Br. J. Surg. Vol. 62 (1975) 23-25
Atrophic gastritis in gastrectomy specimens J . M. S K I N N E R , P. J . H E E N A N A N D R. WHITEHEAD* SUMMARY
Examination of gastrectomy specimens has shown that atrophic gastritis and intestinal metaplasia are widespread and have the same distribution in cancer of the stomach as in gastric ulcer afecting the body. Their distribution is restricted to the distal part of the stomach in pyloric ulcer. After gastrojejunostomy the distribution is also like that seen in cancer. There is a close association of widespread atrophic gastritis and intestinal metaplasia with the development of cancer and a high cancer rate after stomach operation Jor benign conditions. The similarity of distribution of atrophic gastritis and intestinal metaplasia in the stomach with body ulcer to that in cancer and after gastrojejunostomy points to a higher cancer risk in the stomach containing a body ulcer.
IT has been shown by Stalsberg and Taksdal (1971) that 15 years after patients have been operated on for peptic ulcer the incidence of carcinoma of the stomach is greatly increased. There is a very close relationship between the development of cancer and the presence of atrophic gastritis and intestinal metaplasia(Morson, 1955a; Siurala and Seppala, 1960; Blackburn et al., 1968). It is equally well known that ulcers in different parts of the stomach are associated with a different distribution of gastritis and that gastritis progresses after the ulcer has been treated (Gear et al., 1971). Thus it is important to know how the extent of atrophic gastritis and intestinal metaplasia associated with gastric ulcers in different sites compares with that associated with carcinoma of the stomach and how previous surgery may alter the situation. We have therefore examined gastrectomy specimens from patients operated on for carcinoma and gastric ulcer and paid particular attention to the type and distribution of chronic gastritis and the presence of intestinal metaplasia, the site of the ulcer or cancer and any previous surgery. Materials and methods Stomachs from all gastrectomies performed in the Radcliffe Infirmary, Oxford, from 1970 to 1973 were examined. Gastrectomy specimens prior to 1970 were deemed unsuitable because the sampling was limited and not accurately recorded. Consequently, a prospective study was planned and the stomachs were opened along the greater curve, just anterior to the omentum, and pinned out on to a cork board before being placed into standard 10 per cent formol-saline fixative for 2 days. The position of the ulcer or tumour was noted. Following fixation, blocks of tissue between 2-5 and 3.5 cm in length were taken as follows:
1. Along the entire lesser curve. 2. Alternate blocks along the greater curve but always including the lines of resection. 3. Two blocks from the posterior wall and two from the anterior wall of the body area of the stomach. 4. Through the ulcer or cancer if not already included in blocks 1-3. Sections 4-5 p in thickness were cut and stained by haemotoxylin and eosin, periodic acid-Schiff, Foot’s reticulin and a modified Maxwell’s method (see Whitehead, 1973). One case of sarcoma and one of secondary malignant melanoma were excluded. In each block the presence of superficial gastritis, atrophic gastritis and intestinal metaplasia was noted, as defined in the classification of gastritis of Whitehead (1973). No attempt was made to grade the lesions. For the purposes of this study the pyloric region is defined as that area of stomach in the fixed specimens bounded at its lower end by the duodena1 mucosa and at its upper end by a line drawn between a point 2 cm above the duodenal mucosa on the greater curve and 4 cm on the lesser curve. The pyloric region does of course vary in extent, and pseudopyloric metaplasia is often present on the lesser curve near the margins of ulcers even when they are very high. Our definition consequently is one of convenience, in order to record the information. Ulcers occurring in this zone were termed ‘pyloric ulcers’ and in the rest of the stomach ‘body uIcers’.
Results The results are shown in Table I. Atrophic gastritis and intestinai metaplasia are uncommon in pyloric ulcers and occur almost entirely in the pyloric region as defined, or in the adjacent lesser or greater curve blocks. The less severe lesion of superficial gastritis alone is also seen in the pyloric region in about half the pyloric ulcer cases. In body ulcers the distribution is more widespread and in nearly all cases was seen in all the blocks. This distribution is similar to that seen in cases of cancer. In the cases of gastrectomy following previous gastrojejunostomy for duodenal ulcer (in 3 cases associated with stoma1 ulcer and 3 with pyloric ulcer) the distribution of atrophic gastritis and intestinal metaplasia is again similar to that in cancer.
Discussion Although Stalsberg and Taksdal (1971) found that there was no correlation between the extent of gastritis and metaplasia in gastrectomy specimens * Department of Pathology, Radcliffe Infirmary, Oxford. Requests for reprints to R. Whitehead.
