Esophageal and Stomach Cancers
Esophageal Cancer
Epidemiology and etiology
A. Epidemiology. The most common esophageal neoplasm worldwide is squamous cell cancer, a fact which is due, in most part, to the dietary and socioeconomic factors that affect large segments of the world’s population. Endemic areas for squamous cell cancer include the Caspian Littoral in
B. Etiology. 1. Carcinogens:
a. Long-term use of tobacco and alcohol increases the incidence of both squamous cell carcinoma and adenocarcinoma of the esophagus; b. Human papillomavirus (HPV) infection is associated with squamous cell carcinoma of the esophagus; c. Dietary carcinogens relevant to the development of squamous cell esophageal cancers include the following: (1) Plants growing in soil deficient in molybdenum reduce their content of vitamin C and cause hyperplasia of esophageal mucosa, a precursor of cancer. (2) Elevated nitrates in the drinking water and soup kettles that concentrate the nitrate. (3) Food containing fungi: Geotrichum candidum (pickles, air-dried corn), Fusarium sp., and Aspergillus sp. (corn). (4) Bread that is baked once a week and eaten when moldy (G. candidum). (5) Dried persimmons, a rough food that injures the esophageal mucosa when eaten (China)
2. Predisposing factors for squamous cell esophageal cancer
a. Howel-Evans syndrome or tylosis (hyperkeratosis of the palms and soles) is a rare genetic disease that is transmitted as a mendelian-dominant trait (nearly 40% develop esophageal cancer).
b. Lye stricture (up to 30%); c. Esophageal achalasia (30%); d. Esophageal web (20%); e. Plummer-Vinson syndrome (iron-deficiency anemia, dysphagia from an esophageal web, and glossitis, 10%); f. Short esophagus (5%); g. Peptic esophagitis (1%); h. Other conditions associated with squamous cell esophageal cancer.
3. Predisposing factors for adenocarcinoma of the esophagus
a. Barrett’s esophagus is metaplastic replacement of squamous with intestinalized columnar epithelium; b. Obesity; c. Reflux esophagitis.
II. Pathology and natural history
A. Histology. Squamous cell tumors constitute 98% of esophageal cancers in the upper and middle esophagus; the remainders are adenocarcinomas and rare sarcomas, small cell carcinomas, or lymphomas.
B. Location of cancer in the esophagus: 1. Cervical: 10%; 2. Upper thoracic: 40%; 3. Lower thoracic: 50%.
C. Clinical course. Esophageal cancer is highly lethal; more than 90% of affected patients die from the disease. About 75% present initially with mediastinal nodal involvement or distant metastases. Death is usually caused by local disease that results in malnutrition or aspiration pneumonia.
III. Diagnosis
A. Symptoms and signs. Dysphagia is the most common complaint. Patients become unable to swallow solid foods and eventually liquids. Symptoms rarely develop until the esophageal lumen is greatly narrowed and metastases have occurred. Pain may or may not be present. Physical findings other than cachexia, palpable supraclavicular lymph nodes, or hepatomegaly are rare.
B. Diagnostic studies.
1. Preliminary studies include physical examination, complete blood count (CBC), liver function tests (LFTs), chest radiograph, esophagoscopy, and barium esophagogram. Brushings can be obtained and lesions can undergo biopsy using endoscopy.
2. Computed tomography (CT) scan staging predicts invasion or metastases with an accuracy rate of more than 90% for the aorta, tracheobronchial tree, pericardium, liver, and adrenal glands; 85% for abdominal nodes; and 50% for paraesophageal nodes.
3. Endoscopic ultrasound; 4. Laparoscopy; 5. Bronchoscopy; 6. Magnetic Resonance Imaging.
7. Positron Emission Tomography; 8. Neck Ultrasonography. 9. Biologic markers (EGF, TGF-a, PDGF), oncogenes (c-myc, int-2, hst-1, cyclin D, EGFR, HER-2/neu, h-ras), tumor suppressor genes (Rb, p53, p73, APC, MCC, p27), CEA.
