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Relation between early and advanced gastric cancer
Relation Between Early and Advanced Gastric Cancer
Ulf ahman, MD, Stockholm, Sweden Sverre Em&, MD, Stockholm, Sweden Carlos Rubio, MD, Stockholm, Sweden
Gastric adenocarcinoma, although its incidence is slowly decreasing in most Western countries [1,2], still constitutes a serious problem due to its extremely poor prognosis. When diagnosed and treated in the early stage, however, it is highly curable. This form of gastric carcinoma is known as early gastric cancer and is histologically defined as gastric adenocarcinoma confined to the mucosa or the mucosa and submucosa, regardless of the presence of lymph node metastases [3]. Early gastric cancer will be discussed in relation to more deeply invading carcinomas, designated herein as advanced gastric cancer. The long-term survival rate in a group of patients with gastric carcinoma depends largely on the share of early gastric cancer in the series. It is therefore necessary to define this share, usually as the fraction of early gastric cancer among all resected cases. Japanese authors report a 30 to 40 percent incidence of early gastric cancer in resected specimens, whereas non-Japanese investigators report appreciably smaller rates, commonly 5 to 10 percent. One explanation for this difference could be the high incidence of gastric cancer in Japan, which has initiated vigorous attempts to detect tumors in an early stage. The ultimate attempt at early diagnosis, screening of asymptomatic subjects for gastric cancer, has been successfully performed in Japan for more than 2 decades. Mass screening accounts for 40 percent of the early gastric cancer diagnosed in Japan [4]. In mass survey patients, the 5 year survival rate is 50 to 65 percent, possibly due to a 35 to 45 percentage of early gastric cancer among cancers detected; in symptomatic Japanese patients the corresponding rates are 10 to 30 and 23 to 25 percent, respectively
[51. From the Departments of Surgery and Pathology, Karolinska Hospital, Stockholm, Sweden. Requeslsforreprirltsshcufdbe addreWdtoulf6hman,fvD.DqMment of Surgery.Karolinska Hospital, S-104 01 Stockholm, Sweden.
Volume 140. SetHember 1980
Another conceivable reason for difference in the incidence rate of early gastric cancer is a different biologic behavior of Japanese gastric cancer. Current evidence, however, suggests that Japanese and non-Japanese gastric cancers do not differ in nature [6]. Our interest should hence focus on diagnostic approaches, particularly methods of early diagnosis. We analyzed our recent material (1976 to 1979) on gastric adenocarcinoma with special emphasis on the occurrence of early gastric cancer. Comparing this material with a previous gastric cancer series (1944 to 1963) collected from the same geographic area [7,8] disclosed a significantly increased incidence of early gastric cancer. Possible reasons for the increase and implications for long-term results will be discussed. Material
and Methods
During a 3.5 year period, from January 1976 to June 1979, our department of surgery cared for 75 consecutive inpatients with a histologic diagnosis of gastric adenocarcinema. Fifty-nine percent were males. A preponderance of the patients were in the 7 and 8th decades of life (Figure 1). Forty patients (53 percent) underwent operation with a “curative” intent, defined as the surgeon’s opinion that all grossly neoplastic tissue had been removed. Total gastrectomy was performed in 21 patients and partial gastrectomy in 19. Five patients had “palliative” gastric resection, and 30 patients had only an exploratory operation. The case histories were scrutinized concerning diagnostic procedures, with special emphasis on possible differences in the diagnostic approach in the two periods. Endoscopic biopsies, gastrectomy specimens, biopsies from unresectable tumors and autopsy specimens were examined histologically. When early gastric cancer was suspected, multiple tissue samples were obtained from the resected specimen. The postoperative observation time and the
351
Ohman et al
(n=ll)
2
I\ \
I .6 SC %
AGC cur.op. in=291
AGE, YEARS
Figure 1. Age dktributlon of 75 patients ( 44 men and 3 1 women) wtth gas&k carckoma ( 1976 to 1979).
( YEARS AFTER YEARS AFTER
251%
EGC
\:/I7 1
2
3
OP. IEGC+AGC mop.) DIAGN. (AGC non-ml
Figure 3. Survival fates In 75 consecutive pat/en& wtth gasbk camkoma (1976 k 1979). AGC = advancedgasmc cancer; EGC = ear@ gas&k cancer.
20. p < ,001 15.
