pre-cancerous conditions of the cervix uteri and their

PRE-CANCEROUS CONDITIONS OF THE CERVIX UTERI AND THEIR TREAT- MENT*

By J. CHAKRAVERTI, m.b. (Cal.), m.c.o.g., Assoc. Professor of Obstetrics and Gynaecology of the Carmichael Medical College, Calcutta, Gynaecologist and Obstetrician to Sir Kcdarnalh Maternity Hospital Calcutta, Visiting Surgeon to Chittaranjan Sevamdan,

Calcutta

A summary of the survey of the reports of the Public Health Commissioner with the Govern- ment of India (Russell. 1935) shows that the

* Read at a clinical meeting of the Obstetric and

Gynaecological Society of Bengal, 011 4th July, 1937.

662 THE INDIAN MEDICAL GAZETTE [Nov., 1938

incidence of cancer in India stands at a figure not far removed from that in western countries. It also shows that the highest incidence is during the age period of 40 to 50 years, i.e., ten years earlier than in Japan or in western countries and the United States of America.

As regards regional distribution, a preponder- ating incidence of carcinoma in one organ is counterbalanced by lesser incidence in other

organs and disparity between the incidence

figures of different provinces appears to be the subject of the same attempt at equilibrium. On the average, the incidence of cancer in the

female generative organs is over 50 per cent of

all cancers. Of this, cancer of the cervix is the highest, over 75 per cent. As far as is known at

present, primary carcinoma occurs more fre-

quently in the uterus than in any other organ and it causes death of one out of every thirty- five women over the age of thirty-five years.

No part of a woman's body undergoes such a strain as the cervix which in an adult is only one inch in length and forms a minor and somewhat subservient part of the whole uterus. From birth to involution this part changes widely in structure. In foetal life there is the fusion of the two great genital ducts with their solidifica- tion and canalization. In infancy and childhood, it occupies an abdominal position forming two- thirds of the whole uterus. At puberty, its

position is in the pelvis forming only one-third of the whole organ. In adult life, it is subjected to frequent trauma and exposure to infection. Then comes the changes due to pregnancy, parturition, and at last involution and rest set in. In old age, it is converted into a mere knob or

dimple. The greatest of all these changes is that during parturition when, within a few hours' time, its canal, the calibre of which was only a few millimetres, becomes enormously stretched to allow the passage of the fcetal head.

Naturally the mucous membranes are broken, muscles stretched and lacerated and the whole cervix thrown open to infection. In this small

portion of the uterus there are four different varieties of epithelial lining from below upwards, viz, squamous, high columnar, transitional, and low columnar. It receives the watery alkaline secretion of the body of the uterus, forms a thick glairy mucoid secretion of its own and is bathed in the creamy acid secretion of the vagina?the importance of which is very little known. Lastly, its hidden situation and

comparative insensitivity to pain, combined with the patience and shyness of the sex, favour any diseased condition progressing deeply before

being complained of by the patient. When we

consider the large amount of inconvenience, suffering and misery, often terminating in death, that arise out of the various kinds of disturb- ances originating in this small area, it would

seem that, while much has been said and written, there still remains a lot to be done by those who

are teachers and leaders in gynaecology and obstetrics.

At present the problems that confront the

profession, particularly the specialists in

obstetrics and gynaecology, are :?

(1) Is carcinoma of the cervix curable ?

(2) Is carcinoma of the cervix preventable ?

_

The answer to the first is qualified and condi- tional. It is admitted by all that with modern methods of treatment properly applied many,

i*

not all, cases of carcinoma are curable. We

know of cases of cure of 5 or even 10 years duration but few of 20 years. It would be fair

to say that improvement in the results following the treatment of carcinoma is to be obtained only if the cases are diagnosed in the early stage of the disease. In order to get them early, the cancer-consciousness of the medical profession as well as that of the general public must be

properly awakened. To bring down the death rate of carcinoma of the cervix, much more

is

required than the sharpening of the diagnostic acumen of the family doctors and general practitioners. Of equal importance is the education of the public by allaying their fears, calming their prejudices and removing ignorance which every part of India is full. This is on