23
J. M. Skinner et al. Table I : DISTRlBUTlON OF ATROPHIC GASTRlTl S, INTESTINAL METAPLASlA GASTRITIS Atrophic gastritis Intestinal metaplasia Ulcer No. of type cases P LC LGC UGC BA B P P LC L G C U G C BA BP 23 23 23 20 19 19 21 21 21 18 18 19 21 Body 3 2 0 0 Pyloric 14 5 4 3 2 0 0 3 3 After gastrojejunostomy Pyloric 3 3 Stornal 3 3 Cancer
21
19
3 3
3 3
3
3
2 3
1 3
3 3
3 3
3 3
3 2
19
19
20
20
18
19
19
18
18
2 3 18
AND SUPERFICIAL Superficial gastritis P
LC
0 8
0 1
1 2
0 0
17
0
0 0
0
LGC U G C 0 2 1 0 0 0 0
BA
BP
1
0
0 0
0 0
1 0
0 0
0
0
0
P = pyloric region; LC = lesser curve above the pyloric region; LGC = lower greater curve; U G C = upper greater curve; BA = anterior wall body rnucosa; BP = posterior wall body mucosa.
when operation was carried out for a benign condition and whether or not the patient subsequently developed cancer, they employed rather limited sampling of the specimens and did not clearly indicate the type of lesion for which the gastrectomy was carried out. Our findings for gastritis and metaplasia in gastric ulcer and cancer are similar to those made by Magnus (1946) and Morson (1955b), but neither of these authors distinguished between pyloric and body ulcers. Our findings also confirm those made by Gear et al. (1971) in a multiple fibre-optic biopsy study. The gastritis is widespread in association with ulcer of the body of the stomach and more localized distally in the stomach with prepyloric ulcer. Gear et al. (1971) found less intestinal metaplasia, but this is explained by the fact that it is often a patchy lesion and the bigger the sample of tissue the more likely it is to be found. The distribution of atrophic gastritis and intestinal metaplasia associated with duodenal ulcer (Morson, 1955a) is identical to the distribution we have shown in prepyloric ulcer. This is perhaps not surprising since clinically they behave in a similar manner (Johnson, 1957). We have not been able to examine ordinary gastrectomy specimens in duodenal ulcer but we have confirmed the presence and distribution of gastritis in a fibre-optic biopsy study (Whitehead, 1974). It is of some importance that in 6 cases of duodenal ulcer treated by gastrojejunostomy and subsequent gastrectomy for recurrent ulcers (stoma1 3 and pyloric 3) the stomach had a pattern of gastritis comparable to that seen in body ulcer. This distribution is the same as that seen in cancer of the stomach. It has been designated type B gastritis (Strickland and Mackay, 1973) to distinguish it from type A, i.e. that which is associated with pernicious anaemia. There is considerable evidence that type B gastritis precedes carcinoma (Siurala and Seppala, 1960; Siurala et al., 1966; Imai et al., 1971; Walker et al., 1971). There is every indication, therefore, that patients with gastric ulcer in the body are more cancer-prone than those with ulcer in the pylorus or duodenum. Whilst surgery in the treatment of peptic ulcer obviously has an established place it would appear that there is room for the investigation of methods of treatment of duodenal and pyloric ulcers which would obviate the change into ‘cancer’ pattern gastritis after 24
operation. Gastro-enterostomy operations seem to be particularly prone to cause widespread atrophic gastritis and intestinal metaplasia (Kobayashi et al., 1970) and our findings support this. Operations which conserve the anatomy of the stomach, e.g. highly selective vagotomy, may prove to have a less deleterious effect in terms of subsequent gastritis. As far as body ulcers are concerned, there is a case in ideal circumstances for careful periodic follow-up by endoscopy and biopsy following operation. Acknowledgements Dr Whitehead is in receipt of a grant reference BECCjl, CC/281 from the British Empire Cancer Campaign for Research for technical assistance. The authors would like to thank Mrs Rachel Hunt for typing the manuscript. References BLACKBURN E. K., CALLENDAR S. T., DAClE J. V., DOLL R., GIRDWOOD R. H., MOLLIN D. L., SARACCl R., STAFFORD J. L., THOMPSON R. B., VARADI s. and WETHERLEY-MEIN G. (1 968) Possible association
between pernicious anaemia and leukaemia: a prospective study of 1625 patients with a note on the very high incidence of stomach cancer. Int. J. Cancer 3, 163-170. GEAR M. w. L., TRUELOVE s. c. and WHITEHEAD R. ( I 971) Gastric ulcer and gastritis. Cut 12, 639-645. IMAI T., KUBO T. and WATANABE H. (1971) Chronic gastritis in Japanese with reference to high incidence of gastric carcinoma. J. Natn. Cancer lnst. 47, 179-195. JOHNSON H. D. (1957) Etiology and classification of gastric ulcers. Gastroenterology 33, 121-123. KOBAYASHI s., PROLLA J. c. and KIRSNER J. B. (1970) Late gastric carcinoma developing after surgery for benign conditions. Endoscopic and histologic studies of the anastomosis and diagnostic problems. Am. J. Dig. Dis. 15, 905-912. MAGNUS H. A. (1946) The pathology of simple gastritis. J. Pathol. Eact. 58, 431-439. MORSON B. c. (1955a) Carcinoma arising from areas of intestinal metaplasia in the gastric mucosa. Er. J. Cancer 9, 377-385. MORSON B. c. (1955b) Intestinal metaplasia of the gastric mucosa. Er. J . Cancer 9, 365-376.
