ANNALS
Vol. 188
OF SURGERY
December 1978
No.
6
Clinical Correlates of Resectability and Survival in Gastric Carcinoma THOMAS W. BUCHHOLTZ, M.D., CLAUDE E. WELCH, M.D., RONALD A. MALT, M.D.
The course of 201 patients with carcinoma of the stomach treated from 1962 through 1966 was followed with 97% determinacy for 10 years. The actual five year survival rate was 11%; the ten year rate was 7%. The mean duration of survival was 5.8 + 2.7 (S.D.) months. These results were similar to those reported for the period 1922-1926. Survival was strongly correlated with the surgeon's assessment after exploration. All patients alive after five years had operations thought to be curative, usually partial gastrectomies; the survival rate of this group was 24%. Gastroenterostomy was ineffectual palliation. Better results will require nonsurgical adjuncts, since the correlates of survival are those of minimally invasive cancer.
A T THE TIME THE RESULTS of treatment for gastric
I
carcinoma at this hospital from 1922 through 1926 were reviewed,15 carcinoma of the stomach was the most frequent cause of death from cancer in men and was exceeded in women only by cancers of the breast and uterus. Although its attack rate declined in the subsequent years represented by more recent reports,16'27'28 gastric carcinoma even now is the fifth most frequent cause of deaths from malignant disease in men and eighth in women. 17.21 During the same period the attack rate has decreased, however, the five year survival rates among all patients treated in general hospitals have stayed remarkably constant, at about 1%.14 The rate may be higher at some referral centers and lower at hospitals specializing in cancer. 108.22.23 The salvage rate is stable irrespective of whether patients are treated by limited gastrectomy or by radical gastrectomy with removal of adjacent organs. Reprint requests: Ronald A. Malt, M.D., Massachusetts General Hospital, Boston, Massachusetts 02114. Supported in part by the Henry Greco Fund. Submitted for publication: December 20, 1977.
From the Surgical Services, Massachusetts General Hospital, and the Department of Surgery, Harvard Medical School, Boston, Massachusetts
The problem for the surgeon dealing with an individual patient today is, first, to be able to predict chances of spread and of survival from preoperative clues and, second, to select the proper operation depending on the likelihood of cure or palliation, given the situation found when the abdomen is opened. Distal gastrectomy is most likely to cure small polypoid or ulcerative gastric cancers with an "intestinal" (glandular) histologic pattern and without lymphatic metastases than cancers of other types.4'9'25'29 But the choice of operations for both these cancers and cancers of other kinds in other locations is always a matter of judgment. Proximal and total gastrectomies may be curative for adenocarcinomas near the gastroesophageal junction even when regional lymph nodes are involved with cancer, provided that the resection margins are free of cancer. 1'24 We describe the influence of preoperative findings and of other operative discoveries on prognosis in patients followed for ten years or until their earlier death. Methods
Records were analyzed of all patients with proved carcinoma of the stomach who were discharged from January 1, 1962 through December 31, 1966. The status of 97% of these patients was known in 1976. Variables were tested for significance by x2, y, and R (correlation) methods.
0003-4932/78/1200/0711 $00.75 C J. B. Lippincott Company
711
Ann. Surg.
BUCHHOLTZ, WELCH AND MALT
712 Results
Among 201 patients the ratio of men to women was nearly 2:1 (132:69). The ages of 82% were from 50 to 80 years. Group A blood was present in 40%. There was a family history of gastric cancer in 10%, and 3.5% had pernicious anemia. Abdominal pain was the major complaint in 52%. Hospital attention was sought by 55% within three months of the onset of their symptoms.
A palpable abdominal mass was present in 24%. Occult blood was identified in the stool of 68% of 157 patients tested; achlorhydria was found in 76% of 68 tested. Barium-contrast roentgenograms of the stomach were 93% diagnostic. Of 61 gastroscopic biopsies, 80% showed carcinoma. Operations were performed on 93% of the 201 patients. Cancers arose in the gastric body or antrum in 73%. No cancers arose in gastric remnants after gastrectomies for ulcer. Only 19% of cancers seen at the operating table were limited to the stomach. Regional lymph nodes contained cancer in 76% of patients who were operated upon. Peritoneal metastases were present in 34%, and hepatic metastases were present in 20%. The incidence of adenocarcinoma was 76%, of undifferentiated carcinoma 17%, and of signet-cell carcinoma 6%. Depth of penetration was recorded for 127 specimens. In 83% it was through all layers of the gastric wall; in only 4% was it limited to the mucosa.
