seems only I am afraid that the surgeon must still occupy an important in the treatment of epithelioma of the tongue." right to compare them with a selection taken from the "
"
18-2
"
published sources. Naturally, one’s mind turns first to the publications of Sir Henry Butlina PastPresident of this College, who had the highest reputation for his work on cancer of the tongue.
place ’I
Is not this
a
very remarkable forecast ? It is
humbling to realise that 21 years have passed since it was made, and that progress has been so lamentably
slow. What one would like to be able to do now is Butlin gave a list of 197 cases of carcinoma of the state the results of the treatment of epithelioma tongue, which comprised all those operated on by him, of the tongue by radium and to compare them with the first of which was in 1881 and the last in 1908. those obtained by surgery. At the present time Of these 197 patients, 55 lived for three years or over figures are too few and too recent to be of any without recurrence-that is, he had a survival-rate value, though it is greatly to be hoped that in of 27-9 per cent. at the end of the three-year period. a few years adequate and reliable figures will be The recent St. Bartholomew’s Hospital figure at the available. The Radium Commission has adopted end of three years is 35-7 per cent., so that there is the policy of asking all the national radium centres not much difference between the two. which are being started to keep their records on Butlin also quoted the combined figures of his own uniform case sheets. These records in due course and three other clinics-namely, those of Whitehead, are to be collected and analysed, so that in the near to have at our disposal a very Kronlein, and Kocher. The combined figures of future we may these four clinics showed a survival-rate of 20 per large number ofexpect which should prove of great figures cent. at the end of the three-year period. value. There are, however, a few figures which have been The survival-rates given by a number of other authors are : 18 per cent. by Capetti ; 26-6 per cent. published which are worth looking at. G. E. Birkett,S by Caird ; and 14-3 per cent. by Cobb and Simmonds.3 of the Manchester Radium Institute, who has done The Mayo Clinic figures for the years 1910 to 1922 splendid pioneer work with radium, states :show a survival-rate of :There are no five-year figures available in this country,
to
these great
"
30-8 per cent. at the end of 3 years. 34-4 5 " 4-25 10
but continental workers report about 45 per cent. of fiveyear cures as regards the primary site, and 20 per cent. of absolute cures." ,
"
A general survey of these figures, showing the results of operations for cancer of the tongue taken from clinics in various parts of the world, leads us to the conclusion that the best we can expect from surgery is a survival-rate of from 20 per cent. to 25 per cent. This is the basis on which the results of radium treatment can be compared.
I gather that the figure of complete cures over a three-year period from the Manchester Radium
Institute is 22-50 per cent.
This result
is not
incomparably better than that obtained by surgery. Roux-Berger and Monod,6s from the Radium Institute of Paris, report that during the six years 1920 to 1925, inclusive, they treated 287 cases of epithelioma of the tongue, out of which number 77 were cured. By " cured," they say they mean those RESULTS OF RADIUM. patients who were free from disease on Feb. lst, a percentage of cures of 26-8, or At this point it is appropriate to turn back again to 1927. This gives if a three-year period is taken on a total of 120 consider an almost prophetic utterance made by This is not as high a percentage Sir Henry Butlin 21 years ago, shortly before his cases, 21-6 per cent. of cures as one might have hoped for, and again does death.
not appear to be much better than the results of surgery. Radiumhemmet in Stockholm reports that, from a list of patients treated during the years 1921 to 2 On the Results of Operations for Carcinoma of the Tongue. 1926 (inclusive), 14 are alive and well out of 46 treated ; By Henry T. Butlin. Prepared for the Meeting of the Inter- a survival-rate of 30-4 per cent. This again seems to of at London: 1909. national Society Surgeons Brussels, Sept., Adlard and Sons, 1908. be no better result than that obtained by surgery. At 3 Cancer of the Mouth : Results of Treatment by Operation the same time they report a 78-3 per cent. survivaland Radiation. By Channing Simmonds, Surg., Gyn., and Obstet., 1926, xliii.; Carcinoma of Tongue, Judd and New, 5 Radium Treatment of Buccal Carcinoma, Brit. Jour. of Surg., Surg., Gyn., and Obstet., 1923, xxxvi., i. 1930 ; see also Amer. Jour. of Physical Therapy, 1928, v. 4 On the Early Diagnosis of Cancer of the Tongue and on the Jan., 6 Radiophysiologie et Radiotherapie. By Regaud. Vol. i., Results of Operations in such Cases. By Henry T. Butlin, Brit. fasc. ii., Paris, 1928. Med. Jour., 1909, i. "
At this moment, it would scarcely be too much to say that the air is charged with the emanations of radium. We
225 cases of epithelioma of the lip at the end of two years. It is admitted that these figures are few in number’ and recent, but it looks as if the final results are not startlingly better than those obtained by surgery. There are, however, some qualifying remarks to be made a little later.
