Prognosis of Gastric Ulcer: Twenty-five Year Followup MATTHEW KRAUS, M.D.,* GALE MENDELOFF, M.D.,t ROBERT E. CONDON,
Four hundred twenty-two patients with gastric ulcer treated during 1950-1960 were followed up to 25 years with a mean followup of 9 years. Nonoperative treatment was used in 59% with a hospital mortality of 35%, one-third of these deaths being directly due to gastric ulcer perforation or hemorrhage. Operative treatment was used in 41% of patients. The most common operation (86%) was gastric resection without vagotomy. Overall operative mortality was 16%; 34% for emergency procedures and 6% for elective procedures. Cachexia seemed to be the most important factor related to operative mortality. Nonoperative treatment resulted in more than twice the hospital mortality compared to operative treatment. Approximately one-half of all patients treated nonoperatively had a recurrent gastric ulcer at some time during this this study. The recurrence rate following definitive gastric resection was 1.3% compared with 16% during nonoperative therapy. Three-fourths of recurrences occurred later than two years and nearly half of recurrences after more than 5 years of followup. Patients with a prior history of overt bleeding from gastric ulcer disease particularly were at risk for further bleeding. There were coincidental duodenal ulcers in 10% of our patients and a 0.8% incidence of gastric cancer during followup. Long term followup demonstrates the superiority of operative treatment of gastric ulcer and also reveals the continuous propensity of such ulcers to recurrence following nonoperative treatment. Earlier elective operation in patients with overt bleeding, recurrence or persisting symptoms should decrease overall mortality and result in a lower overall long-term risk of ulcer complications.
L ONG term followup of gastric ulcer patients is needed to assess adequately the results of operative and nonoperative treatment, to appreciate the propensity of gastric ulcers to recur, and to control the disease. We are Presented at the Annual Meeting of the American Surgical Association, New Orleans, Louisiana, April 7-9, 1976. * Chief Resident in Surgery. t Associate Clinical Professor of Surgery. t Chief, Surgical Service and Professor of Surgery.
M.D.t
From the Surgical Service, Wood Veterans Administration Hospital, and The Division of Surgery, The Medical College of Wisconsin, Milwaukee, Wisconsin 53193
reporting a retrospective review of 422 gastric ulcer patients treated during the decade of the 1950's and followed for up to 25 years. Patient Material All patients with an ulcer affecting gastric mucosa treated at the Wood VA Hospital during 1950-1960 were retrospectively studied. Because of past clinical imprecision in the diagnosis of certain varieties of gastric ulcer, it was not possible to categorize separately chronic, acute or stress gastric ulcers. Certain patients with prepyloric and pyloric channel ulcers presented a problem of categorization, since they were identified as gastric ulcers at one time and as pre-pyloric or pyloric channel ulcers at other times. Although often considered to have a variant of duodenal ulcer disease, such patients with prepyloric and pyloric channel ulcers have been included. Patients with duodenal ulcer alone were excluded, but included if the duodenal ulcer occurred in combination with a gastric ulcer. Patients with a proven diagnosis of gastric cancer were excluded and are part of a separate report. The 422 patients originally under study had been reviewed in 1960, but the observations were not published. During 1973-1975, 289 members of the original study group were re-evaluated by chart review, mail question-
471
KRAUS, MENDELOFF AND CONDON
472
TABLE 1. Fasting Gastric Analysis
Gastric Secretory State
Achlorhydria Hyposecretion Normosecretion (1.5-3.0 mEq/hr) Hypersecretion
Gastric Ulcer Alone (n = 238)
Concurrent Gastric and Duodenal Ulcer (n = 32)
No. Pts.
%
No. Pts.
%
34 18
14 8
4 2
13 6
99 87
42 36
14 12
44 37
naire, telephone and personal contact. The others had died or otherwise had been lost to followup in the interval. Patients thus were followed for varying periods up to 25 years. The mean period of followup was 9 years. All patients were male; their mean age was 56 years, and 46% were older than 60 years of age. Patients were divided into two groups depending upon the treatment received during their first, or index, hospitalization between 1950-1960 for gastric ulcer disease. Group I was composed of 248 patients (59o of total) treated nonoperatively. There was no prior history of an ulcer in 177 patients and the index admission was their first treatment for gastric ulcer. A prior history of symptomatic ulcer was present in 71 patients, of whom 31 previously had been documented as gastric ulcers. These latter patients represent proven failure of previous nonoperative treatment of gastric ulcer at the time of entry into the study, despite which further nonoperative therapy was prescribed. Some patients in this group later underwent an operation. Group II comprised 174 patients (41% of total) treated operatively during their index hospitalization for gastric ulcer. There was no prior ulcer history in 88 patients and their operation was the first definitive treatment of their gastric ulcer disease. There were 51 patients in Group II with a documented history of gastric ulcer disease and an additional 35 patients with a history of "ulcer disease" who had an operation during the index admission. Observations The incidence of most symptoms and signs and the results of investigations were essentially identical in both groups. Pretreatment characteristics common to both groups included complaints of epigastric pain and tenderness (77%), historic duration of pain, history of prior hemorrhage (20%o), nutritional status (29%o of both groups were cachectic), other findings of physical examination, demonstration of an ulcer radiologically (69o positive examinations), identification of an ulcer on rigid endoscopy (38% positive), the location of the ulcer (90% were on the lesser curvature), the results of gastric
Ann.
