Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from 227

CANCER OF THE UTERINE By A. H. CHARLES, F.R.C.S., F.R.C.O.G. Gynaecological Surgeon, St. George's Hospital; Surgeon, Samaritan Hospitalfor Women

It is impossible within the compass of a short cervical cancers are Grade I (o to 25 per cent. of article to review all aspects of this disease. It is de-differentiated cells). Tumours with a large proposed, therefore, to concentrate mainly on the proportion of undifferentiated cells are the most diagnosis and treatment. malignant; they are also the most radiosensitive Cancer of the cervix occurs frequently in parous but are not equally radiocurable. women between 40 and 70 years of age. Nulli- Spread of cervical cancer takes place by: parous women represent only 7 per cent. of the (i) Direct extension to the adjacent vaginal cases. The disease is relatively uncommon in mucosa, upwards along the surface into the women of the upper classes and in Jewish women corpus, particularly in endocervical growths, or to of all classes. The comparative immunity enjoyed the parametrium. by Jewesses is probably racial and not due to (2) Lymphatic spread, by the lymphatics of the freedom from contact with smegma, as cancer of parametrium outwards to the nodes lying in the cervix is common in certain African tribes relation to the vessels on the pelvic wall. Lymph- where circumcision is ritual. The most important atic glands are situated along the external iliac factor in aetiology is pregnancy, either through 8 to io in in trauma to the cervix or to the cellular vessels, being number, arranged three activity groups, one lateral, one medial and one in front by copyright. which takes place during pregnancy. Trauma alone of the vessels. The latter group is sometimes is not responsible, as shown by the rarity of absent. Another important gland lies in the cancer in cases of procidentia, though the cervix is obturator fossa. Some smaller glands are dis- constantly exposed to friction and may be ulcer- tributed around the internal iliac artery and its ated. It is the cervix that is exposed for a long branches. The so-called ' paracervical gland ' is time to the action of a continuous cervical dis- seldom if ever seen. Efferents from these groups charge that is liable to develop cancer perhaps of to the common iliac and passing through precancerous stages before true glands pass upwards invasive cancer para-aortic nodes. appears. The stage to which a carcinoma has progressed http://pmj.bmj.com/ is more important than histological grading when Symptomatology considering the probable outcome of treatment. The symptom of greatest significance is bleed- Clinical staging is made in accordance with the ing, which may be irregular or a sudden profuse League of Nations' classification. In Harnett's haemorrhage, or menorrhagia. Occasionally, it cases were as follows: follows coitus. In only 2.9 per cent. of the series (1949) series, staged collected by the British Empire Cancer Campaign Per and reported by Harnett was post-coital bleeding Stage I. The carcinoma is strictly confined No. cent. on September 30, 2021 by guest. Protected the first symptom. A vaginal discharge was the to the cervix ...... 201 23.4 first in 20. cent. of these cases. Stage II. The carcinoma infiltrates the symptom per Pain parametrium on one or both sides, but is seldom the first symptom and indicates advanced has not invaded the pelvic wall. Upper disease. one-third of infiltrated. Spread to corpus ...... 37.0 and Stage III. The carcinomatous infiltration Pathology Diagnosis of the parametrium has invaded the pel- The clinical varieties are: (i) ulcerative, (2) vic wall on one or both sides. Lower proliferative or cauliflower, (3) sclerosing, some- one-third of vagina involved. Isolated times known as the 'worm-eaten ' cervix, and (4) metastases on pelvic wall .. .. 221 23.7 endocervical. Stage IV. Carcinoma involves bladder as determined cystoscopically or a vesico- About 95 per cent. of these tumours are epider- vaginal fistula is present. in- moid cancers, the other 5 per cent. being adeno- volved. Distant metastases present .. II3 13.2 carcinomas. Histological grading is usually made Not staged for lack of data ... 6 .7 in accordance with Broder's classification based on the degree of cell de-differentiation. Very few Total ...... 859 0oo.0 Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from 228 POSTGRADUATE MEDICAL JOURNAL April 1952 In I950, American gynaecologists put forward or top of the vagina, while others take it direct a revision of the League of Nations' classification from the cervix or cervical canal, while Ayre (I949) which they termed the international classification. and Novak (I947) obtain specimens by scraping The only real change in this is to add Stage o to the cervix with a wooden spatula in the one case include carcinoma in situ and intra-epithelial car- and a scalpel or sharp spoon in the other. By cinoma. It must be emphasized that staging is taking a direct scraping from the cervix, the ex- done from clinical data and cannot take into foliated cells are obtained nearer their source and account lymph node infiltration. Some correction this surface biopsy is more accurate than a vaginal of the staging is possible in cases submitted to smear. operation, but such correction would falsify com- Epidermoid cancer of the cervix arises from the parison of the results of operation with the results squamo-columnar junction and, by scraping all of radiotherapy. round its margin, cancer cells are most likely to be The diagnosis of the established case is generally picked up. Ayre found that when vaginal smears obvious on digital and speculum examination. were taken from cervices which appeared sus- Improvement in the results of treatment must picious of cancer and cancer cells were found to come mainly by earlier recognition of the disease be present, subsequent biopsy confirmed cancer and it is to this end that much recent research has in almost Ioo per cent. of cases. However, when been directed. However, for some time,to come, the scrapings were taken from the squamo- the detection of cervical cancer in a curable stage columnar margin of cervices that appeared normal will depend upon the prompt attention of patients and cancer cells were obtained, the subsequent and their doctors to symptoms. In Harnett's biopsy often gave a negative result. The explanation series 20 per cent. of the patients allowed from lay in the difficulty of deciding from which area three to six months to elapse before consulting to take the biopsy. It is necessary to take a ring their doctors and over 25 per cent. allowed more biopsy, thus obtaining all the tissue round the than six months to go by before seeking advice. circumference of the squamo-columnar junction