Atrophic gastritis
and SEPPALA K. (1960) Atrophic gastritis as a possible precursor of gastric carcinoma and pernicious anaemia. Results of follow-up examinations. Acta Med. Scand. 166, 455474. SIURALA M., VARIS K. and WILJASALO M. (1966) Studies of patients with atrophic gastritis: a 10-15 year follow-up. Scand. J. Gnstroenterol. 1, 40-48. STALSBERG H. and TAKSDAL s. (1971) Stomach cancer following gastric surgery for benign conditions. Lancet 2, 1175-1 177. SIURALA M.
and MACKAY I. R. (I 973)A reappraisal of the nature and significance of chronic atrophic gastritis. Am. J . Dig. Dis. 18, 426-440. WALKER I. R., STRICKLAND R. G. and UNGAR B. (1971) Simple atrophic gastritis and gastric carcinoma. Cut 12, 906-91 1. WHITEHEAD R. (1973) Mucosal Biopsy of the Gastrointestinal Tract. London, Saunders, p. 2. WHITEHEAD R. (1974) Unpublished observations. STRICKLAND R. G.
25
Atrophic gastritis in gastrectomy specimens J . M. S K I N N E R , P. J . H E E N A N A N D R. WHITEHEAD* SUMMARY
Examination of gastrectomy specimens has shown that atrophic gastritis and intestinal metaplasia are widespread and have the same distribution in cancer of the stomach as in gastric ulcer afecting the body. Their distribution is restricted to the distal part of the stomach in pyloric ulcer. After gastrojejunostomy the distribution is also like that seen in cancer. There is a close association of widespread atrophic gastritis and intestinal metaplasia with the development of cancer and a high cancer rate after stomach operation Jor benign conditions. The similarity of distribution of atrophic gastritis and intestinal metaplasia in the stomach with body ulcer to that in cancer and after gastrojejunostomy points to a higher cancer risk in the stomach containing a body ulcer.
IT has been shown by Stalsberg and Taksdal (1971) that 15 years after patients have been operated on for peptic ulcer the incidence of carcinoma of the stomach is greatly increased. There is a very close relationship between the development of cancer and the presence of atrophic gastritis and intestinal metaplasia(Morson, 1955a; Siurala and Seppala, 1960; Blackburn et al., 1968). It is equally well known that ulcers in different parts of the stomach are associated with a different distribution of gastritis and that gastritis progresses after the ulcer has been treated (Gear et al., 1971). Thus it is important to know how the extent of atrophic gastritis and intestinal metaplasia associated with gastric ulcers in different sites compares with that associated with carcinoma of the stomach and how previous surgery may alter the situation. We have therefore examined gastrectomy specimens from patients operated on for carcinoma and gastric ulcer and paid particular attention to the type and distribution of chronic gastritis and the presence of intestinal metaplasia, the site of the ulcer or cancer and any previous surgery. Materials and methods Stomachs from all gastrectomies performed in the Radcliffe Infirmary, Oxford, from 1970 to 1973 were examined. Gastrectomy specimens prior to 1970 were deemed unsuitable because the sampling was limited and not accurately recorded. Consequently, a prospective study was planned and the stomachs were opened along the greater curve, just anterior to the omentum, and pinned out on to a cork board before being placed into standard 10 per cent formol-saline fixative for 2 days. The position of the ulcer or tumour was noted. Following fixation, blocks of tissue between 2-5 and 3.5 cm in length were taken as follows:
