Cancer of the Stomach

Cancer of the Stomach Review of Consecutive Ten Year Intervals KENNETH ADASHEK, M.D.,* JAMES SANGER, M.D.,t WILLIAM P. LONGMIRE, JR., M.D.* Records were reviewed for all patients who underwent primary treatment for adenocarcinoma of the stomach at two UCLA hospitals between 1956 and 1975. Division of the data into two, ten-year time periods reveals a pattern of unchanging presentation and pathologic characteristics which probably accounts for the unaltered response to operative therapy. The consistency of certain prognostic findings justifies a surgical approach in which extensive resections are only selectively employed. T HE DECLINING INCIDENCE of gastric cancer represents a persistent puzzle. The National Cancer Institute's Third National Cancer Survey showed a 63% decrease in this disease during the two decades from 1950 to 1970.7 Moreover, the age-adjusted death rate from stomach cancer diminished more than 40% during the periods between 1950-1952 and 1965-1967, a reduction evidently stemming primarily, if not exclusively, from a decrease in incidence of gastric cancer. Cady has claimed that "no progress in the surgical management of this disease has been accomplished since 1950, despite a generally aggressive surgical approach."3 It is certainly distressing that his statement seems to be true despite apparent advances in diagnostic and therapeutic techniques. We have, therefore, been motivated to review our own experience in dealing with stomach cancer, not only to further delineate the natural history of the disease, but also to determine, by comparing two tenyear periods, whether or not any changes can be observed in the recognition, diagnosis, virulence, treatment, or survival of patients with stomach cancer. Analysis of these factors might help to clarify the apparent therapeutic standstill and provide further corroboration of currently recommended surgical therapy. Reprint requests: Kenneth Adashek, M.D., % Editor's Office, UCLA School of Medicine, Los Angeles, California 90024. Supported by NIH Special Research Resources Grant RR-3. Submitted for publication: July 14, 1978. From the *Department of Surgery, UCLA School of Medicine, Los Angeles, and tharbor General Hospital, Torrance, California Methods Records were reviewed for all patients with adenocarcinoma of the stomach who were seen during the years between 1956 and 1975 at UCLA Hospital and Harbor General Hospital. Selected information was recorded for the 501 patients whose initial treatment took place at these hospitals. Patients transferred to either of these hospitals for therapy subsequent to exploration or initial treatment at other institutions were excluded. Follow-up data were retrieved with the help of the Central Tumor Registry at UCLA. Tabulation and analysis were carried out with the help of the Health Sciences Computing Facility at UCLA. The survival rates, computed by the standard life table method,4 were based on the number of persons known to be alive at the beginning of each monthly interval. Patients lost to follow-up were assumed to have the same survival experience as those pursued beyond the particular time of loss to follow-up. Deaths without cancer were treated the same as losses to follow-up for other reasons. Tests of significance comparing the survival experience among groups were accomplished by means of a rank test developed by Breslow.' Results Data were initially analyzed for the entire group of 501 patients who were admitted between January 1, ;956, and December 31, 1975. Certain features were then selected for comparison between the time periods, using the ten year periods 1956 through 1965 and 1966 through 1975. Presenting Characteristics The mean duration of symptoms was 6.85 months. The chief admission complaints, as shown in Table 1, 0003-4932/79/0100/0006 $00.75 (D J. B. Lippincott Company 6

