ELECTIVE TREATMENT OF LYMPH-NODES IN MALIGNANT MELANOMA

345

ELECTIVE TREATMENT OF LYMPH-NODES IN MALIGNANT MELANOMA T. F. SANDEMAN M.D. Edin., F.F.R. SENIOR

RADIOTHERAPIST, PETER MaCCALLUM CLINIC, MELBOURNE, VICTORIA, AUSTRALIA

IF malignant cells spread from the primary growth to the lymphatic channels and thence to lymph-nodes, it is clear that removal of these lymphatic pathways before they are invaded will improve survival-rates. Unfortunately, in many malignant diseases, and malignant melanoma in particular, early hxmatogenous spread reduces the expectation of cure. Douglas (1957) showed by logical deductions from survival curves that at least some patients with early carcinoma of the cervix and breast are already harbouring latent metastases beyond the reach of treatment. It follows that attempts to deal with occult lymphatic spread can never be uniformly successful. Yet if " prophylactic " lymph-node dissection increased the survival-rate significantly without gross morbidity it would appear worth while. Unfortunately published reports on elective treatments in malignant melanoma give little helpful information about the results of dissection on survival-rates. Controlled clinical trials have not been extensive or rigorous. Patients

registered as malignant melanoma at the radium department of the Royal Melbourne Hospital and the Peter All

cases

TABLE I-AGE-DISTRIBUTION IN

172 PATIENTS WITH MELANOMA

whom elective dissection was planned but in whom metastases became clinically evident in the four weeks between operations. The difference in sex-distribution in the two groups is not statistically significant. Table I and fig. 1 show the agedistribution. The proportion of the elderly was higher in group 2. The site of the primary tumour was substantially the same in the two groups, except for the greater relative number of melanomas of the trunk and eye in group 2 (table ll). Results

Cumulative survival-rates (tables ill and IV) and

groups

were

calculated for both drawn (fig. 2).

curves were

TABLE II-SITE DISTRIBUTION

other causes, or patients lost counted as dead of the disease; so a

All deaths from melanoma to

follow-up,

were

or

crude figure was obtained. Determinate figures, based on only those cases available at the stated time in whom the result with respect to their tumour was known are shown in fig. 3. In this curve all patients dead of other causes or lost to follow-up are omitted. The three-year survival for group-1cases was 70 %, and for group 2 60%. At five years the rates were 28%and 43% respectively, and at ten years 8% and 20%. These figures are based on small numbers, but cumulative curves do not often need alteration as the numbers available for assessment rise. Omission of the irradiated cases makes no difference to the curves. 50 patients subsequently came to treatment for enlarged

lymph-nodes. Discussion

MacCallum Clinic from 1930 to 1959 were examined. 282 were accepted as invasive malignant melanoma, excluding superficial melanocarcinoma, active junctional nsevi, and juvenile melanoma: 194 were confined to the primary site at first treatment, and 172 of these had had adequate radical treatment of the primary tumour. 36 of these stage-i cases (11 men and 25 women) had been treated by means of wide excision of the primary melanoma and either en-bloc dissection of the draining nodes if they were close to the tumour or an elective block dissection four to six weeks later. 2 patients had had a radioactive implant to both the primary and the drainage area. After the operation 1 patient had had an implant to both the primary tumour and the nodes, and 1 had had X-ray therapy only. 2 of these 4 were men and 2 were women. This group of 40 patients comprises the "

prophylactically " treated cases (group 1). In the remaining 132 patients (group 2) the primary melanoma had been treated in various ways. 75 had been excised, 43 had had a radioactive implant, and 14 had been irradiated externally. Combinations of treatment were used occasionally, but only the first method likely to be successful is considered here: for instance, biopsy followed by X-ray therapy is listed under the latter. In this group of 132

patients (57 men and 75 women) the draining lymph-nodes were not treated until signs or symptoms warranted treatment. Included in this group are 2 patients for

Several papers on malignant melanoma report survivalrates for patients undergoing block dissection (Lane et al. 1959, Pack 1959, Fortner 1960, Petersen et al. 1962, Fortner et al. 1964). Most of these frame the results according to the pathological findings and draw conclusions according to whether tumour was found or not. In many reports both therapeutic and elective treatments are

346 TABLE III—SURVIVAL DATA ON PATIENTS WHO UNDERWENT PROPHYLACTIC TREATMENT TO LYMPH-NODES

(GROUP 1)

survived. When the results are presented (even although the same patients are reported in both series) centre A’s results will obviously appear the more impressive, particularly if the overall survival is not mentioned, and stages ill and iv (who perhaps were not treated) are omitted. This surprising but significant observation is of paramount importance when the results of centres using the same method of treatment are compared, and even more when treatments of different applicability are contrasted. It is essential that equivalent cases should be compared as a whole group and not be split up according to other criteria. This applies equally to the presentation of results according to the pathological report, since a centre which routinely clarifies all dissection specimens and cuts more sections will find more invaded nodes than one which does not carry out such painstaking work. Any improvement in survival figures in this event is due solely to the diligence of the pathologist and ought not to be credited to the procedure.