1. Along the entire lesser curve. 2. Alternate blocks along the greater curve but always including the lines of resection. 3. Two blocks from the posterior wall and two from the anterior wall of the body area of the stomach. 4. Through the ulcer or cancer if not already included in blocks 1-3. Sections 4-5 p in thickness were cut and stained by haemotoxylin and eosin, periodic acid-Schiff, Foot’s reticulin and a modified Maxwell’s method (see Whitehead, 1973). One case of sarcoma and one of secondary malignant melanoma were excluded. In each block the presence of superficial gastritis, atrophic gastritis and intestinal metaplasia was noted, as defined in the classification of gastritis of Whitehead (1973). No attempt was made to grade the lesions. For the purposes of this study the pyloric region is defined as that area of stomach in the fixed specimens bounded at its lower end by the duodena1 mucosa and at its upper end by a line drawn between a point 2 cm above the duodenal mucosa on the greater curve and 4 cm on the lesser curve. The pyloric region does of course vary in extent, and pseudopyloric metaplasia is often present on the lesser curve near the margins of ulcers even when they are very high. Our definition consequently is one of convenience, in order to record the information. Ulcers occurring in this zone were termed ‘pyloric ulcers’ and in the rest of the stomach ‘body uIcers’.
Results The results are shown in Table I. Atrophic gastritis and intestinai metaplasia are uncommon in pyloric ulcers and occur almost entirely in the pyloric region as defined, or in the adjacent lesser or greater curve blocks. The less severe lesion of superficial gastritis alone is also seen in the pyloric region in about half the pyloric ulcer cases. In body ulcers the distribution is more widespread and in nearly all cases was seen in all the blocks. This distribution is similar to that seen in cases of cancer. In the cases of gastrectomy following previous gastrojejunostomy for duodenal ulcer (in 3 cases associated with stoma1 ulcer and 3 with pyloric ulcer) the distribution of atrophic gastritis and intestinal metaplasia is again similar to that in cancer.
Discussion Although Stalsberg and Taksdal (1971) found that there was no correlation between the extent of gastritis and metaplasia in gastrectomy specimens * Department of Pathology, Radcliffe Infirmary, Oxford. Requests for reprints to R. Whitehead.
23
J. M. Skinner et al. Table I : DISTRlBUTlON OF ATROPHIC GASTRlTl S, INTESTINAL METAPLASlA GASTRITIS Atrophic gastritis Intestinal metaplasia Ulcer No. of type cases P LC LGC UGC BA B P P LC L G C U G C BA BP 23 23 23 20 19 19 21 21 21 18 18 19 21 Body 3 2 0 0 Pyloric 14 5 4 3 2 0 0 3 3 After gastrojejunostomy Pyloric 3 3 Stornal 3 3 Cancer
21
19
3 3
3 3
3
3
2 3
1 3
3 3
3 3
3 3
3 2
19
19
20
20
18
19
19
18
18
2 3 18
AND SUPERFICIAL Superficial gastritis P
LC
0 8
0 1
1 2
0 0
17
0
0 0
0
LGC U G C 0 2 1 0 0 0 0
BA
BP
1
0
0 0
0 0
1 0
0 0
0
0
0
P = pyloric region; LC = lesser curve above the pyloric region; LGC = lower greater curve; U G C = upper greater curve; BA = anterior wall body rnucosa; BP = posterior wall body mucosa.