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Primary tumor (T) |
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TX |
Primary tumor cannot be assessed |
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T0 |
No evidence of primary tumor |
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Tis |
Carcinoma in situ |
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T1 |
Tumor invades lamina propria or submucosa |
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T2 |
Tumor invades muscularis propria |
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T3 |
Tumor invades adventitia |
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T4 |
Tumor invades adjacent structures |
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Regional lymph nodes (N)* |
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NX |
Regional lymph nodes cannot be assessed |
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N0 |
No regional lymph node metastases |
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N1 |
Regional lymph node metastasis |
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Distant metastasis (M) |
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MX |
Distant metastasis cannot be assessed |
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M0 |
No distant metastasis |
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M1 |
Distant metastasis |
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Tumors of the lower thoracic esophagus |
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M1a Metastasis in celiac lymph nodes |
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M1b Other distant metastasis |
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Tumors of the midthoracic esophagus |
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M1a Not applicable |
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M1b Nonregional lymph nodes and/or other distant metastasis |
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Tumors of the upper thoracic esophagus |
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M1a Metastasis in cervical nodes |
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M1b Other distant metastasis |
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Stage grouping |
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Stage 0 |
Tis |
N0 |
M0 |
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Stage I |
T1 |
N0 |
M0 |
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Stage IIA |
T2 |
N0 |
M0 |
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T3 |
N0 |
M0 |
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Stage IIB |
T1 |
N1 |
M0 |
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T2 |
N1 |
M0 |
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Stage III |
T3 |
N1 |
M0 |
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T4 |
Any N |
M0 |
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Stage IV |
Any T |
Any N |
M1 |
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Stage IVA |
Any T |
Any N |
M1a |
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Stage IVB |
Any T |
Any N |
M1b |
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*Regional lymph nodes:Cervical esophageal tumor: scalene, internal jugular, upper cervical, periesophageal, supraclavicular, cervical not otherwise specified Intrathoracic esophageal tumor: tracheobronchial, superior mediastinal, peritracheal, carinal, hilar, periesophageal, perigastric, paracardial, mediastinal not otherwise specified
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A. Surgery. A standard esophagectomy for cancer includes resection of the esophagus with at least a 5-cm margin of normal esophagus above the most proximal gross extent of tumor, the surrounding soft tissues and lymph nodes, and the proximal stomach including lesser curve lymph nodes. One of the primary determinants of survival after esophagectomy is whether an R0 (no residual tumor) resection is performed, compared with R1 (microscopic residual disease) or R2 (gross residual disease) resections. Concerns about the incidence of persistent disease and local recurrence in patients with esophageal cancer prompted the development of more extensive resections of the primary tumor and regional lymph nodes in the late 1960s, termed radical en bloc esophagectomy. The extent of an en bloc esophagectomy varies among surgeons. The most extensive dissection removes tissues abutting the esophagus, including the pleura bilaterally, the pericardium, and tissues anterior to the vertebral bodies, including the azygos vein and thoracic duct. In the case of tumors adjacent to the esophageal hiatus, a rim of diaphragm is removed. An attempt is made to establish proximal and distal margins of resection at least
Extent of Lymph Node Dissection. The standard extent of nodal dissection for patients undergoing resection for cancer of the thoracic esophagus or cardia includes lymph nodes in the periesophageal region adjacent to the primary tumor, those in the subcarinal region, and nodes along the left gastric artery and in the gastrohepatic ligament adjacent to the proximal lesser curvature of the stomach. Recent data suggest that such an operation may be inadequate for staging and may adversely affect long-term survival in patients who undergo potentially curative resection. Routine complete lymph node dissections demonstrate that 20 to 30% of patients with either squamous cell cancers or adenocarcinomas of the esophagus have involvement of cervical lymph nodes at the time of surgery. Extended, or three-field, lymphadenectomy currently is advocated by many surgeons as a standard component of potentially curative resection. Extended lymphadenectomy consists of complete lymph node clearance from three compartments potentially affected by metastatic spread of esophageal cancer. Results of this technique are mixed. Upstaging occurs in up to 30% of patients, which confounds efforts to compare data from nonrandomized studies. Some complications are significantly more common after three-field dissection, including recurrent nerve palsy, tracheal ischemia, anastomotic leak, respiratory insufficiency and other pulmonary complications, and, in some reports, operative mortality. Survival has been shown to be statistically longer after extended lymphadenectomy in only one retrospective report, while other reports demonstrate no significant improvement in survival. Until more conclusive data are available, extended lymphadenectomy should be considered investigational.