Cancers were resected in 70% of patients operated (Table 1), and in 48% of resections all gross neoplasm was removed. Total gastrectomies (27% of resections) almost always involved en-bloc removal of the spleen, pancreatic tail, and omenta. Fatality rates while the patients were hospitalized were 10% for gastric resection, 37% for bypass, and 28% for diagnostic laparotomy or no operation. The overall actual five year survival rate was 11%. The overall actual ten year survival rate was 7%. The mean duration of survival of all patients was 5.8 upon
December 1978
+ 2.7 (S.D.) months. Table 1 shows survival statistics for each form of treatment.
Correlations
Despite apparently unfavorable patterns of disease women, results of treatment were the same as for men. A palpable mass was found in 43% of women vs. 14% of men (p < 0.001). Regional lymphatic metastases were present in 91% of women vs. 69% of men (p = 0.004). Only 7% of patients with a palpable mass had cancer localized to the stomach (p = 0.003). Nonetheless, the five year survival rates of 13% for women and 7% for men were not significantly different (p = 0.33). Although old age was an ominous variable, no importance can be attributed to this correlation without matched or life-table controls. Of 20 patients over 80-years-old, only one survived longer than three years (p < 0.001). The operative fatality rate of this group was 35% as compared with 5% in patients under 50 years old (p = 0.001). No correlation existed between the duration of symptoms and survival. Nonetheless, all seven patients who were asymptomatic survived longer than six months, and four of them survived over three years (p < 0.01). Rarely was distant cancer present unless the regional lymph nodes also contained cancer. In general the sequence was involvement of regional lymph nodes, then adjacent organs, and, last, peritoneal surfaces. There were lymphatic metastases in 96% of 81 patients with extension beyond the stomach. Survival was closely related to the status of perigastric organs. Of 31 patients not having lymphatic metastases, 45% survived five years, but only 8% of 100 patients recorded with metastases in the lymph nodes lived that long (p < 0.001). Of 35 patients not having adjacent organs invaded, 31% survived five years, but only 7% of 91 patients (p < 0.001) with local invasion and lymph-node involvement. Peritoneal or hepatic metastases were even more ominous. Survival longer than 12 months occurred in in
TABLE 1. Treatment and Survival
Patients No. Partial gastrectomy Total gastrectomy Gastroenterostomy Exploratory laparotomy No exploration
106 25 19 37 14 Total 201
Median Survival Months
5-Year Survival %
17. 8.5
17 16 0 0
1.8 2.6 Mean 5.8
+
2.7 (S.D.)
Mean II
Vol. 188 * No. 6
713
GASTRIC CARCINOMA
but 16% of 63 patients with peritoneal metastases (p < 0.01) and 8% of 37 with hepatic metastases (p < 0.001). However, four patients (6%) with omental metastases not grossly apparent survived at least five years after omentectomy. Extra-abdominal metastases in the low mediastinum were chiefly from cancers at the esophagogastric junction (57% of 14 instances (p < 0.001)). They were associated with a worse prognosis than intraabdominal metastases, as no patient with mediastinal metastases survived five years. Neither the location of the primary tumor nor its extragastric extension were necessarily contraindications to resection. When metastases were limited to the perigastric lymph nodes, 97% of 80 patients had resections, but even 43% (39) of 91 patients with widespread cancer underwent resection. Cancers at the esophagogastric junction were especially amenable to resection, inasmuch as 86% of 22 patients with cancer there had the primary cancer removed, as compared with 63% of the entire group of 187 patients operated upon (p < 0.001). The surgeon's assessment after exploration was strongly correlated (p = 0.004) with survival. All 22 patients surviving five years were among the 92 (46% of the total population studied) who had operations deemed potentially curative. Therefore, the five year survival rate of patients operated upon for cure was 24%. Only one patient operated upon for diagnostic reasons survived over one year, and only two who had palliative operations survived between three and five years. Characteristics of the neoplasm itself were prognostic. Ulcerating cancers (58 cases) were more favorable than polypoid (60 cases); they were present in 67% of the 15 patients who survived at seven years (p = 0.006)-the shallower the invasiveness, the better. Among 22 patients with neoplasms confined by the submucosal layer, the five year survival rate was 41% (p < 0.001). Undifferentiated cancers were notably aggressive; among 34 patients 53% were inoperable or unresectable (p = 0.02), and this cell type was most commonly associated with hepatic metastases (p < 0.003). Gastrojejunostomy was an ineffectual means of palliation. Even resection was rarely helpful for relief of symptoms. Only one of 17 patients was relieved of symptoms after a bypass, and only 29% of 45 patients were relieved with a palliative resection. The persistence of symptoms was invariably followed by death within two years in 79 patients. Recurrences after resection were frequent, and they were almost always followed by death. Recur-
TABLE 2. Correlates of Survival in 5-Year Survivors (N = 22) p value
Asymptomatic No mass Non-diagnostic G.I. series Gastric acid No extension to other organs Negative lymph nodes No hepatic metastases Few lymph nodes involved Negative resection margins Invasion only to muscularis No recurrence
0.006 0.03 0.04 0.03
Vol. 188
OF SURGERY
December 1978
No.