Some delay must be attributed to the doctor, but and to submit this tissue to serial section. Ifby copyright. a in Harnett's series, 80 per cent. of the patients small area is punched out of the circumference for were examined vaginally at once or within a month biopsy, it may only represent perhaps i/2oth of of the first consultation. Of those who consulted the tissue in which a carcinoma could be growing. a doctor 80 per cent. were referred to a hospital This work has proved that pre-clinical cancer may at once. Howson and Montgomery (1949) in lurk in a normal-looking cervix, and further that Philadelphia found that in the analysis of 1,140 pre-clinical cancer is not necessarily pre-invasive cases, the average duration of delay attributable or intra-epithelial or carcinoma in situ, but may be to the doctor was 7.4 months. In about half of early invasive cancer. Pre-invasive cancer need the cases of delay, no local examination was made. not necessarily proceed ultimately to an invasivehttp://pmj.bmj.com/ Doctors should make it a rule that if the patient stage, but in some of the cases this undoubtedly declines a vaginal examination when symptoms takes place. point to the possibility of cancer being present, the The interpretation of the material obtained by doctor should decline to order any treatment. vaginal smear or cervical scraping is not easy and Palliatives will only prolong examination delay, a long training is required before the cytologist's while refusal to give any medicine may persuade findings become trustworthy. In America, cancer the patient to submit to examination. Unfor- diagnostic clinics have been set up and cytological tunately, the symptoms may be insignificant until examinations are made from the cervices of all on September 30, 2021 by guest. Protected the growth has reached an advanced stage. If those who present themselves for examination. a reliable method can be found for diagnosis of Again in various gynaecological departments, the cervical cancer at its onset or before clinical signs cervices of all patients attending the out-patient are present, then we shall have a real chance of clinic or admitted to the wards, are submitted to reducing the mortality from this disease. a smear examination. This entails a tremendous In I928, Papanicolaou found cancer cells in the amount of laboratory work and it is estimated that vaginal secretions of women with uterine cancer, it costs about I50 dollars to detect a case of pre- but it was not until 194I that he co-operated with invasive cancer. When a vaginal smear has proved Traut to describe the vaginal-smear method of positive, the presence of pre-clinical cancer must diagnosis of uterine carcinoma (Traut and Papa- be confirmed by a ring biopsy before any treatment nicolaou, I941). Since then, many other clinicians is instituted. have confirmed the vaginal smear as a valuable Attention has been drawn to the dangers of mcasure in the detection of early disease. There biopsy. Although it is not possible utterly to is a considerable variation in technique. Some deny that biopsy could contribute to an accelerated collect the material for the sznear from the minddle spread of the disease, it is essential to obtain the Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from April 1952 CHARLES: Cancer of the Uterine Cervix 229 reliable evidence that biopsy alone can afford When this process involves a gland, the squamous before embarking on radical treatment. It is not epithelium may ultimately completely replace the justifiable to submit a patient to or normal glandular epithelium, producing a collec- radiotherapy on a smear diagnosis alone, as ' false tion of squamous cells that closely resemble car- positives ' are still not uncommon. Nevertheless, cinoma. This is most confusing when the the vaginal smear or cervical scraping can help in squamous cells are found well below the surface. cancer diagnosis and one has to consider how its Here a squamous cell metaplasia may be the use could be developed in this country. To make explanation. The characteristics of the cells and the method available to women in all the large the absence of invasive tendency help to differen- centres of the British Isles and to persuade women tiate these areas from carcinoma. to avail themselves of these facilities seems on contemplation to be an insuperable task in the Leukoplakia present state of economy. It is questionable This condition, well recognized as a pre- whether the incidence of uterine cancer is suf- cancerous lesion of the , occurs infrequently ficiently high to warrant the enormous expen- on the cervix. Clinically, it may be observed as diture which would be involved in the setting up a white patch on the surface of the cervix. Strachan of such centres, when one considers the rival (1949) suggests that there is a considerable ten- claim of clinics urgently needed to combat highly dency for leukoplakia to progress to carcinoma. prevalent diseases, such as pulmonary tuberculosis. Hinselmann (1933) has used the term to cover a wide range of cellular changes which in their Pre-Cancerous Lesions of the Cervix most advanced form (Rubric IV) are frankly car- Many pathologists believe that a condition is cinomatous. Novak and Meyer do not consider either benign or malignant and deny that there is that all grades of leukoplakia are pre-cancerous, a recognizable transitional stage through which but Strachan suggests that leukoplakia may well a lesion passes before a true cancer develops. The be the connecting link between carcinoma and the cervix uteri is the site of chronic irritative cervix. The author has sub- lesions, chronicly damaged by copyright. as a result of child-bearing, perhaps more fre- jected several cases in which leukoplakia was quently than any other area of the body and, in apparent on clinical examination to biopsy, with- addition, is exposed throughout reproductive life out histological appearances of pre-cancer being to hormonal activity. In addition, as mentioned found and, up to the present, follow-up has not previously, it is the site of considerable cellular disclosed a case of cancer having developed. activity and therefore might well be expected to Perhaps this has been prevented by the deep exhibit pre-cancerous changes if such exist. On cauterization which followed the biopsy. The the other hand, the cervix so often shows marked histological appearance of leukoplakia in its early erosion and and a readiness to bleed shows and increased hypertrophy stages hyperkeratosis activity http://pmj.bmj.com/ when touched and yet, when biopsy is performed, in the cells of the basal layers which are close the histological picture is not in any way sugges- together. Hinselmann's interpretation of leuko- tive of cancer. Novak has emphasized that: plakia covers other probable pre-cancerous states 'Some unknown constitutional predisposition or that have been differently named by different dyscrasia plays a fundamental role.' Cervical observers. cancer may develop in a cervix that hitherto has shown no change from the normal, as witness Intra-epithelial Carcinoma: Carcinoma in situ: the development of carcinoma in nulliparous Pre-invasive Cancer on September 30, 2021 by guest. Protected women. However, the far greater frequency of In this condition, the cells exhibit the charac- cervical cancer in women who have had children, teristics of cancer cells without being invasive. together with the frequency with which child- The nuclei are hyperchromatic and mitotic figures bearing women have cervices showing chronic are frequent; the normal differentiation of the irritative lesions, must suggest most strongly the basal cells into three layers is absent. Clumps of relationship between the trauma of pregnancy active epithelial cells are found lying in the stroma and the subsequent development of cancer. unconnected with the surface. One characteristic of cancer is missing-invasion. The basement Epidermidization membrane has not been penetrated. Carcinoma This is a condition which in the past has not in situ may be regarded as histological but not infrequently been mistaken for a carcinoma and clinical cancer (Fig. 2). TeLinde has shown that perhaps has improved the results of several centres. a long latent period may elapse before a pre- In this condition, squamous epithelium burrows invasive cancer becomes invasive, but he and beneath the columnar epithelium covering an Galvin (I944) have demonstrated that in the large erosion, lifting it up and sometimes destroying it. majority of cases this will happen unless the pre- Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from 2 POSTGRADUATE MEICALJOURNAL Apr/l x952

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cancerous lesion is eradicated. Novak considers Treatment by copyright. it a rare lesion and that repeated serial sections This embraces prophylaxis, radiotherapy, sur- will generally reveal true invasive cancer some- gery, combinations of radiotherapy and surgery, where in the cervix. and palliative measures. Prophylaxis Much can be done to prevent a cervix becoming the site of cancer. We know that cervical cancer has been more common among the poorer classes. It may be because these women have childrenhttp://pmj.bmj.com/ t more often than their more well-to-do sisters, but the likely explanation is that they are less inclined to make routine post-natal visits to their doctors ^ .. and take less notice of vaginal discharges. In this way chronic irritative lesions of the cervix are allowed to remain present without treatment for