Surg. * October 1976
secretory studies and the incidence of guaiac positive stools (25% in both groups). Patients were seen during followup at irregular intervals by a variety of observers. Unfortunately, there was no unanimity about recording of patient's complaints; some records were detailed, others were not. Most patients in both groups were symptomatically improved after any treatment. Episodes of post-treatment major complications were clearly identified in the notes. But, we found it impossible to arrive at a reliable judgment concerning the status of most minor symptoms in many patients, and have had to omit comments or conclusions about the effects of treatment on most subjective complaints.
Bleeding The incidence of overt blood loss was the only clinical feature different between the two groups. Surgicallytreated patients (Group II) had an incidence of hematemesis and melena of 38% compared with 21% of gross blood loss in patients treated non-operatively (Group I). Fifty-nine per cent of patients who had a history of bleeding from a gastric ulcer in the past, or evidence of bleeding, however mild, at entry into the study, ultimately required an emergency or elective operation to control their gastric ulcer disease.
Concurrent Duodenal Ulcer A duodenal ulcer was demonstrated in conjunction with the gastric ulcer in 44 of 422 patients by x-ray, endoscopy or during operation. The results of gastric analysis did not differ between patients with only gastric ulcer and those who also had an associated duodenal ulcer (Table 1). Of the patients with a concurrent duodenal ulcer, 23 were treated nonoperatively with a 13% mortality and a recurrence rate of 39%O. An operation was the treatment of 21 patients with a 10o mortality risk and a recurrence rate of 1%o. No patient had a vagotomy, a factor which may have adversely influenced the recurrence risk in operatively treated patients.
Nonoperative Therapy Nonoperative treatment varied from patient to patient. Antacids and a bland diet uniformly were prescribed; anticholinergics and sedation were used less regularly. Nineteen ulcers failed to heal during 6 to 15 weeks of treatment; these patients then had an operation. Forty patients developed a documented recurrence of their ulcer while under therapy; 27 required operative control oftheir disease. The risk of recurrence existed throughout the quarter century of followup (Table 2). Three-fourths of
VOl. 184 . NO. 4
PROGNOSIS OF GASTRIC ULCER
TABLE 2. Time of Appearance of Proven Recurrent Ulcers Among Nonoperatively Treated Patients (Group I)
Duration of Followup to Recurrence (yrs.)
No. of Patients at Risk
No. of Recurrent Ulcers
Recurrence Risk
0-2
1
12 123
14
10 5 2
12 12 6
6-10 11-15 16-25
86 58 31
(%)
proven recurrences occurred after two years, while 43% of recurrences occurred after more than 5 years of
followup. The incidence of complications during nonoperative therapy was 33%. Most of this morbidity is represented by proven recurrent gastric ulcer and by nonhealing ulcers. Severe pain and bleeding due to a suspected recurrent gastric ulcer was present in an additional 5% of patients in Group I. A proven duodenal ulcer was found in a further 3%. A gastric cancer appeared in two patients in this group, 13 and 18 years after entry into the study. The hospital mortality of nonoperative therapy was 35%. Table 3 lists the major causes of death. In categorizing patients for inclusion in Table 3, only the major defect in homeostasis has been assigned responsibility for mortality. Many deaths were related to the generally deteriorated physical state of the patient to which had been added the stress of the gastric ulcer. Mortality in such instances was not ascribed directly to the gastric ulcer. Complications of gastric ulcer in the absence of other major system disease were responsible for a significant proportion of deaths in patients treated nonoperatively. Ten per cent of all deaths among patients in Group I were the direct result of gastric ulcer perforation and 24% were the direct result of exsanguinating hemorrhage. Thus, one-third of deaths occurring in patients treated nonoperatively were due directly to the gastric ulcer and potentially were preventable.
473
TABLE 3. Causes of Death Among Non-Operated (Group I) Patients
Primary Cause of Death
No. of Patients
Perforation of gastric ulcer Exsanguination from gastric ulcer Cardiorespiratory Other systemic cause (CVA, metabolic, hematologic, other GI pathology, etc.)
9 21 18 39
were related to technical problems resulting in a leak from the anastomosis or the duodenal stump, peritonitis, or recurrent bleeding. One patient died of postoperative pancreatitis; 7 died of cardiorespiratory complications and 5 of other systemic causes. While only one-third of all patients in Group II were cachetic, 72% of patients dying after operation were in poor nutritional status. Cachexia was directly related to mortality risk. The mortality risk of patients with a past history of ulcer disease was not different from that of patients without a prior ulcer history. An emergency operation was required in 62 of the 174 operatively treated patients (36%). The indication for emergency operation was bleeding in 44 and perforation in 18 patients. A history of prior symptoms suspicious of ulcer was present in only 45% of patients having an emergency operation. The mortality risk of an emergency operation was 34%'o (21 patients); the risk of recurrent ulcer among survivors was 10%. All patients operated on for hemorrhage had a gastric resection; 15 patients (34%) died and 3 of the 29 surviving patients developed a recurrent ulcer. Eighteen patients had a perforated gastric ulcer and required an emergency operation. Twelve patients simply had the perforation oversewn; 4 died and a recurrent ulcer developed in one of the 8 survivors. A gastric resection was performed in 6 perforated ulcer patients with two operative deaths. While there may have been some selection of patients, resection appeared to carry no more mortality risk than did oversewing of a perforated gastric ulcer. The overall morbidity rate was 58% following an emergency
Operative Therapy TABLE 4. Morbidity and Mortality of Operative Therapy (Group II) The mean age of operatively treated patients was 61 Elective Emergency years, somewhat older than the patient group as a whole. Operations Operations Gastric resection was the most common operation (86%). (n = 112) (n = 62) A three-fourths gastrectomy was described in 90 and a No. % No. % 60% resection in 56 patients. Gastrojejunostomy was the most frequently utilized reconstruction (98 patients); Major complication 30 34 36 58 10 11 13 8 Wound gastroduodenostomy was done in 48 cases. Twelve pa3 5 8 3 leak Anastomotic another 16 a patients had only closure of perforation; 2 2 2 1 Duodenal stump leak 2 2 13 tients had exploration, biopsy or hiatus hernia repair but 8 Postoperative bleeding 10 10 19 12 Cardiorespiratory ulcer. no direct treatment of the gastric 5 6 3 2 Other Overall, the early operative morbidity rate was 40Wo Postoperative 6 7 34 21 death and the mortality risk was 16% (Table 4). Fifteen deaths
KRAUS, MENDELOFF AND CONDON
474
TABLE 5. Late Postoperative Complications (Group II)
Complication
No. of Patients
Proven recurrence Suspected recurrence Overt bleeding Pain Excessive weight loss
6 4 2 2 1 1 4 3
Diarrhea Anemia Cholelithiasis
operation; the most major complication occurring in each patient is recorded in Table 4. Elective operations were performed in 112 patients.
