LEADING ARTICLES

Cancer of the Œsophagus

THE LANCETLONDON : SATURDAY, FEB. 9, 1957

TWENTY years ago the oesophagus was a surgicalno man’s land separating the laryngologist from theabdominal surgeon-and both approached it with

trepidation. The results of surgery for malignantdisease of the oesophagus were very poor ; and thebest that could be said for radiotherapy was that itoften precipitated the end by causing a perforationof the oesophagus. The picture has changed. The

opportunities offered by advances in anaesthesia,by the new antibiotics, and by a more physiologicalapproach to postoperative care have been seizedwith enthusiasm by the surgeon 1 ; and super-voltage machines have enormously increased the

power and range of radiotherapy. So impressive arethese new methods of treatment, and so many arethe alternatives suggested for different types of growthand patient, that, if steady progress is to be achieved,their relative merits must now be carefully weighed.SMITHERS 2 rightly insists that, restricted though itsuse may be to a few centres, modern radiotherapy(like modern surgery) should be judged by the bestit can offer ; and, reviewing 314 cases of cancerof the œsophagus, seen at the Royal Marsden Hospitalbetween 1936 and 1951, he is in an excellent positionto form such a judgment. 65 patients in this carefullyanalysed series are grouped as

" untreated " ; but

they include those who had such minor palliativeprocedures as the passage of Souttar’s tubes, gastro-stomy, or jejunostomy. None survived for two years ;and 95% were dead within six months. These dismal

figures closely agree with the recently publishedfindings of MUSTARD and IBBERSON 3 from theToronto General Hospital: and they confirm thelow opinion in which gastrostomy and jejunostomyare generally held. Both operations shorten ratherthan prolong life, inflict rather than alleviate suffering.This is the grim background against which all the

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bolder forms of treatment must be evaluated.In the Royal Marsden Hospital series 20 of the

S14 patients had the growth resected : 5 of themsurvived for two years and 1 of them is still aliveafter eight years. In the Toronto series (381 cases,seen by various members of the General Hospitalstaff in the years 1947-53) the tumour was operatedon in 133 patients and resection was possible in 100.

. Of these 133, 48 died before they left hospital ;; but 7 survived for five years or more. SMITHERS: also describes the results in 229 patients treated by

rddiotherapy : 20 survived for two years and 7 forfive years. (Of these 7 patients 4 eventually died ofunrelated intercurrent disease ; but 2 succumbed to

1. See leading article, Lancet, 1955, ii, 653.2. Smithers, D. W. Ann. R. Coll. Surg. Engl. 1957, 20, 36.3. Mustard, R. A., Ibberson, O. Ann. Surg. 1956, 144, 927.

late recurrence of cancer.) The Canadian results in55 irradiated patients show 10 two-year survivals and1 five-year survival. Such figures are, of course,meaningless, if not actually misleading, unless noteis taken of the many things which influence theselection of patients : and, indeed, a considerationof these is in some ways more illuminating than acontemplation of the numerical end-results. Themost notorious variable in internal selection is theanatomical definition of the oesophagus; and its

bearing on statistical findings, especially those

relating to cancer, is well illustrated by the Canadianseries. This group includes among tumours of the

upper third of the oesophagus, cancers of the laryngo-pharynx, a type of growth which differs from moredistal growths in its age and sex incidence (it pre-dominantly affects middle-aged women), as wellas in its accessibility and response to treatment.

Perhaps because of the " almost infinitely repeatedtrauma of the food bolus squeezing through the

crico-pharyngeal sphincter," 3 malignant disease is

very common in this short segment of the alimentarytract ; and no less than 27 % of all

"

oesophageal "

tumours in the Toronto series started in this region.At the lower end of the gullet it was impossible toexclude with complete certainty all cancers arisingfrom the stomach ; and though every effort was madeto do so, it is perhaps significant that both the longsurvivors with lesions of the abdominal cesophagushad adenocarcinomas. Other variables, such as

standards of skill, differences in the personal experi-ence of the surgeon or radiotherapist, and the close-ness of the cooperation between them, make it hardto compare results from different sources. Never-theless, such comparisons are one of the few sourcesof guidance for the future ; true results are, afterall, only beginnings.