rate of
treatment. These may be accounted for in the main by the fact that the growths were extensive and infiltrating. Quite a number were advanced and inoperable. We were not trying to produce a unique record of cures, but endeavouring rather to see what could and what could not be done. One thing that is perfectly clear is that if the primary growth is treated early it can be made to disappear by the use of radon in the great majority of cases, leaving a useful mobile organ. We know also from the work of others that the same result may be obtained by radium element. I repeat that we are not arguing here in favour of the emanation against the element, but merely trying to record the facts as we have seen them. The second point is that the patients who have died, and there have been ten-a third of the total numberhave been advanced cases of carcincma, cases which
OF THE SURGICAL UNIT, 1928-29. We now present to you a detailed account of those patients treated in the Surgical Unit during the years 1928 and 1929. The number is not great, but a careful study of even a small number of patients cannot fail to be of value, and certain deductions can be drawn. The method of treatment of the primary growth of the tongue has been by radon seeds, of a strength varying from 1-5 me. to 3 me. The seeds were in platinum capsules of a thickness of 03 mm., encased increased later to 0-5 mm., so as to minimise burning. On an average the seeds were left in for seven days. The reason why radon seeds were used and not radium I needles was, in the first instance, merely one of con- ’ venience. Seeds were available at a time when suitable needles were not, and further it appeared to us that seeds were more adaptable than needles for placing in the folds and crannies of the mouth. We hold no brief for radon as opposed to radium, but we only want to find out the truth. There seems to be an impression that the emanation is not as effective as the element on account of the rapid disintegration of radon. Physicists say that there ought to be no difference between the action of radon and radium, provided that a suitable dose be given. Our own observations tend to bear this out. The glands in the neck have been treated in the main by a barrage of radium needles, inserted at the same time as the seeds in the tongue and arranged according to the accompanying diagram. Needles containing radium element were used in this instance as it was desired to irradiate large areas of tissue containing lymphatic glands. The needles were inserted by puncture and, as far as we know, no damage showing method of irradiating lymphatic areas with The Diagram was done to any of the structures in the neck. radium needles. (Figures refer to milligrammes of radium for the of needles treating glands element in needles.) advisability using of the neck, or of dissecting the glands, or of combining surgery with radium treatment, will be discussed later. would have been classed as inoperable surgically, cases which had in all probability dissemination of Deductions Drawn from an Ana7ysis of 30 Cases. disease at the time of treatment. This is to emphasise There are certain points arising out of a close study once again the point that treatment, if it is to be of these figures which are worthy of comment. In successful, must be before the disease is advanced the majority of cases the tongue has been materially and disseminated. affected by the action of the radon seeds ; in the The third point that arises prominently from these majority the original primary tumour or ulcer has figures is the unsatisfactory state of our knowledge disappeared entirely in the course of a few weeks of the right method of treating the lymphatic glands. and the tongue has been left a mobile useful organ. It will be noted that the method of treatment adopted In one instance (Case 10) the carcinoma was, as by us has varied. In the majority of cases the far as we could see, entirely unaffected by the action method of irradiation by radium needles inserted of radon seeds, and later the tongue was excised. The through punctures in the skin has been used. This reason why this epithelioma did not react to the rays method has appeared to us to be satisfactory when is unknown to us. Perhaps it was non-sensitive to applied to the lymphatic gland areas in cases of radiations. Histolcgically it fell into Grcup 1 carcinoma of the breast. But it has not turned out classification, that is to say, it showed well-marked uniformly satisfactoiy for the glands secondary to cell-nest formation. Perhaps the seeds were below carcinoma of the tongue. In seven instances, Nos. 6, 9, 14, 20, 22, 24, and 27, strength ; perhaps they were not placed accurately. In another instance (Case 25), a woman with an easily the glands have not responded. Six of the patients accessible ulcer close to the tip of the tongue, the have died, and one-Case 27-will probably die seen. carcinoma was not materially influenced by the action In a number of patients regression or disappearance of the radon seeds and her tongue has been excised. of the glands has been noticed after irradiation, and, The histological findings show that she also falls into although this is encouraging, it is not proof that the the Grade 1 classification. Perhaps these cases glands were secondarily infected with carcincma and might be used as an argument for the use of the that they were sterilised by radiation. It is wellelement rather than the emanation. known that glands which are palpable clinically are The question of the non-radio-sensitivity of some often shown histologically to be inflammatory and tumours is very puzzling and requires investigation. not carcinomatous We have no direct evidence It emphasises the fact that we are still very much in that radium puncture does actually sterilise carcinothe dark about the whole problem, and that our matous glands. In some instances the glands have treatment is still empiric. There were six other been dissected, and it is possible that this should be, patients in whom the tongue was not healed by the at any rate for the present, the method of choice.
A SURVEY
OF THE
WORK
226
T
’THE PROBLEM OF TREATING THE LYMPHATIC GLANDS. The most difficult problem that has to be asked at the present time is the best method of treating the lymphatic glands. Workers from various parts of the world stress this point, and unanimity of opinion has not been reached. As stated before, we have been employing the method of irradiating the
lymphatic punctures
areas
by inserting radium needles through skin, and this has not proved
in the
ANALYSIS
OF
THIRTY CASES
OF
Bl.