The most common indications were failure of a gastric ulcer to heal or a gastric lesion suspicious for cancer. Other indications were intractable symptoms and obstruction. Gastric resection was done in 96 of these patients. Sixteen patients had exploration, biopsy, gastroenterostomy or hiatus hernia repair but no resection. The perioperative morbidity rate after elective operations was 30%o and the mortality risk was 6%. Long-term complications following operation occurred in 19 patients (17%), including six proven recurrences (Table 5). There were no deaths related to late surgical complications.
Discussion Any retrospective review of case material, such as the
Ann.
Surg. * October 1976
mended to patients who bleed sufficiently from a chronic gastric ulcer to produce melena or a hematemesis. Further delay in securing surgical control of gastric ulcer disease needlessly exposes such patients to the increased mortality risk of a future emergency operation to control recurrent hemorrhage. A history of a prior documented gastric ulcer was present'in 28% of patients in Group I'. An additional 16% developed a recurrent gastric ulcer while undergoing nonoperative therapy. Thus, 44% of patients treated nonoperatively had a proven recurrent gastric ulcer at some time in the course of their disease. A past history of "ulcer disease," the type of ulcer- not being specified, was present in a further' 10% of Group I patients; some of these are likely to have been gastric ulcers. The observation of a high incidence of gastric ulcer recurrence previously has been made many times. '5 9 The conclusion to be derived from the data still deserves re-emphasis: gastric ulcer disease has a high recurrence rate when managed nonoperatively. The proven recurrence rate after operative treatment (Group II) was 3.5%. Four of the 6 recurrent ulcer patients either had an associated duodenal ulcer treated without vagotomy or had an operation (oversew perforation, gastrojejunostomy alone) inadequate to control gastric ulcer disease. Among 146 patients having a definitive resection for their ulcer disease, the two recurrences represent a recurrent ulcer rate of 1.3%. In the literature, recurrence of gastric ulcer after resection is re-
present report, is fraught with difficulties arising from ported as 0_3%.1l3s5.6.15,16 inconsistent application of treatments' and inability to apOf note in this study is the finding that nearly threepreciate the true incidence of minor symptoms and events. fourths of all gastric ulcer recurrences following nonMajor events, such as a death or serious complication, operative therapy occurred at greater than two years, and usually are better documented. With this caveat, our 43% of recurrences occurred at greater than 5 years
study is in accord with the observations of others.1'2'9'16 Gastric ulcers occur in older patients, their ulcers are predominantly on the lesser curvature of the stomach, and 10%o have a concurrent duodenal ulcer. We did not find any difference in the results of gastric analysis between patients with gastric ulcers alone compared with those having concurrent gastric and duodenal ulcers. Thirty-six per cent of our patients in both groups were acid hypersecretors (Table 1). The identity of acid secretory patterns between the two groups may not fulfill a priori expectations, but has been observed previously in another VA based study.11 Bleeding from a gastric ulcer appeared to be an ominous prognostic sign. Forty-six per cent of patients operated on for bleeding had a past or present history of a bleeding episode. In our total patient population, if a patient had had a bleeding episode at some time, he had a 59 per cent chance of requiring an operative procedure, often under emergency circumstances. On the basis of this experience, we believe that an operation should be recom-
(Table 2). This is in direct conflict with traditional teaching,11 although similar findings have been noted by others after long-term followup.I The tendency of gastric ulcers to recur is persistent. This finding emphasizes the necessity for continuous and close long-term observation of patients who are denied the benefits of an operation. The hospital mortality risk for all patients treated by operation was 16%; 34% for emergency procedures and 6% for elective procedures. It should be noted that while this mortality experience was in older, cachectic, poor risk patients operated on from 15 to 25 years ago, such a mortality rate would not be acceptable in 1976. The mortality rates quoted in the literature are lower than ours, being 2-5%1 3 14 for combined elective and emergency procedures, 3-24%1.8,13.16 for emergency procedures only, and 0- 3% after an elective operation.1'8'9'16 Welch16 has shown that mortality increases with age; in his report, the risk of a postoperative death in patients older than 60 years was twice that of younger patients. Although the mean age (61) of our patients dying post-
Vol. 184 * No. 4
PROGNOSIS OF GASTRIC ULCER
operatively was somewhat higher than the mean age (56) of all patients in this study, age alone did not seem to be related to mortality risk. An important observation was that cachexia was present in 72% of our postoperative deaths, as compared to 29%Wo of the total operated group. Poor nutritional state seemed to be the single preoperative factor directly related to increased operative mortality risk. The hospital mortality risk of nonoperative treatment overall was 35%. Of these deaths, one-third were directly related to bleeding or perforation of the gastric ulcer in the absence of other major co-existing disease. At least some of these deaths must be viewed as preventable, since the patients were under a physician's care and could have been operated upon electively. While conclusions drawn from a comparison of mortality rates of nonoperative versus operative therapy would be invidious if based on our study alone, our observation is neither new nor unique.7 1 Kirsner and associates7 observed several years ago that the mortality risk of nonoperative treat,ment of gastric ulcer was as great or greater than the risks then being reported for operative treatment. Over the 25 year period of followup, only two gastric cancers developed, both in patients being treated nonoperatively. This incidence is lower than others report' 4'9'11'14, but a similar incidence has been noted by Lindskov and associates.10 Milwaukee is an area with an incidence of gastric carcinoma somewhat higher than that of the United States as a whole.'2 We believe that these cases are within the range of cancer incidence to be expected in our population and provide no evidence that benign gastric ulcers degenerate into gastric cancers.
