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Fifteen-year survival following surgery of carcinoma of the stomach
Fifteen-Year
Survival
Carcinoma GLENN
II.
Following
Surgery
of
of the Stomach*
LUBASH,
M.D.
and LEO R.
CARDILLO,
M.D.
New York, New York first seen by his private physician in 1939, at the age of sixty, with a complaint of persistent indigestion relieved by sodium bicarbonate. The following year gastrointestinal fluoroscopy revealed no abnormality. Symptoms increased, however, and epigastric discomfort became pronounced. Almost all ingested food was vomited and there was a weight loss of 50 pounds. He was admitted to another hospital on May 8, 1941, where gastroscopy and a repeated gastrointestinal series revealed a fungating antral lesion. At laparotomy, in spite of the fact that the growth was extensive and invaded the omentum, it was resected with a narrow margin and gastrojejunostomy was performed. No metastases were seen in the liver or lymph nodes. Pathological examination of the specimen revealed that the entire pyloric region was occupied by an ulcerated tumor mass 8 cm. in length and 10 cm. in circumference. The distal margin of the tumor was 4 to 8 mm. from the duodenum. Histologically, there were irregular “glandular units formed by epithelial cells showing moderate degrees of pleomorphism, gigantism, hyperchromatism and heterotopia.” (Figs. 1 and 2.) There was marked desmoplasia and the tumor elements extended into the serosa and omenturn. The pathological diagnosis was adenocarcinoma of the stomach, grade 4. Following surgery, the patient had no further symptoms and periodic gastrointestional x-ray films disclosed no evidence of recurrence. On June 28, 1955, the patient was admitted to the medical wards of Bellevue Hospital because of pulmonary edema due to arteriosclerotic heart disease. This responded to the administration of oxygen, intravenous aminophylline, parenteral morphine sulfate and digitalis. Physical examination revealed no findings relevant to his former illness except the abdominal scar of the operation. There were no enlarged lymph nodes and the liver was palpable but not enlarged. Urinalysis, hemogram and liver function tests were within normal limits. Seven stool examinations were negative for blood by guaiac test; several others taken when the patient was on a diet without meat restriction were trace to 1 plus. Proctoscopy and barium enema were normal. Two upper gastrointestinal series revealed a high subtotal
LTHOUGH prolonged
survival of patients with carcinoma of the stomach is notably rare, prognosis is more favorable if the lesion is resectable. This and other factors influencing
A
FIG. 1. Low power view of tumor. survival will be discussed in relation to a patient who survived fifteen years following resection of a symptomatic and apparently highly invasive gastric carcinoma. CASE REPORT
J. S. (Bellevue Hospital Case 36150-55), a seventysix year old white, Russian born Jewish man, was
* From the Second (Cornell) Medical Division, Bellevue Hospital, and the Department Medical College, New York, New York.
324
AMERICAN
of Medicine, Cornell University
JOURNAL
OF
MEDICINE
Carcinoma
of the Stomach-Lubash,
FIG. 3. Upper enterostomy.
Fro. 2. High power view of glandular
tumor elements.
