Stomach cancer

Stomach Cancer Janet F. Wang

N the United States, the incidence of stomach cancer has shown a dramatic downward trend since 1930. Prior to 1945, mortality of men from stomach cancer exceeded deaths from any other type of cancer.’ The survival rate, however, remains low becausethe diseaseis usually not detected until it has reached an advanced stage. In contrast, stomach cancer is the leading cause of death in Japan, and there is an emphasison early detection which has led to improved survival rates. Much of our understanding of the pathogenesisof this tumor has come from studies in Japan and among Japanesemigrants. This paper will review the epidemiology, etiology, diagnosis, biologic behavior, treatment, and major nursing care issues of stomach cancer.

I

EPIDEMIOLOGY

The age-adjusteddeath rate per 100,000 population from stomachcanceris highest in CostaRica (male, 63.2; female, 27.8), followed by Japan (male, 58.8; female, 27.5), and Chile (male, 51.8; female, 22.3). These rates are at least seventimes greater than those in the United States(male, 7.8; female, 3.7).2 In 1988, the American Cancer Society estimates there will be 24,800 new casesof stomach cancer and 14,400 deaths in the United States.*Men develop the disease more commonly than women. This is a diseaseof underdevelopedcountries and of lesser developed regions within a country. ETIOLOGY

The exact causeof stomachcancer is unknown, but several risk factors that are primarily dietary have been identified as having an association. Dietary Factors Studies of groups in Japan, Hawaii, South Africa, Bombay, Singapore, and many other countries indicate that it is the diet rather than the physical environment that is important in determining the risk of developing stomachcancers.3Salty fish and salt-cured salami, sausage,and ham have been related to increasedrisk of stomachcancer among the native Japanese.4Time-trend analysis in Japan Seminars in Oncology Nursing, Vol 4, No 4 (November),

1988: pp 257-264

has demonstrateda parallel between the decline in per capita consumption of salted fish and vegetables and mortality from stomach cancer.’ Before the use of refrigeration becamecommonplace, salt intake was higher becauseit was used to preserve food for winter. Although it has not been demonstrated conclusively that salt can produce atrophic gastritis, this condition is extremely common among people with a high salt intake.6 Salt is probably not directly related to stomach cancer through carcinogenic properties. Instead, it is thought that its strong osmotic properties slow the emptying of the stomachand promote atrophic gastritis which lowers the acidity. Delayed emptying and low acidity may favor endogenousnitrite production, and it is the nitrite and its metabolites that are thought to be carcinogens.7 Nitrite and nitrate have been used to cure meat, fish, and vegetables in many societies.* In the United States, from 1925 to 1980, the content of nitrate and nitrite in cured meat decreasedby 75%) while stomachcancer declined by two thirds. 3 Animal experiments indicate that N-nitroso compounds are carcinogenic and are capable of inducing stomach cancer.’ Carcinogenic nitroso compoundsare thought to be formed in the human stomachthrough an interaction between nitrite and a suitable substrate, but the details of the reaction are not completely clear. lo The evidence indicates that dietary nitrate/nitrite alone may not be sufficient, yet no other common diet-related substances have been shown to have the same potential for initiating the process.6 The increasing use of refrigeration since 1900 may have had a major impact on the decline of stomach cancer. In the past, food was preserved through salting, smoking, and pickling. In Japan, the proportion of households with electric refrigerators increased after 1960, approximately the sametime that stomachcancer mortality rates beFrom the Graduate Academic Unit. School of Nursing, West Virginia University, Morgantown. Address reprint requests to Janet F. Wang, PhD, RN, Associate Professor, Graduate Academic Unit, School of Nursing, West Virginia University, Morgantown, WV 26506. 0 1988 by Grune & Stratton, Inc. 0749-2081/88/0404-0003$05.0010

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gan to decline. l1 Refrigeration has also facilitated a higher intake of foods rich in vitamins C, E, and A, and milk and dairy products,6all of which may act as protectors of the gastric lining from carcinogenic effects. A strong negative associationbetween stomach cancer mortality and fresh vegetable and fruit intake has been observed.‘* A large-scale cohort study conductedbetween 1966and 1981in Japan13 found that daily intake of green and yellow vegetables reduced the risk of stomach cancer. Consumption of fruits and vegetables is associated with an increaseddietary intake of vitamins C, E, and A. These three vitamins might inhibit the chemical processassociatedwith carcinogenesisof the stomach. It has been demonstratedin animals that vitamin C has the ability to inhibit intragastric formation of both nitrosamine from nitrite and amine precursors6 Vitamin A may provide a protective mechanism for all epithelial tissue. Milk is also protective of the stomach. Hirayama” found a negative association between stomach cancer and milk consumption. High fat intake has generally been considered a protective factor against stomach cancer. In countries with a high fat intake and a high rate of colon cancer, such as the United States,New Zealand, Australia, and Scotland, there are fewer cases of stomach cancer.7 Socioeconomic Status