years. on September 30, 2021 by guest. Protected A good deal of preventive therapy can be in- stituted without undue delay now that so many women are delivered in hospital, and the eroded cervix may be recognized at a post-natal visit and kept under observation. If it does not heal within 'A a few months, the cervix should be subjected to a thorough cauterization. Thorough cauterization is seldom represented by superficial application of the nasal cautery in the out-patient department. If the cervix is the site of a chronic cervicitis of such a degree as to give rise to a constant vaginal discharge, it is necessary to destroy the cervical cauterization FIG Carcinoma., * in. it (-*Ea. .4 glands by deep under anaesthetic. The wearing of for a long time should FIG. 2.-Carcinoma in situ (H. and E. X 40). be abandoned. Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from April 1952 CHARLES: Cancer of the Uterine Cervix I If hysterectomy is indicated for any condition. hours in one case may represent an entirely dif- the operation should include removal of the cervix, ferent tumour dose to the same number of milli- gramme-hours in another case. The expression Definitive Treatment: Radiotherapy milligramme-hours ignores the vital factor of For the past 30 years radiotherapy has held the distance. field. For a proper understanding of the scope The technique of applying intracavitory irradia- and the limitations of radiotherapy one must tion varies considerably, but'in this country, until possess a simple appreciation of the properties very recently, the Stockholm method using the involved. The radium atom emits alpha, beta and well-known rectangular boxes was that most widely gamma rays. The gamma rays are those employed used. These boxes are satisfactory if carefully therapeutically, the others having no treatment applied, far out in the vagina, and securely main- value and in practice are screened off from the tained in position, but they are liable to slip, tissues. The intensity of irradiation falls off because a rectangular box is not best suited to the rapidly as the distance from the source increases. cavity in which it is lodged. It obeys the law of inverse squares. In other Radiotherapists have defined two points as words, the intensity of irradiation diminishes in being convenient at which to calculate the tumour proportion to the square of the distance from its dose. Point A is set 2 cm. from the midline and source. 2 cm. above the vaginal fornix; point B is 5 cm. Obedience to this law represents one of the from the midline and 2 cm. above the vaginal major difficulties in treatment of a tumour. The fornix. Point A roughly corresponds to where ideal would be to subject all parts of the tumour the uterine artery crosses the ureter and, therefore, and its lymphatic field to an equal, cancericidal represents a point where a vital normal structure dose. In order to do this, it would be necessary lies. The dosage at point A should be as high as to distribute the radium homogeneously through- possible without endangering the ureter. Some- out the area to be irradiated. This is never where in the region of 7,50or to 8,ooor is the usual achieved and, in the case of cervical cancer, the dose employed, and this is cancericidal to mostby copyright. best distribution of radium is far from the ideal. squamous-celled tumours. The efficacy of the Attempts to distribute the radium by implanta- treatment is limited because, from an intracavitary tion of needles over a large area of the field have source, a tumour dose of 7,50or at point A is only not been successful and today we rely mainly on about 2,ooor at point B, a dose which is not intracavitary radiation, by which one can give a curative. cancericidal dose to the central area but not to If the parametrium is involved as far out as the those peripheral areas which may harbour cancer pelvic wall and glands are invaded, it is necessary cells. Moreover, in setting out to kill the cancer to supplement the radium by external irradiation. cells, one must have regard for the normal struc- Once again, the tumour dose from external http://pmj.bmj.com/ tures adjacent to the tumour, which may be irradiation is limited by the normal structures irreparably damaged if an excessive dose is applied. through which the X-rays have to pass and it is Practice has shown that it is necessary to give not possible by external irradiation alone to expose a dose a little short of the maximum which can the parametrium and the glands to a cancericidal be withstood by the normal tissues, and that the dose without irreparable damage to the skin and results of therapy will improve with increased other intervening structures. It is clear, therefore, dosage up to a certain level and then decline if that for radiation therapy there is a therapeutic this level is exceeded because high-dosage effects limit that cannot embrace all tumours. on September 30, 2021 by guest. Protected then play a detrimental part. The ureter, bladder In the Manchester technique, a tandem in the and rectum may be damaged and general necrosis and two rubber ovoids in the vagina in the pelvis may follow if the dose is excessive. separated by spreaders of various sizes are used. For correlation of results and co-operation with The ovoids are of three sizes to fit vaginae of physicists and radiotherapists, we must express different dimensions and, by careful experiment and our radium dosage in ' r6ntgens.' To speak of calculation, a unit system was devised where, by milligramme-hours merely implies that so much varying the number of units of radium in the radium is placed in the vagina and uterus for so ovoids according to their size, the same dose at many hours. The uterine applicator is fairly point A was obtained from the small ovoids con- constant in position, but the vaginal applicators taining three units, the medium containing four vary in their distance from points A and B accord- units or the large containing five units. ing to the size of the tumour, the cervix, the The uterine tubes are in three sizes, long, vagina or the applicator and, equally important, medium and short, the long containing five units, according to the constancy with which the applica- the medium three and the short two. It is desir- tor remains in position. So many milligramme- able to use the longest tube and the largest ovoid Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from POSTGRADUATE MEDICAL JOURNAL April I952 which can be applied and to space the ovoids as appreciable increase in the five-year survival widely as possible. The larger ovoid providing rate. greater distance between the radium and the While dosimetry acts as a useful guide to treat- vaginal mucosa will lessen the dose received by ment, it must not be followed slavishly in each the mucosa and thus allow a larger depth dose individual case, for variance in the anatomy and without damage. Tod worked out an optimum pathology and in the biological response will often dose in the paracervical triangle from the results dose modification. of treatment judged by survival and the effects of require radium injury, and she showed that above a certain At the Samaritan Hospital the unit employed figure the results declined as high-dosage effects is 5 mgm. and the applications are made at weekly took their toll. Optimum dosages as given by intervals on three occasions. The ovoids are held her are in place by gauze packing which, despite all efforts (Tod, 1947): to find a better substitute, still remains the most 8,ooo to 8,50or In ten days measured at point A efficient medium for widely varying tumours and for radium alone. vaginae. The application is made with the in the knee-chest 10,000 to ro,5oor Combined dose at point A for patient position thereby making radium plus external X-radiation use of the full distention of the vagina by the over five to six weeks' treatment atmospheric pressure. In this position, it is com- time. paratively easy to place the ovoids in the desired If the dose is increased in an attempt to deliver situation and to insert the packing in such a way up to 6,ooor at point B, high-dose effects on the that the rectum is protected and the ovoids are normal tissues negative any benefit that in theory fixed in position (see Figs. 4, 5 and 6). The dose should be obtained from the higher dose at the which has been employed is 7,500 to 8,ooor at pelvic wall. In practice, with the Manchester point A, but this is reduced to 7,ooor in older technique, using the longest intra-uterine tube women. The position of the radium is checked and by X-ray after each application. The radium is the largest applicators in wide vaginae, the removed and reapplied if there is any gross mal-by copyright. dose at point B is little more than 3,ooor and position. The dosage rate per hour of the various generally only about 2,5oor. Under the most combinations has been calculated by the physicist. favourable conditions, a dose of 6,ooor could be Calculation is not for each individual obtained at a maximum of 4 cm. from the midline. necessary A study of the isodose curves plotted for intra- case, provided the X-ray shows the normal pattern cavitary irradiations demonstrates the high dose and distances. delivered to the region of the cervix, base of Individual curves are plotted if the size and bladder and rectovaginal septum and the rapidity shape of the tumour does not allow the applicators with which it falls off at the to lie At periphery. Cantril symmetrically. subsequent applications, http://pmj.bmj.com/ (1950) has compared the paracervical and lateral alterations in quantity of radium and time are parametrial tissue doses in the various techniques made in order to submit all the tumour area to and found that in the Stockholm and Paris an adequate dose. Supplementary X-radiation is methods it is i,ooo to 2,ooor less than in the most used for tumours in late Stage II or Stage III in favourable Manchester application, but he stresses an attempt to boost up the dose at point B, though that: ' Whatever the technique used and how- the sum of irradiation from radium and X-rays ever the dosage is assessed, it is not only dangerous unfortunately falls short of what may be required. but in most instances futile to force the dose in By splitting the radium application into three on September 30, 2021 by guest. Protected the more peripheral zones of the pelvis to a pre- doses, it was found that there were less com- determined effectual dose.' plications such as pyrexia, sickness, proctitis, When external irradiation is added to the maxi- cystitis and the like than when the same dose was mum intracavitary irradiation, it is necessary to obtained by two longer applications. shield the central area of the pelvis in order that When the cervical tumour is large, it may it should not be overdosed. render the application of radium difficult and, in X-ray therapy is usually given by multiple cases of exfoliative growth almost filling the upper high-voltage X-ray beams, but super-voltage reaches of the vagina, it is advantageous to treat X-ray treatment is being employed to a larger the patient by X-rays first, and this generally extent. There are technical advantages to be brings about a marked reduction in the size of the gained in the higher voltage range because the tumour. The dose employed at the Samaritan is depth dose is more favourable and, probably what usually about 2,5oor to the centre of the pelvis is more important, the bone absorption of irradia- delivered over 14 days. The subsequent intra- tion is relatively less. However, it is doubtful cavitary dose must be reduced so that the optimum whether super-voltage therapy will give an is not exceeded in the central region. Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from April I952 CHARLES: Cancer of the Uterine Cervix 233