the whole a far more difficult problem which Js

not strictly within the scope of this discussion-

The other problem?Is carcinoma of the cervix preventable ? It sounds rather absurd for ^ disease to be called preventable when its real

aetiology is still unknown. True it is that,

despite strenuous research work, all over the

world the real cause of cancer is still in dark- ness. I am not a pessimist in this respect and I hope some day, in the near future, some luck) man may find out the real cause of cancer

like

Schaudinn's discovery of the spirocheete. When we stop to consider that little more than sixty

years have passed since the origin of cancerous growth has really been understood, we need

no

be discouraged with the progress that has

already been made. The contribution to literature has been enormous and our knowledge has

been much clarified regarding the predisposing factors, aetiology, gradation, prognosis anc

treatment of carcinoma.

Carcinoma of the cervix differs widely fr?.nl carcinoma of the other regions of the body J? its onset, behaviour, progress and response

t

treatment. It has been shown that the cond1 tion is preceded by pregnancy in over 90 PeI. cent of cases. In other instances a history

0

inflammation, erosion or some instrumental011^ such as dilatation, can usually be traced.

Cer

vicitis and erosion are prone to follow lacerat10 from child-bearing and the former may ?ue any instrumentation of the cervix. I think t*1

important aetiological factor is not lacerat101^ but rather the consequent inflammation al1

chronic irritation.

Nov., 1938] TREATMENT OF CARCINOMA OF THE CERVIX : CHAKRAVERTI 663

hereas every one will admit the existence of

^cancerous conditions, it is extremely difficult ev

ae"ne them to one's satisfaction. It is, how-

vi r'. n?t a disease of separate entity. On re-

b ,w^ng the literature which is mostly contri-

one ^ German and American scientists,

wn ,ls.struck by the loose manner in which the

for iS .use^' According to TeLinde (1933), nil f {;esôn to be considered ' pre-cancerous' it

nom established that the incidence of carci-

,a developing in such cases is greater than

jeg; carcinoma in persons free from such a

in'?n' in other words, it is a condition developed ln-the c9urse ?f the healing of a very chronic j) -VC1^S with or without laceration. K. V.

eno ^30), in his well-known paper on 'An corv"11^ ^le basic cause and nature of the

citi '1Ca* cancer and the relation between cervi- ? and cervical cancer', states :?

to ca!!7icitis or erosion of the cervix is definitely related *hrou?j1,n0Pla cervix. This relationship is effected an as- .? aSency of a factor common to both, viz,

fjpithep01^6^ inflammatory exudate in contact with the is con \Uln* This is the intermediate causal factor and

? to bG ?tant. The basic cause of cervical carcinoma is

with n ]inid *n îs constant factor which is associated a11 cell reaction, including that of cancer inception.

eojjhe line of junction of the squamous and

os ^nar epithelium is usually at the external

enj+u Practice, it is found that the cylindrical eerv"'UIn ma^ exênd to the outside of the j UP *1X+ ?r ^1G scluamous epithelium may extend corr ^.e canal, the line of junction being

glanHP?nd.inSly Pâced. In the former, the

pr0n which are situated outside the cervix are

the G become infected. In chronic cervicitis

ttiac rnuco~Purulent discharge from the glands cjen

erates the squamous epithelium, leaving a

resi ,

d surface with scattered islands of more

tion ePithelium. This stage of inflamma-

linii/S Caêd erosion. The cylindrical epithelial e^d^' êss susceptible to the inflammatory

cha ?> gfows down over the raw area without

sub?-?ng character. As the inflammation

bath fS -ê columnar epithelium, no longer

sQUa mucus, loses its vitality, while the

^ttem?US ePitbelium regains its vigour. The

?utsir grows back to its normal position on the ejg

?f the cervix by proliferating under the

reni??. cylindrical epithelium and gradually everfC\n^ If the cervix has been lacerated or

t? |.j e some of the cervical glands are exposed

Hal Qe Vagma. In growing over the new exter-

epithSi^ the edge of a laceration, the squamous the p-i

1Urn surrounds and invades the ducts of

a p]^ ands.^ Sometimes it fills a duct and forms

tanCp,g which may grow inwards for some dis- erogif.' ?r.' rarely, may extend beyond the area

of

into *n^? ^le cervical canal and deep down

gland le muscle, involving normally-placed

glan iS" This is called epidermization of the

\y.s and ducts of the cervix. seen

en a cross section through such a part is

the j er the microscope, a first glance gives

fact -?pression suggestive of carcinoma. In ' may be wrongly diagnosed as carcinoma

L

by one not trained in gymecological pathology and occasionally experts have been known to differ in their opinion as to the nature of these islands of squamous epithelium. In such an

event, the guiding points for establishing a diagnosis of malignancy are :?