6
Clinical Correlates of Resectability and Survival in Gastric Carcinoma THOMAS W. BUCHHOLTZ, M.D., CLAUDE E. WELCH, M.D., RONALD A. MALT, M.D.
The course of 201 patients with carcinoma of the stomach treated from 1962 through 1966 was followed with 97% determinacy for 10 years. The actual five year survival rate was 11%; the ten year rate was 7%. The mean duration of survival was 5.8 + 2.7 (S.D.) months. These results were similar to those reported for the period 1922-1926. Survival was strongly correlated with the surgeon's assessment after exploration. All patients alive after five years had operations thought to be curative, usually partial gastrectomies; the survival rate of this group was 24%. Gastroenterostomy was ineffectual palliation. Better results will require nonsurgical adjuncts, since the correlates of survival are those of minimally invasive cancer.
A T THE TIME THE RESULTS of treatment for gastric
I
carcinoma at this hospital from 1922 through 1926 were reviewed,15 carcinoma of the stomach was the most frequent cause of death from cancer in men and was exceeded in women only by cancers of the breast and uterus. Although its attack rate declined in the subsequent years represented by more recent reports,16'27'28 gastric carcinoma even now is the fifth most frequent cause of deaths from malignant disease in men and eighth in women. 17.21 During the same period the attack rate has decreased, however, the five year survival rates among all patients treated in general hospitals have stayed remarkably constant, at about 1%.14 The rate may be higher at some referral centers and lower at hospitals specializing in cancer. 108.22.23 The salvage rate is stable irrespective of whether patients are treated by limited gastrectomy or by radical gastrectomy with removal of adjacent organs. Reprint requests: Ronald A. Malt, M.D., Massachusetts General Hospital, Boston, Massachusetts 02114. Supported in part by the Henry Greco Fund. Submitted for publication: December 20, 1977.
From the Surgical Services, Massachusetts General Hospital, and the Department of Surgery, Harvard Medical School, Boston, Massachusetts
The problem for the surgeon dealing with an individual patient today is, first, to be able to predict chances of spread and of survival from preoperative clues and, second, to select the proper operation depending on the likelihood of cure or palliation, given the situation found when the abdomen is opened. Distal gastrectomy is most likely to cure small polypoid or ulcerative gastric cancers with an "intestinal" (glandular) histologic pattern and without lymphatic metastases than cancers of other types.4'9'25'29 But the choice of operations for both these cancers and cancers of other kinds in other locations is always a matter of judgment. Proximal and total gastrectomies may be curative for adenocarcinomas near the gastroesophageal junction even when regional lymph nodes are involved with cancer, provided that the resection margins are free of cancer. 1'24 We describe the influence of preoperative findings and of other operative discoveries on prognosis in patients followed for ten years or until their earlier death. Methods
Records were analyzed of all patients with proved carcinoma of the stomach who were discharged from January 1, 1962 through December 31, 1966. The status of 97% of these patients was known in 1976. Variables were tested for significance by x2, y, and R (correlation) methods.
0003-4932/78/1200/0711 $00.75 C J. B. Lippincott Company
711
Ann. Surg.
BUCHHOLTZ, WELCH AND MALT
712 Results
Among 201 patients the ratio of men to women was nearly 2:1 (132:69). The ages of 82% were from 50 to 80 years. Group A blood was present in 40%. There was a family history of gastric cancer in 10%, and 3.5% had pernicious anemia. Abdominal pain was the major complaint in 52%. Hospital attention was sought by 55% within three months of the onset of their symptoms.
A palpable abdominal mass was present in 24%. Occult blood was identified in the stool of 68% of 157 patients tested; achlorhydria was found in 76% of 68 tested. Barium-contrast roentgenograms of the stomach were 93% diagnostic. Of 61 gastroscopic biopsies, 80% showed carcinoma. Operations were performed on 93% of the 201 patients. Cancers arose in the gastric body or antrum in 73%. No cancers arose in gastric remnants after gastrectomies for ulcer. Only 19% of cancers seen at the operating table were limited to the stomach. Regional lymph nodes contained cancer in 76% of patients who were operated upon. Peritoneal metastases were present in 34%, and hepatic metastases were present in 20%. The incidence of adenocarcinoma was 76%, of undifferentiated carcinoma 17%, and of signet-cell carcinoma 6%. Depth of penetration was recorded for 127 specimens. In 83% it was through all layers of the gastric wall; in only 4% was it limited to the mucosa.
Cancers were resected in 70% of patients operated (Table 1), and in 48% of resections all gross neoplasm was removed. Total gastrectomies (27% of resections) almost always involved en-bloc removal of the spleen, pancreatic tail, and omenta. Fatality rates while the patients were hospitalized were 10% for gastric resection, 37% for bypass, and 28% for diagnostic laparotomy or no operation. The overall actual five year survival rate was 11%. The overall actual ten year survival rate was 7%. The mean duration of survival of all patients was 5.8 upon
December 1978
+ 2.7 (S.D.) months. Table 1 shows survival statistics for each form of treatment.
