GASTROENTEROLOGY 1991;101:711-715
Cancer Incidence Following Subtotal Gastrectomy GRANT N. STEMMERMANN,
ABRAHAM M. Y. NOMURA,
and PO-HUANG CHYOU Japan-Hawaii Cancer Study, Kuakini Medical Center, Honolulu, Hawaii
Hawaiian Japanese men (n = 432) who had undergone subtotal gastrectomy for peptic ulcers before 1971-1975 were followed up for detection of cancer development. They showed a significant increase in colon cancer risk (P = 0.008) and lung cancer risk (P = 0.002) compared with 6161 nongastrectomized men. The association with lung cancer persisted after adjustment for cigarette use (P = 0.03). Alcohol consumption was associated with colonic cancer in this cohort, and gastrectomized men consumed more alcohol than nongastrectomized men; however, the association of gastrectomy with colon cancer persisted after adjustment for alcohol use (P = 0.02). Gastrectomized men were lighter and had lower serum lipid levels than controls, suggesting that undernutrition might favor the development of some cancers. The type of gastroenteric anastomosis did not influence the cancer risk level in the colon or lung. he committee on Diet, Nutrition and Cancer of the National Academy of Sciences has concluded that cancer of most major sites may be influenced by diet (1). As the committee’s name indicates, diet and nutrition are not synonymous. Individual differences in intestinal motility and nutrient absorption determine how much nutrition will be derived from any given diet, whereas differences in basal metabolism and physical activity determine whether absorbed nutrients meet daily energy requirements. Nutritional physiology is permanently altered following gastrectomy. A subtotal gastrectomy affects nutrition directly through its influence on absorption and indirectly by causing patients to maintain a pattern of eating that is the least likely to cause postprandial discomfort (2). We have had the opportunity to weigh the impact of subtotal gastrectomy on the risk of developing cancer in a cohort of 6573 Hawaiian Japanese men, among whom 412 (5%) underwent subtotal gastrectomy for benign diseases before examinations that were con-
T
ducted between the years 1971 and 1975. Prior studies of these men with and without intact stomachs showed that gastrectomy is associated with measurable changes in physical status and increased mortality (3,4). The diets of men with and without gastrectomy were similar in respect to macronutrient intake, but the postgastrectomy men weighed less than controls and had lower concentrations of serum cholesterol and triglycerides (3). Modest increases in consumption of caffeine and alcohol by men with gastrectomies did not appear sufficient to explain these differences. Gastrectomized men had a higher total rate of mortality, with significantly more deaths from lung cancer and stroke compared with men with intact stomachs (4). This study was undertaken to determine whether some of the results of the mortality study could be confirmed with a much larger number of cancer cases available for analysis in the ongoing prospective study of this cohort of Hawaiian Japanese men.
Materials and Methods Eight thousand six Hawaiian Japanese men living on the island of Oahu and born between 1900 and 1919 underwent baseline examination between 1965 and 1968 (5). The surviving men were invited back for another examination in the years 1971-1975; 6860 subjects were examined at that time, and they have been subsequently studied for the incidence of cancer or death due to all causes. After removing 127 men whose cancers were not confirmed histologically and 160 men in whom cancer had been diagnosed before examination, there were 412 men who had undergone gastrectomy for peptic ulcers and 6161 men with intact stomachs at the time of the 1971-1975 examinations. The site of the ulcer could be confirmed from
Abbreviations used in this paper: CI, confidence
interval:
relative risk. 0 1991 by tbe American Gastroenterological 0016-5085/91/$3.00
Association
RR,
712
STEMMERMANNET AL.