The prevalence of stomach cancer is higher in lower socioeconomicgroups, approximately twice that of the upper socioeconomicgroup. The higher stomach cancer rate by socioeconomic status has been observed in most countries studied.63’4A large-scale cohort study conducted in Japan (1966 to 1981) confiied that the lower socioeconomic group had a higher rate of stomachcancer.” This difference may be related to dietary differences between socioeconomic groups. Heredity

There may be a familial tendency to stomach cancer.i5 Studies of twins have not demonstrateda convincing genetic component,6 but “cancer families ’ ’ are increasingly being documented in whom there is an increasedincidence of gastrointestinal (GI) cancer. Individuals with type A blood may also have an increasedrisk of stomachcancer.

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Migrant Studies

Our most powerful tool in understanding gastic cancer has been the study of migrant populations. Personsmigrating from a country with a high rate of stomachcancer to one with a low rate continue to exhibit the rate of their country of origin, but their children and grandchildren show a shift in incidence to that of their new country. Firstgeneration Japanese-Americans born in Hawaii show a higher rate than whites in Hawaii and the continental United States, but this rate is lower than that of the Japanese-Americansborn in Japan who immigrated to Hawaii. l&l7 Similar phenomenahave also been observed in Icelanders who migrated to Canada,18Europeans migrating to Australia,ig South Americans migrating to the United States,and Puerto Ricans moving to New York City.*’ Second-generationmigrants tend to manifest stomachcancer rates that are still more similar to those of their host country.*‘~** Since original migrants maintain their high risk, which their descendentsgradually lose, we have strong evidence for the early and lifetime action of some factor that changesslowly from one generation to the next, and the best candidatefor that risk factor is diet. Gastric Ulcer and Gastritis

For many years, chronic gastric ulcer was thought to play a role in the etiology of gastric cancer. This belief hasbeenabandoned,and now it is generally thought that gastric cancers often ulcerate but gastric ulcers rarely, if ever, become malignant.’ However, lesions that lead to chronic atrophic gastritis with low or absent stomach acid are still potentially premalignant, though perhaps at a lower risk than was formerly believed, and perhaps only in conjunction with a high-risk diet. A stomach remnant, remaining for many years after gastrectomy for a benign condition, may predisposea person to stomach cancer.g It is speculated that long-term exposure to alkaline juices and the consequent development of gastritis are responsible for the occurrence of cancer in the gastric remnant.23Gastric atrophy, commonly seenin pernicious anemia, also predisposes to malignant change. Evidence from clinical and epidemiological studies indicates that a lengthy and complex series of mucosal changesoccurs before stomach cancer

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develops in persons with chronic gastritis. These include (1) inflammation and atrophy, (2) metaplasia, and (3) dysplasia.24Gastritis may predispose to cancer by modifying the microenvironment in a way that favors the formation of carcinogens, perhaps by proliferation of bacteria that convert nitrate to nitrite.7’24 This complex interaction of dietary, hereditary, and other etiologic factors in the uroduction of gastric cancer is summarizedin CLINICAL FEATURES

Stomachcancer may not produce symptomsuntil it is at an advancedstage. The initial complaint is usually mild epigastric discomfort, a vague sensation of fullnesss or gas pain, or the pattern of typical peptic ulcer relieved by antacids. Since the signs and symptoms of stomach cancer are often indistinguishable from those of benign ulcer or

esophagitis, patients may overlook their discomfort and not seek care at an early stage of illness. Eventually, when the pain becomes more severe and a physician’s care is sought, the cancer is often at an advancedstage. Approximately 30% of all patients with early stomach cancer have a long history of dyspepsia which is indistinguishable from chronic peptic ulcer disease.I3 The difficulty in diagnosis is differentiating between the symptoms of a benign and a malignant upper GI disorder. Studies indicate that the first symptoms of patients who later present with advanceddiseaseare similar to those found in patients with benign ulcer. Patients with small cancers will exhibit pain relieved by antacids, anticholinergics, and dietary management. Some patients may experience anorexia, abdominal pains, a feeling of fullness and bloating, a bad taste in the mouth, and constipation. The classic symptoms of

ENVIRONMENTAL

FACTORS

(CHEMICAL

AND

PHYSICAL)

Stomach Cancer (Possible Ftelatlon to

Changes

High

of the Gastrtc

Bacteria

Environment

Flora of the Stomach

Combined with Acldlc Juice to Form N-Nitroso Compounds

Changes

of Gastrx

Gastric l”test,nal Diffuse

AtypIcal

and pathogenesis

Cells

Eplthelwm Eplthellum

Early Stomach

Fig 1. Possible etiology of stomach cancer.