10
I
5.
n. 1944-63
191.5-n
YEAR OF OPERATION
Ftgure 2. Percent of ear/y gastrk cancers ( EGC) in stomach specfmens resected for gastric carcinoma in 1944 to 1963 and 1976 to 1979.
survivalperiodweredeterminedin eachof the 75patients. For the evaluationof differencesbetweenthe two series, chi-squareanalysiswith Yates’ correctionand Fisher’s exactprobabilitytest were used. Results Eleven patients, or 15 percent of all patients with a diagnosis of gastric carcinoma, had early gastric cancer. Calculated on another basis, 24 percent of 45 resected specimens were classified as early gastric cancer and 76 percent as advanced gastric cancer. Thus early gastric cancer constituted one fourth of all specimens resected for carcinoma. The patients with early gastric cancer were aged 39 to 73 years (median 62); seven were men. Two of these patients
352
had previously undergone partial gastrectomy for peptic ulcer. All of the tumors were removed with the intention of cure; six total and five partial gastrectomies were performed. In the earlier series (1944 to 1963), there were 23 patients with early gastric cancer among 378 cases of resected gastric carcinoma and 7 patients with early gastric cancer in 21 ulcer-cancer cases, that is, a total of 30 early gastric cancers (7.5 percent) in 399 resected specimens (Figure 2). The difference in this incidence rate and our recent result is highly significant (chi-square = 11.88; p
The American Journal ol Surgery
Earlyand AdvancedGastricCancer
Twenty-nine patients were “curatively” operated on for advanced gastric cancer; the mortality within 1 month of operation was 2 of 15 after total gastrectomy and 1 of 14 after partial gastrectomy. The survival rate 1 to 3 years postoperatively is shown in Figure 3. We attempted to compare survival rates after curative operations for early and advanced gastric cancer. After 6 months’ observation, all 10 patients with early gastric cancer were alive, while 8 of 26 patients with advanced gastric cancer had died; the difference is probably significant (one-tailed exact p = 0.05). The number of patients observed for 1 and 2 years is too small for statistical evaluation. The 5 year survival rates in our 1944 to 1963 series will be mentioned for comparison. Of 30 resected early gastric cancer patients, 21(70 percent) survived 5 years, while of 369 patients operated on for advanced gastric cancer, only 57 (15 percent) survived 5 years. In 2 of the 11 patients with early gastric cancer in the present study, carcinoma arised in the gastric “stump.” The patients had undergone partial gastrectomy 23 and 33 years earlier because of benign gastric lesions. Both tumors were resectable, and the patients are alive and well 14 and 26 months, respectively, after operation. Of 64 patients with advanced gastric cancer, 10 had gastric stump carcinoma. The tumors were diagnosed 18 to 41 years (median 23) after partial gastrectomy for peptic ulcer disease. Only three of the tumors were resectable, and all 10 patients have died a median of 2 months after diagnosis. Comments The recent 15 percent incidence of early gastric cancer among patients with gastric carcinoma compares favorably with contemporary reviews. The increase from 7.5 to 24 percent in the incidence of early gastric cancer among resected specimens at our hospital is a significant improvement and appears to be due to the use of gastroscopy and biopsy. Two large Japanese series report an average incidence of early gastric cancer of 18 percent [9,lO]; however, both reports stress a substantial increase over successive periods of time, with rates of 36 and 28 percent in the late 1960s. In North American gastric cancer series the average incidence of early gastric cancer is 3 to 6 percent [ll-141. In a South American series the average rate was 9 percent, which increased during recent years to 30 percent [15]. In a report from Australia, 5 (19 percent) of 26 patients with gastric carcinoma who underwent endoscopy had early gastric cancer [16].