GASTROENTEROLOGYVol. 101, No. 3
medical records in 357 cases; there were 226 gastric ulcers (63%) and 131 duodenal ulcers (37%) (4). At the time of examination between 1971 and 1975, each subject’s weight and blood pressure were measured. Information was collected on the following: cigarette smoking history, alcohol intake, and weight at age 25. Blood samples were obtained to measure serum cholesterol concentration and hematocrit using methods described elsewhere (6). Cancer surveillance was conducted through a daily review of hospital discharges and computer linkage with the Hawaii Tumor Registry. The population was residentially stable. Based on a 19-year follow-up survey of study subjects since 1968 it was determined that only 1.3% of the men could not be located on Oahu. Consequently, the number of cancers among cohort men missed by this surveillance was considered probably negligible. The hospital records of all men who had undergone gastrectomy at the time of examination were assessed to determine the indication for gastrectomy and the type of anastomosis used. A gastroduodenostomy had been performed on 227 patients and a gastrojejunostomy in 174 patients. The type of anastomosis could not be ascertained in 11 patients. The age-adjusted mean values of physical and chemical attributes were calculated for men with and without gastrectomies. A test based on one-way, unbalanced analysis of covariance methods was used to determine if there was a statistically significant difference (P I 0.05) between the two groups of subjects in mean values of selected epidemiological factors (7). We estimated the relative risks (RRs) and 95% confidence intervals (CI) of the specific cancers for gastrectomized men compared with nongastrectomized men using the proportional hazards regression approach (8). All RRs were adjusted for age at examination. Estimates of RRs for cancer of the colon and lung with simultaneous adjustments for age, monthly alcohol intake, and cigarette smoking were also determined. All regression models were fitted using iterative maximum-likelihood methods (9). The Research Committee of the Kuakini Medical Center has endorsed the Japan-Hawaii Cancer Study, finding it to Table 1. Age-Adjusted Means of Selected Measurements
Nongastrectomy” Variables Age at examination, (unadjusted) Weight (Ib) Weight (lb), age 25 Systolic blood (mm Hg) Diastolic
for Subjects With and Without Gastrectomy Before Reexamination
All gastrectomies Mean
Gastroduodenostomy
f SE
No.
2 SE
6161
60.5
2 0.1
412
61.5
f
0.3”
6117
139.5
2 0.3
408
130.6
f
1.0”
6099
128.8
2 0.2
409
131.0
2 0.8”
6160
137.3
2 0.3
412
134.3
2 1.0”
Gastrojejunostomy
Mean
+ SE
No.
227
61.5
2 0.4”
226
130.2
2 1.3d
225
130.4
227
135.1
No.
Mean
+ SE
174
61.4
? 0.4b
171
131.2
+ 1.5d
2 1.0
173
132.0
+ 1.2’
2 1.4
174
133.1
r 1.5’
yr
(%)
(mgldL 1 No. of cigarettes/day
‘P I 0.01. dP 5 0.001. “P 5 0.0001.
(mean * SE) compared with the nongastrectomized men who consumed 18.2 + 0.5 oz/mo. They had smoked 40.2 ? 1.5 pack-years’ worth of cigarettes compared with the nongastrectomized men, who had smoked 27.6 + 0.4 pack-years’ worth. When the lung cancer relative risk was adjusted for the amounts of alcohol and cigarettes used, the P value changed from 0.002 to 0.03, whereas the P value for colon cancer changed from 0.008 to 0.02. The distribution of cancer within each portion of the colon of gastrectomized men was similar to the distribution of this tumor in the remainder of the cohort, and was as
pressure
Serum cholesterol,
“Comparison
The physical and chemical attributes of gastrectomized and nongastrectomized men are shown in Table 1. Gastrectomized men deviated from nongastrectomized men in every category listed. With the exception of blood pressure and weight at age 25, the type of anastomosis had little influence on the direction or extent of the variation. The relative risks for cancers among men with and without gastrectomies are shown in Table 2. The RR for all cancers was higher (1.2) for men with gastrectomy, b.ut this difference was not statistically significant. The colon and lung showed statistically significant relative risks among gastrectomy subjects. Higher rates of cigarette and alcohol consumption have been recorded among cohort men with gastrectomies than among the nongastrectomized men. Their mean rate of alcohol consumption was 26.6 + 1.8 oz/mo
Mean
No.