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FIG. 4.-Patient in knee-chest position; uterine tandem inserted.

Complications of Radiotherapy Pyometra in the absence of pyrexia seldom gives Infection is the complication which most fre- rise to trouble unless the uterus is perforated on September 30, 2021 by guest. Protected quently gives difficulty. When the growth is during the insertion of the radium. Preliminary infected, much benefit may be obtained by pre- drainage is advisable if there is pyrexia. liminary external X-ray treatment combined with Vesical reaction as shown by urgency and fre- the use of sulphonamides, antibiotics, vaginal quency, does not often interfere with treatment douching and treatment of anaemia. If pyosal- but care should be taken in subsequent applica- pinges or tubo-ovarian abscesses are present, they tions to pack the radium well away from the are best dealt with surgically before radium treat- bladder base. ment is given. The only fatality from radiation Proctitis is usually of a mild and transitory therapy at the Samaritan Hospital in the last five nature characterized by diarrhoea and tenesmus, years occurred in a case where chronic tubo- and clears up spontaneously. It is more likely to ovarian infective masses were confused with para- occur when the uterus is retroverted. Use of the metrial spread and infection flared up after the knee-chest position for applying radium helps to radium was applied. The tubes-and were obviate the risk of proctitis. When the reaction is later removed but, after a long illness, the patient more severe, benefit may be obtained from saline succumbed. rectal washouts and liquid paraffin by mouth. Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from 234 POSTGRADUATE MEDICAL JOURNAL April 1952 by copyright. http://pmj.bmj.com/

FIG. 5.-Patient in knee-chest position; large ovoids and spacer inserted.

Radiation sickness is seldom severe when lesser cases, an ulcer is in the base of very produced on September 30, 2021 by guest. Protected treatment is confined to the pelvis. Pyridoxine, the bladder giving rise to frequency and pain, 10 mgm. three times-a day, is useful for this with moderate pyrexia. Chemotherapy and bladder complaint. lavage will generally produce a cure in time, but a few cases may require ureteric transplantation. Late Complications Ureteral stenosis may develop late from the These are lesions of late radium necrosis which effects of radium necrosis and cause the death of may affect the cervix, bladder, parametrium or a patient otherwise cured. In the majority of rectum. Radium necrosis of the cervix may leave cases, however, ureteric obstruction is the result an ulcer which is difficult to distinguish from a of the growth and not the treatment. Where the recurrence and time alone will give the answer. ureters are seriously obstructed, transplantation is The late effects on the urinary apparatus may be indicated, if the expectation of life warrants an serious. Bladder necrosis may occur with normal operation. dosage carefully applied or when the applicators Late rectal reaction may occur months after have pressed too tightly or when the growth has treatment. There will have been proctitis at the invaded the bladder. In the latter instance, a time of treatment. The late reaction is accom- vesico-vaginal fistula will probably result. In panied by tenesmus and painful defaecation with Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from April I952 CHARLES. Cancer of the Uterine Cervix 235

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...... --Ii- http://pmj.bmj.com/ FIG. 6.-X-ray of pelvis showing long intra-uterine tandem containing five units and medium ovoids containing four units each, separated 'bv spacer. the passage of blood and mucus. An ulcerated Report, 195 ) obtained in I943 and previous years area may be found on the anterior rectal wall with from 37 centres in i countries reviewed by a surrounding induration, and the lesion has been committee consisting of Heyman, Donaldson and called pseudo-carcinoma. Meigs provides the latest bulk figures which fulfil on September 30, 2021 by guest. Protected Treatment is conservative. Sometimes a late the above conditions: reaction may heal with much fibrosis resulting in 41,046 patients were treated. Of these, rectal stenosis or the tissues may necrose to pro- 31.8 per cent. were alive and well after duce a recto-vaginal fistula. five years; The mortality of radiation treatment is between cent. were alive with i and 2 cent. 1.5 per cancer; per 64.8 per cent. had died of cancer or inter- Results of Radiotherapy current disease; In order to determine the value of radiotherapy i per cent. had been lost. it is essential to study the sum of results from a Five-year survival rates for stages are: number of centres at which there is no selection 61 per cent. for Stage I. of cases. Pre-cancerous conditions must be ex- 40 per cent. for Stage II. cluded and patients who died of intercurrent 22 per cent. for Stage III. disease included among those who died of cancer. 6.5 per cent. for Stage IV. The sixth volume of statements of results (Annual Certain clinics produce figures that are far Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from 236 POSTGRADUATE MEDICAL JOURNAL April 1952

