STOMACH CANCER FOLLOWING GASTRIC SURGERY FOR BENIGN CONDITIONS

STOMACH CANCER FOLLOWING GASTRIC SURGERY FOR BENIGN CONDITIONS

1175 these problems by sampling directly from the thyroid veins." At this stage it is reasonable to suggest that, if a patient has not previously had...

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1175

these problems by sampling directly from the thyroid veins." At this stage it is reasonable to suggest that, if a patient has not previously had an operation and the catheter studies indicate that one particular gland is involved, this area should be explored first; but it will probably still be wise to identify the other glands lest they too are affected. When the catheter studies are interpreted as suggesting that the gland is within the mediastinum and the patient has not previously had an operation, it would still be wise to explore the neck first, in case there is an anomaly of the venous system leading to an incorrect conclusion. If the patient has previously had an unsuccessful operation, and the catheter findings indicate that one particular gland is overactive, it may suffice to explore just that area. (J.

We thank the Medical Research Council for a grant to one of us L. H. O’R.) and the physicians and surgeons who referred

patients to us. REFERENCES

1. 2.

3.

4. 5. 6. 7.

8. 9.

10. 11.

O’Riordan, J. L. H., Woodhead, J. S., Kendall, B. E. Q. Jl Med. 1971, 40, 573. O’Riordan, J. L. H., Watson, L., Woodhead, J. S. Clin. Endocr. (in the press). Reitz, R. E., Pollard, J. J., Wang, C. A., Fleischli, D. J., Cope, O., Murray, T. M., Deftos, L. J., Potts, J. T. New Engl. J. Med. 1969, 281, 348. Pyrah, L. N., Hodgkinson, A., Anderson, C. K. Brit. J. Surg. 1966, 53, 245. Addison, G. M., Hales, C. N., Woodhead, J. S., O’Riordan, J. L. H. J. Endocr. 1971, 49, 521. O’Riordan, J. L. H., Potts, J. T., Aurbach, G. D. Endocrinology, 1971, 89, 234. Keeling, D. H., Todd-Pokropek, A. E. in Medical Radioisotope Scintigraphy; p. 745. International Atomic Energy Agency, Vienna, 1969. Reiss, E., Canterbury, J. M. New Engl. J. Med. 1969, 280, 1381. Doppman, J. L., Melson, G. L., Evens, R. G., Hammond, W. G. Invest. Radiol. 1969, 4, 97. Doppman, J. L., Hammond, W. G. Radiology, 1970, 95, 603. Powell, D., Doppman, J. L. 1971 Proceedings of 53rd Meeting of the Endocrine Society, abstract 42.

lower thanthe frequency of gastric in carcinoma the general population. We report here an interval-dependent association between gastric cancer and previous surgery in a necropsy series from

to, 4-or

even

Oslo.

Necropsy Material During the years 1960-69, 17,070 patients

over 20 years of age were examined post mortem at Ullevål Hospital, which serves the city of Oslo as a general hospital. In 630 of these patients gastric cancer was either present at necropsy or was otherwise related to the death of the patient. For each case of gastric cancer the nearest following necropsy of a patient of the same sex and year of birth, and without gastric cancer, was taken as a control. Necropsy reports for cases and controls were studied, and, wherever the possibility of previous surgery for a benign condition of the stomach or duodenum was indicated, further information was sought from clinical records. Additional information on ulcer site and the type and year of operation was kindly provided by Dr. K. Westlund from the files used in a prospective study.6