Volume 140, September 1980
In a collective review from Sweden, however, only 5 percent of 210 patients with gastric cancer who underwent gastroscopy had early gastric cancer [I 71. A report from Canada describes an aggressive and multifaceted diagnostic approach that resulted in the detection of five cases of early gastric cancer in 1 year, whereas no case was diagnosed in the preceding 10 years [18]. European investigators report rather uniform incidence rates of early gastric cancer, often 5 to 7 percent [7,19-241. However, both lower (2 percent [6]) and higher rates (10 to 12 percent [3,4,25-271) have been reported. The crucial point is that several reports from Europe, including the present one, emphasize that the incidence of early gastric cancer is continuously increasing with time [6,19,21,23,28]. These reports suggest that the incidence in Europe is now greater than 10 percent and probably about 15 to 20 percent. This implicates an ongoing evolution parallel to that in Japan, although lagging some 15 years behind, since in that country a 20 percent incidence of early gastric cancer was noted in the mid-1960s [9,10]. Recent data imply, however, that the gastroscopic yield of early gastric cancer in Europe has made no progress during the 1970s. Among more than 300,000 gastroscopic examinations performed all around Europe in 1968 to 1973, only 1,170 early gastric cancer’s were diagnosed, that is, 6.3 percent of all gastric carcinomas [29]. The inquiry was repeated 3 years later, covering the 1974 to 1977 period and more than 550,000 gastroscopies; 1,280 cases of early gastric cancer were discovered, giving the same rate of 6.3 percent [30]. The prerequisite for discovery of an early gastric cancer in Sweden, and in most other European countries as well, is a patient presenting with symptoms referable to gastric disease. Among 649 patients from Europe with early gastric cancer, 94 percent presented with subjective complaints, mainly uncharacteristic abdominal pain [28]. Several workers emphasize that patients with early gastric cancer often have ulcer-like symptoms [31,32]; these symptoms may disappear after medical treatment such as cimetidine therapy, thereby delaying the correct diagnosis [33]. Screening of asymptomatic subjects for gastric carcinoma has hitherto not been routinely used or considered feasible outside Japan [12,34,35]. The duration of the presymptomatic stage in gastric carcinoma is not known, nor has it been conclusively demonstrated that early gastric cancer, if left untreated, invariably proceeds to advanced gastric cancer. Since current evidence favors the
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ijhman et al
hypothesis that most early gastric cancerous tumors are, in fact, early stages of advanced gastric cancer [3], we believe, with support from the present findings, that a high index of suspicion and an aggressive diagnostic approach in symptomatic patients will result in the detection of more early gastric cancer. Our 11 patients operated on for early gastric cancer are currently alive and well. The number of patients is small and the observation period short. Our previous experience with early gastric cancer [7,8], however, suggests that a 5 year survival rate of about 70 percent may be hoped for. Some optimism is also derived from other European reports of 60 to 75 percent 5 year survival [3,19]. Several investigators report experiences similar to ours, that is, that all patients with early gastric cancer surviving postoperatively are alive and well, although long-term survival rates are still a matter of speculation [25-271. The results of treatment in Japan appear extremely gratifying. Two Japanese reports, comprising more than 1,000 patients operated on for early gastric cancer, account for 99.5 to 100.0 percent 5 year survival rates after operation for mucosal cancer and 95.1 to 95.3 percent when submucosal invasion has occurred [36,37]. If the present report offers hope for long-term cure in patients with early gastric cancer, it also confirms the dismal prognosis in advanced gastric cancer. All patients who have undergone exploratory operation or palliative resection for advanced gastric cancer have died. Of 12 patients operated on “curatively” for advanced gastric cancer and observed for more than 3 years, only 2 were alive; thus a majority of the curative operations for advanced gastric cancer were, in retrospect, palliative. This disappointing result is no improvement over the 15 percent 5 year survival rate in our 1944 to 1963 series. In fact, the treatment results in patients with advanced gastric cancer have been unchanged during the last 30 to 40 years [11,12,14,38-401. Twelve patients in the present series, that is, 16 percent of the patients with gastric cancer, had gastric stump carcinoma. This rate indicates that stump cancer is a serious problem and raises the question of regular gastroscopic check-ups starting 10 to 15 years after partial gastrectomy for peptic ulcer [41-45]. Although the number of patients with stump cancer is small in the present series, the outcome in this group of patients seems to confii the miserable prognosis for advanced gastric cancer and the confidence in the prognosis for early gastric cancer. Patients with resected stomachs may constitute a fruitful field in the search for early gastric cancer. In a recent report, 108 patients with resected stom-
354
achs were reoperated on for various reasons including malignancy. At reoperation, 33 advanced and 23 early gastric cancers were found; 1 advanced and 7 early gastric cancers were not recognized preoperatively despite gastroscopy and biopsy [46]. In conclusion, the present analysis demonstrates that early gastric cancer can be discovered in a significant number of patients and suggests that gastroscopy and biopsy are the basis for this improvement in the management of patients with gastric carcinoma. Since patients with early gastric cancer have a substantially better long-term survival rate than those with advanced gastric cancer, increased diagnosis of early gastric cancer can improve the cure rates in future series of patients operated on for gastric cancer, albeit not to the levels cited in Japanese reports. The present analysis confirms the dismal prognosis for advanced gastric cancer and documents that no improvement in the treatment results has occurred since the 1940s. Screening of asymptomatic patients for gastric carcinoma is not feasible in this country at present. However, the risk of cancer after partial gastrectomy for benign disease makes screening of this selected group of patients desirable. Summary Of 75 consecutive inpatients with gastric carcinoma during a 3.5 year period, 40 underwent operation with the intention of cure, 5 had palliative gastric resection and 30 had exploratory celiotomy only. Early gastric cancer was found in 11 cases, that is, 15 percent of patients with ‘gastric carcinoma or 24 percent of patients subjected to gastrectomy. The patients with early gastric cancer were operated on with the intention of cure. Comparison with a previous series from the same geographic area shows that the ratio between early gastric cancer and all gastric cancer increased significantly. This improvement in the management of patients with gastric carcinoma can be ascribed to the use of gastroscopy and biopsy. The survival rates in patients with early gastric cancer are excellent. The prognosis in patients with advanced gastric cancer, on the other hand, is poor and has remained so for the last 30 to 40 years. Twelve of the 75 patients had gastric stump carcinoma; 2 of these were early gastric cancer. Screening of asymptomatic patients for gastric cancer is at present an impossible task in most Western countries, but the risk of cancer after partial gastrectomy for benign lesions makes screening desirable in this selected group of patients.