It is often said that, by and large, modern radio-therapy and surgery achieve similar results in carci-noma of the oesophagus. Such remarks reveal a

tendency to stray prematurely to the foot of thecolumn marked " total " rather than examine thedata in full; for all surgical series contain a pre-ponderance of lower-third tumours, accounting some-times for as many as 50% or 60%,4 5 and dispro-portionately few upper-third cancers. In groups of

patients treated by radiotherapy, though results forall sites may be inferior, the growths are usuallymore evenly distributed.2 6 7 At least one reason isnot far to seek : surgery is undoubtedly at its bestin the lower reaches of the oesophagus, and leastsuccessful near the upper end. Radiotherapy, on theother hand, has proved most effective in the upperoesophagus (whence metastases to subdiaphragmaticlymph-nodes are late and uncommon).

There is even less justification for saying thattoday’s five-year survivals reflect only the naturalhistory of the disease. Gloomy as the prognosis ofoesophageal cancer still is, treatment has certainlyrestored health to a few patients, prolonged life insome, and made existence tolerable for many. Surgerycan do much in the way of palliation : and it coulddo more if surgeons were less reluctant- to admitthat the chances of absolute cure-even in the best

4. Sweet, R. H. J. Amer. med. Ass. 1954, 155, 422.5. Franklin, R. H., Shipman, J. J. Brit. med. J. 1952, i, 947.6. Köhler, R. Acta radiol. Stockh. 1951, 35, 207.7. Nielsen, J. Ibid, 1945, 26, 361.

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hands are still remote, and that the best radicaloperations are not always the best palliative ones.Now that a sound palliative operation can ensureseveral months, or even years, of comparative comfort,it is self-deception to say - after an unsatisfactoryresection and anastomosis (often a patched-upaffair at the end of a gruelling three-hour session)that it will at least relieve the patient of his dis-comfort. Should the patient survive (and his chanceis hardly better than even) he would have been betterserved with no resection ; and, what is more disturb-ing, nine times out of ten this has been plain fromthe beginning. " On passe souvent de l’amour a1’ambition, mais on ne passe guere de 1’ambitiona l’amour" 8 : it is a sad paradox that the numberof different radical operations recommended (andpresumably practised) today almost certainly exceedstheir total number of survivors. Even those thatlook sound on paper should be judged with at leastone eye on the mortality figures—which are sobering.HUMPHREYS and MOORE 9 report from the PresbyterianHospital in New York that of all patients seen therewith primary oesophageal cancer (162 cases in ten

years) there was not 1 five-year survivor. At the NewHaven Hospital, during a similar period, the only 3survivors had adenocarcinomas, probably originatingin the stomach. 10 PARKER and JENKINS 11 couldfind only 1 five-year cure at the Roper Hospital,Charleston, in a review of 210 cases ; and RAVITCH,12though he does not give the total number of patientsthat were seen, could find none at the Johns HopkinsHospital. There may be scope for improvementsin operative technique ; but neither its presentimperfections nor delay in diagnosis can take muchblame for these results. In contrast to radical opera-tions, MUSTARD and IBBERSON are convinced that

palliative by-pass operations have real merit and thatthey are usually feasible. " The ability to swallow ispromptly restored and maintained regardless ofwhether or not the primary lesion can subsequentlybe successfully dealt with." 3 At present MUSTARDand IBBERSON perform an anterior mediastinal by-pass,using a jejunal Roux loop 13 or a colonic segment, inall " good-risk " patients with malignant obstruction.As an alternative, a palliative intubation 14 has themerit of simplicity, and it can be used for growthsat all levels.