TotalTot Stage I Stage II Stage III Stage IV Relative Institution Years No. % % % curability No. Well No. Well No. Well No. Well % Allgemeines Kranken- haus St. Georg, Ham- burg ...... 1935-39 607 83 63.8 195 51.3 291 33.3 38 5.3 41.6 Institut du Radium, Paris . .. 99-4I 2199 298 63.4 942 42.8 739 27.6 220 9.I 37.1 Marie Curie Hospital, London .. . 1925-41 1514 1i8 77.1 420 56.4 769 28.2 207 7.7 37.1 Radium Centre, Copen- hagen .. .. 1938-39 468 49 63 224 5 .8 142 35-9 53 15.1 44.4 Tumor Institute, Swed- ish Hospital, Seattle.. 1935-44 249 34 88.2 87 51.7 104_4_32.6 24 8 44.1 better than the average. The following gives a Surgery selection of the best: Wertheim (1905) began his operation in 1898 Improvement has been considerable over the and he had 30 deaths in the first Ioo operations. past quarter of a century. At the Radiumhemmet, In I905, he read a paper at Leicester claiming a Stockholm, from 1914 to 1933, the absolute five- 40 per cent. five-year cure. It was this paper that year cure rate was 22.3 per cent., while for I934 stimulated Bonney to take up the operation and to it was cent. has to 1943 38 per Heyman (I947) extend it. Bonney introduced the routineby copyright. emphasized that this is largely brought about by removal of the pelvic lymph glands and extended individualization of the treatment and states that his operation to remove as much of the vagina as some modification of the standard technique was possible. Bonney's operability rate was estimated advisable in 45 per cent. of the patients treated, at 63 per cent. He operated on every case in generally on account of infection. He draws which he thought there was a chance of a cure. attention to the extensive use of electrofulguration His operability rate among private patients was for local recurrences. Thoren (1945) reports that 80 per cent. of 38 patients with proved recurrence i were In I941, he published the results of 500 opera- alive more than four under such treatment. on a a years tions five-year basis and 415 on ten-yearhttp://pmj.bmj.com/ The place of supplementary external X-radia- basis (Bonney, 1941). The five-year survival rate tion is illustrated by some recent figures of results was 40 per cent. and the ten-year survival rate at the Holt Radium Institute, Manchester. X- 31 per cent. The operative death rate was 14 per radiation reduced the relative five-year survival cent. Of every Ioo unselected cases seen, his rate in Stages I and II from 56 per cent. to 46 per absolute survival on a five-year basis was 26 per cent. but improved the results in Stages III and cent. and on a ten-year basis 21 per cent. His IV cases from 2o per cent. to 27 per cent. operative mortality rate fell to ii per cent. in the last 200 cases. on September 30, 2021 by guest. Protected Failure of Radiation Therapy With the advance of radiotherapy, radical sur- Earlier it has been emphasized that staging of gery fell into disrepute largely because of the high the disease is a clinical appreciation of the extent initial mortality, but once again gynaecologists are of the growth and cases placed in Stage I may looking towards surgery to achieve further have undetected lymph node involvement. This advances in the treatment of cervical cancer. will explain a proportion of the 20 per cent. Major surgery has been made so much safer by failure in the treatment of so-called Stage I cases. the great improvement in anaesthetics, the dis- Lacassagne (1941), Baud (1948) and Cantril (1950) covery of sulphonamides and antibiotics, and un- have all drawn attention to the fact that failure in limited supplies of blood. Operative mortality the treatment of early cases very seldom arises today should not exceed 2 per cent., except for because of failure to control the disease in the the extended operation occasionally employed for cervix itself. Most of the failures are attributable Stage IV growths. to unsuspected advancement of the disease to the The renewed employment of surgery need not nodes or outside the pelvis, a few to inadequacy lead to a conflict with the radiotherapists for, in of the dose and a few to radio-resistant tumours. great measure, the methods of treatment can Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from April I952 CHARLES: Cancer of the Uterine Cervix 237 progress side by side each assisting the other. In the early cases, however, there is bound to be for the case that does best with competition, :eit;:/Y surgery is the one that the radiotherapist is most likely to cure. The ideal case for surgical attack .'...,:,' ....: is a Stage I or early Stage II growth occurring in ··i "~.:,..~~::..~.,...r a woman otherwise healthy, of moderate age and figure. We have seen that even in Stage I cases . :.* there is at least a 15 to 20 per cent. failure from ~ ,;:. ~' irradiation. It remains to be seen whether under I modern conditions those failures can be eliminated i ll ' ' " by surgery. The reasons advanced that this may X, .... be so are: (I) If the cervix is removed, there can be no recurrence there (against this argument is 4q' ::14i the very small incidence of local recurrence after 6' "r adequate irradiation); (2) that certain tumours of ....~:.:j,~1:~' .,· '. the cervix are radio-resistant; and (3) the most kq important, that patients with clinical Stage I cases may have involvement of the pelvic lymph nodes which many believe cannot be cured by irradiation. Meigs (1951) reports the five-year results of 75 patients treated by radical hysterectomy with dissection of the lymph nodes (Stages I and II). Fourteen had positive lymph nodes and four of these are alive at the end of five years. Twenty- by copyright. seven patients had radiotherapy in addition to surgery and of these 19 survived. Of the remain- ing 48 who had surgery alone, 39 survived (88.3 per cent.) and of 51 patients with Stage I cancer FIG. 3.-Colloid carcinoma of cervix (H. and E. X 30). 44 (86.3 per cent.) were alive after five years, including three in whom the lymph nodes were invaded. In 1949, he stated that Ioo successive patients at the Massachussetts General Hospital, (I945) on the effects of radiation by studying the Pondville and Palmer Memorial early histological changes produced in Hospital Hospital biopsies http://pmj.bmj.com/ had been operated upon without a death and 200 taken during and after treatment. with only one death. It can be seen that among Glucksman (1949) investigated the relation of selected patients with an early-stage cancer tumour type to expectation of cure. Three series operated upon by Meigs, the cure rate is higher of patients were considered, comprising (i) those than that obtained by radiotherapy, but for a true treated by a modified Stockholm method, not in comparison we ought to know how many similar all cases complete, (2) those fully treated by a patients were rejected for operation on grounds Stockholm method and (3) those fully treated by other than the stage of the growth. a Paris method. In each series, the analysis was on September 30, 2021 by guest. Protected With regard to radio-resistant cases, Heyman significant. Differentiated epitheliomas all gave (1949) is sceptical of their existence and, until the better results than the anaplastic epitheliomas, results of operation upon so-called radio-resistant which is contrary to the statements of some cases have been collected, entertains doubt whether authors who contend that a higher proportion of this type of case is not only resistant to irradiation anaplastic than of differentiated tumours of the but to any form of treatment because of the high cervix are radiocurable. degree of malignancy. It is well known that differentiated tumours A section of a colloid cervical carcinoma is spread less rapidly and less extensively than un- shown in Fig. 3. This tumour showed no reaction differentiated tumours and offer a far better chance at all to two applications of radium (5,ooor) and of cure by surgery. The same is true for radio- was then submitted to radical hysterectomy. The therapy. Anaplastic tumours often exhibit a glands were invaded on both sides and the patient dramatic response to radiation by rapid diminution only survived the operation by some eighteen in size, but their radiocurability rate is statistically months. A great deal of work has been done by lower than differentiated tumours of the same stage Warren, et al. (I939) and by Glucksman and Spear of advancement. Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from 238 POSTGRADUATE MEDICAL JOURNAL April I952 In Glucksman's series, on a five-year basis, the cent. five-year cure rate and i6-18 per cent. ten- differentiated carcinomas showed 19± 2.9 per year cure rate. The argument for operating on cent. better results for the whole group of tumours the early cases is therefore clear. If the mortality and a significant advantage in each clinical stage. and morbidity can be kept low, as it can nowadays, He sought to find whether the histological and really thorough surgery carried out, it should changes brought about by radiation would prove be possible to do appreciably better by surgery a reliable guide to radiocurability for any given than by radium. tumour. Clinical assessment is not good enough. The Combination of Surgery and Radiotherapy histological method of assessment is based on the Most operators today employ either pre-opera- fact that biopsies taken from the growing edge of tive or post-operative radiotherapy or both. Pre- the tumour include many young foci which are operative radium treatment is widely used and representative of the tumour as a whole, and information has not yet crystallized as to the ideal which demonstrate early changes under the pre-operative dose or as to the interval which influence of radiation that are of prognostic value. should elapse between the radium treatment and Successful radiotherapy converts viable cells the operation. However, the tendency is towards into non-viable cells. employment of a dose two-thirds of that used if The effect of radiation on the cells of a tumour surgery is not contemplated. This would be of is both direct and indirect. The indirect effect is the order of 5 to 5,500 r. Six weeks has been produced by its action on the blood vessels and suggested as the best time to allow between stroma. Both influence cell population of active irradiation and operation because this interval foci. Multiplication of resting cells may be inhi- allows the reaction to radium to subside so that bited or differentiation induced so producing non- the tissues are less oedematous and bleeding less viability. Cells undergoing mitosis may be killed. troublesome. Two to three weeks after irradiation Glucksman emphasizes that the most important may be the least favourable as infection is more feature of is their to radiocurable tumours ability likely then. by copyright. respond to radiation by increased differentiation Before operation, the blood must be examined and on the contrary, it is the persistence of un- to determine the cell count and haemoglobin level altered foci that denotes resistance to radiation. and where necessary a pre-operative transfusion is The work is difficult and requires great experience given. The urine must be examined for the to select the right material for biopsy, to prepare presence of infection and any present eradicated. it and to interpret it. The cytological changes vary Cystoscopy is performed to establish as far as with the dose and the time between radiation and possible freedom of the bladder from growth. If biopsy. Glucksman states that the cell count in bullous oedema is present, this indicates involve- foci is the most reliable ment. The mucosa of the bladder is raised in comparable young method, up http://pmj.bmj.com/ though this is often unnecessary in radio-resistant an irregular fashion. Areas may bleed when cases showing no response. touched. Red discoloration is a bad sign. Some- From the cell count the response to radiation is times, the growth may obviously have penetrated put in three grades: (i) favourable; when all the mucosa. While bladder involvement does not resting and mitotic cells are replaced by differentia- absolutely preclude a surgical attack as will be dis- ting and degenerating cells, (2) partial when there cussed later, it rules out the ordinary Wertheim is some change from viable to non-viable cells, procedure. and (3) unfavourable when only minor changes Further pre-treatment investigation should in- on September 30, 2021 by guest. Protected are found. Glucksman claims that the five-year clude estimation of the blood urea, urea clearance follow-up of the clinical results in patients for test and an intravenous pyelogram. Before opera- whom a definite histological prognosis was given tion is commenced, a slow intravenous saline drip early in treatment has provided agreement in 97 is established which can be changed to a blood per cent. The therapeutic value of histological drip as necessary. The anaesthetic can be pento- prognosis will lie in diverting to surgery wherever thal, gas and oxygen, curare sequence or spinal. feasible patients for whom radiotherapy offers no The operation is carried out through a long hope of cure. In many such cases, the lymph median incision or in the obese through a wide glands will be invaded and surgery prove unsuc- transverse muscle-cutting incision. The operation cessful. But since it offers the only hope, opera- includes a thorough dissection of the glands from tion should be attempted and a few will survive. the common iliac vessels to the obturator foramen, Turning to the apparently early case with gland the dissection of the ureter without stripping it invasion, it is unlikely that any of such cases entirely of its surrounding areolar tissue in order survived five years when treated by irradiation. to preserve its blood supply, removal of the para- With gland-involved cases, Bonney had a 22 per metrial tissues right out to the pelvic wall, Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from April 1952 CHARLES: Cancer of the Uterine Cervix 239