gastrectomy with patent gastroenterostomy stoma and well visualized afferent and efferent loops. (Fig. 3.) No mucosal abnormalities were noted. On September 16, 1955 the patient was discharged, weighing his usual 101 pounds. He remained free of gastrointestinal symptoms and essentially well until July 29, 1956, when he died unexpectedly during sleep, at home. No postmortem examination was obtained. COMMENTS
The ominous prognosis of carcinoma of the stomach is indicated by previous studies. The highest five-year survival rate that we were able to find in the literature is 12.5 per cent, reported by Shahon and associates from the University of Minnesota [7]. Other, perhaps more representative figures range from 5.6 to 8.8 per cent [2-d]. Survival for fifteen years has been notably infrequent, accounting for 0.32 and 0.47 per cent of cases in two large series [7,3] of 925 and 1,264 patients with gastric carcinoma. Other sources [d-8] mentioned one to six survivals of this length in their series. It should be remembered, however, that a normal age-corrected population undergoes attrition due to other causes. Survival rates for such a population as quoted by Berkson FEBRUARY,
1959
325
Curdillo
gastrointestinal
series showing
gastro-
and associates [9] are 89.0 per cent at five years, 75.2 per cent at ten years and 58.3 per cent at fifteen years. In spite of the possibility of longevity in this disease, the attitude of most clinicians confronted with a case such as described is one of skepticism as to the compatibility of the diagnosis with the long survival. In the case herein recorded, review of the slides dispelled all doubt. Part of the reason for this attitude may be the rarity of detailed case reports of survivals of this length. We were able to find only four such cases [ 7@72] in the English literature. The case reported herein is believed to be particularly significant in view of the anaplastic nature of the tumor and the small margin of resection. In retrospect, there was partial justification for the initial poor prognosis. Broder’s histological grading of primary tumor tissue according to anaplasia has been considered a fairly reliable rough guide to prognosis, grade 4 bearing the most ominous outlook. This degree of anaplasia and the invasion of the gastric wall and omenturn, taken together with the narrow margin of resection, indicated a short survival for this patient. Other factors, however, might have provided a basis for more optimism. First, no lymph node metastases were seen at operation. Second, the fact that the lesion was resectable at all is important in spite of the narrow margin. Ransom [3], in his series, reported that 11.8
326
Carcinoma
of the Stomach-Lubash,
per cent of patients with resectable lesions survived for fifteen years. Berkson et al. [9] have found that 17.2 per cent of patients with resectable lesions who leave the hospital alive will survive fifteen years. Third, and perhaps most important, is the long duration of symptoms prior to diagnosis. This apparent paradox was first noted by Balfour [ 731 in 1937 and more recently by others [2,7,14]. In this regard, MacDonald and Kotin’s monograph [75] presents the case for an inherent “biological predeterminism in gastric cancer” as the limiting factor of curability in resectable cases. They point out that “the duration of symptoms bears some relation to resectability, but curability increases with duration of symptoms in resectable cases.” In other words, those tumors which give the longest duration of symptoms and are still resectable are the slowest growing and the most amenable to cure. An important exception would be the resectable gastric cancer which, in the guise of a peptic ulcer, might produce early symptoms. There is other evidence that certain of these tumors undergo periods of very slow growth. Morgan and others [ 16,77] have had the opportunity to obtain repeated x-ray studies of patients who have refused operation for asymptomatic lesions suspected of being gastric carcinoma. Some of these have been followed in a “silent period” for more than three years with little change in x-ray appearance. Other factors mentioned in the literature which seem to have less prognostic import are: location and size of the tumor, gastric acidity, age at onset, and sex of the patient. SUMMARY
A case history of a patient with prolonged survival following resection of a symptomatic, invasive gastric carcinoma is presented. The prognosis was at first considered hopeless because of the small margin of resection and the anaplastic nature of the tumor. While review of the literature reveals the overall outlook in this disease to be poor, several factors seem to enhance the opportunity for survival. Chief among these are resectability of the tumor, as indicated by the absence of distant metastases or extensive local spread, and low histological grade. The concept of “biological predeterminism” is believed to be significant. Paradoxically, those tumors with the longest duration of symptoms which are still resectable have the best prognosis,
Cardillo
apparently because growth potential.