The Amerkan Journal ol Surgery
Early and Advanced
References 1. Stevenson JK. Gastric carcinoma. In: Surgery of the stomach and duodenum, 2nd ed (Harkins HN, Nyhus LM, eds). Boston: Little, Brown, 1989:387. 2. Menguy RB. Gastrjc cancer. In: Principles of surgery, 2nd ed (Schwartz SI. ed). New York: McGraw-Hill, 1974:1079. 3. Johansen AA. Early gastric cancer. Curr Top Pathol 1978; 83:l. 4. BLittner D, Pichlmayr R, Seifert E. Das Magenfruhcarcinom. Chirurg 1975;48:85. 5. Kaneko E, Nakamura T, Umeda N, Fujino M, Niwa H. Outcome of gastric carcinoma detected by gastric mass survey in Japan. Gut 1977;18:828. 8. Evans DMD, Craven JL, Murphy F, Cleary BK. Comparison of early gastric cancer in Britain and Japan. Gut 1978; 19: 1. 7. 6hman U, Wetterfors J, Moberg A. Primary gastric cancer and its prognosis. Acta Chir Stand 1972; 138:378. 8. iihman U, Wetterfors J, Moberg A. Ulcer-cancer of the stomach. Acta Chir Stand 1972;138:391. 9. Muto M, Maki T, Majlma S, Yamaguchi I. Improvement in the end-results of surgical treatment of gastric cancer. Surgery 1988;83:229. 10. Nagayo T, Yokoyama H. Gastric cancer. Early phases and diagnostic features. JAMA 1974;228:888. 11. Cady B, Ramsden DA, Stein A, Haggitt RC. Gastric cancer. Contemporary aspects. Am J Surg 1977; 133:423. 12. Buchholtz TW, Welch CE, Malt RA. Clinical correlates of resectability and survival in gastric carcinoma. Ann Surg 1978;188:711. 13. Olearchyk AS. Gastric carcinoma. A critical review of 243 cases. Am J Gastroenterol 1978;70:25. 14. Adashek K, Sanger J, Longmire WP Jr. Cancer of the stomach. Review of consecutive ten year intervals. Ann Surg 1979; 189:8. 15. Paulino F, Roselli A. Early gastric cancer; report of twenty-five cases. Surgery 1979;85: 17 1. 18. Fevre DI, Qeen PHR, Barratl PJ, Nagy GS. Review of five cases of early gastric carcinoma. Gut-1978; 17:41. 17. Ghman U. Replik angiende prognosen vid ventrikelcancer. Liikartidningen 1978;73:2539. 18. Qizilbash A, Harnarlne C, Castelli M. Early gastric carcinoma. Value of combined use of endoscopy, air contrast x-ray films, cytology, and multiple biopsy specimens. Arch Pathol Lab Med 1977;101:810. 19. Dobroschke J, Schwemmle K, Hermanek P, Rosch W. Therapie-ecgebnisse beim Magenfruhkarzinom. Dtsch Med Wochenschr 1978;101:1409. 20. GloomF. Das Oberfltichsnkarzinom (Friihkarzinom) des Magens. Schweiz Med Wochenschr 1978; 108:2 1. 21. Machado G, Davies JD, Tudway AJC, Salmon PR, Read AE. Superficial carcinoma of the stomach. Br Med J 1978; 2~77. 22. Grundmann E. Early gastric cancer-today. Pathol Res Pratt 1978;18=7. 23. Schlag P, Merkle P, Wetzel S, Radl W, Meister H, Herfarth C. Diagnostische und therapeutische Aspekte des Magenfruhkarzinoms. Dtsch Med Wochenschr 1978:103:773. 24. Frenning B. Cancer ventriculi. L&artidningen,_l9~9;78:218. 25. Br6mster D, Elffcrs LE, EngqvistA, Reichard H, Dst A. Ytlig (eller tidig) ventrikelcancer. Redovisning av arton opererade och efterundersokta fall. Lakartidningen 1_977;74:2748. 28. Bromster D, Elffors LE, Engqvist A, Ost A, Reichard H. Superficial (or early) gastric cancer. A report of 18 cases with a