removal of the pelvic peritoneum down to the Percentage bottom of the pouch of Douglas and removal of a results cuff of vagina well beyond the lowest extent of Treatment the growth. Five Ten Where the cervical tumour is large, or where the years years growth has spread down the vagina to a consider- A. Radium plus surgery .. .. 54 51 able extent, it is an advantage to precede the B. Radiotherapy alone .. . 8 13 abdominal operation by a vaginal stage suchas C. Average of A and B .. .. 40 35 that described by Brunschwig (I951). With the patient in the lithotomy position, a Schuchardt If the I3 deaths in the five-year series and the 8 incision is deaths in the ten-year series due to intercurrent disease made deeply on the left side and carried were excluded the survival rates would be about 5 per upwards in the vagina one third of'the way to the cent. better than the above figures. cervix. A circular incision through the entire thickness of the vagina is then made. Bladder and Combined Radiotherapy and Iliac rectum are dissected from this cuff which is Lymph-Adenectomy closed over a gauze pad. The rectum may then This method is based on the assumption that be separated from the posterior vaginal wall until radiotherapy can take care of the primary growth the peritoneum of the pouch of Douglas is iden- while surgery clears the lymphatic field. It is tified and incised. This will facilitate the subse- thus comparable with interstitial irradiation for quent freeing of the closed vaginal cuff from above. epithelioma of the tongue combined with block Alternatively, in the same type of case, Howkins' dissection of the glands of the neck. Taussig (I951) synchronous combined abdominovaginal (1943) adopted a transperitoneal approach for the hysterectomy may be employed in which two lymph node dissection. In 1943, he reported teams work together, one from above and one I75 operations of this type and produced five- from below. The whole of the vagina may be year results better by approximately io per cent. removed by this method without increasing the than the results obtained in a group of cases of by copyright. operating time to any great extent. similar extent in which comparable radiation had Post-operatively, most difficulty is likely to arise been given but the glands not dissected. from bladder paresis, since the sympathetic supply The glandular field of the cervix can be dis- to the bladder is necessarily injured in the opera- sected through an extraperitoneal approach, which tion. Continuous bladder drainage with an in- has the advantage of less disturbance to the patient dwelling catheter is continued for a week and, and it can be done one side at a time in patients after its removal, regular catheterization for resi- who are not too fit. Retroperitoneal lymph node dual urine must be continued until this has been dissection for cervical cancer was introduced by reduced' to 2 oz. Normal bladder function is Nathanson. The author has employed it some http://pmj.bmj.com/ generally restored, but this may sometimes be six to ten weeks after irradiation for cases in delayed for months. Stage II or early Stage III where it was considered The radical vaginal hysterectomy of Shauta is that radiotherapy had controlled the local growth seldom employed in this country. Complete gland as judged by clinical signs and post-radiation dissection is impossiblethrough a vaginalapproach. biopsies. It is especially suitable for cases who Schlink (1950) of Sydney has employed a com- are not good risks for the extended Wertheim bined treatment of radium and Wertheim's operation by reason of other disease or obesity. hysterectomy since 1930. From I930 to I944, It would appear to offer a greater chance of cure on September 30, 2021 by guest. Protected inclusive, 532 patients were seen and examined for the plump woman with a wide pelvis suffering with a view to treatment and 511 treated. The from cancer that has spread beyond the cervix. absolute survival rate for all patients seen was Such a case presents a problem in which radio- 32 per cent. five years and 28.3 per cent. ten years, therapy alone has little chance of success if the and for all patients treated the survival rate was lymph nodes are invaded, for they will be lying 33.5 per cent. five years and 29.3 per cent. ten a long way from the centre of the pelvis and years. Of the 532 patients, 246 were treated by denied the full effects of supplementary external radium plus surgery and 253 by radium alone. X-radiation by intervening fat and bone. In 33, the treatment was nil or incomplete. The incision is made along the line of the Schlink further analyses his results excluding inguinal canal from the pubis to a point about Stage IV cases, stating that those clinics which 2 in. above the anterior superior iliac spine. claim five-year cures for this stage must have External oblique, internal oblique and transversalis mis-grouped them clinically. With the exclusion muscles are divided in the line of the incision until of Stage IV cases, very creditable figures emerge, the peritoneum is exposed. The inferior epigastric as follows: vessels are divided and ligatured. The peri- Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from 240 POSTGRADUATE MEDICAL JOURNAL April 1952 toneum is then pushed medially together with tion may be carried out in separate abdominal the round ligament, which may be divided if and vaginal stages or by a combined synchronous necessary. The ureter is found adherent to the technique. posterior surface of the peritoneum and is dis- Brunschwig (195I) reported in I951 that out placed medially. A thorough dissection of the of 29 patients subjected to partial exenteration, glands is carried out from about the middle of the including removal of bladder and uretero-colic common iliac artery or higher if indicated. The transplantation, 6 were well from several months glands, fat and aerolar tissue covering the common to 29 months after surgery. Complete pelvic iliac, external and internal iliac vessels is cleared exenteration, including removal of the colon, was completely, as is the obturator fossa. The done for 53 patients with invasion of both bladder obturator nerve is preserved. A drain is left in and rectum, 9 of these were well 13 to 32 months the lower angle of the wound for 24 hours. Mac- afterwards; 23 per cent. of the patients under- kintosh Marshall says he regards the dissection as going exenteration died within 30 days. The complete when he can run an aneurysm needle operation is also suitable for certain cases with beneath the iliac vessels throughout their length. extensive radium necrosis, including fistula forma- Results of this procedure are as yet too scanty tion. The place of this massive operation will for a decision to be reached as to its efficacy, but only be decided with the passage of years. Bonney on theoretical grounds it would appear to offer (I949), while admiring Brunschwig's work, says: hope in a type of case that hitherto had such a poor 'There comes a point variable according to the outlook. It is difficult, however, to be sure that particular surgeon's mental make-up when the the primary lesion has been controlled by radia- great risk of an operation coupled with the very tion. If extended trial of supervoltage X-radiation slight chance of permanent cure or even a year proves that cancer can be destroyed in lymph or two of comfortable life, bulks so large that he nodes, then the need for the above procedure recoils from the likelihood of having to play the would disappear. part of an executioner.' At a recent follow-up clinic the author reviewedby copyright. Ultra Radical Surgery 50 cases of cervical carcinoma treated by radio- Brunschwig, of New York, has evolved the therapy and found only two suitable for such operation of partial or complete pelvic exenteration surgery on technical grounds, both were well over for uncontrolled cancer of the cervix. Two types 70 years of age and too frail. of operation are possible: (i) In which radical While the problem of wet end- left hysterectomy with lymph node dissection is after complete pelvic exenteration has been fairly extended to include the removal of the bladder, satisfactorily solved by the Rutzen baghermetically vagina and vulva combined with colic implantation sealed to the skin round the colostomy, this of the ureter, and (2) in which all pelvic viscera operation with its necessarily high initial mortalityhttp://pmj.bmj.com/ are excised, including vagina, uterus, adnexae, and doubtful curative value must have a very bladder, lower ureters and pelvic colon combined small field. The operation of partial exentera- with implantation of the divided ureters into the tion, however, is a big advance. From time to sigmoid colon, which is brought out on the surface time one meets a growth in a comparatively thin as an end-colostomy. The rationale of such woman which has involved the bladder while operations is that autopsy on patients dying of there is little demonstrable spread in other direc- cervical cancer often reveals that the growth has tions. Such a case, if treated by thorough not spread beyond the pelvis. Such operations irradiation, would almost surely develop a vesical on September 30, 2021 by guest. Protected can be applied to cases where bladder or rectal fistula if this is not present already. The opera- fistulae are present or where radiation has failed. tion of partial exenteration in the above circum- A number of patients with advanced pelvic stances is comparatively easy; in many ways easier growth are otherwise in fair shape and although than the ordinary extended Wertheim procedure, this type of operation carries a high risk it gives for early ligature of the internal iliac vessels and a chance to patients otherwise doomed. Before division of the ureters renders the subsequent embarking on such an operation, it is essential to dissection of the pelvis, including the bladder and establish as far as possible that distant metastases vagina, relatively simple. are absent, that the kidneys are in good order, After transplanting the ureters into the colon and to restore the erythrocyte count, haemoglobin and closing the abdomen, the pelvic viscera are content, plasma protein level and electrolytic removed from below. Better still, a second team balance to normal. It is imperative to combat may carry out the perineal phase while the first any urinary infection and to sterilize the bowel as operator completes the abdominal phase. In very far as possible by pre-operative administration of favourable cases, where the growth only involves sulphasuxidine and sulphathalidine. The opera- the upper part of the vagina and bladder, the Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from April I952 CHARLES: Cancer of the Uterine Cervix 241 whole operation can be completed from above, the the case to a neuro-surgeon with a view to division being divided just above the orifice and of the spinothalamic tract. the vagina at the same level. Oozing from the cut ends is controlled by sutures inserted with a Leucotomy and Chordotomy boomerang needle. Wylie McKissock in a personal communication says that when the pain is widely disseminated and Palliative Treatment the expectation of life is short, leucotomy may be A great deal can be done to render comfortable regarded as the best treatment. The patients by the last days of a patient who is beyond cure, and then are usually under considerable doses of it must be remembered that many patients with morphia, which may be withdrawn. The patient advanced disease live for a long time. The biggest when asked if she has pain, replies 'Yes' but she sources of misery are pain and fistulae. Palliative no longer complains of pain. When the expecta- uretero-colic transplantation for vesical fistula tion of life is longer and the pain localized to one should be employed more often. Where a recto- side, chordotomy is better. vaginal fistula is present and the bladder intact, a divided loop colostomy makes life far more Summary and Conclusions bearable. Gynaecologists all over the world are recon- Pain in the terminal stages of cervical cancer is sidering their approach to the problem. Advances often present both day and night and is due to have been made and more will follow. The aim sensory nerves becoming involved in the growth. must be to allow each patient to receive the Relief may be given in several ways. The com- treatment most likely to effect a cure and com- monest employed is the administration of morphia. placency with a five-year survival rate must go. The disadvantages of this are the constant need The Radium Commission have done much to to increase the dose, nausea and vomiting in some ensure that radiotherapy is adequately carried out patients, and the excitement produced in others. and to prevent haphazard employment of radium The operation of pelvic sympathectomy gives in ill-equipped institutions. Now that it is clear by copyright. relief when the pain is visceral in origin, but not that surgery still has a place in the treatment, the when it is somatic. operations must only be done by trained teams in For intr.ctable pain of sciatic nature intraspinal hospitals with full facilities for pre-operative in- injection of absolute alcohol should be tried. vestigation and post-operative resuscitation. This is a simple procedure done with the patient Radiotherapy remains the standard treatment placed on the side opposite to that where the but should be carried out under the combined pain is worse. Her pelvis is elevated and her direction of gynaecologist and radiotherapist. The body flexed with the head slightly lowered. In man who treats malignant disease in many parts this position the sensory nerve roots lie hori- of the body by irradiation and by no other method, http://pmj.bmj.com/ zontally and the motor nerve roots usually lie is not the man who should have sole responsibility outside the field. In any case, they are less sensi- for the treatment of cases of carcinoma of the tive to the effects of alcohol than the sensory cervix. The gynaecologist should operate when nerve roots. The fourth lumbar interspace is surgery offers the best chance but not allow his identified and an ordinary lumbar puncture needle enthusiasm for surgery to persuade him to operate inserted. When the needle isjn the subarachnoid when radiation would be better. cc. of absolute or cent. alcohol After careful consideration of results and dis-