DISCUSSION DR. WILLIAM H. REMINE (Rochester, Minnesota): In order to give support to what the authors said in their final remarks, I would like to approach it from a little different angle, however. A study that was conducted at our institution by a group of gastroenterologists and I think it shows some very important features. These were 664 cases of gastric ulcer that were thought by all methods-all of our modalities of study-to be benign in every way. As you break this down, there were 664 patients. With medical management, thinking that these were all benign lesions, there was complete relief in 21%, incomplete relief in 34.5% and operation had to be performed on almost 40%o of these patients. Nine per cent of them died with cancer. These were cases studied by gastroenterologists, not by our surgeons. But the point is that if only 21% of these patients are getting satisfactory relief for a benign lesion with medical management, then I think it becomes rather obvious that, unless these patients get immediate results with medical management, there's very little point in continuing it. We're getting into an age of complacency because of the marked decline in the incidence of carcinoma of the stomach. In 1935, it was 35 or 36 cases per 100,000. Today it's less than 5 cases per 100,000. So
the incidence of malignancy, it's true, is low but in my experience in
475 References
1. Angel, R. T., Giacobine, J. W., Jordan, G. L.: A Current Evaluation of the Problem of Gastric Ulcers. Am. J. Surg. 114:730, 1967. 2. Braasch, J. W., Chaudhuri, D. P., Gregg, J. A., et al.: The Changing Scene in the Treatment of Gastric Ulcer. Surg. Clin. N. Amer. 51:607, 1971. 3. Connolly, J. E.: Vagotomy and Drainage Procedure for Gastric Ulcer. Arch. Surg. 96:586, 1968. 4. Fenger, C., Amdrup, E., Christiansen, P., et al: Gastric Ulcer I. Acta Chir. Scand., 139:455, 1973. 5. Harvey, H. D.: Twenty-five Year Experience with Elective Gastric Resection for Gastric Ulcer. Surg. Gynecol. Obstet., 113: 191, 1961. 6. Johnson, H. D.: Bilroth I and Polya Operations (Letter to Editor). Lancet, 1:298, 1956. 7. Kirsner, J. B., Clayman, C. B., Palmer, W. L.: The Problem of Gastric Ulcer. Arch. Intern. Med., 104:995, 1959. 8. Kraft, R. O., Myers, J., Overton, S., et al.: Vagotomy and the Gastric Ulcer. Am. J. Surg., 121:122, 1971. 9. Larson, N. E., Cain, J. C., Bartholomew, L. G.: Prognosis of Medically Treated Small Gastric Ulcer. N. Engl. J. Med., 264: ll9and 330, 1961. 10. Lindskov, J., Nielsen, J., Amdrup, E., et al.: Causes of Death in Patients with Gastric Ulcers. Acta Chir Scand., 141:670, 1975. 11. Littman, A., et al.: V. A. Cooperative Study on Gastric Ulcers. Gastroenterology 61:566, 1971. 12. Mason, T. J., McKay, F. W., Hoover, R., et al.: Atlas of Cancer Mortality for U.S. Counties: 1950-1969. Washington, United States Department of Health Education and Welfare (DHEW-NIH Publ. 75-780). 13. Nielsen, J., Amdrup, E., Christiansen, P., et al.: Gastric Ulcer II. Acta Chir Scand., 139:460, 1973. 14. Sapala, J. A. and Ponka, J. L.: Operative Treatment of Benign Gastric Ulcers. Am. J. Surg., 125:19, 1973. 15. Sawyers, J. L., Scott, H. W. and Grahm, C.: Clinical Trial of Vagotomy and Pyloroplasty in the Treatment of Benign Gastric Ulcers. Am. J. Surg., 121:119, 1971. 16. Welch, C. E. and Burke, J. F.: Gastric Ulcer Reappraisal. Surgery, 65:708, 1969.