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follow-up. Akt Gastrologie 1978;7:9. 27. Reisslgl K, Schwamberger K, Troyer E. Magenfruhkarzinom; Diagnostik, Therapie, Frijh und Spatergebnisse. Diagnostik 1978;11:154. 28. Miller G. Froelicher P, Kaufmann M, Maurer W. Ten years’ endoscopic diagnosis of early gastric cancer in Europe. J Cancer Res Cltn Oncol 1979;93:99. 29. Miller G, Kaufmann M. Das Magenfnihkarzinom in Europa. 1170 Falle aus den Jahren 1988-1973. Dtsch Med Wochenschr 1975:100:1948. 30. Miller G, Froelicher P. Das, Magenfruhkarzinom in Europa. Resultate einer Umfrage von 1978. Z Gastroenterol 1978; 18878. 31. Mennisken C. Udewald C, Hupen M, Manegold BC. Operative Ergebnisse beim Magenfruhkarzinom. Akt Gastrologie 1977;8:497. 32. Kriedemann E, Mateev B. Gutz HJ, Wildner GP. Klinische und radiologische Erschsinungsformen des Magenfriihkarzinoms in Gegenuberstellung mit endoskopischen Untersuchungsergebnissen und Operationsbefunden (Eine Analyse von 40 eigenen Fallen). Arch Geschwulstforsch 1979;49:29. 33. Taylor RH, Lovell D, Menzies-Gow N, La Brooy SJ, Misiewicz JJ. Misleading response of malignant gastric ulcers to cimetidine. Lancet 1978;1:888. 34. Morrissey JF. The diagnosis of early gastric cancer. A survey of experience in the United States. Gastrointest Endosc 1978;23:13. 35. Editorial. Screening for gastric cancer in the West. Lancet 1978;1:1023. 38. Hayashida T, Kidokoro S. End results of early gastric cancer collected from 22 institutions. Stom lntest (Japan) 1989; 4:1077. 37. Takasugi T, Sasagawa M, Yamada T, Ichikawa H, Kitaoka H, Hirota T. A study on end results of early gastric cancer. Analysis with actuarial survival rate. Stom lntest (Japan) 1977;12:933. 38. Lundh G, Burn JI, Kolig G, et al. A co-operative international study of gastric cancer. Ann R Coll Surg Engl 1974;54: 219. 39. Berndt H, Dietrich D, Gregor M, Hansche G, Hansche R, Witt K. Btisartige NeubiMungen des Magens in Berlin, Hauptstadt’ der DDR, von 1955 bis 1973 (Eine analyse der Erfassungsund Behandlungssituation). Arch Geschwulstforsch 1978; 48:15. 40. DuPont JB Jr, Lee JR, Burton GR, Cohn I Jr. Adenocarcinoma of the stomach; review of 1497 cases. Cancer 1978; 41:941. 41. Domellof L, Eriksson S, Janunger K-G. Late precancerous changes and carcinoma of the gastric stump after Billroth I resection. Am J Surg 1976;132:28. 42. Dornellof L, Eriksson S, Janunger KG. Carcinoma and possible precancerous changes of the gastric stump after Billroth II resection. Gastroenterology 1977;73:482. 43. Schrumpf E, Stadaas J, Myren J, Serck-Hanssen A, Aune S, Osnes M. Mucosal changes in the gastric stump 20-25 years after partial gastrectomy. Lancet 1977;2:487. 44. Eberlein TJ. Lorenzo FV, Webster MW. Gastric carcinoma following operation for peptic ulcer disease. Ann Surg 1978;187:251. 45. Ewetth S, Bergstrand 0, Hellers 0, 6s.t A. The incidence of carcinoma in the gastric remnant after resection for benign ulcer disease. A& Chir Stand (Suppl) 1978;482:2. 48. Eriksson S, Liedberg G. Kirurgisk behandling av gastrit. L&kartidningen 1978;75:4897.