(mm &I
*P _
Cancer Incidence Following Subtotal Gastrectomy GRANT N. STEMMERMANN,
ABRAHAM M. Y. NOMURA,
and PO-HUANG CHYOU Japan-Hawaii Cancer Study, Kuakini Medical Center, Honolulu, Hawaii
Hawaiian Japanese men (n = 432) who had undergone subtotal gastrectomy for peptic ulcers before 1971-1975 were followed up for detection of cancer development. They showed a significant increase in colon cancer risk (P = 0.008) and lung cancer risk (P = 0.002) compared with 6161 nongastrectomized men. The association with lung cancer persisted after adjustment for cigarette use (P = 0.03). Alcohol consumption was associated with colonic cancer in this cohort, and gastrectomized men consumed more alcohol than nongastrectomized men; however, the association of gastrectomy with colon cancer persisted after adjustment for alcohol use (P = 0.02). Gastrectomized men were lighter and had lower serum lipid levels than controls, suggesting that undernutrition might favor the development of some cancers. The type of gastroenteric anastomosis did not influence the cancer risk level in the colon or lung. he committee on Diet, Nutrition and Cancer of the National Academy of Sciences has concluded that cancer of most major sites may be influenced by diet (1). As the committee’s name indicates, diet and nutrition are not synonymous. Individual differences in intestinal motility and nutrient absorption determine how much nutrition will be derived from any given diet, whereas differences in basal metabolism and physical activity determine whether absorbed nutrients meet daily energy requirements. Nutritional physiology is permanently altered following gastrectomy. A subtotal gastrectomy affects nutrition directly through its influence on absorption and indirectly by causing patients to maintain a pattern of eating that is the least likely to cause postprandial discomfort (2). We have had the opportunity to weigh the impact of subtotal gastrectomy on the risk of developing cancer in a cohort of 6573 Hawaiian Japanese men, among whom 412 (5%) underwent subtotal gastrectomy for benign diseases before examinations that were con-
T
ducted between the years 1971 and 1975. Prior studies of these men with and without intact stomachs showed that gastrectomy is associated with measurable changes in physical status and increased mortality (3,4). The diets of men with and without gastrectomy were similar in respect to macronutrient intake, but the postgastrectomy men weighed less than controls and had lower concentrations of serum cholesterol and triglycerides (3). Modest increases in consumption of caffeine and alcohol by men with gastrectomies did not appear sufficient to explain these differences. Gastrectomized men had a higher total rate of mortality, with significantly more deaths from lung cancer and stroke compared with men with intact stomachs (4). This study was undertaken to determine whether some of the results of the mortality study could be confirmed with a much larger number of cancer cases available for analysis in the ongoing prospective study of this cohort of Hawaiian Japanese men.
Materials and Methods Eight thousand six Hawaiian Japanese men living on the island of Oahu and born between 1900 and 1919 underwent baseline examination between 1965 and 1968 (5). The surviving men were invited back for another examination in the years 1971-1975; 6860 subjects were examined at that time, and they have been subsequently studied for the incidence of cancer or death due to all causes. After removing 127 men whose cancers were not confirmed histologically and 160 men in whom cancer had been diagnosed before examination, there were 412 men who had undergone gastrectomy for peptic ulcers and 6161 men with intact stomachs at the time of the 1971-1975 examinations. The site of the ulcer could be confirmed from
Abbreviations used in this paper: CI, confidence
interval:
relative risk. 0 1991 by tbe American Gastroenterological 0016-5085/91/$3.00
Association
RR,
712
STEMMERMANNET AL.