EPITHELIOMA
=
bilateral,
OF THE
*
entirely satisfactory,
so we are searching for a better The Westminster Hospital, in their Reports for 1929, have given some information concerning their results. They seem to have got their best results from dissection of the glands followed by the use of a radium collar. For the purpose of this lecture I wrote to Mr. Birkett asking what is the method of choice employed at the Manchester Radium Institute. He replies as follows :-
palpable glands I have in the past expectant attitude and kept the patient under close observation. Should glands become palpable, then a block dissection is performed, combined with implantaare no an
usually adopted
tion of about 15 needles for
a
week.
TONGUE TREATED
WITH
RADON
OR
RADIUM.
From carcinoma of oesophagus.
method.
" If there
available and beds, I should be inclined to use a method of external radiation...... I can say definitely that my method of choice is a block dissection if glands are palpable, and that it is confined to the affected side." There is an important communication on this subject from the Radium Institute of Paris. It would appear from this that it is their opinion (I trust I do not misrepresent them) that in all cases of epithelioma of the tongue the glands of the neck should be completely excised ; and further, that the
Had I the radium
excised glands should all be examined histologically, and, that if any show cancerous infection then further treatment of the neck by radium. From these remarks it is clear that there is one thing on which all workers agree. They agree that the treatment of the primary tumour of the tongue by radium presents no great difficulty, and the key to the complete cure of the patient lies in the effective treatment of the lymphatic area. With this end in view, we are proposing now a much more active treatment of the glands than we have given in the past. This may be summarised briefly as follows :1. When the glands are not clinically enlarged: Block dissection of the affected side, followed by
227
histological examination. If the glands are not it has failed to cure cancer of the tongue. Now it has infected, nothing more; if the glands are infected, been shown that radium will heal a tongue without a mutilating operation, leaving the organ perhaps a application of a radium collar. 2. When glands are clinically enlarged : Block little scarred but mobile and useful. A distinct step dissection of the affected side, followed by histological forward has been made, and, in my judgment, the examination. If the glands are not infected, nothing future treatment of cancer of the tongue lies with more; if the glands are macroscopically infected, radium. The treatment of the lymphatic glands still remains insertion of radium needles after the dissection, or a difficulty, and for that reason, if for no other, it application of a radium collar. 3. When glands are enlarged, fixed, and inoperable : seems clear that radium therapy cannot and should An attempt will be made to bring them to a stage of not be divorced from surgery in the modern treatment operability by the use of radium needles or radium of cancer. collar. One last point is overwhelmingly clear-namely, CONCLUSIONS. that the treatment of cancer, if it is to be successful, The use of radium is at one and the same time must be undertaken early, whether that treatment is disappointing, fascinating, and perplexing. It is to be by radium, by surgery, or by anything else. fascinating because it will bring about the A great many of our patients come to us too late for disappearance of a local tumour in an astonishing effective treatment. The medical profession cannot way in a few weeks, and it holds out the bright be held to blame for this. General practitioners are prospectof a cure of this dread scourge. It is well educated and do not hold their patients long perplexing because we have not as yet any idea of before sending them to the surgeon. The difficulty how it acts, and why in one instance it seems to work lies with the patients. It is often months from the like a charm and in another to be of no value. It is onset of symptoms before they will ask advice from disappointing because we cannot secure a hundred their doctor, and during this time the fatal disseminaper cent. of cures. Though we must admit that this tion may have taken place. The public needs is disappointing there is no reason why we should be 1 educating. Is it not the duty of the medical profession down-hearted. Surgery has done its best and yet, to say so to say so in emphatic terms, and to keep in spite of the high standard which the art has reached, on saying so ?
Hunterian Lecture ON
IMMUNITY FROM A NEW POINT OF VIEW. Delivered
before
the Hunterian
Jan.
BY
AND
on
M.D. PARIS,
VICHY).
THIS evening I am asking you to consider the problem of immunity from the angle of the hydrologist, and I am delighted to show you something of the fascinating problems that are confronting those of us who study modern hydrology and who find themselves, to their own surprise, promoted from the modest rank of water doctors " to the high dignity of pioneers in the field of biology. I do not intend in this short time to endeavour to solve any particular problem, but just to discuss a few particular things which havepuzzled us. "
WHY DOES OPIUM INDUCE SLEEP ?" You remember the question ? I must take you back to Moliere. In the interlude of " Le Malade Imaginaire," a play written at the expense of the doctor and for his greatest benefit, there is a grotesque ceremony, where a candidate is given the M.D. degree by a jury of pointed bonnets. He is quizzed in Latin, the true international language (which we call dead merely because we let it sleep). And this is the question asked by the President : " Cur opium facit dormire ? Answer : " Quia est in ea virtus dormitiva qui facit dormire." The jury is delighted : " Bene, bene, bene respondere. Dignus, dignus es intrare in nostro docto corpore." We laugh too, with the public. But stop and "
"
consider what you would answer to such a question. Indeed, " bene respondere "-" good answer." It is modest. It expresses with candid simplicity the ignoramus of Science confronted with the dark mystery of causes. Felix qui potuit Happy would be the one who could ascertain causes. No, it ...