Reconstruction after Esophagectomy. Re-establishing alimentary tract continuity after esophageal resection in a manner that permits ingestion of a normal diet is an important component of surgery for esophageal cancer. Options for reconstruction include using the stomach as a substitute or interposing a segment of colon or jejunum between the proximal esophageal remnant and the stomach (or duodenum after total gastrectomy). The use of the stomach for reconstruction is by far the most common technique because the stomach has the most reliable blood supply among any of the reconstructive options and because only a single anastomosis is required, compared with the three anastomoses necessary for bowel interposition. Cervical anastomoses are favored by many surgeons because they decrease the incidence of acid reflux into the esophageal remnant and because anastomotic leaks are usually easily managed by simple cervical drainage. The disadvantages of cervical anastomoses are a higher incidence of recurrent laryngeal nerve injury and more frequent anastomotic leaks. Whether the additional tumor-free proximal margin provided by a cervical anastomosis offers a survival advantage has not been proven. Use of the posterior mediastinum (esophageal bed) for reconstruction optimizes emptying of the reconstructive organ but may predispose to tumor infiltration if a complete resection is not performed.
B. Palliating an obstructed esophagus can be accomplished by several procedures and permits enteral nutrition.
1. Laser therapy may relieve obstruction and bleeding. Endoscopic laser therapy has less than a 1% mortality rate but may require prior mechanical dilation. Although successful laser therapy may require multiple endoscopic sessions, it can be done on an outpatient basis, and its overall cost is still much lower than the cost of palliative surgery. Photosensitization of esophageal tumors using an injectable porphyrin derivative can increase the laser energy absorbed by the tumor with palliative benefit but is associated with generalized dermal photo-sensitivity to sunlight lasting 4 to 6 weeks.
2. Esophageal stenting. At least 17 devices are available for esophageal intubation. About 15% of patients with malignant esophageal obstruction are candidates for tube placement. The success rate is 90% to 97%.
3. Feeding gastrostomy is not advisable because it does not palliate dysphagia, which forces patients with complete or nearly complete esophageal obstruction to expectorate saliva and secretions, does not increase life expectancy, and has its own morbidity and mortality.
4. External-beam irradiation or endoluminal brachytherapy can result in tumor regression with palliation in some cases. Up to 70% to 80% of patients with dysphagia may note improved swallowing after external-beam irradiation.
C. Single-modality treatment: 1. Radiotherapy alone. Radiotherapy to a dose of 6000 cGy resulted in 1-, 2-, 3- and 5-year survival rates of 33%, 12%, 8%, and 7% of patients treated on the radiation arm of a randomized trial in which responding patients were permitted to go on to resection at physician discretion. 2. Surgery alone. The surgical procedures employed in esophagectomy depend on the location and preference of the surgeon and include principally transhiatal esophagectomy or the Ivor-Lewis procedure, which requires both thoracotomy and laparotomy. In the 25% to 30% of patients in whom complete resection is possible, 5-year survival rates of 15% to 30% are reported.
3. Chemotherapy alone is seldom an effective palliative modality in patients with esophageal cancer, and when chemotherapy is employed, it should be coupled with mechanical or radiotherapeutic approaches for palliation of dysphagia. Like in gastric cancer, multiagent chemotherapy-induced responses tend to be short lived.