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Ulf ahman, MD, Stockholm, Sweden Sverre Em&, MD, Stockholm, Sweden Carlos Rubio, MD, Stockholm, Sweden
Gastric adenocarcinoma, although its incidence is slowly decreasing in most Western countries [1,2], still constitutes a serious problem due to its extremely poor prognosis. When diagnosed and treated in the early stage, however, it is highly curable. This form of gastric carcinoma is known as early gastric cancer and is histologically defined as gastric adenocarcinoma confined to the mucosa or the mucosa and submucosa, regardless of the presence of lymph node metastases [3]. Early gastric cancer will be discussed in relation to more deeply invading carcinomas, designated herein as advanced gastric cancer. The long-term survival rate in a group of patients with gastric carcinoma depends largely on the share of early gastric cancer in the series. It is therefore necessary to define this share, usually as the fraction of early gastric cancer among all resected cases. Japanese authors report a 30 to 40 percent incidence of early gastric cancer in resected specimens, whereas non-Japanese investigators report appreciably smaller rates, commonly 5 to 10 percent. One explanation for this difference could be the high incidence of gastric cancer in Japan, which has initiated vigorous attempts to detect tumors in an early stage. The ultimate attempt at early diagnosis, screening of asymptomatic subjects for gastric cancer, has been successfully performed in Japan for more than 2 decades. Mass screening accounts for 40 percent of the early gastric cancer diagnosed in Japan [4]. In mass survey patients, the 5 year survival rate is 50 to 65 percent, possibly due to a 35 to 45 percentage of early gastric cancer among cancers detected; in symptomatic Japanese patients the corresponding rates are 10 to 30 and 23 to 25 percent, respectively
[51. From the Departments of Surgery and Pathology, Karolinska Hospital, Stockholm, Sweden. Requeslsforreprirltsshcufdbe addreWdtoulf6hman,fvD.DqMment of Surgery.Karolinska Hospital, S-104 01 Stockholm, Sweden.
Volume 140. SetHember 1980
Another conceivable reason for difference in the incidence rate of early gastric cancer is a different biologic behavior of Japanese gastric cancer. Current evidence, however, suggests that Japanese and non-Japanese gastric cancers do not differ in nature [6]. Our interest should hence focus on diagnostic approaches, particularly methods of early diagnosis. We analyzed our recent material (1976 to 1979) on gastric adenocarcinoma with special emphasis on the occurrence of early gastric cancer. Comparing this material with a previous gastric cancer series (1944 to 1963) collected from the same geographic area [7,8] disclosed a significantly increased incidence of early gastric cancer. Possible reasons for the increase and implications for long-term results will be discussed. Material
and Methods
During a 3.5 year period, from January 1976 to June 1979, our department of surgery cared for 75 consecutive inpatients with a histologic diagnosis of gastric adenocarcinema. Fifty-nine percent were males. A preponderance of the patients were in the 7 and 8th decades of life (Figure 1). Forty patients (53 percent) underwent operation with a “curative” intent, defined as the surgeon’s opinion that all grossly neoplastic tissue had been removed. Total gastrectomy was performed in 21 patients and partial gastrectomy in 19. Five patients had “palliative” gastric resection, and 30 patients had only an exploratory operation. The case histories were scrutinized concerning diagnostic procedures, with special emphasis on possible differences in the diagnostic approach in the two periods. Endoscopic biopsies, gastrectomy specimens, biopsies from unresectable tumors and autopsy specimens were examined histologically. When early gastric cancer was suspected, multiple tissue samples were obtained from the resected specimen. The postoperative observation time and the
351
Ohman et al
(n=ll)
2
I\ \
I .6 SC %
AGC cur.op. in=291
AGE, YEARS
Figure 1. Age dktributlon of 75 patients ( 44 men and 3 1 women) wtth gas&k carckoma ( 1976 to 1979).
( YEARS AFTER YEARS AFTER
251%
EGC
\:/I7 1
2
3
OP. IEGC+AGC mop.) DIAGN. (AGC non-ml
Figure 3. Survival fates In 75 consecutive pat/en& wtth gasbk camkoma (1976 k 1979). AGC = advancedgasmc cancer; EGC = ear@ gas&k cancer.
20. p < ,001 15.
10
I
5.
n. 1944-63
191.5-n
YEAR OF OPERATION
Ftgure 2. Percent of ear/y gastrk cancers ( EGC) in stomach specfmens resected for gastric carcinoma in 1944 to 1963 and 1976 to 1979.