TABLE IV-SURVIVAL DATA ON PATIENTS WHO HAD NO PROPHYLACTIC TREATMENT TO NODES

(GROUP 2)

included in the same figures, and it is impossible to gauge the effect of a purely elective approach. Although they avoided this mistake, Lund and Ihnen (1955) and Price and Duval (1963) did not give adequate information on the survival-rate over a stated time. McWhirter (1957) showed that the results of any series presented according to the stage will vary with the strictness of the staging. Table v shows how this can

happen. group of 100 patients is seen at two different Centre A applies staging criteria rigorously and allots few cases to the early category. Centre B is not so strict. The patients are treated, and at the end of five years 50 of them have

The

same

centres.

Fig. 2-Cumulative survival

curves

for the two groups.

Block and Hartwell (1961) from observations in a comparable series of cases concluded that elective treatment added little to the patient’s chances of survival, except possibly when the site of the tumour was in the head and neck. On the other hand, Conley and Pack (1963), in an extensive review of their experience in head and neck melanomas, reported figures from which it is possible to deduce that 60% of patients treated by elective neck dissection survived, whereas, of those who were not so dealt with, 71 % were alive at the end of five years. The recurrence-free rate showed a similar trend. Cade (1957) concluded that, when an en-bloc procedure could not be carried out, nothing was lost by observing the nodes and treating them as the need arose. There are too few cases in the present series for separate assessment of the cases treated by en-bloc dissection and the cases in which treatment was discontinuous. This important overall survival figure assumes statistical significance only if the compared series are truly equal. All cases must be suitable for treatment by either method. Allocations to one or other policy must be random in any prospective trial. Since the reasons for not dissecting are seldom given it is unwise to place too much reliance on the figures. For example, selection for dissection on the of penetration of the dermis would lead to all the depth " " superficial melanocarcinomas (Allen and Spitz 1953), with their better results, appearing in group 2. In the

Fig. 3-Determinate survival

curves

for the two groups.

347 TABLE V-RESULTS OF DIFFERENT STANDARDS OF STAGING ON THE SURVIVAL OF THE SAME GROUP OF PATIENTS (AFTER MCWHIRTER 1957) *

i to represent a stage before invasion of lymph-nodes, centre A would show a survival-rate of 90% and centre B 65%. Centre A a survival-rate of 52-5% for cases with nymph-node would show invasion, wherein the figure for centre B would be 38-4%.

Taking stage

present series these cases were excluded. The more usual selection is to the detriment of the cases in group 2, since is

more commonly precluded only by the of either the patient (because of age or unsuitability general health) or the primary (because of size or overlap of several drainage areas as on the trunk). In the period of this study policy changed with only a few exceptions, to routine dissection. This is reflected in the numbers of determinate cases available for analysis at different periods in the two groups. In view of this lack of correspondence of material, no statistical comparison can be made, but tentative conclusions are unavoidable. The crude and determinate survival-rates at three years show a 10% advantage to group 1. This may be due to the greater number of elderly patients and more rapidly growing primary tumours among the untreated. At five years, however, this advantage is more than reversed, and, although the figures are small, the trend continues and even increases to ten years. It is difficult to avoid the conclusion that, far from saving patients, dissection may in fact be either disseminating or promoting the growth of the tumour, possibly by interfering with the natural host defences. Operative-mortality rates are low, but morbidity is seldom critically examined. Fortner et al. (1964), reporting 206 groin dissections in detail, state that nearly 20% showed operative and postoperative complications ranging from phlebothrombosis to burst abdomen. Swollen limbs, tight scars, and restriction of joint movement are not mentioned, but these, and such inconveniences as accessory and facial nerve palsies at other sites, seem too high a price for an apparently non-existent survival. If elective dissection is not carried out, and the nodes later require treatment, the results are by no means hopeless. 12 patients are still alive and well. The cumulative three-year survival-rate as measured from the treatment of the original lesion is 58% (29 out of 50 available); or from the time of treatment of the nodes 43% (21 out of 49 available). At five years the respective figures 41% (20 out of 49) and 23% (10 out of 44). At ten years the figures are 26% (11 out of 43) and 14% (6 out of 43). The explanation of this high survival-rate, which exceeds or equals (depending on the time of mensuration) the survival-rate in most published reports of dissection of invaded nodes, lies in the elimination of patients in whom general dissemination becomes apparent before their nodes show signs of invasion. Hence unnecessary meddling is avoided, and host defences (which may be more important than method of treatment) are interfered with