recent years there are more cases of inoperable cancer of the stomach than there were 10 or 15 years ago. This is an important factor to keep in mind, and I would certainly go along with the authors in urging to have earlier surgical management of gastric ulcer. DR. M. MICHAEL EISENBERG (Minneapolis, Minnesota): It is very useful to keep in mind that the failure rate for the so-called test of healing on medical management approaches 25% initially, and that even those who do heal have an approximately 42% recurrence rate within the first two years, and other studies have shown up to an 80o recurrence rate within five years. These data should be combined with data that show that mortality for the perforated gastric ulcer is roughly twice that for the duodenal ulcer. Finally examine the literature on elective surgery for benign gastric ulcer, in which there are numerous series of substantial size, many of them over a hundred patients, in which mortality and recurrence rates both approach zero. Then one comes to the virtually inescapable conclusion (even without raising the specter of which ulcers are malignant and which ulcers are benign) that the most conservative approach to gastric ulcer is probably surgery initially, and not medical. I think it's essential, however, not to overstate the data or to exagger-
Four hundred twenty-two patients with gastric ulcer treated during 1950-1960 were followed up to 25 years with a mean followup of 9 years. Nonoperative treatment was used in 59% with a hospital mortality of 35%, one-third of these deaths being directly due to gastric ulcer perforation or hemorrhage. Operative treatment was used in 41% of patients. The most common operation (86%) was gastric resection without vagotomy. Overall operative mortality was 16%; 34% for emergency procedures and 6% for elective procedures. Cachexia seemed to be the most important factor related to operative mortality. Nonoperative treatment resulted in more than twice the hospital mortality compared to operative treatment. Approximately one-half of all patients treated nonoperatively had a recurrent gastric ulcer at some time during this this study. The recurrence rate following definitive gastric resection was 1.3% compared with 16% during nonoperative therapy. Three-fourths of recurrences occurred later than two years and nearly half of recurrences after more than 5 years of followup. Patients with a prior history of overt bleeding from gastric ulcer disease particularly were at risk for further bleeding. There were coincidental duodenal ulcers in 10% of our patients and a 0.8% incidence of gastric cancer during followup. Long term followup demonstrates the superiority of operative treatment of gastric ulcer and also reveals the continuous propensity of such ulcers to recurrence following nonoperative treatment. Earlier elective operation in patients with overt bleeding, recurrence or persisting symptoms should decrease overall mortality and result in a lower overall long-term risk of ulcer complications.
L ONG term followup of gastric ulcer patients is needed to assess adequately the results of operative and nonoperative treatment, to appreciate the propensity of gastric ulcers to recur, and to control the disease. We are Presented at the Annual Meeting of the American Surgical Association, New Orleans, Louisiana, April 7-9, 1976. * Chief Resident in Surgery. t Associate Clinical Professor of Surgery. t Chief, Surgical Service and Professor of Surgery.
M.D.t
From the Surgical Service, Wood Veterans Administration Hospital, and The Division of Surgery, The Medical College of Wisconsin, Milwaukee, Wisconsin 53193
reporting a retrospective review of 422 gastric ulcer patients treated during the decade of the 1950's and followed for up to 25 years. Patient Material All patients with an ulcer affecting gastric mucosa treated at the Wood VA Hospital during 1950-1960 were retrospectively studied. Because of past clinical imprecision in the diagnosis of certain varieties of gastric ulcer, it was not possible to categorize separately chronic, acute or stress gastric ulcers. Certain patients with prepyloric and pyloric channel ulcers presented a problem of categorization, since they were identified as gastric ulcers at one time and as pre-pyloric or pyloric channel ulcers at other times. Although often considered to have a variant of duodenal ulcer disease, such patients with prepyloric and pyloric channel ulcers have been included. Patients with duodenal ulcer alone were excluded, but included if the duodenal ulcer occurred in combination with a gastric ulcer. Patients with a proven diagnosis of gastric cancer were excluded and are part of a separate report. The 422 patients originally under study had been reviewed in 1960, but the observations were not published. During 1973-1975, 289 members of the original study group were re-evaluated by chart review, mail question-
471
KRAUS, MENDELOFF AND CONDON
472
TABLE 1. Fasting Gastric Analysis
Gastric Secretory State
Achlorhydria Hyposecretion Normosecretion (1.5-3.0 mEq/hr) Hypersecretion
Gastric Ulcer Alone (n = 238)
Concurrent Gastric and Duodenal Ulcer (n = 32)
No. Pts.
%
No. Pts.
%
34 18
14 8
4 2
13 6
99 87
42 36
14 12
44 37
naire, telephone and personal contact. The others had died or otherwise had been lost to followup in the interval. Patients thus were followed for varying periods up to 25 years. The mean period of followup was 9 years. All patients were male; their mean age was 56 years, and 46% were older than 60 years of age. Patients were divided into two groups depending upon the treatment received during their first, or index, hospitalization between 1950-1960 for gastric ulcer disease. Group I was composed of 248 patients (59o of total) treated nonoperatively. There was no prior history of an ulcer in 177 patients and the index admission was their first treatment for gastric ulcer. A prior history of symptomatic ulcer was present in 71 patients, of whom 31 previously had been documented as gastric ulcers. These latter patients represent proven failure of previous nonoperative treatment of gastric ulcer at the time of entry into the study, despite which further nonoperative therapy was prescribed. Some patients in this group later underwent an operation. Group II comprised 174 patients (41% of total) treated operatively during their index hospitalization for gastric ulcer. There was no prior ulcer history in 88 patients and their operation was the first definitive treatment of their gastric ulcer disease. There were 51 patients in Group II with a documented history of gastric ulcer disease and an additional 35 patients with a history of "ulcer disease" who had an operation during the index admission. Observations The incidence of most symptoms and signs and the results of investigations were essentially identical in both groups. Pretreatment characteristics common to both groups included complaints of epigastric pain and tenderness (77%), historic duration of pain, history of prior hemorrhage (20%o), nutritional status (29%o of both groups were cachectic), other findings of physical examination, demonstration of an ulcer radiologically (69o positive examinations), identification of an ulcer on rigid endoscopy (38% positive), the location of the ulcer (90% were on the lesser curvature), the results of gastric
Ann.
Surg. * October 1976
secretory studies and the incidence of guaiac positive stools (25% in both groups). Patients were seen during followup at irregular intervals by a variety of observers. Unfortunately, there was no unanimity about recording of patient's complaints; some records were detailed, others were not. Most patients in both groups were symptomatically improved after any treatment. Episodes of post-treatment major complications were clearly identified in the notes. But, we found it impossible to arrive at a reliable judgment concerning the status of most minor symptoms in many patients, and have had to omit comments or conclusions about the effects of treatment on most subjective complaints.