VOl. 189.9 NO. I CANCER OF THE STOMACH 7 TABLE 1. Chief Complaint Among 501 Patients Symptoms No. of Patients Per Cent Pain 193 38 Weight loss 120 24 Vomiting 119 24 Weakness 86 17 Bleeding 80 16 Dyspepsia 81 16 Dysphagia 64 13 Anorexia 20 4 were pain and weight loss, and these are also the most frequent symptoms reported in other series, in some instances noted in more than 50% of patients. The physical findings of weight loss or a palpable abdominal mass in almost one-third of patients (Table 2) likewise confirm previous reports.6 Diagnosis Table 3 indicates that more than 90% of patients undergoing upper GI x-rays were found to have one or more abnormalities. The dominant findings was a filling defect (62%), with ulceration noted in 9% and obstruction in 15%. However, a substantial number of these patients were explored with the specific diagnosis still in considerable doubt. Moreover, of the patients undergoing gastroscopy, only about half had a biopsyproven diagnosis of carcinoma established prior to laparotomy. It is interesting that the cytologic and secretory studies, which are less frequently employed, were nevertheless as accurate diagnostically as gastroscopy. Operative Therapy Only 74% of the 501 patients came to laparotomy, with a resection rate of 44% for the entire population of patients admitted, and a curative resection rate of 26% (Table 4). The 222 resections represented 60% of the patients undergoing operation; the 132 resections for cure comprised 36% of the operated patients. The overall operative mortality rate was 13% of the 369 operated patients (Table 5 lists the specific complications), and the overall five year survival rate was 10% of the 501 patients who underwent initial treatment at our hospitals. TABLE 2. Findings on Physical Examination No. of Patients Per Cent Weight loss 145 29 Abdominal mass 146 29 Cervical lymph nodes 35 7 Rectal shelf 8 2 TABLE 3. Diagnostic Studies Employed Positive Results (% of Patients No. of Patients Per Cent Tested) Upper GI series 471 94 91 Gastroscopy 162 32 54 Gastric washings 111 22 59 Gastric acid studies 49 10 61 Characteristics of the Pathology The data in Table 6 confirm what was implied by the symptoms and physical findings. This disease is usually seen when it is already advanced; in more than half the resected specimens, the cancer had penetrated through the serosa. In most cases the lesions were larger then 4 cm, and in 44% the tumor had spread to secondary lymph nodes, which are perigastric nodes remote from the primary tumor (equivalent to N2 involvement using the TNM classification). These characteristics are similar to the findings reported by Kennedy.6 Survival Data Operative mortality and five year survival for curative resections are listed in Table 7 according to the type of resection performed. The particularly dismal results following total gastrectomy undoubtedly reflect the fact that the more extensive procedure, carrying the maximum operative risk, is applied to the patients with the most advanced disease. Although the other survival figures are more encouraging, it must be noted that 10-12% of patients who die of disease succumb more than five years after resection,25 so that cure rates are undoubtedly even lower than the five year survivals reported in Table 7. Table 8 records cumulative survival as a function of various features of the pathology. The total number of patients in each category is less than the total number of curative resections reported, because in each category specific data could not be obtained for a small number of patients. The degree of lymph node involvement is seen to correlate significantly with survival for all three categories of involvement. Depth of penetra- TABLE 4. Operative Therapy Among 501 Patients Type of Surgery No. of Patients Per Cent Laparotomy 369 74 Total resections 222 44 Curative resections 132 26 Palliative resections 90 18 Palliative bypass 62 12 Exploration only 85 17

8 TABLE 5. Major Postoperative Complications % of All Operated Cases Complication No. of Patients (369) Pneumonia 42 11 Anastomotic leak 29 8 Cardiac 23 6 Bleeding 15 4 Pancreatitis 6 2 Anastomotic obstruction 6 2 Renal failure 6 2 Pulmonary embolism 3 1 tion shows a significant correlation for serosal involvement as compared with lesser degrees of penetration, and in fact serosal involvement appears to be as prognostically unfavorable as involvement of secondary lymph nodes. However, since we have not isolated patients with serosal involvement and negative nodes, nor those with nodal involvement and shallow penetration, comparing these features is speculative. We found that the size of the tumor provides a suggestive but not significant indication of prognosis, using a 4 cm dividing point, but Cady noted a positive correlation with prognosis when ulcerative