An understandable distaste for compromise maypartly explain why radiotherapy (by tradition, if notin fact, palliation par excellence) still rarely gets theconsideration it deserves. Despite a cure-rate of 7%for tumours of the upper third, AIRD 15 feels thatdeep therapy has little to offer for cesophageal carci-noma and though " in the middle oesophagus a fairlyeffective tumour dose can be obtained by rotating thepatient in the beam ... results are not satisfactory ;and in the lower part of the cesophagus this form oftreatment is entirely useless." No-one will dispute8. LaRochefoucauld, F. Maximes, no. 490, 1652.9. Humphreys, G. H., Moore, R. L. Surg. Clin. N. Amer. 1953,

33, 389.10. Shedd, D. P., Crowley, L. G., Lindskog, G. E. Surg. Gynec.

Obstet. 1955, 101, 53.11. Parker, E. F., Jenkins, L. B. J. thorac. Surg. 1955, 29, 373.12. Ravitch, M. M., Bahnson, H. T., Johns, T. N. P. Ibid, 1952,

24, 256.13. Robertson, R., Sarjeant, T. R. Ibid, 1950, 20, 689.14. Coyas, A. Lancet, 1955, ii, 647.15. Aird, I. Companion in Surgical Studies. Edinburgh 1957.

these statements : but will they not encourage the lessexperienced to discard a method which has proveduseful, within its limitations, in favour of one which ismore spectacular but more lethal ? As an alternativeto survival-rates of less than 1 % after radical surgeryin the mid oesophagus (and an almost prohibitive opera-tive mortality), radiotherapy can usually restore thepatient’s ability to swallow ; "with a minimum ofdiscomfort, with a stay in hospital of a few weeks...and with virtually no treatment mortality the majorityof those patients ... swallow well until their death." 2There may or may not be a place for combined therapy- either by preoperative irradiation or the use of radio-active - gold- grain implants 16-but there is certainlya place for combined efforts in selecting cases forwhichever form of treatment holds out most promise.SMITHERS believes that " both methods are likelyto improve still further in the next few years and theyhave their individual sites of maximum advantage :but competition to the patient’s disadvantage insteadof cooperation to produce the best results is still fartoo common." In the treatment of cancer of theoesophagus, no less than elsewhere, isolated surgicalsuccesses, however Homeric in their dash and brihi-ance, do not justify the Homeric afterthought that" the rest were’vulgar death unknown to fame." 17

16. Fleming, J. A. C., Barrett, N. R. In British Practice in Radio-therapy. London, 1955.

17. Homer’s Iliad. Book II, line 394.18. Leonard, J. C. Brit. med. J. 1953, i, 1311.19. Dilling, N. V. Lancet, 1953, i, 1230.

New Drugs, Old DangersAMoNG the many new drugs that have lately been

introduced, the most prominently displayed are theorganic chemicals for the relief of pain and insomnia,and the so-called "

tranquillisers." The chemicalstructure of many of these drugs raises suspicion thatthey may damage the blood-forming tissues andthe blood-vessels ; and evidence is accumulating toshow that this suspicion is justified. The chancesthat a given drug will harm a particular patient areprobably very small ; and the mounting record ofblood disorders may be largely a reflection of the greatnumber of patients who are now being given these

drugs, rather than a sign of serious toxicity.Nevertheless, there is good reason to emphasise againthat many of these substances can kill and that others

may yet turn out to be potentially lethal. We reviewbelow some of the examples of drug-induced blooddisorders that have come to notice in the past twoor three years.

Phenylbutazone (’ Butazolidine ’) was introduced forthe treatment of rheumatoid arthritis and other painfuljoint conditions. LEONARD,18 who reviewed the literaturein 1953, collected 356 instances of toxic reactions among1526 treated patients, and these included 11 cases ofagranulocytosis. He himself recorded 1 patient who hadfatal aplastic anaemia and 1 who had granulocytopeniabut recovered. This second patient had been treated forsix weeks when sore throat and fever began ; the white-cell count was 1600 per c.mm. with 34 % polymorphs :he was treated with penicillin and recovered. DiLLixe 19

also described a fatal agranulocytosis due to sensitivity tophenylbutazone. This patient had 600 mg. daily forfive days, but when cedema developed the drug wasstopped ; after seven days treatment was resumed and450 mg. was given daily. Three days later she had severesymptoms ; the white-cell count was 2000 per c.mm..no polymorphs were found, and the patient died three