survivalperiodweredeterminedin eachof the 75patients. For the evaluationof differencesbetweenthe two series, chi-squareanalysiswith Yates’ correctionand Fisher’s exactprobabilitytest were used. Results Eleven patients, or 15 percent of all patients with a diagnosis of gastric carcinoma, had early gastric cancer. Calculated on another basis, 24 percent of 45 resected specimens were classified as early gastric cancer and 76 percent as advanced gastric cancer. Thus early gastric cancer constituted one fourth of all specimens resected for carcinoma. The patients with early gastric cancer were aged 39 to 73 years (median 62); seven were men. Two of these patients
352
had previously undergone partial gastrectomy for peptic ulcer. All of the tumors were removed with the intention of cure; six total and five partial gastrectomies were performed. In the earlier series (1944 to 1963), there were 23 patients with early gastric cancer among 378 cases of resected gastric carcinoma and 7 patients with early gastric cancer in 21 ulcer-cancer cases, that is, a total of 30 early gastric cancers (7.5 percent) in 399 resected specimens (Figure 2). The difference in this incidence rate and our recent result is highly significant (chi-square = 11.88; p
The American Journal ol Surgery
Earlyand AdvancedGastricCancer
Twenty-nine patients were “curatively” operated on for advanced gastric cancer; the mortality within 1 month of operation was 2 of 15 after total gastrectomy and 1 of 14 after partial gastrectomy. The survival rate 1 to 3 years postoperatively is shown in Figure 3. We attempted to compare survival rates after curative operations for early and advanced gastric cancer. After 6 months’ observation, all 10 patients with early gastric cancer were alive, while 8 of 26 patients with advanced gastric cancer had died; the difference is probably significant (one-tailed exact p = 0.05). The number of patients observed for 1 and 2 years is too small for statistical evaluation. The 5 year survival rates in our 1944 to 1963 series will be mentioned for comparison. Of 30 resected early gastric cancer patients, 21(70 percent) survived 5 years, while of 369 patients operated on for advanced gastric cancer, only 57 (15 percent) survived 5 years. In 2 of the 11 patients with early gastric cancer in the present study, carcinoma arised in the gastric “stump.” The patients had undergone partial gastrectomy 23 and 33 years earlier because of benign gastric lesions. Both tumors were resectable, and the patients are alive and well 14 and 26 months, respectively, after operation. Of 64 patients with advanced gastric cancer, 10 had gastric stump carcinoma. The tumors were diagnosed 18 to 41 years (median 23) after partial gastrectomy for peptic ulcer disease. Only three of the tumors were resectable, and all 10 patients have died a median of 2 months after diagnosis. Comments The recent 15 percent incidence of early gastric cancer among patients with gastric carcinoma compares favorably with contemporary reviews. The increase from 7.5 to 24 percent in the incidence of early gastric cancer among resected specimens at our hospital is a significant improvement and appears to be due to the use of gastroscopy and biopsy. Two large Japanese series report an average incidence of early gastric cancer of 18 percent [9,lO]; however, both reports stress a substantial increase over successive periods of time, with rates of 36 and 28 percent in the late 1960s. In North American gastric cancer series the average incidence of early gastric cancer is 3 to 6 percent [ll-141. In a South American series the average rate was 9 percent, which increased during recent years to 30 percent [15]. In a report from Australia, 5 (19 percent) of 26 patients with gastric carcinoma who underwent endoscopy had early gastric cancer [16].
Volume 140, September 1980
In a collective review from Sweden, however, only 5 percent of 210 patients with gastric cancer who underwent gastroscopy had early gastric cancer [I 71. A report from Canada describes an aggressive and multifaceted diagnostic approach that resulted in the detection of five cases of early gastric cancer in 1 year, whereas no case was diagnosed in the preceding 10 years [18]. European investigators report rather uniform incidence rates of early gastric cancer, often 5 to 7 percent [7,19-241. However, both lower (2 percent [6]) and higher rates (10 to 12 percent [3,4,25-271) have been reported. The crucial point is that several reports from Europe, including the present one, emphasize that the incidence of early gastric cancer is continuously increasing with time [6,19,21,23,28]. These reports suggest that the incidence in Europe is now greater than 10 percent and probably about 15 to 20 percent. This implicates an ongoing evolution parallel to that in Japan, although lagging some 15 years behind, since in that country a 20 percent incidence of early gastric cancer was noted in the mid-1960s [9,10]. Recent data imply, however, that the gastroscopic yield of early gastric cancer in Europe has made no progress during the 1970s. Among more than 300,000 gastroscopic examinations performed all around Europe in 1968 to 1973, only 1,170 early gastric cancer’s were diagnosed, that is, 6.3 percent of all gastric carcinomas [29]. The inquiry was repeated 3 years later, covering the 1974 to 1977 period and more than 550,000 gastroscopies; 1,280 cases of early gastric cancer were discovered, giving the same rate of 6.3 percent [30]. The prerequisite for discovery of an early gastric cancer in Sweden, and in most other European countries as well, is a patient presenting with symptoms referable to gastric disease. Among 649 patients from Europe with early gastric cancer, 94 percent presented with subjective complaints, mainly uncharacteristic abdominal pain [28]. Several workers emphasize that patients with early gastric cancer often have ulcer-like symptoms [31,32]; these symptoms may disappear after medical treatment such as cimetidine therapy, thereby delaying the correct diagnosis [33]. Screening of asymptomatic subjects for gastric carcinoma has hitherto not been routinely used or considered feasible outside Japan [12,34,35]. The duration of the presymptomatic stage in gastric carcinoma is not known, nor has it been conclusively demonstrated that early gastric cancer, if left untreated, invariably proceeds to advanced gastric cancer. Since current evidence favors the