(1) breaking of the basement membrane; (2) hyperchromatic and mitotic characters

of the nuclei; (3) irregular and indefinite cell outline; (4) in contradistinction epidermization fol-

lows the gland outlines, i.e., 1 trellis-like network

of the glands', instead of the haphazard invasion of malignancy.

Lastly, a detailed study of a series of sections will clear the salient features of benignancy or malignancy. This process of repair does not always follow

an orderly sequence. The chronic cervicitis may flare up and subside from time to time. The two types of epithelium are thus put into a state of restlessness, sometimes over a long period. In view of the unstable equilibrium of epithelial growth it is not at all unnatural that the latter

may be excessive and thus encourage the devel-

opment of carcinoma (Pemberton and Smith, 1929). Another point in favour of the view that the exudation of chronic cervicitis stimulates cancer formation is that patients with proce- dentia very rarely suffer from cancer of the cervix.

Leucoplakia of the cervix is another condition which predisposes to cancer formation. Leuco-

plakia was known long ago but its importance and frequency were not realized till Herr Hinselmann began to discover the small size of the areas by the aid of the colposcope. My experience of leucoplakia is very meagre as I have seen but few cases in my practice. They may be rare here or we might find them more frequently if the colposcope were used to detect them. In regard to its tendency to malignancy, some workers claim that leucoplakia of the cervix is not a pre-cancerous lesion. But Hinselmann (Davis, 1934) states that all leuco-

plakia observed for a long enough time has become malignant and he cites cases. The changes are seen mostly in the cells themselves and not in their invasive power. The diagnosis of early cervical carcinoma is

often difficult, but it means much to the patient as it gives her a relatively good chance for life. While chronic cervicitis, erosion and lacerations are considered as pre-cancerous, the superposi- tion of any of the following conditions on them must raise suspicion of early carcinoma.

(1) A localized hard nodular feel. This must be

distinguished from deep-seated, pent-up secretion under tension in a Nabothian follicle. Puncture with a

surgical needle will settle the question. Sometimes, glairy fluid as much as two teaspoonfuls comes out.

(2) Indurated area on either lip, especially if the

overlying surface is granular. (3) Small ulcerated area. (4) Extreme localized vascularity. (5) Deposition of calcium salts, (6) Friability of surface, s ,

664 THE INDIAN MEDICAL GAZETTE [Nov., 1938

It requires experience and careful speculum examination in good light to detect these conditions, while the application of Schiller's test and modern colposcopy are certainly additional aids involving finer technique in detecting them earlier.

Biopsy and microscopic examinations, however, are the only means of establishing the diagnosis with certainty. By histo-pathological examination diagnosis becomes easy in most of the cases, the condition being obviously benign or malignant. In some cases, however, the diagnosis is

difficult, and in a very small percentage it may be almost impossible. By a careful weighing of the clinical history, a thorough local examination combined with the results of special tests, if

possible colposcopy and where necessary biopsy and microscopy, carcinoma will rarely be over- looked even in its early stage. Sometimes, objections are raised to biopsy on

the grounds of (1) acceleration, (2) dissemination and (3) infection of the growth. Personally, I think the danger of spread by instruments is overrated. Even on theoretical grounds the

danger can be minimized by searing the cut surfaces of the wound with a cautery. Biopsy is best performed with a sharp knife or punch. The tissue should be excised from the most sus-

picious area with a certain amount of healthy tissue retaining the mucous surface. A colposcope helps considerably in performing biopsy more perfectly and finely. After receiving the tissue it should be cut into three pieces and the pathologist asked to put them in one block. Thus a series of sections at three different levels is made and there will hardly be a chance of missing a suspected area. Excluding the com- petency of the pathologist, much depends on the surgeon for the result of the biopsy. The