OK A PHYSICAL BASIS. has been trained to consider the generation chemical constitution of all bodies and more especially drugs. There is little doubt that the new generation will consider matter from a quite different angle. The modern physicist-I might say the British physicisthas taught us to look at the atomic world from the gravitation point of view. To the ancient astronomer nothing looked more eternally at rest than the stars, but science has told us stories about their wanderings that no mortal mind could have imagined. The modern biologist is going in turn through a similar experience. All the phenomena of life, without exception, are derived from chemico-physical reactions in water, and therefore it is important that we, as physicians, should learn to imagine the gravitation in the atomic world, the games of the molecules, of the ions, of the electrons, which determine the phenomena of which we see the manifestations ; diffusion. osmotic pressure, the equilibrium of the molecular concentration, the reactions of the colloids, and so ma,ny other procedures which were never even mentioned a quarter of a century ago. We smile when we are questioned on the sedative virtues of opium. But when we are asked, for instance, how antitetanic serum immunises against
BIOLOGY
Our
27th, 1930,
GUSTAVE MONOD, M.R.C.P. LOND. (PARIS
Society
is not the answer that is wrong ; it is the question. It should not be Cur. It should be Quomodo. Let us to-night stand at the strong-room door of Not that we can pretend to break Science. through, but perhaps we may see a little gleam of light peeping underneath.
We seem to we answer quite seriously. explanation. We use a most bewildering phraseology. But when all is considered I wonder if
tetanus, then see
an
have expressed any other truth than this : that antitetanic serum has an antitetanic virtue which neutralises tetanic toxin. Again how ? Might what we now know of the constitution of matter help us in other ways ? We know that atoms are like many suns gravitating at various speeds, but we know nothing of their relative speeds. It might be that atoms only react on atoms when there is a certain ratio between their rate of revolutions. An idea of this is given to us by the familiar experience of changing gear when driving a car. To avoid jerks we modify the relative ?peed of the cog wheels to make them engage. Perhaps there may be a similar phenomenon in the case of a
we
A Contribution TO THE STUDY OF THE
TREATMENT OF EPITHELIOMA OF THE TONGUE BY RADIUM.
That is to say, there was a survival-rate of 17’ 1 per cent. (It is interesting to note in passing that if the period of observation had been continued for longer than five years the percentage of so-called " cures " would be still further diminished, for of the patients noted above as remaining well for five years three showed recurrences at the close of six years, and two at the end of seven years.) Mr. R. F. Phillips, Luther Holden Scholar, who is now working on the end-results of patients suffering from buccal carcinoma (including carcinoma of
Being a Hunterian Lecture delivered before the Royal tongue, floor of mouth, cheek, lip, tonsils, and palate), College of Surgeons of England on Jan. 29th, 1930, has supplied the following interesting figures which BY G. E. GASK, C.M.G., D.S.O., F.R.C.S. ENG., may later throw some light on the problem being PROFESSOR OF SURGERY IN THE UNIVERSITY OF LONDON.
studied.
degrees
He holds that buccal carcinomata show grades of malignancy, which may be
or
IN presenting this study I wish to say that it is really a contribution from the members of the Surgical Unit of St. Bartholomew’s Hospital, of which
I am the mouthpiece. We feel that the time has come to consider, more in detail than was previously possible, the relative value of treatment of carcinoma of the tongue by the old-established method of surgical excision and the new, much hoped for, rather spectacular, and not yet fully established treatment by radium. The amount of information at our disposal is still too small to arrive at definite conclusions, but it is important to consider what there is, seeing that in a short time the amount of radium in the country will be considerably increased. Following the Thanksgiving Fund for His Majesty’s recovery and the foundation of the Radium Commission, a number of national radium centres are about to be started in the University medical teaching centres of England, Scotland, and Wales, so that in a short time we may expect a great stimulus to the radium treatment of patients suffering from cancer, and among these there are sure to be many suffering from cancer of the tongue. It seems to us, therefore, an opportune moment to take stock of the knowledge which is now available, to table the results obtained by surgery, and to scrutinise with care and without fear or favour the results and methods of radium treatment. RESULTS OF SURGERY. We have tried first to reach the approximate figure of the cures of cancer of the tongue obtained by surgery, so as to have a fixed point for comparison between surgery and radium therapy. Operations for removal of the tongue have been performed by surgeons now for many years, and we ought to be able to give accurate detailed figures for the results of surgery in all the different phases of the disease. Unfortunately, the medical profession has appeared unbusinesslike in the matter of compiling statistics, and slow in adopting follow-up schemes, with the result that it is difficult to find a large number of conclusive figures. Statistics are cold, heartless, things, which do not recommend themselves to optimists, but it is necessary to inflict some of them on
you.
Statistics
of St. Bartholomew’s Hospital. follow-up department was started at this hospital for the purpose of tracing the end- ’! results of all patients suffering from cancer of the tongue. The results are shown on the accompanying graph. Included in this series are all those patients who were deemed operable, and were, in fact, operated on in one way or another by the various surgeons attached to the hospital. The results of the varying types of operations are not differentiated, as it was thought that the figures wanted were those that In 1922
a
showed the value of surgery
as
a
whole.