Correlations
Despite apparently unfavorable patterns of disease women, results of treatment were the same as for men. A palpable mass was found in 43% of women vs. 14% of men (p < 0.001). Regional lymphatic metastases were present in 91% of women vs. 69% of men (p = 0.004). Only 7% of patients with a palpable mass had cancer localized to the stomach (p = 0.003). Nonetheless, the five year survival rates of 13% for women and 7% for men were not significantly different (p = 0.33). Although old age was an ominous variable, no importance can be attributed to this correlation without matched or life-table controls. Of 20 patients over 80-years-old, only one survived longer than three years (p < 0.001). The operative fatality rate of this group was 35% as compared with 5% in patients under 50 years old (p = 0.001). No correlation existed between the duration of symptoms and survival. Nonetheless, all seven patients who were asymptomatic survived longer than six months, and four of them survived over three years (p < 0.01). Rarely was distant cancer present unless the regional lymph nodes also contained cancer. In general the sequence was involvement of regional lymph nodes, then adjacent organs, and, last, peritoneal surfaces. There were lymphatic metastases in 96% of 81 patients with extension beyond the stomach. Survival was closely related to the status of perigastric organs. Of 31 patients not having lymphatic metastases, 45% survived five years, but only 8% of 100 patients recorded with metastases in the lymph nodes lived that long (p < 0.001). Of 35 patients not having adjacent organs invaded, 31% survived five years, but only 7% of 91 patients (p < 0.001) with local invasion and lymph-node involvement. Peritoneal or hepatic metastases were even more ominous. Survival longer than 12 months occurred in in
TABLE 1. Treatment and Survival
Patients No. Partial gastrectomy Total gastrectomy Gastroenterostomy Exploratory laparotomy No exploration
106 25 19 37 14 Total 201
Median Survival Months
5-Year Survival %
17. 8.5
17 16 0 0
1.8 2.6 Mean 5.8
+
2.7 (S.D.)
Mean II
Vol. 188 * No. 6
713
GASTRIC CARCINOMA
but 16% of 63 patients with peritoneal metastases (p < 0.01) and 8% of 37 with hepatic metastases (p < 0.001). However, four patients (6%) with omental metastases not grossly apparent survived at least five years after omentectomy. Extra-abdominal metastases in the low mediastinum were chiefly from cancers at the esophagogastric junction (57% of 14 instances (p < 0.001)). They were associated with a worse prognosis than intraabdominal metastases, as no patient with mediastinal metastases survived five years. Neither the location of the primary tumor nor its extragastric extension were necessarily contraindications to resection. When metastases were limited to the perigastric lymph nodes, 97% of 80 patients had resections, but even 43% (39) of 91 patients with widespread cancer underwent resection. Cancers at the esophagogastric junction were especially amenable to resection, inasmuch as 86% of 22 patients with cancer there had the primary cancer removed, as compared with 63% of the entire group of 187 patients operated upon (p < 0.001). The surgeon's assessment after exploration was strongly correlated (p = 0.004) with survival. All 22 patients surviving five years were among the 92 (46% of the total population studied) who had operations deemed potentially curative. Therefore, the five year survival rate of patients operated upon for cure was 24%. Only one patient operated upon for diagnostic reasons survived over one year, and only two who had palliative operations survived between three and five years. Characteristics of the neoplasm itself were prognostic. Ulcerating cancers (58 cases) were more favorable than polypoid (60 cases); they were present in 67% of the 15 patients who survived at seven years (p = 0.006)-the shallower the invasiveness, the better. Among 22 patients with neoplasms confined by the submucosal layer, the five year survival rate was 41% (p < 0.001). Undifferentiated cancers were notably aggressive; among 34 patients 53% were inoperable or unresectable (p = 0.02), and this cell type was most commonly associated with hepatic metastases (p < 0.003). Gastrojejunostomy was an ineffectual means of palliation. Even resection was rarely helpful for relief of symptoms. Only one of 17 patients was relieved of symptoms after a bypass, and only 29% of 45 patients were relieved with a palliative resection. The persistence of symptoms was invariably followed by death within two years in 79 patients. Recurrences after resection were frequent, and they were almost always followed by death. Recur-
TABLE 2. Correlates of Survival in 5-Year Survivors (N = 22) p value
Asymptomatic No mass Non-diagnostic G.I. series Gastric acid No extension to other organs Negative lymph nodes No hepatic metastases Few lymph nodes involved Negative resection margins Invasion only to muscularis No recurrence
0.006 0.03 0.04 0.03