or polypoid carcinomas were stratified more precisely. Comparison by Time Period Table 9 shows the decrease in absolute number of patients seen, with male-to-female ratios essentially ADASHEK, SANGER AND LONGMIRE TABLE 6. Ann. Surg. January 1979 Characteristics of the Pathology in Resected Cases No. of Patients Per cent Depth of penetration Mucosa or submucosa 14 6* Muscularis 72 32* Serosa 125 56* Not recorded 11 5* Extent in gastric wall <4 cm 67 30 >4 cm 140 63 Not recorded 15 7 Lymph nodes involved All nodes negative 68 31 Primary nodes positive 27 12 Secondary nodes positive 97 44 Not recorded 30 14 * Per cent of 222 resected cases. unchanged. This 14% decrease in the number of stomach cancer patients occurred during intervals when there was a 70% increase in the number of all adult hospital admissions. Population shifts prevent any conclusions about changing incidence of the disease, but the numbers are suggestive of a bona fide reduction. In Table 10 certain characteristics of symptoms and physical findings are compared. The mean duration of symptoms for both groups is almost identically short. The American Joint Committee on Cancer Staging and End Results Reporting found a longer duration of symptoms to be correlated with longer survival, perhaps indicating that such patients had slower growing TABLE 7. Curative Resections -Operative Mortality and Survival by Type of Resection Operative Mortality Type of Resection No. of Patients Per cent Number Per cent 5 Year Survival Total gastrectomy 27 20 4 15 10% Subtotal gastrectomy 86 65 6 7 38% Esophagogastrectomy 19 14 2 11 37% All curative resections 132 100 12 9 32% TABLE 8. Curative Resections -Cumulative Survival by Pathologic Characteristics No. of Median Patients % 2 Mos. 6 Mos. 1 Yr. 2 Yrs. 3 Yrs. 5 Yrs. # Mos. Depth of penetration* Mucosa or submucosa 14 11.92.83.83.59.44.44 28.6 Muscularis 55 42.98.86.72.53.51.45 44.2 Serosa 59 45.96.81.61.40.25.15 15.4 Extent in gastric wailt -4cm 53 40.92.90.71.54.48.37 35.5 >4 cm 74 56 1.00.79.66.42.33.28 19.3 Lymph nodest All negative 56 42.98.94.79.63.57.44 45.1 Primary positive 24 18 1.00.91.65.49.42.34 23.8 Secondary positive 40 30.95.69.55.25.18.18 12.6 *p =.169. tp =.374. tp=.001.

Vol. 189. NO.1I TABLE 9. Comparison by Time Period-Basic Information CANCER OF THE STOMACH No. of patients 269 232 Per cent male 62 61 Per cent female 38 39 Family history of stomach cancer 7 3 tumors.6 If this is the case, then our data on duration of symptoms might suggest that we are seeing a disease of unchanging virulence. The diminished incidence of palpable mass lesions and demonstrable weight loss would not seem to support such a conclusion. However, we also compared characteristics of the pathology by time period (using the data in Table 6), and found no significant difference in distribution within any category. The increased incidence of dysphagia probably reflects the increase in proximal lesions seen during the second ten year period. The most important changes in diagnostic evaluation were the increased use of gastroscopy during the recent decade, and the improved accuracy of the test itself in establishing a diagnosis (Table 11). These are likely reasons for the smaller percentage of patients whose laparotomy was considered part of their diagnostic work-up. The major benefit seems to have been the fact that fewer patients underwent exploration only (21% vs. 12%, Table 12). The positive biopsy rate of 60% of patients who had endoscopy is a clear improvement, but still falls short of the expectations of most clinicians, and points out the limitations of this procedure. The resection rates shown in Table 12 are based on the total patient population in each time period. Total resections correspond to 55% of operated cases in 1956-65, and 66% of operated cases in 1966-75. Similarly, the curative resection rates were 34% of operated TABLE 10. Comparison by Time Period- Characteristics of Presentation Duration of symptoms (mean no. of months) 6.9 6.8 Chief complaint Pain 38% 40% Vomiting 24% 24% Bleeding 19% 13% Dysphagia 9% 17% Physical examination Weight loss 37% 19% Abdominal mass 38% 19% Cervical lymph nodes 8% 6% Rectal shelf 2% 2% TABLE 11. Comparison by Time Period -Diagnosis 1956-1965 1966-1975 Upper GI Filling defect 63% 61% Linitis 12% 10% Ulceration Obstruction 15% 16% 23% 14% Gastroscopy