Three
years is not a long enough period to judge of any form of treatment of cancer, so only those patients have been included in this review who might have survived five years from the date of their original operation. Of these there were 70, of which only 12 remained aliveand well and free from recurrence at the end of five years from the date of their operation. 5553
Epithelioma of tongue. Five-year survival-rate of 70 patients operated on at St. Bartholomew’s Hospital.
measured and foretold by their histology. Following Broders’sl work, Mr. Phillips has examined the histology of the tumours from a large number of patients who have been treated at St. Bartholomew’s Hospital between the years 1924 to 1927. These are divided into four grades, according as they show cells approaching the normal tissues or differing greatly from the normal1 and approaching the embryonic type. Thus, Grade 1 contains those cases which show much cell-nest formation and few mitoses, and Grade 4 those cases which show no cell-nest formation and much mitosis : whereas Grades 2 and 3 are intermediate. The 159 patients observed fell into the following
grades :-
1 Broders, A. C.: Grading of Carcinoma and Practical Application, Minn. Med., 1925, viii., 736; and Epithelioma of Cavities and Internal Organs of Head and Neck, Arch. Surg., Chicago, 1925, xi., 1.
E
224
Thus, it will be seen that the largest number falls into Grade 2 and the smallest into Grade 4, the most malignant category. Mr. Phillips next worked out what happened to the patients in these various grades and tabled the survival-rate in each. He believes that the prognosis or chance of survival is definitely related to the type of growth. Thus, he finds that the survival-rate in
are told that epithelioma of the tongue can be cured by radium. Had I been asked my opinion on this question a month ago, I should have said that, although two or three people in different parts of the world have claimed this power for radium, the general belief is that rodent ulcer is the only variety of malignant disease which radium is competent to cure. And I should have added that the only case of epithelioma of the mouth in my own practice to which radium had been applied (by the most skilful man with the best material) had ended disastrously. But I have, Per cent. within the last few days, seen a case in which a typical Grade 1 is 36-4 2 is at the end of three years. epithelioma of the inside of the cheek is so much better, 3 is 8.0 under the application of radium, at the end of four months, 4 is 0 (all dead). that it looks as if it would be quite cured. And this had Number of patients followed, 90. apparently been accomplished without inflammation or sloughing or profound ulceration of the disease. I understand that radium in this case was applied by means of It should be interesting to find out whether any the disc. the As this epithelioma was about It inches in of these grades are more or less susceptible or sensitive diameter and ulcerated all over, when I saw it four months to radium. There is some evidence to support the view ’, ago, there seems no reason to doubt that small epitheliomata that the cases falling into the first group-namely, of the tongue may be removed by radium, probably with those showing marked cell-nest formation with little a better scar than would be left by any other efficient agent. But, having said this, it must not be forgotten that the mitosis, are less sensitive to radium than those highly removal of the primary disease is only part of the cure of is in 4. More work malignant types required, epithelioma. Group Even the smallest, the youngest, and as however, before this can be stated proved. apparently the most insignificant epithelioma of the tongue is capable of affecting the lymphatic glands, as the cases I have related show. So that, unless radium is discovered Selection from Published Sources. to possess a far-reaching influence, spreading from the seat The results of surgery obtained by us at St. of the primary disease to the associated lymphatic glands, Bartholomew’s Hospital are so bad that it seems only I am afraid that the surgeon must still occupy an important in the treatment of epithelioma of the tongue." right to compare them with a selection taken from the "
"
18-2
"
published sources. Naturally, one’s mind turns first to the publications of Sir Henry Butlina PastPresident of this College, who had the highest reputation for his work on cancer of the tongue.
place ’I
Is not this
a
very remarkable forecast ? It is
humbling to realise that 21 years have passed since it was made, and that progress has been so lamentably
slow. What one would like to be able to do now is Butlin gave a list of 197 cases of carcinoma of the state the results of the treatment of epithelioma tongue, which comprised all those operated on by him, of the tongue by radium and to compare them with the first of which was in 1881 and the last in 1908. those obtained by surgery. At the present time Of these 197 patients, 55 lived for three years or over figures are too few and too recent to be of any without recurrence-that is, he had a survival-rate value, though it is greatly to be hoped that in of 27-9 per cent. at the end of the three-year period. a few years adequate and reliable figures will be The recent St. Bartholomew’s Hospital figure at the available. The Radium Commission has adopted end of three years is 35-7 per cent., so that there is the policy of asking all the national radium centres not much difference between the two. which are being started to keep their records on Butlin also quoted the combined figures of his own uniform case sheets. These records in due course and three other clinics-namely, those of Whitehead, are to be collected and analysed, so that in the near to have at our disposal a very Kronlein, and Kocher. The combined figures of future we may these four clinics showed a survival-rate of 20 per large number ofexpect which should prove of great figures cent. at the end of the three-year period. value. There are, however, a few figures which have been The survival-rates given by a number of other authors are : 18 per cent. by Capetti ; 26-6 per cent. published which are worth looking at. G. E. Birkett,S by Caird ; and 14-3 per cent. by Cobb and Simmonds.3 of the Manchester Radium Institute, who has done The Mayo Clinic figures for the years 1910 to 1922 splendid pioneer work with radium, states :show a survival-rate of :There are no five-year figures available in this country,
to
these great
"
30-8 per cent. at the end of 3 years. 34-4 5 " 4-25 10
but continental workers report about 45 per cent. of fiveyear cures as regards the primary site, and 20 per cent. of absolute cures." ,
"
A general survey of these figures, showing the results of operations for cancer of the tongue taken from clinics in various parts of the world, leads us to the conclusion that the best we can expect from surgery is a survival-rate of from 20 per cent. to 25 per cent. This is the basis on which the results of radium treatment can be compared.