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ijhman et al
hypothesis that most early gastric cancerous tumors are, in fact, early stages of advanced gastric cancer [3], we believe, with support from the present findings, that a high index of suspicion and an aggressive diagnostic approach in symptomatic patients will result in the detection of more early gastric cancer. Our 11 patients operated on for early gastric cancer are currently alive and well. The number of patients is small and the observation period short. Our previous experience with early gastric cancer [7,8], however, suggests that a 5 year survival rate of about 70 percent may be hoped for. Some optimism is also derived from other European reports of 60 to 75 percent 5 year survival [3,19]. Several investigators report experiences similar to ours, that is, that all patients with early gastric cancer surviving postoperatively are alive and well, although long-term survival rates are still a matter of speculation [25-271. The results of treatment in Japan appear extremely gratifying. Two Japanese reports, comprising more than 1,000 patients operated on for early gastric cancer, account for 99.5 to 100.0 percent 5 year survival rates after operation for mucosal cancer and 95.1 to 95.3 percent when submucosal invasion has occurred [36,37]. If the present report offers hope for long-term cure in patients with early gastric cancer, it also confirms the dismal prognosis in advanced gastric cancer. All patients who have undergone exploratory operation or palliative resection for advanced gastric cancer have died. Of 12 patients operated on “curatively” for advanced gastric cancer and observed for more than 3 years, only 2 were alive; thus a majority of the curative operations for advanced gastric cancer were, in retrospect, palliative. This disappointing result is no improvement over the 15 percent 5 year survival rate in our 1944 to 1963 series. In fact, the treatment results in patients with advanced gastric cancer have been unchanged during the last 30 to 40 years [11,12,14,38-401. Twelve patients in the present series, that is, 16 percent of the patients with gastric cancer, had gastric stump carcinoma. This rate indicates that stump cancer is a serious problem and raises the question of regular gastroscopic check-ups starting 10 to 15 years after partial gastrectomy for peptic ulcer [41-45]. Although the number of patients with stump cancer is small in the present series, the outcome in this group of patients seems to confii the miserable prognosis for advanced gastric cancer and the confidence in the prognosis for early gastric cancer. Patients with resected stomachs may constitute a fruitful field in the search for early gastric cancer. In a recent report, 108 patients with resected stom-
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achs were reoperated on for various reasons including malignancy. At reoperation, 33 advanced and 23 early gastric cancers were found; 1 advanced and 7 early gastric cancers were not recognized preoperatively despite gastroscopy and biopsy [46]. In conclusion, the present analysis demonstrates that early gastric cancer can be discovered in a significant number of patients and suggests that gastroscopy and biopsy are the basis for this improvement in the management of patients with gastric carcinoma. Since patients with early gastric cancer have a substantially better long-term survival rate than those with advanced gastric cancer, increased diagnosis of early gastric cancer can improve the cure rates in future series of patients operated on for gastric cancer, albeit not to the levels cited in Japanese reports. The present analysis confirms the dismal prognosis for advanced gastric cancer and documents that no improvement in the treatment results has occurred since the 1940s. Screening of asymptomatic patients for gastric carcinoma is not feasible in this country at present. However, the risk of cancer after partial gastrectomy for benign disease makes screening of this selected group of patients desirable. Summary Of 75 consecutive inpatients with gastric carcinoma during a 3.5 year period, 40 underwent operation with the intention of cure, 5 had palliative gastric resection and 30 had exploratory celiotomy only. Early gastric cancer was found in 11 cases, that is, 15 percent of patients with ‘gastric carcinoma or 24 percent of patients subjected to gastrectomy. The patients with early gastric cancer were operated on with the intention of cure. Comparison with a previous series from the same geographic area shows that the ratio between early gastric cancer and all gastric cancer increased significantly. This improvement in the management of patients with gastric carcinoma can be ascribed to the use of gastroscopy and biopsy. The survival rates in patients with early gastric cancer are excellent. The prognosis in patients with advanced gastric cancer, on the other hand, is poor and has remained so for the last 30 to 40 years. Twelve of the 75 patients had gastric stump carcinoma; 2 of these were early gastric cancer. Screening of asymptomatic patients for gastric cancer is at present an impossible task in most Western countries, but the risk of cancer after partial gastrectomy for benign lesions makes screening desirable in this selected group of patients.
The Amerkan Journal ol Surgery
Early and Advanced
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