Bleeding The incidence of overt blood loss was the only clinical feature different between the two groups. Surgicallytreated patients (Group II) had an incidence of hematemesis and melena of 38% compared with 21% of gross blood loss in patients treated non-operatively (Group I). Fifty-nine per cent of patients who had a history of bleeding from a gastric ulcer in the past, or evidence of bleeding, however mild, at entry into the study, ultimately required an emergency or elective operation to control their gastric ulcer disease.
Concurrent Duodenal Ulcer A duodenal ulcer was demonstrated in conjunction with the gastric ulcer in 44 of 422 patients by x-ray, endoscopy or during operation. The results of gastric analysis did not differ between patients with only gastric ulcer and those who also had an associated duodenal ulcer (Table 1). Of the patients with a concurrent duodenal ulcer, 23 were treated nonoperatively with a 13% mortality and a recurrence rate of 39%O. An operation was the treatment of 21 patients with a 10o mortality risk and a recurrence rate of 1%o. No patient had a vagotomy, a factor which may have adversely influenced the recurrence risk in operatively treated patients.
Nonoperative Therapy Nonoperative treatment varied from patient to patient. Antacids and a bland diet uniformly were prescribed; anticholinergics and sedation were used less regularly. Nineteen ulcers failed to heal during 6 to 15 weeks of treatment; these patients then had an operation. Forty patients developed a documented recurrence of their ulcer while under therapy; 27 required operative control oftheir disease. The risk of recurrence existed throughout the quarter century of followup (Table 2). Three-fourths of
VOl. 184 . NO. 4
PROGNOSIS OF GASTRIC ULCER
TABLE 2. Time of Appearance of Proven Recurrent Ulcers Among Nonoperatively Treated Patients (Group I)
Duration of Followup to Recurrence (yrs.)
No. of Patients at Risk
No. of Recurrent Ulcers
Recurrence Risk
0-2
1
12 123
14
10 5 2
12 12 6
6-10 11-15 16-25
86 58 31
(%)
proven recurrences occurred after two years, while 43% of recurrences occurred after more than 5 years of
followup. The incidence of complications during nonoperative therapy was 33%. Most of this morbidity is represented by proven recurrent gastric ulcer and by nonhealing ulcers. Severe pain and bleeding due to a suspected recurrent gastric ulcer was present in an additional 5% of patients in Group I. A proven duodenal ulcer was found in a further 3%. A gastric cancer appeared in two patients in this group, 13 and 18 years after entry into the study. The hospital mortality of nonoperative therapy was 35%. Table 3 lists the major causes of death. In categorizing patients for inclusion in Table 3, only the major defect in homeostasis has been assigned responsibility for mortality. Many deaths were related to the generally deteriorated physical state of the patient to which had been added the stress of the gastric ulcer. Mortality in such instances was not ascribed directly to the gastric ulcer. Complications of gastric ulcer in the absence of other major system disease were responsible for a significant proportion of deaths in patients treated nonoperatively. Ten per cent of all deaths among patients in Group I were the direct result of gastric ulcer perforation and 24% were the direct result of exsanguinating hemorrhage. Thus, one-third of deaths occurring in patients treated nonoperatively were due directly to the gastric ulcer and potentially were preventable.
473
TABLE 3. Causes of Death Among Non-Operated (Group I) Patients
Primary Cause of Death
No. of Patients
Perforation of gastric ulcer Exsanguination from gastric ulcer Cardiorespiratory Other systemic cause (CVA, metabolic, hematologic, other GI pathology, etc.)
9 21 18 39
were related to technical problems resulting in a leak from the anastomosis or the duodenal stump, peritonitis, or recurrent bleeding. One patient died of postoperative pancreatitis; 7 died of cardiorespiratory complications and 5 of other systemic causes. While only one-third of all patients in Group II were cachetic, 72% of patients dying after operation were in poor nutritional status. Cachexia was directly related to mortality risk. The mortality risk of patients with a past history of ulcer disease was not different from that of patients without a prior ulcer history. An emergency operation was required in 62 of the 174 operatively treated patients (36%). The indication for emergency operation was bleeding in 44 and perforation in 18 patients. A history of prior symptoms suspicious of ulcer was present in only 45% of patients having an emergency operation. The mortality risk of an emergency operation was 34%'o (21 patients); the risk of recurrent ulcer among survivors was 10%. All patients operated on for hemorrhage had a gastric resection; 15 patients (34%) died and 3 of the 29 surviving patients developed a recurrent ulcer. Eighteen patients had a perforated gastric ulcer and required an emergency operation. Twelve patients simply had the perforation oversewn; 4 died and a recurrent ulcer developed in one of the 8 survivors. A gastric resection was performed in 6 perforated ulcer patients with two operative deaths. While there may have been some selection of patients, resection appeared to carry no more mortality risk than did oversewing of a perforated gastric ulcer. The overall morbidity rate was 58% following an emergency
Operative Therapy TABLE 4. Morbidity and Mortality of Operative Therapy (Group II) The mean age of operatively treated patients was 61 Elective Emergency years, somewhat older than the patient group as a whole. Operations Operations Gastric resection was the most common operation (86%). (n = 112) (n = 62) A three-fourths gastrectomy was described in 90 and a No. % No. % 60% resection in 56 patients. Gastrojejunostomy was the most frequently utilized reconstruction (98 patients); Major complication 30 34 36 58 10 11 13 8 Wound gastroduodenostomy was done in 48 cases. Twelve pa3 5 8 3 leak Anastomotic another 16 a patients had only closure of perforation; 2 2 2 1 Duodenal stump leak 2 2 13 tients had exploration, biopsy or hiatus hernia repair but 8 Postoperative bleeding 10 10 19 12 Cardiorespiratory ulcer. no direct treatment of the gastric 5 6 3 2 Other Overall, the early operative morbidity rate was 40Wo Postoperative 6 7 34 21 death and the mortality risk was 16% (Table 4). Fifteen deaths
KRAUS, MENDELOFF AND CONDON
474
TABLE 5. Late Postoperative Complications (Group II)
Complication
No. of Patients
Proven recurrence Suspected recurrence Overt bleeding Pain Excessive weight loss
6 4 2 2 1 1 4 3
Diarrhea Anemia Cholelithiasis
operation; the most major complication occurring in each patient is recorded in Table 4. Elective operations were performed in 112 patients.