of their
relatively
limited
Acknowledgments: We wish to express our appreciation to Dr. Nathan Mitchell, who made slides available in this case, and to Dr. Morris Appleman, who provided us with information about the patient’s course. We are indebted to Dr. Ian Gresser, who prepared the pictures of the pathological material. We wish to thank Dr. Marvin Kuschner, Director of Pathology at Bellevue Hospital, who kindly reviewed the histological material, and Dr. Thomas P. Almy, Director of the Second (Cornell) Medical Division, who reviewed the manuscript and offered valuable suggestions. REFERENCES 1. SHAHON, D. B., HOROWITZ, S. and KELLY, W. D. Cancer of the stomach. Surgery, 39: 204, 1956. 2. SWYNNERTON,B. F. and TRUELOVE, S. C. Carcinoma of the stomach. Byit. M. J., I: 287, 1952. 3. RANSOM,H. K. Cancer of the stomach. Surg., Gynec. & Obst., 96: 275, 1953. 4. SAFAR, P. and CLIFFTON, E. E. Carcinoma of the stomach. Cancer, 6: 1165, 1953. 5. HARVEY. H.. TITHERINCTON. J.. STOUT. A. and ST. JOHN, F. Gastric cancer: Cancer, 4: 7i7, 1951. 6. BLOODGOOD,J. C. What every doctor should know about cancer of the stomach and what a gastrointestinal study means. Surg., Gynec. & Obst., 47: 216, 1928. 7. PALMER, W. L. The duration of gastric cancer. Gastroenterology, 1: 723, 1943. 8. BLACK, M. M., OPLER, S. R. and SPEER, F. D. Microscopic structure of gastric carcinoma and their regional lymph nodes in relation to survival. Surg., Gynec. @ Obst., 98: 725, 1954. 9. BERKSON, J., WALTERS, W., GRAY, H. K. and PRIESTLY, J. Mortality and survival in cancer of the stomach. Pm. Staff Meet., Mayo Clin., 27: 137, 1952. 10. ANGLEM, T. J. Fifteen year survival after total gastrectomy for cancer. Ann. Surg., 139: 368, 1954. 11. PACK, G. T. Cancer of the stomach: twenty year cures. Surgery, 35: 920, 1954. 12. DECK, E. Long term survival following partial gastrectomy for cancer of the stomach: New Zealand M. J.. 51: 417. 1952. 13. BALFOUR, D. C.‘Factors of significance in the prognosis of cancer of the stomach. Ann. Surg., 105: 733, 1937. 14. MOORE, J. R. and MORTON,H. S. Gastric carcinoma. Ann. Surg., 141: 185, 1955. 15. MACDONALD, J. and KOTIN, P. Biologic predeterminism in gastric carcinoma as the limiting factor of curability. Surg., Gynec. B Obst., 98: 148; 1954. 16. ROACH. J. F.. SLOAN, R. and MORGAN. R. H. The detection of gastric carcinoma by photofluorographic methods. Am. J. Roentgenol., 67: 68, 1952. 17. SLOAN, R. D., MORGAN, R. H. and WOLFSON, J. J. Gastric pathology detected by photofluorographic means. J. Nat. Cancer Inst., 13: 1067, 1953. AMERICAN
JOURNAL
OF MEDICINE
Survival
Carcinoma GLENN
II.
Following
Surgery
of
of the Stomach*
LUBASH,
M.D.
and LEO R.
CARDILLO,
M.D.
New York, New York first seen by his private physician in 1939, at the age of sixty, with a complaint of persistent indigestion relieved by sodium bicarbonate. The following year gastrointestinal fluoroscopy revealed no abnormality. Symptoms increased, however, and epigastric discomfort became pronounced. Almost all ingested food was vomited and there was a weight loss of 50 pounds. He was admitted to another hospital on May 8, 1941, where gastroscopy and a repeated gastrointestinal series revealed a fungating antral lesion. At laparotomy, in spite of the fact that the growth was extensive and invaded the omentum, it was resected with a narrow margin and gastrojejunostomy was performed. No metastases were seen in the liver or lymph nodes. Pathological examination of the specimen revealed that the entire pyloric region was occupied by an ulcerated tumor mass 8 cm. in length and 10 cm. in circumference. The distal margin of the tumor was 4 to 8 mm. from the duodenum. Histologically, there were irregular “glandular units formed by epithelial cells showing moderate degrees of pleomorphism, gigantism, hyperchromatism and heterotopia.” (Figs. 1 and 2.) There was marked desmoplasia and the tumor elements extended into the serosa and omenturn. The pathological diagnosis was adenocarcinoma of the stomach, grade 4. Following surgery, the patient had no further symptoms and periodic gastrointestional x-ray films disclosed no evidence of recurrence. On June 28, 1955, the patient was admitted to the medical wards of Bellevue Hospital because of pulmonary edema due to arteriosclerotic heart disease. This responded to the administration of oxygen, intravenous aminophylline, parenteral morphine sulfate and digitalis. Physical examination revealed no findings relevant to his former illness except the abdominal scar of the operation. There were no enlarged lymph nodes and the liver was palpable but not enlarged. Urinalysis, hemogram and liver function tests were within normal limits. Seven stool examinations were negative for blood by guaiac test; several others taken when the patient was on a diet without meat restriction were trace to 1 plus. Proctoscopy and barium enema were normal. Two upper gastrointestinal series revealed a high subtotal
LTHOUGH prolonged
survival of patients with carcinoma of the stomach is notably rare, prognosis is more favorable if the lesion is resectable. This and other factors influencing
A
FIG. 1. Low power view of tumor. survival will be discussed in relation to a patient who survived fifteen years following resection of a symptomatic and apparently highly invasive gastric carcinoma. CASE REPORT
J. S. (Bellevue Hospital Case 36150-55), a seventysix year old white, Russian born Jewish man, was
* From the Second (Cornell) Medical Division, Bellevue Hospital, and the Department Medical College, New York, New York.