pathologist should be considered as a consultant and not a prophet. He should be supplied with all the available information in order to arrive at a right decision. In a doubtful case the

opinion of a second pathologist should be sought. When twp pathologists disagree regarding the diagnosis of a section from the cervix, it can be concluded with considerable assurance that the growth is benign. But the patient should be kept under observation and another section made two months later. It is here that close co-operation should exist between the clinician and the pathologist, neither of whom should be guided by preconceived ideas and prejudices in the study of cervices undergoing these chronic inflammatory processes. I think this would be the only possible means of finding out the link between pre-cancerous conditions and early carcinoma of the cervix.

Most treacherous, however, is an endocervical carcinoma. The portio vaginalis and external os look healthy. The cervix as a whole is bulky, spindle or barrel shaped. The endocervical mucous membrane is found to be vascular and

granular, as determined by the passage of a

sound. Only the curette and microscope will

settle the diagnosis. Fortunately, this type 0

carcinoma is very rare. , ,

Because it is admitted that there is a distinc

relationship between carcinoma and chronic in'

flammatory conditions of the cervix and becaii-c the time interval from the onset of one to the

development of the other is not known, it

always advisable to treat the pre-cancerou- conditions at the earliest possible opportunity- Gynaecologists and obstetricians are so engrosser with bigger problems and bigger operations tha this part of the question here in India is en-

trusted to the hands of a junior officer of tn(-

out-patient department. As most of pre-cancerous conditions foll?vv

childbirth, the question of prophylaxis arise?-

Here, if my information be correct, the c-eryi is neither examined nor stitched for laceration unless there is sufficient post-partum haemorrhage from the torn area. In some clinics, laceration* of the cervix are treated as a routine measuie-

Personally, I think our practice is better as tli^16 is less risk of increasing the morbidity which

is

already too high in Bengal in comparison no >

only with other countries but also other province in India. But I would certainly emphasize tn^ importance of examination of every puerp^r woman once post-natally in the fourth to six week. This will reveal and give a chance

rectify many gynaecological affections, P1

cancerous conditions being some of them.

Treatment

Gynaecologists owe a lot to Hunner (Eden and

^

Lockyer, 1935) who first used the cautery ^

the treatment of chronic cervicitis and erosion 1906. He used the Paquelin cautery which

^

replaced by the nasal electric cautery ^ Dickenson. Cauterization of the cervlX,r-ve properly done, will save many lives and & comfort to a greater percentage of women

tn<

any other simple procedure in surgery. It nl." be emphasized, however, that it is an operati.^ that must be performed properly, otherwise results will be disappointing. This is true in

more chronic, deep-seated infections of the c

vix, where there is a great excess of connect tissue and the glands lie far beneath the suria ^ In a moderately bad case cauterization has

.

be repeated a second or third time at an intei '

of four to six weeks. Just a word a.b

cauterization?the linear cauterization of

canal must be done deep inside, gradually ̂ e^0-ce ing superficial at the external os, other^e eversion of the lips results after healing. glands in the portio vaginalis are attacked point puncture from the surface.

It is safer to hospitalize the patient cauterization. Topical application of ca|lS-s a of which there are many, is useless, and

1 .g

mere waste of time, energy and money. \ Q{ sometimes beneficial in a limited numbei j cases in which the erosion is super11 and follows a recent labour or abortion

n

I h?v

J

Nov.. 19381 ACTION OF DRUGS ON MALARIA : DAS GUPTA & CHOPRA 665 v

n?t had the opportunity of using the zinc- chloride porous pencils of Aleck Bourne?a dis- tinct advantage of this method is that the treatment can be safely carried out in the out-patient apartment. I have also had no experience of conization of the cervix which in the United States is practised widely.

If the erosion is complicated by laceration the cervix should be repaired. Usually the area of erosion is included in the denudation. If not, the remaining part has to be cauterized. If the erosion is complicated by multiple laceration ^hich has passed beyond the stage of repair

the cervix is very bulky and there is some degree of prolapse?low amputation of the cervix ^**11 be the treatment of choice. Either Sturmdorf or Bonney's method usually gives a

smooth external os.