Eplthelium

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advancedstomachcancerare abdominal pain, dyspepsia, anorexia, anemia, vomiting, and dysphagia. The most striking feature of advancedgastric cancer is that 78% of patients have significant weight loss comparedwith only 18.9% of patients with early disease.25When symptoms such as ascites, jaundice, and bone pain appear, the cancer has metastasized. Approximately 50% of patients will experience nausea and vomiting, which is typical with primary tumors of the pylorus that progressto partial gastric obstruction. Others show dysphagia as the presenting symptom of a lesion of the cardioesophageal region. These symptoms suggestdiseaseof the lower esophagus, with vague substemal oppression and an inability to swallow, which progressesfrom solid foods, especially meat, to soft food, and finally liquids.26 Anemia can develop from chronic occult blood loss.*’

ulcers should be encouragedto seek regular medical follow up. Patientsshould also be classified as belonging to communities with a high or low risk of gastric cancer.** American Indians, Hispanics, blacks, and immigrants from Japan, some Latin American countries, Russia, and Scandinavia are at high risk, while native white Americans are at low risk. Physical examination is often unfruitful in stomach cancer, since only 37% of patients have a palpable abdominal mass.25The double-contrast barium meal allows study of the fine mucosal patterns; however, problems still arise in distinguishing between benign and malignant lesions. Radiological diagnosis must be followed by endoscopic biopsy and cytology.29 Endoscopyplays a major role in the diagnosis of stomachcancer. Early detection methods have resulted in a detection rate of 1.0/l ,000 in persons40 to 69 years of age.25Itabashi et a13’ report that accuracy of definitive histological diagnosis through endoscopy was 87% at the initial biopsy, and repeatedbiopsy raised the percentageof correct definitive diagnosis to 96%. In countries where the population is considered high-risk, mass radiological screening methods with widespread use of endoscopy have led to an increase in early detection. For example, the frequency of detection of early stomach cancer in western countries is approximately 6% to lo%, comparedwith 30% in Japan, where massscreening is used.27In a case-controlledstudy, the risk of dying from stomach cancer among screenedcases was 50% less than that of unscreenedcases.31

DETECTION AND DIAGNOSIS

Detection and diagnosis of early stomachcancer have improved through refinement of established radiological techniques and the use of endoscopy. These are complementary diagnostic studies and usually take place sequentially. Early detection of stomach cancer may be life-saving. Kitoka et al*’ reported survival rates of 96% in Japanesewho were diagnosed at a very early stage, and survival is generally better in Japandue to early diagnosis. Patients who are in a high-risk group, such as those with pernicious anemia, achlorhydria, hypochlorhydria, gastric atrophy, and chronic peptic

Early Stomach

Cancer

\ /

\ /

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\ /

)

Advanced Stomach Cancer 5.Year Depth of Invasion Mucosa

(SW

Submucosa

00

PW

Proper Muscle Layer

70

(SW

Subeerosa

(S)

Serosa up to the eeroea

S2: Full thickness lnflltratlon 53: lnflltratlon extendlng to Involve adjacent organs rate of Japanase

101

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Fig 2. Depth of invasion and B-year survival