324
AMERICAN
of Medicine, Cornell University
JOURNAL
OF
MEDICINE
Carcinoma
of the Stomach-Lubash,
FIG. 3. Upper enterostomy.
Fro. 2. High power view of glandular
tumor elements.
gastrectomy with patent gastroenterostomy stoma and well visualized afferent and efferent loops. (Fig. 3.) No mucosal abnormalities were noted. On September 16, 1955 the patient was discharged, weighing his usual 101 pounds. He remained free of gastrointestinal symptoms and essentially well until July 29, 1956, when he died unexpectedly during sleep, at home. No postmortem examination was obtained. COMMENTS
The ominous prognosis of carcinoma of the stomach is indicated by previous studies. The highest five-year survival rate that we were able to find in the literature is 12.5 per cent, reported by Shahon and associates from the University of Minnesota [7]. Other, perhaps more representative figures range from 5.6 to 8.8 per cent [2-d]. Survival for fifteen years has been notably infrequent, accounting for 0.32 and 0.47 per cent of cases in two large series [7,3] of 925 and 1,264 patients with gastric carcinoma. Other sources [d-8] mentioned one to six survivals of this length in their series. It should be remembered, however, that a normal age-corrected population undergoes attrition due to other causes. Survival rates for such a population as quoted by Berkson FEBRUARY,
1959
325
Curdillo
gastrointestinal
series showing
gastro-
and associates [9] are 89.0 per cent at five years, 75.2 per cent at ten years and 58.3 per cent at fifteen years. In spite of the possibility of longevity in this disease, the attitude of most clinicians confronted with a case such as described is one of skepticism as to the compatibility of the diagnosis with the long survival. In the case herein recorded, review of the slides dispelled all doubt. Part of the reason for this attitude may be the rarity of detailed case reports of survivals of this length. We were able to find only four such cases [ 7@72] in the English literature. The case reported herein is believed to be particularly significant in view of the anaplastic nature of the tumor and the small margin of resection. In retrospect, there was partial justification for the initial poor prognosis. Broder’s histological grading of primary tumor tissue according to anaplasia has been considered a fairly reliable rough guide to prognosis, grade 4 bearing the most ominous outlook. This degree of anaplasia and the invasion of the gastric wall and omenturn, taken together with the narrow margin of resection, indicated a short survival for this patient. Other factors, however, might have provided a basis for more optimism. First, no lymph node metastases were seen at operation. Second, the fact that the lesion was resectable at all is important in spite of the narrow margin. Ransom [3], in his series, reported that 11.8
326
Carcinoma
of the Stomach-Lubash,
per cent of patients with resectable lesions survived for fifteen years. Berkson et al. [9] have found that 17.2 per cent of patients with resectable lesions who leave the hospital alive will survive fifteen years. Third, and perhaps most important, is the long duration of symptoms prior to diagnosis. This apparent paradox was first noted by Balfour [ 731 in 1937 and more recently by others [2,7,14]. In this regard, MacDonald and Kotin’s monograph [75] presents the case for an inherent “biological predeterminism in gastric cancer” as the limiting factor of curability in resectable cases. They point out that “the duration of symptoms bears some relation to resectability, but curability increases with duration of symptoms in resectable cases.” In other words, those tumors which give the longest duration of symptoms and are still resectable are the slowest growing and the most amenable to cure. An important exception would be the resectable gastric cancer which, in the guise of a peptic ulcer, might produce early symptoms. There is other evidence that certain of these tumors undergo periods of very slow growth. Morgan and others [ 16,77] have had the opportunity to obtain repeated x-ray studies of patients who have refused operation for asymptomatic lesions suspected of being gastric carcinoma. Some of these have been followed in a “silent period” for more than three years with little change in x-ray appearance. Other factors mentioned in the literature which seem to have less prognostic import are: location and size of the tumor, gastric acidity, age at onset, and sex of the patient. SUMMARY
A case history of a patient with prolonged survival following resection of a symptomatic, invasive gastric carcinoma is presented. The prognosis was at first considered hopeless because of the small margin of resection and the anaplastic nature of the tumor. While review of the literature reveals the overall outlook in this disease to be poor, several factors seem to enhance the opportunity for survival. Chief among these are resectability of the tumor, as indicated by the absence of distant metastases or extensive local spread, and low histological grade. The concept of “biological predeterminism” is believed to be significant. Paradoxically, those tumors with the longest duration of symptoms which are still resectable have the best prognosis,
Cardillo
apparently because growth potential.