The most common indications were failure of a gastric ulcer to heal or a gastric lesion suspicious for cancer. Other indications were intractable symptoms and obstruction. Gastric resection was done in 96 of these patients. Sixteen patients had exploration, biopsy, gastroenterostomy or hiatus hernia repair but no resection. The perioperative morbidity rate after elective operations was 30%o and the mortality risk was 6%. Long-term complications following operation occurred in 19 patients (17%), including six proven recurrences (Table 5). There were no deaths related to late surgical complications.
Discussion Any retrospective review of case material, such as the
Ann.
Surg. * October 1976
mended to patients who bleed sufficiently from a chronic gastric ulcer to produce melena or a hematemesis. Further delay in securing surgical control of gastric ulcer disease needlessly exposes such patients to the increased mortality risk of a future emergency operation to control recurrent hemorrhage. A history of a prior documented gastric ulcer was present'in 28% of patients in Group I'. An additional 16% developed a recurrent gastric ulcer while undergoing nonoperative therapy. Thus, 44% of patients treated nonoperatively had a proven recurrent gastric ulcer at some time in the course of their disease. A past history of "ulcer disease," the type of ulcer- not being specified, was present in a further' 10% of Group I patients; some of these are likely to have been gastric ulcers. The observation of a high incidence of gastric ulcer recurrence previously has been made many times. '5 9 The conclusion to be derived from the data still deserves re-emphasis: gastric ulcer disease has a high recurrence rate when managed nonoperatively. The proven recurrence rate after operative treatment (Group II) was 3.5%. Four of the 6 recurrent ulcer patients either had an associated duodenal ulcer treated without vagotomy or had an operation (oversew perforation, gastrojejunostomy alone) inadequate to control gastric ulcer disease. Among 146 patients having a definitive resection for their ulcer disease, the two recurrences represent a recurrent ulcer rate of 1.3%. In the literature, recurrence of gastric ulcer after resection is re-
present report, is fraught with difficulties arising from ported as 0_3%.1l3s5.6.15,16 inconsistent application of treatments' and inability to apOf note in this study is the finding that nearly threepreciate the true incidence of minor symptoms and events. fourths of all gastric ulcer recurrences following nonMajor events, such as a death or serious complication, operative therapy occurred at greater than two years, and usually are better documented. With this caveat, our 43% of recurrences occurred at greater than 5 years
study is in accord with the observations of others.1'2'9'16 Gastric ulcers occur in older patients, their ulcers are predominantly on the lesser curvature of the stomach, and 10%o have a concurrent duodenal ulcer. We did not find any difference in the results of gastric analysis between patients with gastric ulcers alone compared with those having concurrent gastric and duodenal ulcers. Thirty-six per cent of our patients in both groups were acid hypersecretors (Table 1). The identity of acid secretory patterns between the two groups may not fulfill a priori expectations, but has been observed previously in another VA based study.11 Bleeding from a gastric ulcer appeared to be an ominous prognostic sign. Forty-six per cent of patients operated on for bleeding had a past or present history of a bleeding episode. In our total patient population, if a patient had had a bleeding episode at some time, he had a 59 per cent chance of requiring an operative procedure, often under emergency circumstances. On the basis of this experience, we believe that an operation should be recom-
(Table 2). This is in direct conflict with traditional teaching,11 although similar findings have been noted by others after long-term followup.I The tendency of gastric ulcers to recur is persistent. This finding emphasizes the necessity for continuous and close long-term observation of patients who are denied the benefits of an operation. The hospital mortality risk for all patients treated by operation was 16%; 34% for emergency procedures and 6% for elective procedures. It should be noted that while this mortality experience was in older, cachectic, poor risk patients operated on from 15 to 25 years ago, such a mortality rate would not be acceptable in 1976. The mortality rates quoted in the literature are lower than ours, being 2-5%1 3 14 for combined elective and emergency procedures, 3-24%1.8,13.16 for emergency procedures only, and 0- 3% after an elective operation.1'8'9'16 Welch16 has shown that mortality increases with age; in his report, the risk of a postoperative death in patients older than 60 years was twice that of younger patients. Although the mean age (61) of our patients dying post-
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PROGNOSIS OF GASTRIC ULCER
operatively was somewhat higher than the mean age (56) of all patients in this study, age alone did not seem to be related to mortality risk. An important observation was that cachexia was present in 72% of our postoperative deaths, as compared to 29%Wo of the total operated group. Poor nutritional state seemed to be the single preoperative factor directly related to increased operative mortality risk. The hospital mortality risk of nonoperative treatment overall was 35%. Of these deaths, one-third were directly related to bleeding or perforation of the gastric ulcer in the absence of other major co-existing disease. At least some of these deaths must be viewed as preventable, since the patients were under a physician's care and could have been operated upon electively. While conclusions drawn from a comparison of mortality rates of nonoperative versus operative therapy would be invidious if based on our study alone, our observation is neither new nor unique.7 1 Kirsner and associates7 observed several years ago that the mortality risk of nonoperative treat,ment of gastric ulcer was as great or greater than the risks then being reported for operative treatment. Over the 25 year period of followup, only two gastric cancers developed, both in patients being treated nonoperatively. This incidence is lower than others report' 4'9'11'14, but a similar incidence has been noted by Lindskov and associates.10 Milwaukee is an area with an incidence of gastric carcinoma somewhat higher than that of the United States as a whole.'2 We believe that these cases are within the range of cancer incidence to be expected in our population and provide no evidence that benign gastric ulcers degenerate into gastric cancers.