GASTROENTEROLOGYVol. 101, No. 3
medical records in 357 cases; there were 226 gastric ulcers (63%) and 131 duodenal ulcers (37%) (4). At the time of examination between 1971 and 1975, each subject’s weight and blood pressure were measured. Information was collected on the following: cigarette smoking history, alcohol intake, and weight at age 25. Blood samples were obtained to measure serum cholesterol concentration and hematocrit using methods described elsewhere (6). Cancer surveillance was conducted through a daily review of hospital discharges and computer linkage with the Hawaii Tumor Registry. The population was residentially stable. Based on a 19-year follow-up survey of study subjects since 1968 it was determined that only 1.3% of the men could not be located on Oahu. Consequently, the number of cancers among cohort men missed by this surveillance was considered probably negligible. The hospital records of all men who had undergone gastrectomy at the time of examination were assessed to determine the indication for gastrectomy and the type of anastomosis used. A gastroduodenostomy had been performed on 227 patients and a gastrojejunostomy in 174 patients. The type of anastomosis could not be ascertained in 11 patients. The age-adjusted mean values of physical and chemical attributes were calculated for men with and without gastrectomies. A test based on one-way, unbalanced analysis of covariance methods was used to determine if there was a statistically significant difference (P I 0.05) between the two groups of subjects in mean values of selected epidemiological factors (7). We estimated the relative risks (RRs) and 95% confidence intervals (CI) of the specific cancers for gastrectomized men compared with nongastrectomized men using the proportional hazards regression approach (8). All RRs were adjusted for age at examination. Estimates of RRs for cancer of the colon and lung with simultaneous adjustments for age, monthly alcohol intake, and cigarette smoking were also determined. All regression models were fitted using iterative maximum-likelihood methods (9). The Research Committee of the Kuakini Medical Center has endorsed the Japan-Hawaii Cancer Study, finding it to Table 1. Age-Adjusted Means of Selected Measurements
Nongastrectomy” Variables Age at examination, (unadjusted) Weight (Ib) Weight (lb), age 25 Systolic blood (mm Hg) Diastolic
for Subjects With and Without Gastrectomy Before Reexamination
All gastrectomies Mean
Gastroduodenostomy
f SE
No.
2 SE
6161
60.5
2 0.1
412
61.5
f
0.3”
6117
139.5
2 0.3
408
130.6
f
1.0”
6099
128.8
2 0.2
409
131.0
2 0.8”
6160
137.3
2 0.3
412
134.3
2 1.0”
Gastrojejunostomy
Mean
+ SE
No.
227
61.5
2 0.4”
226
130.2
2 1.3d
225
130.4
227
135.1
No.
Mean
+ SE
174
61.4
? 0.4b
171
131.2
+ 1.5d
2 1.0
173
132.0
+ 1.2’
2 1.4
174
133.1
r 1.5’
yr
(%)
(mgldL 1 No. of cigarettes/day
‘P I 0.01. dP 5 0.001. “P 5 0.0001.
(mean * SE) compared with the nongastrectomized men who consumed 18.2 + 0.5 oz/mo. They had smoked 40.2 ? 1.5 pack-years’ worth of cigarettes compared with the nongastrectomized men, who had smoked 27.6 + 0.4 pack-years’ worth. When the lung cancer relative risk was adjusted for the amounts of alcohol and cigarettes used, the P value changed from 0.002 to 0.03, whereas the P value for colon cancer changed from 0.008 to 0.02. The distribution of cancer within each portion of the colon of gastrectomized men was similar to the distribution of this tumor in the remainder of the cohort, and was as
pressure
Serum cholesterol,
“Comparison
The physical and chemical attributes of gastrectomized and nongastrectomized men are shown in Table 1. Gastrectomized men deviated from nongastrectomized men in every category listed. With the exception of blood pressure and weight at age 25, the type of anastomosis had little influence on the direction or extent of the variation. The relative risks for cancers among men with and without gastrectomies are shown in Table 2. The RR for all cancers was higher (1.2) for men with gastrectomy, b.ut this difference was not statistically significant. The colon and lung showed statistically significant relative risks among gastrectomy subjects. Higher rates of cigarette and alcohol consumption have been recorded among cohort men with gastrectomies than among the nongastrectomized men. Their mean rate of alcohol consumption was 26.6 + 1.8 oz/mo
Mean
No.
(mm &I
*P _