treatment

as

little

as

possible. Summary

Of 172 patients with malignant melanomas 40 who underwent elective treatment showed a crude five-year

survival-rate of 28 °o; in 132 who formed a " nontreated " control group the five-year survival-rate was 43 %. Such retrospective surveys are always suspect, and a properly controlled clinical trial is needed to establish the place of elective nodal surgery. This paper is based on part of an M.D. thesis for the University of Edinburgh in 1963. I should like to thank the honorary staff at the Royal Melbourne Hospital and my colleagues at the Peter MacCallum Clinic for allowing me access to their cases; the medical director for permission to publish; and Dr. R. Motteram and Dr. S. 0. M. Were of the pathology department. REFERENCES

Allen, A. C., Spitz, S. (1953) Cancer, Philad. 6, 1. Block, G. E., Hartwell, S.W. (1961) Ann. Surg. 154, 74. Cade, Sir S. (1957) Brit. med. J. i, 121. Conley, J. J., Pack, G. T. (1963) Surg. Gynec. Obstet. 116, 15. Douglas, J. R. S. (1957) Med. J. Aust. i, 536. Fortner, J. G. (1960) Med. clin. N. Amer. 145, 643. Booker, R. J., Pack, G. T. (1964) Surgery, 55, 485. Lane, N., Lattes, R., Malm, J. (1959) Ann. Surg. 150, 989. Lund, R. H., Ihnen, M. (1955) Surgery, 38, 652. McWhirter, R. (1957) J. Fac. Radiol., Lond. 8, 220. Pack, G. T. (1959) Surgery, 46, 447. Petersen, N. C., Bodenham, D. C., Lloyd, O.C. (1962) Brit. J. plast. Surg. 15, 49. Price, W. E., Duval, M.E. (1963) Arch. Surg. 87, 747. —

RECOVERY FROM PROLONGED OLIGURIA IN ACUTE GLOMERULONEPHRITIS DAVID PERSOFF* M.B., M.Sc. Lond. FORMER HOUSE-PHYSICIAN

From the

Department of Medicine, Hammersmith Hospital, Du Cane Road, London, W.12 years interest has been focused

on the proform acute of glomerulonephritis. Harrison longed oliguric et al. (1964) have defined prolonged oliguria as a urinary output of less than 400 ml. daily in adults, and 200 ml. daily in children, for more than 8 days. Before techniques of dialysis were used, this form of acute glomerulonephritis was usually fatal in the acute attack (Earle and Seegal 1957). Results of dialysis have often been disappointing, especially among adults (Merrill 1957, Kassirer and Schwartz 1961). Thus, in a typical series of sixteen cases of acute glomerulonephritis, Schreiner et al. (1960) found that more than 17 days of oliguria was incompatible with survival, despite dialysis. It is satisfactory, therefore, to report the recovery of a man from an attack of acute glomerulonephritis complicated by 27 days of oliguria, which necessitated five haemodialyses to keep him alive while renal function returned. He is the first adult patient in the records of the Hammersmith Hospital to have made such a recovery and remain well during 22 months of follow-up.

IN

recent

Case-report The patient was a previously fit man of 39 years, with no relevant past history. He gave a history of sore throat 2 weeks before admission to hospital, successfully treated with penicillin ; passage of about a cupful of smoky urine daily for a week; and nausea, epigastric pain, hiccups, general malaise, and aching muscles for 3 days. At Fulham Hospital he was found to be oliguric (24-hour urine 6 ml., containing protein, red blood-cells, and granular casts), ursemic (blood-urea 250 mg. per 100 ml.), and hyperkalxmic (serum-potassium 8 mEq. per litre). He was transferred to the Hammersmith Hospital next day after treatment of his hyperkalxmia with ’Resonium A’. On admission he looked ill and was hiccuping, but was quite alert. His pulse was irregular at 50 per minute and bloodpressure was 120/70 mm. Hg. There was no peripheral oedema. Fine crepitations were heard throughout the lung fields. He had bilateral loin tenderness. The electrocardiogram (E.C.G.) *

Present address: Department of Neurosurgery, St. George’s Hospital, the Atkinson Morley’s Hospital, Wimbledon, London, S.W.19.

at