Survival

with

stomach

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50 40 22 7

STOMACH

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CANCER

TREATMENT

BIOLOGIC CHARACTERISTICS

AND NURSING CARE

Staging

Surgery

A variety of staging systemshave been used to predict survival after surgical resection, but the depth of penetration of the primary lesion and lymph node involvement are the important factors. Survival is dependenton the depth of penetration. Carcinoma in situ is limited to the mucosa only. Early stomach cancer is defined as carcinoma that is confined to the mucosa, or mucosa and submucosa. Penetration through the serosareduces survival. Figure 2 illustrates data from Japanese studies3*illustrating the effect of depth of penetration on survival. When lymph nodes are involved survival is further reduced, but usually nodal diseaseis separated by involvement of resectablenodesor unresectable nodes, with the former thought to have a better prognosis. Obviously, distant metastasis,usually to the liver, connotes a grave prognosis. Retrospective analysis of gastrography and barium meals of untreated casesof early stomach cancer suggeststhat this progressionof diseasefrom early to advanced stages requires a period of 3 to 8 years.9 The majority of stomach cancers arise in the pylorus and antrum, and more frequently in the lesser curvature than the greater curvature. Curtis et a133found significant differences in survival by tumor site. Patients with tumors located in the cardia or fundus had a poor prognosis, while location along the lesser curvature was associatedwith the best survival. Lesions have also been classified as pol ypoid , ulcerating, or infiltrating. Polypoid lesions have a better prognosis than the ill-defined infiltrating lesions.

Complete surgical resectionof an early localized stomach cancer is the only method of cure. More often, at least in the United States, surgery is palliative even though the intent may be to cure. When the goal is cure, the surgeonresectsen bloc all visible tumor and a margin of tumor-free tissue. Palliative procedures are performed to alleviate gastric symptomsthe patient is experiencing, such as obstruction. A subtotal gastrectomyis the most common surgical procedure performed, and thus part of the stomach remains intact. For cancer occurring in the mid or distal stomach, radical subtotal gastrectomy is the treatment of choice. This procedure involves removal of at least 75% to 80% of the stomach and adjacent lymph nodes and omentum. GI continuity is restored either to the duodenum (Billroth I) or by closing the duodenum and anastomosing the gastric remnant to the jejunum (Billroth II).35 A total gastrectomy may be necessary for more advanced tumors. This procedure involves removal of the entire stomach, then the transectedduodenum is closed, and the esophagus is anastomosedto the jejunum.

Histology

Almost all gastric cancersare adenocarcinomas. Lawrence34describedlesions as either intestinal or diffuse, with a better prognosis for the intestinal type. There are interesting associations with epidemiological factors. The intestinal type of cancer is common in areas of high incidence, such as Japan, and the incidence of this type is the only one that has declined recently. The diffuse type of tumor tends to have a poorer prognosis, and the well-circumscribed tumors have a much better outlook than do those with infiltrating margins.29

Limitation of Primary Treatment

Recurrent diseaseis common after radical resection and occurs at both local and distant sites. Local recurrencemay be in the stomachbed, stomach remnant, or residual lymph nodes. Distant metastasesmay occur at many sites, but are most common in the liver or peritoneal cavity. Secondlook operations have disclosed evidence of recurrent cancer in 80% of patients, and the recurrence was entirely local in 53.7%.36 This inability of surgery to remove all cancer cells and prevent the development of recurrence in most casesis the limitation of surgery as a single modality of therapy in stomach cancer. Early detection has improved survival in Japan, where the high incidence makes such an approach costeffective, but other attempts to improve surgical cure rates have failed. Numerous attempts at adjuvant radiotherapy or chemotherapy have been undertakenin this country with occasional suggestive results, but on the whole, neither modality is presently advised postoperatively.

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Preoperative Care

Chemotherapy

Nurses play an important role in the care of patients before and after surgery. Nutritional assessment and preparation are of major importance preoperatively. If a patient is undernourished, several days may be devoted to improving nutritional status using hyperalimentation or an elemental diet. Most patients scheduled for stomach surgery will undergo prophylactic bowel preparation with antibiotics.

Cytotoxic agents have been evaluated as postsurgical adjuvant therapy for cure and treatmentin advanced stomach cancer. In advanced disease, chemotherapeuticagentshave been usedprimarily for the control of symptoms. 5-Fluorouacil(5-FU) is the most widely studied agent. A controlled surgical adjuvant study by the Gastrointestinal Tumor Study Group compared patients following resection who were randomized to receive 5-FU and semustinewith a control group. Forty-four percent of patients receiving adjuvant chemotherapy survived 5 years as compared with the control group who had a 5-year survival rate of 26%.38 Unfortunately, most controlled trials of adjuvant chemotherapy have shown no benefit, and its use must still be considered experimental. Intraperitoneal adjuvant chemotherapyfor patients at high risk for recurrencehas been suggestedas a possible experimental approach in view of the failure of most adjuvant regimens. Palliative chemotherapy for recurrent diseaseis disappointing. More than 30 years ago, 5-FU was demonstrated to produce an objective tumor shrinkage in up to 20% of patients, and since that time many attempts have been made to find other agents used alone, or in combination with 5FU, that would improve on the results of 5-FU alone. On occasion it has seemedthat a more effective regimen was developed, but in each case further study revealed that 5-FU alone was equally active. Recently, a popular regimen (5-FU plus doxorubitin plus mitomycin) was shown to be no better than 5-FU alone.39The most recent attempt to improve the therapeuticpotency of 5-FU is to use it in combination with leucovorin, and this may offer some advantagein colorectal cancer but it cannot be said to be established in gastric cancer.40