I gather that the figure of complete cures over a three-year period from the Manchester Radium
Institute is 22-50 per cent.
This result
is not
incomparably better than that obtained by surgery. Roux-Berger and Monod,6s from the Radium Institute of Paris, report that during the six years 1920 to 1925, inclusive, they treated 287 cases of epithelioma of the tongue, out of which number 77 were cured. By " cured," they say they mean those RESULTS OF RADIUM. patients who were free from disease on Feb. lst, a percentage of cures of 26-8, or At this point it is appropriate to turn back again to 1927. This gives if a three-year period is taken on a total of 120 consider an almost prophetic utterance made by This is not as high a percentage Sir Henry Butlin 21 years ago, shortly before his cases, 21-6 per cent. of cures as one might have hoped for, and again does death.
not appear to be much better than the results of surgery. Radiumhemmet in Stockholm reports that, from a list of patients treated during the years 1921 to 2 On the Results of Operations for Carcinoma of the Tongue. 1926 (inclusive), 14 are alive and well out of 46 treated ; By Henry T. Butlin. Prepared for the Meeting of the Inter- a survival-rate of 30-4 per cent. This again seems to of at London: 1909. national Society Surgeons Brussels, Sept., Adlard and Sons, 1908. be no better result than that obtained by surgery. At 3 Cancer of the Mouth : Results of Treatment by Operation the same time they report a 78-3 per cent. survivaland Radiation. By Channing Simmonds, Surg., Gyn., and Obstet., 1926, xliii.; Carcinoma of Tongue, Judd and New, 5 Radium Treatment of Buccal Carcinoma, Brit. Jour. of Surg., Surg., Gyn., and Obstet., 1923, xxxvi., i. 1930 ; see also Amer. Jour. of Physical Therapy, 1928, v. 4 On the Early Diagnosis of Cancer of the Tongue and on the Jan., 6 Radiophysiologie et Radiotherapie. By Regaud. Vol. i., Results of Operations in such Cases. By Henry T. Butlin, Brit. fasc. ii., Paris, 1928. Med. Jour., 1909, i. "
At this moment, it would scarcely be too much to say that the air is charged with the emanations of radium. We
225 cases of epithelioma of the lip at the end of two years. It is admitted that these figures are few in number’ and recent, but it looks as if the final results are not startlingly better than those obtained by surgery. There are, however, some qualifying remarks to be made a little later.
rate of
treatment. These may be accounted for in the main by the fact that the growths were extensive and infiltrating. Quite a number were advanced and inoperable. We were not trying to produce a unique record of cures, but endeavouring rather to see what could and what could not be done. One thing that is perfectly clear is that if the primary growth is treated early it can be made to disappear by the use of radon in the great majority of cases, leaving a useful mobile organ. We know also from the work of others that the same result may be obtained by radium element. I repeat that we are not arguing here in favour of the emanation against the element, but merely trying to record the facts as we have seen them. The second point is that the patients who have died, and there have been ten-a third of the total numberhave been advanced cases of carcincma, cases which
OF THE SURGICAL UNIT, 1928-29. We now present to you a detailed account of those patients treated in the Surgical Unit during the years 1928 and 1929. The number is not great, but a careful study of even a small number of patients cannot fail to be of value, and certain deductions can be drawn. The method of treatment of the primary growth of the tongue has been by radon seeds, of a strength varying from 1-5 me. to 3 me. The seeds were in platinum capsules of a thickness of 03 mm., encased increased later to 0-5 mm., so as to minimise burning. On an average the seeds were left in for seven days. The reason why radon seeds were used and not radium I needles was, in the first instance, merely one of con- ’ venience. Seeds were available at a time when suitable needles were not, and further it appeared to us that seeds were more adaptable than needles for placing in the folds and crannies of the mouth. We hold no brief for radon as opposed to radium, but we only want to find out the truth. There seems to be an impression that the emanation is not as effective as the element on account of the rapid disintegration of radon. Physicists say that there ought to be no difference between the action of radon and radium, provided that a suitable dose be given. Our own observations tend to bear this out. The glands in the neck have been treated in the main by a barrage of radium needles, inserted at the same time as the seeds in the tongue and arranged according to the accompanying diagram. Needles containing radium element were used in this instance as it was desired to irradiate large areas of tissue containing lymphatic