Results

Only patients who had undergone gastric surgery a benign condition 5 years or more before death

for

TABLE

I-FREQUENCY OF

5 YEARS

GASTRIC SURGERY FOR A BENIGN CONDITION

OR MORE PRIOR TO DEATH AMONG GASTRIC-CANCER

PATIENTS AND MATCHED NECROPSY CONTROLS

included in the group of patients previously operated on. As is shown in table I, previous operations were commoner among men than among women. In both sexes, previous operations were nearly three times

were

STOMACH CANCER FOLLOWING GASTRIC SURGERY FOR BENIGN CONDITIONS HELGE STALSBERG Cancer

SIGBJÖRN

TAKSDAL

Registry of Norway and Department of Pathology, Ullevål Hospital, Oslo 1, Norway

Among 630 cases of gastric cancer submitted to necropsy the frequency of previous gastric surgery for benign conditions was lower than among matched controls for patients operated on less than 15 years before death, but was increased to about six times the frequency among controls for patients operated on 25 years and more before death. There was no evidence for a difference in this respect between patients operated on for stomach ulcer and patients operated on for duodenal ulcer, nor between partial gastrectomy with gastrojejunostomy and gastrojejunostomy alone. Summary

Introduction

THE frequency with which carcinoma

develops in the

gastric stump following surgery for benign conditions has variously been reported as higher than,1—3 similar

common among patients with among controls. The difference is as

gastric cancer as statistically highly

significant (P<00005). The association with previous gastric surgery was characteristic of cancer of all sites. When the control group was split into patients having cancer of sites other than stomach and those with no cancer, no difference in the frequency of previous gastric surgery was revealed between the subgroups (table n). Previous operations for gastric ulcer and previous operations for duodenal ulcer were both commoner among gastric-cancer patients than among controls, and there was no predominance of one ulcer site over the other (table III). Of the eight controls who had

not a

TABLE II-FREQUENCY OF GASTRIC SURGERY FOR A BENIGN CONDITION 5 YEARS OR MORE PRIOR TO DEATH AMONG CONTROLS WITH OR WITHOUT CANCER OF SITES OTHER THAN STOMACH

1176 TABLE III-BENIGN CONDITIONS FOR WHICH GASTRIC SURGERY HAD BEEN PERFORMED

longer intervals there was a sharply increasing over-representation of previous operations among gastric-cancer patients (table v). This trend is statistically highly significant (x test for trend 8: P<0.005). The effect of previous gastric surgery on the accuracy of gastric-cancer diagnosis without necropsy was

than among controls. With

For this purpose a control group of 55 gastric-cancer patients without previous gastric surgery, and with the same sex and age distribution as for those previously operated on, was constructed as follows: for each previously operated gastric-cancer patient in the necropsy material, the next following gastric-cancer patient without previous operation for a benign condition, of the same sex and year of birth±years, was taken as a control. The analysis (table vi) showed that a definite dia-

estimated. *

Includes patients operated less than 5 years before death.

TABLE IV-TYPES OF OPERATION PERFORMED FOR BENIGN CONDITIONS

undergone the operation 15 years or more before death, and in whom the site of the ulcer was known, four had been operated on for gastric ulcer and four

gnosis of gastric cancer was significantly less common among patients previously operated on than in the unoperated group (n<0.05). Discussion

for duodenal ulcer. The types of operation performed showed a similar distribution among stomach-cancer patients and controls, partial gastrectomy with gastroenterostomy by the Billroth 11 method being the commonest operation in both groups (table IV). The mean interval between the operation for a benign condition and death, excluding intervals of less than 5 years, was 26-4 years in gastric-cancer patients and 17-0 years in control patients. The distribution of intervals is analysed in table v. Among controls, the number of patients previously operated on decreased gradually with increasing intervals. Among gastriccancer patients, the majority of previous operations had been performed more than 15 years before death. Thus, previous operations less than 15 years before death were less common among gastric-cancer patients

The use of a necropsy series for analysing the association between gastric surgery and later development of stomach cancer has two great advantages. First, the presence or absence of gastric cancer is ascertained with the greatest possible accuracy. Clinically, the diagnosis of gastric cancer is generally more difficult to make in patients who have previously undergone gastric surgery than in unoperated patients, as demonstrated by the lower rate of correct prenecropsy diagnoses in previously operated patients. A second advantage of the necropsy approach is that the observation period covers the full lifespan of each patient. Our data indicate that, until 15 years have passed since operation, the risk of developing stomach cancer may even be lower in the operated patient than in the general population, and it is only thereafter that the increased and steadily increasing cancer risk of