space 0.75 §5 per on September 30, 2021 by guest. Protected is injected very slowly, taking two minutes. No cussion with many authorities, the following C.S.F. is withdrawn into the syringe. Patients scheme for treatment is put forward. Good risk are kept on their side for at least an hour after the cases with early growths should have radical injection. The patient complains of numbness surgery. The remainder should have radiotherapy, in the leg or that it feels hot and that she cannot to which may be added extraperitoneal lymph move her leg. If there is pain on both sides, the node dissection when the pelvis is large and the injection may be repeated a week later with the local growth apparently controlled. Growths in- patient lying on the opposite side. There is a volving the bladder but otherwise free should possibility that the alcohol may injure the spinal have partial pelvic exenteration. The position of cord, but if the injection is confined to hopeless complete pelvic exenteration remains undecided cases this is of small moment if pain is relieved. and will, of course, be a limited one. Gynaecolo- Greenhill (1947) claims complete relief in 60 per gists who have recently visited the United States cent. and partial relief in io per cent. Maeve and seen patients who had survived after this Kenny (I947) advocates caudal anaesthesia, using operation, found they looked well and were con- 40-60 ml. of proctocaine. When these measures tented with their existence. fail and paini s unbearable, it is justifiable to refer Several surgeons in England are performing Postgrad Med J: first published as 10.1136/pgmj.28.318.227 on 1 April 1952. Downloaded from 242 POSTGRADUATE MEDICAL JOURNAL April 1952 complete exenteration when radiotherapy has Acknowledgments failed. When their results are collected after a The author's thanks are due to Miss Margaret lapse of years, the correct place of the operatlon Tod and Dr. Jackson Richmond for their advice may be determined. on radiotherapy, and to Professor T. Crawford More use should be made of pain-relieving for preparation of the pathological material and operations for advanced cases. micro-photographs.