of their
relatively
limited
Acknowledgments: We wish to express our appreciation to Dr. Nathan Mitchell, who made slides available in this case, and to Dr. Morris Appleman, who provided us with information about the patient’s course. We are indebted to Dr. Ian Gresser, who prepared the pictures of the pathological material. We wish to thank Dr. Marvin Kuschner, Director of Pathology at Bellevue Hospital, who kindly reviewed the histological material, and Dr. Thomas P. Almy, Director of the Second (Cornell) Medical Division, who reviewed the manuscript and offered valuable suggestions. REFERENCES 1. SHAHON, D. B., HOROWITZ, S. and KELLY, W. D. Cancer of the stomach. Surgery, 39: 204, 1956. 2. SWYNNERTON,B. F. and TRUELOVE, S. C. Carcinoma of the stomach. Byit. M. J., I: 287, 1952. 3. RANSOM,H. K. Cancer of the stomach. Surg., Gynec. & Obst., 96: 275, 1953. 4. SAFAR, P. and CLIFFTON, E. E. Carcinoma of the stomach. Cancer, 6: 1165, 1953. 5. HARVEY. H.. TITHERINCTON. J.. STOUT. A. and ST. JOHN, F. Gastric cancer: Cancer, 4: 7i7, 1951. 6. BLOODGOOD,J. C. What every doctor should know about cancer of the stomach and what a gastrointestinal study means. Surg., Gynec. & Obst., 47: 216, 1928. 7. PALMER, W. L. The duration of gastric cancer. Gastroenterology, 1: 723, 1943. 8. BLACK, M. M., OPLER, S. R. and SPEER, F. D. Microscopic structure of gastric carcinoma and their regional lymph nodes in relation to survival. Surg., Gynec. @ Obst., 98: 725, 1954. 9. BERKSON, J., WALTERS, W., GRAY, H. K. and PRIESTLY, J. Mortality and survival in cancer of the stomach. Pm. Staff Meet., Mayo Clin., 27: 137, 1952. 10. ANGLEM, T. J. Fifteen year survival after total gastrectomy for cancer. Ann. Surg., 139: 368, 1954. 11. PACK, G. T. Cancer of the stomach: twenty year cures. Surgery, 35: 920, 1954. 12. DECK, E. Long term survival following partial gastrectomy for cancer of the stomach: New Zealand M. J.. 51: 417. 1952. 13. BALFOUR, D. C.‘Factors of significance in the prognosis of cancer of the stomach. Ann. Surg., 105: 733, 1937. 14. MOORE, J. R. and MORTON,H. S. Gastric carcinoma. Ann. Surg., 141: 185, 1955. 15. MACDONALD, J. and KOTIN, P. Biologic predeterminism in gastric carcinoma as the limiting factor of curability. Surg., Gynec. B Obst., 98: 148; 1954. 16. ROACH. J. F.. SLOAN, R. and MORGAN. R. H. The detection of gastric carcinoma by photofluorographic methods. Am. J. Roentgenol., 67: 68, 1952. 17. SLOAN, R. D., MORGAN, R. H. and WOLFSON, J. J. Gastric pathology detected by photofluorographic means. J. Nat. Cancer Inst., 13: 1067, 1953. AMERICAN
JOURNAL
OF MEDICINE