TABLE V-NUMBER OF PATIENTS WHO HAD UNDERGONE GASTRIC SURGERY FOR A BENIGN CONDITION 5 YEARS OR MORE PRIOR TO

operated patients appears. In prospective studies

DEATH AND INTERVAL BETWEEN OPERATION AND DEATH

*

In calculation of the

ratios, the 3 controls with unknown intervals have been distributed proportionately to the known interval groups.

VI-ACCURACY OF DIAGNOSIS PRIOR TO NECROPSY IN GASTRIC-CANCER PATIENTS WITH OR WITHOUT PREVIOUS GASTRIC SURGERY FOR BENIGN CONDITION

TABLE

4,6,7 that have failed to demonstrate an increase in risk of gastric cancer among patients treated surgically for peptic ulcer, limited observation periods and low necropsy-rates have presumably contributed to the outcome. Necropsy material is biased by the selection of patients for necropsy. However, a comparison of our material with data from official statistics 9,10shows that it is highly unlikely that the association between gastric cancer and previous gastric surgery could have been an artefact produced by selection factors. The total number of necropsies at Ulleval Hospital represented 33 ° 1 % of all deaths in Oslo during the period of study, and the necropsied cases of stomach cancer were 38-2% of the recorded number of deaths from stomach cancer in Oslo. The apparent over-representation of gastric-cancer cases in the necropsy material is not more than might be expected from the improved diagnostic accuracy and the inclusion of some cases in which the gastric cancer was not causally related to death. If the association between gastric cancer and previous operations were to be explained by a selection of cases for necropsy, we should have to postulate that our necropsy material included virtually every patient with a previous stomach operation for a benign con-

1177

dition who died from or with stomach cancer in the city of Oslo during the period. We can confidently exclude this possibility, as there are other hospitals in the city with a similar admission policy, and in our surgical material from the same period an additional

thirty-one patients with gastric cancer following previous gastric surgery for a benign condition were examined. Moreover, the increasing association between gastric cancer and previous surgery with increasing time between operation and death cannot reasonably be ascribed to a selection of cases for

BLOOD-GROUPS AND SECRETOR STATUS IN PATIENTS WITH SALIVARY-GLAND TUMOURS

J. V. GARRETT J. S. WHITTAKER

A. NICHOLSON J. C. RIDWAY

C. M. BOWMAN Christie Hospital and Holt Radium Institute and Withington

Hospital, Manchester The distribution of ABO and Rh blood-groups and secretor status in 407 patients in the Manchester area with salivary-gland tumours was determined. No significant increase in any blood-group or of secretors or non-secretors was found in any of the histological classifications or in the series as a whole. This negative finding contrasts with earlier series from Glasgow and New York, for which excesses of group-A patients were

Summary

necropsy. Our data give

no support to the suggestion 2 that on for stomach ulcer are at a higher operated patients risk of developing gastric cancer than patients operated on for duodenal ulcer, since both ulcer sites were about equally over-represented among gastric-cancer patients compared with controls. Similarly, partial gastrectomy