REFERENCES 'Annual Report (I95I) on the Results of Radiotherapy in Cancer of HOWSON, J. Y., and MONTGOMERY, J. (19+9), Amer. J. the Uterine Cervix.' Geneva: World Health Organization. Obstet. Gynec.. 57, o098. British Empire Cancer Campaign. Philadelphia: Donner KENNEY, MAEVE (1947), Brit. med. J., ii, 862. Foundation. Stockholm: the Cancerforeningen. LACASSAGNE, A., et al. (I941), ' Radiotherapie des Cancer du AYRE, J. E. (1949), Trans. izth Brit. Congr. Obstet. Gynaec. Col. d'Utero,' Paris, Masson et Cie. BAUD, JULIET (I948), J. Amer. med. Ass., 138, 1138-1142. MEIGS, J. V. (I95I), Amer. J. Roentgen., 65, 698. BONNEY, V. (I949), Trans. I2th Brit. Congr. Obstet. Gynaec. NOVAK, E. (1947), 'Gynaecological and Obstetrical Pathology,' BONNEY, V. (I941), Brit. J. Obstet. Gynaec., 48, 421. Philadelphia, W. B. Saunders, p. 98. BRUNSCHWIG, A. (195I), Amer. J. Obstet. Gynec., 6I, 1193. PAPANICOLAOU, G. N. (1928), Proc. 3rd Race Bettermen. BRUNSCHWIG, A. (I95I), Amer. J. Roentgen., 65, 720. Conference, p. 538. CANTRIL, S. T. (1950), 'Radiation Therapy in the Management SCHLINK, H. H. (1950), J. Obstet. Gynaec., 57, 714. of Cancer of the Uterine Cervix,' Charles C. Thomas, Spring- STRACHAN, G. I. (1949), Trans. I4h Brit. Congr. Obstet. Gynaec. fields, Ill., U.S.A., p. I79. TAUSSIG, F. J. (1943), Amer. J. Obstet. Gynec., 45, 733. GLUCKSMAN, A., and SPEAR, F. G. (x945), Brit. J. Radiol., TELINDE, R. W., and GALVIN, G. (I944), Amer. J. Obstet. 18, 313. Gynec., 48, 774. GLUCKSMAN, A. (1949), Trans. 12th Brit. Congr. Obstet. Gynaec. THOREN, S. (1945), Acta Radiol., 26, 249. GREENHILL, J. P. (i947), Brit. med. .., ii, 859. TOD, MARGARET C. (1947), Ibid., 28, 564. HARNETT, W. L. (1949), Brit. J. Cancer, 111, 433. TRAUT, H. F., and PAPANICOLAOU, G. N. (1941), Amer. J. HEYMAN, J. (I947), J. Amer. med. Ass., 135, 412. Obstet. Gynec., 42, 193. HEYMAN, J. (1949), Trans. I2th Brit. Congr. Obstet. Gynaec. WARNER, S., MEIGS, J. V., JAFFE, H. L., and SEVERANCE, HINSELMANN, H. (1933), Zeitsch. Geb. Gynaek., C.I, 42. A. (1939), Surg. Gynec. Obstet., 69, 645. A. Brit. med. ii,

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