Postoperative Care

Postoperative care of patients follows the general principles of that for major abdominal surgery. Several specific problems can occur with gastric cancer surgery. Gastrointestinal decompression. After the patient’s operation, continuous gentle decompression is maintained through a gastric tube. The tube must be irrigated with saline or water to maintain patency. The nasogastric tube will be in place until the patient passesgas rectally, which often takes 1 to 3 weeks. The patient will feel nauseatedif the tube does not function effectively. Records of intravenous intake and the amount of gastric fluid output should be monitored. Dumping syndrome. Gastric resection reduces the size of the stomach and creates nutritional problems. The dumping syndrome is characterized by an immediate feeling of epigastric fullness, diarrhea, palpitations, diaphoresis, and dizziness. This syndrome is most likely to occur in patients who have had total gastrectomies.The rapid emptying of hyperosmolar materials from the gastric remnant into the small bowel causes fluid shifts from the intravascular spaceinto the jejunum.37 Nursing care of the patient experiencing dumping syndrome includes a regimen of frequent small meals with a diet high in fat and protein, and low in carbohydrates. Fluids must be restricted at meals but may be taken 30 to 40 minutes before or after eating. Megablastic anemia. Total or radical partial gastrectomy removes the source of intrinsic factor required for the absorption of vitamin B,, in the ileum. Megablastic anemiawill eventually develop after hepatic storesbecomedepleted. The monthly administration of parenteral vitamin B,, will correct the problem.

Radiation Therapy

Radiation therapy has not beenhighly successful in treating cancer of the stomach. Becauseof the potential damage to abdominal organs and decreasedhealing of the anastomosisafter surgery, irradiation is rarely used preoperatively. Radiation therapy may be used for palliation in some cases, but there is no evidence that it increasessurvival. Radiation to the upper abdomen can produce anorexia and nausea, which may exacerbate the

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patient’s already poor nutritional status. Transient malabsorption may occur as a result of diffuse damageto the bowel mucosain the irradiated field. Symptomssuch as inflammation, endarteritis, and fibrosis, with possible stricture formation or ulceration, may further compromise absorption function.23 The nurse must be surethat the patient maintains adequatefood and fluid intake orally or parenterally. Sensitivity to the patient’s need for comfort and control of symptoms is essential in the care of the patient during the treatment period. Intraoperative radiotherapy is currently being studied in patients with unresectabledisease. This therapy may permit the delivery of adequatedoses while sparing the surrounding normal tissues. CONCLUSION

Stomach cancer continues to have a poor prognosis, even as its incidence is decreasingthroughout the world. Techniques for early detection have improved but are often not cost-effective in lowincidence areas.Thus, the health profession has an obligation to identify high-risk patients and to investigate gastric symptomsaggressively, while increasing clinical researchefforts. Epidemiological studies indicate that diet and stomach cancer are closely related. Preventive measuresfor stomachcancerinclude guidelines for

high-risk groups. When teaching the high-risk population, nurses may provide information and advise the patients to modify their diets. However, it is important to note that many dietary items that appear to correlate with cancer at one site are inversely correlated with the development of cancer at another site. Preventive measuresfor stomachcancer include (1) use of food refrigeration; (2) decreasein the consumption of salt and smoke-cured and pickled meat or fish; (3) increased consumption of milk and dairy products; and (4) increasedconsumption of fresh fruit and vegetables. In a society such as the United States, where stomachcancer is substantially less common and is on the decline, it would not be cost-effective to conduct massendoscopic screeningprograms such as those performed in Japan. Unless a costeffective technique is developed by further research, it is unlikely that massscreening will take place in western countries. Since most patients seeking care are already in the advancedstageof the illness, a greater emphasis must be placed on clinical researchdirected at identifying more effective forms of radiation and chemotherapy to improve the survival rate after primary therapy. At present, an effective adjuvant regimen does not exist, and such a regimen, if developed, would substantially increase survival since the operative cure rate is presently quite low.

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