when operation was carried out for a benign condition and whether or not the patient subsequently developed cancer, they employed rather limited sampling of the specimens and did not clearly indicate the type of lesion for which the gastrectomy was carried out. Our findings for gastritis and metaplasia in gastric ulcer and cancer are similar to those made by Magnus (1946) and Morson (1955b), but neither of these authors distinguished between pyloric and body ulcers. Our findings also confirm those made by Gear et al. (1971) in a multiple fibre-optic biopsy study. The gastritis is widespread in association with ulcer of the body of the stomach and more localized distally in the stomach with prepyloric ulcer. Gear et al. (1971) found less intestinal metaplasia, but this is explained by the fact that it is often a patchy lesion and the bigger the sample of tissue the more likely it is to be found. The distribution of atrophic gastritis and intestinal metaplasia associated with duodenal ulcer (Morson, 1955a) is identical to the distribution we have shown in prepyloric ulcer. This is perhaps not surprising since clinically they behave in a similar manner (Johnson, 1957). We have not been able to examine ordinary gastrectomy specimens in duodenal ulcer but we have confirmed the presence and distribution of gastritis in a fibre-optic biopsy study (Whitehead, 1974). It is of some importance that in 6 cases of duodenal ulcer treated by gastrojejunostomy and subsequent gastrectomy for recurrent ulcers (stoma1 3 and pyloric 3) the stomach had a pattern of gastritis comparable to that seen in body ulcer. This distribution is the same as that seen in cancer of the stomach. It has been designated type B gastritis (Strickland and Mackay, 1973) to distinguish it from type A, i.e. that which is associated with pernicious anaemia. There is considerable evidence that type B gastritis precedes carcinoma (Siurala and Seppala, 1960; Siurala et al., 1966; Imai et al., 1971; Walker et al., 1971). There is every indication, therefore, that patients with gastric ulcer in the body are more cancer-prone than those with ulcer in the pylorus or duodenum. Whilst surgery in the treatment of peptic ulcer obviously has an established place it would appear that there is room for the investigation of methods of treatment of duodenal and pyloric ulcers which would obviate the change into ‘cancer’ pattern gastritis after 24
operation. Gastro-enterostomy operations seem to be particularly prone to cause widespread atrophic gastritis and intestinal metaplasia (Kobayashi et al., 1970) and our findings support this. Operations which conserve the anatomy of the stomach, e.g. highly selective vagotomy, may prove to have a less deleterious effect in terms of subsequent gastritis. As far as body ulcers are concerned, there is a case in ideal circumstances for careful periodic follow-up by endoscopy and biopsy following operation. Acknowledgements Dr Whitehead is in receipt of a grant reference BECCjl, CC/281 from the British Empire Cancer Campaign for Research for technical assistance. The authors would like to thank Mrs Rachel Hunt for typing the manuscript. References BLACKBURN E. K., CALLENDAR S. T., DAClE J. V., DOLL R., GIRDWOOD R. H., MOLLIN D. L., SARACCl R., STAFFORD J. L., THOMPSON R. B., VARADI s. and WETHERLEY-MEIN G. (1 968) Possible association
between pernicious anaemia and leukaemia: a prospective study of 1625 patients with a note on the very high incidence of stomach cancer. Int. J. Cancer 3, 163-170. GEAR M. w. L., TRUELOVE s. c. and WHITEHEAD R. ( I 971) Gastric ulcer and gastritis. Cut 12, 639-645. IMAI T., KUBO T. and WATANABE H. (1971) Chronic gastritis in Japanese with reference to high incidence of gastric carcinoma. J. Natn. Cancer lnst. 47, 179-195. JOHNSON H. D. (1957) Etiology and classification of gastric ulcers. Gastroenterology 33, 121-123. KOBAYASHI s., PROLLA J. c. and KIRSNER J. B. (1970) Late gastric carcinoma developing after surgery for benign conditions. Endoscopic and histologic studies of the anastomosis and diagnostic problems. Am. J. Dig. Dis. 15, 905-912. MAGNUS H. A. (1946) The pathology of simple gastritis. J. Pathol. Eact. 58, 431-439. MORSON B. c. (1955a) Carcinoma arising from areas of intestinal metaplasia in the gastric mucosa. Er. J. Cancer 9, 377-385. MORSON B. c. (1955b) Intestinal metaplasia of the gastric mucosa. Er. J . Cancer 9, 365-376.
Atrophic gastritis
and SEPPALA K. (1960) Atrophic gastritis as a possible precursor of gastric carcinoma and pernicious anaemia. Results of follow-up examinations. Acta Med. Scand. 166, 455474. SIURALA M., VARIS K. and WILJASALO M. (1966) Studies of patients with atrophic gastritis: a 10-15 year follow-up. Scand. J. Gnstroenterol. 1, 40-48. STALSBERG H. and TAKSDAL s. (1971) Stomach cancer following gastric surgery for benign conditions. Lancet 2, 1175-1 177. SIURALA M.
and MACKAY I. R. (I 973)A reappraisal of the nature and significance of chronic atrophic gastritis. Am. J . Dig. Dis. 18, 426-440. WALKER I. R., STRICKLAND R. G. and UNGAR B. (1971) Simple atrophic gastritis and gastric carcinoma. Cut 12, 906-91 1. WHITEHEAD R. (1973) Mucosal Biopsy of the Gastrointestinal Tract. London, Saunders, p. 2. WHITEHEAD R. (1974) Unpublished observations. STRICKLAND R. G.
25