performed 12% 56% Positive biopsy-per cent of patients tested 30% 60% Explored for diagnosis 70% 51% cases in the first time period, and 41% in the second time period. The most striking findings are the remarkably similar operative mortality and five year survival rates for the two time periods. As indicated in Table 13, figures for the specific subgroups undergoing subtotal gastrectomy also demonstrate minimal differences between time periods. The numbers of patients in the total gastrectomy and esophagogastrectomy groups are too small for meaningful comparison of mortality and survival data between groups. Cumulative survival as a function of the pathology (penetration, extent, node involvement), also compared across time periods, was not significantly different. Discussion ReMine et al.8 reported survival rates for patients with stomach cancer who were seen in a 1940-49 time period, and noted minimal improvement for similar patients treated between 1950-59. Cady compared patterns of surgical therapy and found little change between 1950 and 1966. Our observations have been similar to theirs and bring the evaluation up to 1975. Five year survival in our series remains at 10% for all patients admitted with stomach cancer, and at 32% for patients undergoing resection for cure. Analysis of our cases reveals that from the standpoint of symptoms and pathologic findings, we are not seeing patients any TABLE 12. Comparison by Time Period-Operative Therapy Laparotomy 71% 76% Total resections 39% 51% Curative resections 24% 31% Exploration only 21% 12% Operative mortality All cases 11% 15% Curative resections 9% 9% Five year survival All cases 8% 10% Curative resections 31% 32% 9

10 ADASHEK, SANGER AND LONGMIRE Ann. Surg. * January 1979 TABLE 13. Comparison by Time Period-Operative Mortality and Survival by Type of Curative Resections Operative Mortality Type of Resection No. of Patients Per Cent Number Per cent 5 Year Survival 1956-1965 Total gastrectomy 15 23 2 13 Subtotal gastrectomy 43 67 2 5 40% Esophagogastrectomy 6 9 2 33 1966-1975 Total gastrectomy 12 18 2 17 Subtotal gastrectomy 43 63 4 9 34% Esophagogastrectomy 13 19 0 earlier in their course. The impact of increasing use of endoscopy seems to be that some patients may be spared a needless exploration, but it has not resulted in finding disease during more curable stages. The persistently dismal survival rates for patients with serosal penetration or secondary lymph node involvement seem to indicate that extensive resections have a limited application. For example, while routine prophylactic removal of potential sites of nodal metastases has been recommended by some authors, given the prognosis when such distant nodes are positive, we would advise against this practice whenever the extended resection would add significantly to operative mortality. This caution applies chiefly to dissection at the celiac axis and at the tail of the pancreas. On the other hand, if gross disease is present in locations adjacent to the stomach, an aggressive approach is probably justified when the tumor can be completely excised, although we still believe that indications for resection of the tail of the pancreas are rare. Acknowledgments We wish to acknowledge the help of Mildred Weiss and Jane McMahon at the UCLA Central Tumor Registry, and Lee Youkeles in the Department of Biomathematics. Computing assistance was obtained from the Health Sciences Computing Facility at UCLA. References 1. Breslow, H.: A Generalized Kruskal-Wallis Test for Comparing K Samples Subject to Unequal Patterns of Censorship. Biometrika, 47:579, 1970. 2. Cady, B., Ramsden, D. A. and Choe, D. S.: Treatment of Gastric Cancer. Surg. Clin. North Am., 56:599, 1976. 3. Cady, B., Ramsden, D. A. and Haggitt, R. C.: Gastric Cancer- Contemporary Aspects. Am. J. Surg., 133:423, 1977. 4. Cutler, S. J. and Ederer, F.: Maximum Utilization of the Life- Table Method in Analyzing Survival. J. Chron. Dis., 8: 699, 1958. 5. Hoerr, S. O.: Prognosis for Carcinoma of the Stomach. Surg. Gynecol. Obstet., 137:205, 1973. 6. Kennedy, B. J.: TNM Classification for Stomach Cancer. Cancer, 26:971, 1970. 7. Nealon, T. F.: Management of the Patient with Cancer. Philadelphia, W. B. Saunders Co., 1976. 8. ReMine, W. H., Priestly, J. T. and Berkson, J.: Cancer of the Stomach. Philadelphia, W. B. Saunders, Co., 1964.