glands. The needles were inserted by puncture and, as far as we know, no damage showing method of irradiating lymphatic areas with The Diagram was done to any of the structures in the neck. radium needles. (Figures refer to milligrammes of radium for the of needles treating glands element in needles.) advisability using of the neck, or of dissecting the glands, or of combining surgery with radium treatment, will be discussed later. would have been classed as inoperable surgically, cases which had in all probability dissemination of Deductions Drawn from an Ana7ysis of 30 Cases. disease at the time of treatment. This is to emphasise There are certain points arising out of a close study once again the point that treatment, if it is to be of these figures which are worthy of comment. In successful, must be before the disease is advanced the majority of cases the tongue has been materially and disseminated. affected by the action of the radon seeds ; in the The third point that arises prominently from these majority the original primary tumour or ulcer has figures is the unsatisfactory state of our knowledge disappeared entirely in the course of a few weeks of the right method of treating the lymphatic glands. and the tongue has been left a mobile useful organ. It will be noted that the method of treatment adopted In one instance (Case 10) the carcinoma was, as by us has varied. In the majority of cases the far as we could see, entirely unaffected by the action method of irradiation by radium needles inserted of radon seeds, and later the tongue was excised. The through punctures in the skin has been used. This reason why this epithelioma did not react to the rays method has appeared to us to be satisfactory when is unknown to us. Perhaps it was non-sensitive to applied to the lymphatic gland areas in cases of radiations. Histolcgically it fell into Grcup 1 carcinoma of the breast. But it has not turned out classification, that is to say, it showed well-marked uniformly satisfactoiy for the glands secondary to cell-nest formation. Perhaps the seeds were below carcinoma of the tongue. In seven instances, Nos. 6, 9, 14, 20, 22, 24, and 27, strength ; perhaps they were not placed accurately. In another instance (Case 25), a woman with an easily the glands have not responded. Six of the patients accessible ulcer close to the tip of the tongue, the have died, and one-Case 27-will probably die seen. carcinoma was not materially influenced by the action In a number of patients regression or disappearance of the radon seeds and her tongue has been excised. of the glands has been noticed after irradiation, and, The histological findings show that she also falls into although this is encouraging, it is not proof that the the Grade 1 classification. Perhaps these cases glands were secondarily infected with carcincma and might be used as an argument for the use of the that they were sterilised by radiation. It is wellelement rather than the emanation. known that glands which are palpable clinically are The question of the non-radio-sensitivity of some often shown histologically to be inflammatory and tumours is very puzzling and requires investigation. not carcinomatous We have no direct evidence It emphasises the fact that we are still very much in that radium puncture does actually sterilise carcinothe dark about the whole problem, and that our matous glands. In some instances the glands have treatment is still empiric. There were six other been dissected, and it is possible that this should be, patients in whom the tongue was not healed by the at any rate for the present, the method of choice.
A SURVEY
OF THE
WORK
226
T
’THE PROBLEM OF TREATING THE LYMPHATIC GLANDS. The most difficult problem that has to be asked at the present time is the best method of treating the lymphatic glands. Workers from various parts of the world stress this point, and unanimity of opinion has not been reached. As stated before, we have been employing the method of irradiating the
lymphatic punctures
areas
by inserting radium needles through skin, and this has not proved
in the
ANALYSIS
OF
THIRTY CASES
OF
Bl.
EPITHELIOMA
=
bilateral,
OF THE
*
entirely satisfactory,
so we are searching for a better The Westminster Hospital, in their Reports for 1929, have given some information concerning their results. They seem to have got their best results from dissection of the glands followed by the use of a radium collar. For the purpose of this lecture I wrote to Mr. Birkett asking what is the method of choice employed at the Manchester Radium Institute. He replies as follows :-
palpable glands I have in the past expectant attitude and kept the patient under close observation. Should glands become palpable, then a block dissection is performed, combined with implantaare no an
usually adopted
tion of about 15 needles for
a
week.
TONGUE TREATED
WITH
RADON
OR
RADIUM.
From carcinoma of oesophagus.
method.