Vadium.?In the treatment of chronic inflammation and erosion, my experience is very meagre. Although it has not been proved scientifically hat the treatment of the diseased cervix is a

Prophylactic against cancer formation, there are some suggestive facts in support of this. In a

^nes of 3,814 trachelorrhaphies, 740 amputa- *ons and 1,408 cauterizations of the cervix, a otal of 5,962 cases covering a period of 52 yeais

j1. the Free Hospital for Women in Boston, only 1Ve }vere known to have developed cancer of the cervix and these were all in the trachelorrhaphy i?r?up. More convincing are the figures of , euin, who in 613 cases of cancer of the cervix 0lmd only two in which a previous cervical epair had been performed. Thus, in these series ,ot .?ne patient whose cervical specimen was i Picious but not malignant has been found to ave developed cancer.

figures are too small to be compared with si m e- mentioned above and my experience is not '

tnciently mature to enable me to make a bold n ernent. I can, however, say that none of my 1 re~cancerous cervices treated on the above lines as developed cancer yet. i hysterectomy.?For nearly a decade hysterec- i my, particularly by the vaginal route, has een very widely performed here in fairly young omen, the indication being pre-cancerous

, 1Vlx. Of late the condition has gone from bad , ^orse, so much so that students of the present c y put down pre-cancerous condition of the

tnlTlx as one "the indications for hysterec- . y ! Literature fails to support this extreme

cannot trace the origin of this idea

aff^ ^as sProad out like a conflagration and hne nearly all the specialists here. To be

^ am n?t- an exception to this craze. But

lrif0 has come when we should stop for a tj )lnent and review the results of our actions in tjQe Past and present and decide what should be

m future. Ore We say, we are justified in removing an 8an so important to the sex because we are

(Continued at foot of next column)

(Continued from previous column)

unable to differentiate with certainty a non-

cancerous from an early carcinoma stage ? Per-

sonally, I think hysterectomy should not be done for pre-cancerous conditions which can usually be cured. On the slightest suspicion of early malignancy, biopsy and microscopic examinations should be made to settle the diagnosis. In case of doubt one must wait, observe and see. As Ewing says

' It is not true that a pathological condition must be either cancer or not cancer. It may be neither the one nor the other'.

Trouble may arise from keeping a patient waiting for a long time in suspense. In such a case it is difficult, if not impossible, for the doctor to take his patient into his confidence and, in the happy event of a negative finding, it would be only human for the patient to protest with no uncertain voice that there had been a lot of fuss and considerable expense for nothing. It often happens that the doctor is more worried from the difficulty of trying to convince a patient and her relations that something ought to be done than by ignorance of what advice to give. Hysterectomy should be reserved for cases in which other methods of treatment are not possible and the pre-cancerous condition is complicated by other diseases, e.g., fibroid, inflammatory adnexa, uncontrollable uterine bleeding and prolapse of the uterus after menopause, etc. On the rare occasion, when hysterectomy is

contemplated because of pre-cancerous conditions, it would be wise and safe to have a second

opinion. By this means not only does the

patient get a fuller benefit of professional opinion but the members of the profession arc also mutually benefited.

References

Bailey, K. V. (1930). Joum. Surg. Gyn. and Obstet., Vol. L, p. 688. Davis, C. H. (1934). Gynaecology and Obstetrics.

Vol. Ill, P- 5. W. F. Prior Company, Inc., Hagers- town. Eden. T. W., and Lockyer, C. (1935). Gynecology

for Students and Practitioners. J. and A. Churchill, London. Pemberton, F. A., and Smith, G. V. S. (1929). Amer.

Joum. Obstet. and Gyn., Vol. XVII, p. 165. Russell, A. J. H. (1935). Ann. Rep. Pub. Health

Commissioner, Govt, of India, 1933. Manager of

Publications, Delhi. TeLinde. R. W. (1933), Joum, Amer. Med. Assoc.,

Vol. CI, p, 1211

pre-cancerous conditions of the cervix uteri and their

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