DISCUSSION DR. WILLIAM H. REMINE (Rochester, Minnesota): In order to give support to what the authors said in their final remarks, I would like to approach it from a little different angle, however. A study that was conducted at our institution by a group of gastroenterologists and I think it shows some very important features. These were 664 cases of gastric ulcer that were thought by all methods-all of our modalities of study-to be benign in every way. As you break this down, there were 664 patients. With medical management, thinking that these were all benign lesions, there was complete relief in 21%, incomplete relief in 34.5% and operation had to be performed on almost 40%o of these patients. Nine per cent of them died with cancer. These were cases studied by gastroenterologists, not by our surgeons. But the point is that if only 21% of these patients are getting satisfactory relief for a benign lesion with medical management, then I think it becomes rather obvious that, unless these patients get immediate results with medical management, there's very little point in continuing it. We're getting into an age of complacency because of the marked decline in the incidence of carcinoma of the stomach. In 1935, it was 35 or 36 cases per 100,000. Today it's less than 5 cases per 100,000. So
the incidence of malignancy, it's true, is low but in my experience in
475 References
1. Angel, R. T., Giacobine, J. W., Jordan, G. L.: A Current Evaluation of the Problem of Gastric Ulcers. Am. J. Surg. 114:730, 1967. 2. Braasch, J. W., Chaudhuri, D. P., Gregg, J. A., et al.: The Changing Scene in the Treatment of Gastric Ulcer. Surg. Clin. N. Amer. 51:607, 1971. 3. Connolly, J. E.: Vagotomy and Drainage Procedure for Gastric Ulcer. Arch. Surg. 96:586, 1968. 4. Fenger, C., Amdrup, E., Christiansen, P., et al: Gastric Ulcer I. Acta Chir. Scand., 139:455, 1973. 5. Harvey, H. D.: Twenty-five Year Experience with Elective Gastric Resection for Gastric Ulcer. Surg. Gynecol. Obstet., 113: 191, 1961. 6. Johnson, H. D.: Bilroth I and Polya Operations (Letter to Editor). Lancet, 1:298, 1956. 7. Kirsner, J. B., Clayman, C. B., Palmer, W. L.: The Problem of Gastric Ulcer. Arch. Intern. Med., 104:995, 1959. 8. Kraft, R. O., Myers, J., Overton, S., et al.: Vagotomy and the Gastric Ulcer. Am. J. Surg., 121:122, 1971. 9. Larson, N. E., Cain, J. C., Bartholomew, L. G.: Prognosis of Medically Treated Small Gastric Ulcer. N. Engl. J. Med., 264: ll9and 330, 1961. 10. Lindskov, J., Nielsen, J., Amdrup, E., et al.: Causes of Death in Patients with Gastric Ulcers. Acta Chir Scand., 141:670, 1975. 11. Littman, A., et al.: V. A. Cooperative Study on Gastric Ulcers. Gastroenterology 61:566, 1971. 12. Mason, T. J., McKay, F. W., Hoover, R., et al.: Atlas of Cancer Mortality for U.S. Counties: 1950-1969. Washington, United States Department of Health Education and Welfare (DHEW-NIH Publ. 75-780). 13. Nielsen, J., Amdrup, E., Christiansen, P., et al.: Gastric Ulcer II. Acta Chir Scand., 139:460, 1973. 14. Sapala, J. A. and Ponka, J. L.: Operative Treatment of Benign Gastric Ulcers. Am. J. Surg., 125:19, 1973. 15. Sawyers, J. L., Scott, H. W. and Grahm, C.: Clinical Trial of Vagotomy and Pyloroplasty in the Treatment of Benign Gastric Ulcers. Am. J. Surg., 121:119, 1971. 16. Welch, C. E. and Burke, J. F.: Gastric Ulcer Reappraisal. Surgery, 65:708, 1969.
recent years there are more cases of inoperable cancer of the stomach than there were 10 or 15 years ago. This is an important factor to keep in mind, and I would certainly go along with the authors in urging to have earlier surgical management of gastric ulcer. DR. M. MICHAEL EISENBERG (Minneapolis, Minnesota): It is very useful to keep in mind that the failure rate for the so-called test of healing on medical management approaches 25% initially, and that even those who do heal have an approximately 42% recurrence rate within the first two years, and other studies have shown up to an 80o recurrence rate within five years. These data should be combined with data that show that mortality for the perforated gastric ulcer is roughly twice that for the duodenal ulcer. Finally examine the literature on elective surgery for benign gastric ulcer, in which there are numerous series of substantial size, many of them over a hundred patients, in which mortality and recurrence rates both approach zero. Then one comes to the virtually inescapable conclusion (even without raising the specter of which ulcers are malignant and which ulcers are benign) that the most conservative approach to gastric ulcer is probably surgery initially, and not medical. I think it's essential, however, not to overstate the data or to exagger-