" If there
available and beds, I should be inclined to use a method of external radiation...... I can say definitely that my method of choice is a block dissection if glands are palpable, and that it is confined to the affected side." There is an important communication on this subject from the Radium Institute of Paris. It would appear from this that it is their opinion (I trust I do not misrepresent them) that in all cases of epithelioma of the tongue the glands of the neck should be completely excised ; and further, that the
Had I the radium
excised glands should all be examined histologically, and, that if any show cancerous infection then further treatment of the neck by radium. From these remarks it is clear that there is one thing on which all workers agree. They agree that the treatment of the primary tumour of the tongue by radium presents no great difficulty, and the key to the complete cure of the patient lies in the effective treatment of the lymphatic area. With this end in view, we are proposing now a much more active treatment of the glands than we have given in the past. This may be summarised briefly as follows :1. When the glands are not clinically enlarged: Block dissection of the affected side, followed by
227
histological examination. If the glands are not it has failed to cure cancer of the tongue. Now it has infected, nothing more; if the glands are infected, been shown that radium will heal a tongue without a mutilating operation, leaving the organ perhaps a application of a radium collar. 2. When glands are clinically enlarged : Block little scarred but mobile and useful. A distinct step dissection of the affected side, followed by histological forward has been made, and, in my judgment, the examination. If the glands are not infected, nothing future treatment of cancer of the tongue lies with more; if the glands are macroscopically infected, radium. The treatment of the lymphatic glands still remains insertion of radium needles after the dissection, or a difficulty, and for that reason, if for no other, it application of a radium collar. 3. When glands are enlarged, fixed, and inoperable : seems clear that radium therapy cannot and should An attempt will be made to bring them to a stage of not be divorced from surgery in the modern treatment operability by the use of radium needles or radium of cancer. collar. One last point is overwhelmingly clear-namely, CONCLUSIONS. that the treatment of cancer, if it is to be successful, The use of radium is at one and the same time must be undertaken early, whether that treatment is disappointing, fascinating, and perplexing. It is to be by radium, by surgery, or by anything else. fascinating because it will bring about the A great many of our patients come to us too late for disappearance of a local tumour in an astonishing effective treatment. The medical profession cannot way in a few weeks, and it holds out the bright be held to blame for this. General practitioners are prospectof a cure of this dread scourge. It is well educated and do not hold their patients long perplexing because we have not as yet any idea of before sending them to the surgeon. The difficulty how it acts, and why in one instance it seems to work lies with the patients. It is often months from the like a charm and in another to be of no value. It is onset of symptoms before they will ask advice from disappointing because we cannot secure a hundred their doctor, and during this time the fatal disseminaper cent. of cures. Though we must admit that this tion may have taken place. The public needs is disappointing there is no reason why we should be 1 educating. Is it not the duty of the medical profession down-hearted. Surgery has done its best and yet, to say so to say so in emphatic terms, and to keep in spite of the high standard which the art has reached, on saying so ?
Hunterian Lecture ON
IMMUNITY FROM A NEW POINT OF VIEW. Delivered
before
the Hunterian
Jan.
BY
AND
on
M.D. PARIS,
VICHY).
THIS evening I am asking you to consider the problem of immunity from the angle of the hydrologist, and I am delighted to show you something of the fascinating problems that are confronting those of us who study modern hydrology and who find themselves, to their own surprise, promoted from the modest rank of water doctors " to the high dignity of pioneers in the field of biology. I do not intend in this short time to endeavour to solve any particular problem, but just to discuss a few particular things which havepuzzled us. "
WHY DOES OPIUM INDUCE SLEEP ?" You remember the question ? I must take you back to Moliere. In the interlude of " Le Malade Imaginaire," a play written at the expense of the doctor and for his greatest benefit, there is a grotesque ceremony, where a candidate is given the M.D. degree by a jury of pointed bonnets. He is quizzed in Latin, the true international language (which we call dead merely because we let it sleep). And this is the question asked by the President : " Cur opium facit dormire ? Answer : " Quia est in ea virtus dormitiva qui facit dormire." The jury is delighted : " Bene, bene, bene respondere. Dignus, dignus es intrare in nostro docto corpore." We laugh too, with the public. But stop and "
"
consider what you would answer to such a question. Indeed, " bene respondere "-" good answer." It is modest. It expresses with candid simplicity the ignoramus of Science confronted with the dark mystery of causes. Felix qui potuit Happy would be the one who could ascertain causes. No, it ...
OK A PHYSICAL BASIS. has been trained to consider the generation chemical constitution of all bodies and more especially drugs. There is little doubt that the new generation will consider matter from a quite different angle. The modern physicist-I might say the British physicisthas taught us to look at the atomic world from the gravitation point of view. To the ancient astronomer nothing looked more eternally at rest than the stars, but science has told us stories about their wanderings that no mortal mind could have imagined. The modern biologist is going in turn through a similar experience. All the phenomena of life, without exception, are derived from chemico-physical reactions in water, and therefore it is important that we, as physicians, should learn to imagine the gravitation in the atomic world, the games of the molecules, of the ions, of the electrons, which determine the phenomena of which we see the manifestations ; diffusion. osmotic pressure, the equilibrium of the molecular concentration, the reactions of the colloids, and so ma,ny other procedures which were never even mentioned a quarter of a century ago. We smile when we are questioned on the sedative virtues of opium. But when we are asked, for instance, how antitetanic serum immunises against
BIOLOGY
Our
27th, 1930,
GUSTAVE MONOD, M.R.C.P. LOND. (PARIS
Society
is not the answer that is wrong ; it is the question. It should not be Cur. It should be Quomodo. Let us to-night stand at the strong-room door of Not that we can pretend to break Science. through, but perhaps we may see a little gleam of light peeping underneath.
We seem to we answer quite seriously. explanation. We use a most bewildering phraseology. But when all is considered I wonder if
tetanus, then see
an
have expressed any other truth than this : that antitetanic serum has an antitetanic virtue which neutralises tetanic toxin. Again how ? Might what we now know of the constitution of matter help us in other ways ? We know that atoms are like many suns gravitating at various speeds, but we know nothing of their relative speeds. It might be that atoms only react on atoms when there is a certain ratio between their rate of revolutions. An idea of this is given to us by the familiar experience of changing gear when driving a car. To avoid jerks we modify the relative ?peed of the cog wheels to make them engage. Perhaps there may be a similar phenomenon in the case of a
we