with gastroenterostomy and gastroenterostomy alone were both over-represented among gastric-cancer patients. Both findings are in good agreement with the necropsy data from Vienna reported by Kuhlmayer and Rokitansky. 1 The gradual increase in relative gastric-cancer risk of operated patients with increasing time since the operation seems to suggest a continuous carcinogenic influence rather than a single carcinogenic event at some limited time during the patient’s life. The likeliest explanation for our findings seems to be that the increased risk of gastric cancer is directly related to the establishment of a gastrojejunostomy with resulting gastritis 11 and reflux of bile and intestinal and pancreatic juices into the stomach. The incidence of, and mortality from, gastric cancer vary widely among countries, and a distinct decrease in both has been noted in several countries over the past decades.l2,13Thus, whatever the mechanism for the increased risk of gastric cancer in patients operated on for peptic ulcer, the background on which it acts and possibly the magnitude of its effect will be different in different parts of the world and at different times. Finally, we wish to emphasise that the risk of subsequent gastric cancer is only one of several factors to be considered in deciding whether to treat peptic ulcer surgically. We thank Mrs. Bodil Tjade for help, and Dr. Knut Westlund for access to his files on patients treated for peptic ulcer at Ulleval Hospital in 1917-39. REFERENCES 1. 2. 3.

Kühlmayer, R., Rokitansky, O. Arch. klin. Chir. 1954, 278, 361. Helsingen, N., Hillestad, L. Ann. Surg. 1956, 143, 173. Hilbe, G., Salzer, G. M., Hussl, H., Kutschera, H. Arch. klin. Chir. 1968, 323, 142. 4. Liavaag, K. Ann. Surg. 1962, 155, 103. 5. Jode, L. R. De Br. J. Surg. 1961, 48, 512. 6. Westlund, K. Acta med. scand. 1963, 174, suppl. 402. 7. Denck, H., Salzer, G. Gastroenterologia, 1957, 88, 94. 8. Maxwell, A. E. Analysing Qualitative Data. London, 1961. 9. Iversen, T. Annual Reports of the Oslo Board of Health 1960-64.

Oslo 1962-66. 10. Causes of Death 1965-69. Central Bureau of Statistics of Norway, Oslo, 1967-71. 11. Kobayashi, S., Prolla, J. C., Kirsner, J. B. Am. J. dig. Dis. 1970, 15, 905. 12. Doll, R., Muir, C., Waterhouse, J. (editors). Cancer Incidence in Five Continents; vol. II. Geneva, 1970. 13. Segi, M., Kurihara, M., Matsuyama, T. Cancer Mortality for Selected Sites in 24 Countries; no. 5 (1964-65). Sendai, 1969.

reported. Introduction

INVESTIGATIONS of blood-group distribution and disease are beset with pitfalls 1,2; and the natural tendency to publish a series when the results are positive and not to do so when they are negative tends to leave the picture unfairly biased. We report here an analysis of ABO groups, Rh groups, and secretor status in patients with salivary tumours in a personal series (A. N.) treated and followed-up through the Christie Hospital or

Withington Hospital. Patients and Methods Most of the

cases are

from the Manchester area, the

rest

coming from the wider area covered by the Manchester Regional Hospital Board in Lancashire, Cheshire, and Westmorland. The investigation started in 1967, and much of the earlier material, from 1947 onwards, could not be used. 407 patients were tested for ABO group, but secretor status was determined in only 276 because this test was not introduced until some years after the start of the ABO studies, and the earlier cases living at a distance from Manchester are followed-up at peripheral clinics where laboratory facilities for assessing the secretor status are not available. Methods ABO grouping was done with standard antisera supplied by the National Blood Transfusion Service, and both cells and serum were tested. Rh testing was done by tube technique with anti-D serum also supplied by the National Blood Transfusion Service. A saline extract of Ulex europceus seeds with a titre of at least 1/16 against group-0 cells were used as an anti-H. Secretor status was determined by mixing antiserum or U. europceus extract with serial dilutions of saliva and by mixing saliva diluted 1/2 with dilutions of antiserum and incubating for 1 hour. Each mixture of serum and saliva was then tested on a tile for ability to agglutinate the appropriate cells. Secretors were considered to be those whose saliva, diluted at least 1/4, neutralised the antiserum or extract. Non-secretors were those whose saliva diluted 1/2 showed no neutralising power against antiserum or extract diluted 1/16. Controls The control series of ABO and Rh groups was obtained