4. Photodynamic Therapy (PDT) is emerging as an option for treating patients with carcinoma in situ or superficial cancers who are unable to tolerate or who refuse resection. PDT is performed by first systemically administering a photosensitive compound, and after its uptake in tumor, strong areas of concern are endoscopically treated with low-level laser light to activate the compound, causing selective cell death through release of toxic oxygen metabolites. The complete response rate of 75 to 80% endures for several years, suggesting that some patients may be cured with this therapy. PDT also is being investigated as one of several techniques, including laser photocoagulation, argon beam cautery, and electrocautery, for ablating Barrett’s muscosa as a means of preventing the development of adenocarcinoma. Current staging techniques are relatively inaccurate, and up to 50% of patients who undergo resection for high-grade dysplasia in Barrett’s esophagus have invasive cancer.
Stomach Cancer
I. Epidemiology and etiology
A. Incidence. The prevalence and death rates of gastric carcinoma (particularly distal cancers) have been markedly and significantly decreasing in all regions of the world and in all age groups by about 2% to 7% per year. Deaths due to gastric cancer have decreased to 20% of that seen in the 1930s in the United States, although it remains the second leading cause of cancer death worldwide. Dietary factors and improvement in food storage are believed to be the major factors causing this decline. Improvements include reduction in toxic methods of food preservation (such as smoking and pickling), a decline in salt consumption, greater use of refrigeration, and increased consumption of fruits and vegetables. Mortality from gastric cancer is highest in
B. Etiology. 1. Diet. Gastric cancer has been linked to the ingestion of red meats, cabbage, spices, fish, salt-preserved or smoked foods, a high-carbohydrate diet, and low consumption of fat, protein, and vitamins A, C, and E. Selenium dietary intake may be inversely proportioned to the risks of gastric cancer but not of colorectal cancer. 2. H. pylori infection is associated with an increased risk for gastric adenocarcinoma and may be a cofactor in the pathogenesis of non-cardiac gastric cancer. The H. pylori organism was identified in 89% of patients with intestinal-type cancer in the malignant and nearby inflammatory tissue, whereas it was present in 32% of tissues taken from patients with diffuse-type cancers. This raises the possibility now under investigation in prospective randomized trials that eradicating H. pylori through antibiotic treatment and bismuth administration may be preventive of both atrophic gastritis and intestinal-type gastric cancer. 3. Heredity and race. African, Asian, and Hispanic Americans have a higher risk for gastric cancer than whites. The diffuse histologic pattern is the predominant pathologic type seen in families with multiple affected members. 4. Pernicious anemia, achlorhydria, and atrophic gastritis carries an increased relative risk for gastric cancer said to be 3 to 18 times. 5. Previous gastric resection. Gastric stump adenocarcinomas, which occur with a latency period of 15 to 20 years, are more common in patients after surgical treatment for benign peptic ulcer disease, particularly those who have hypochlorhydria and reflux of alkaline bile. 6. Mucosal dysplasia is graded from I to III, with grade III showing marked loss in cell differentiation and increased mitosis. The risk for cancer appears to be proportional to the extent of metaplastic mucosa. 7. Gastric polyps. As many as half of adenomatous polyps show carcinomatous changes in some series. Hyperplastic polyps (more than 75% of all gastric polyps) do not appear to have malignant potential. Patients with familial adenomatous polyposis (FAP) have a higher incidence of gastric cancer. 8. Chronic gastritis. In chronic atrophic gastritis of the corpus or antrum, H. pylori infection and environmental and autoimmune (as in pernicious anemia) causes are thought to be associated with an increased risk for gastric cancer. In Menetrier’s disease (hypertrophic gastritis), an increase in the incidence of gastric cancer is also observed. 9. Other risk factors. Gastric cancer is more common in men older than 50 years of age and in people with blood group A.
II. Pathology and natural history
A. Histology and classification: About 95% of gastric cancers are adenocarcinomas; 5% are leiomyosarcomas, lymphomas, carcinoids, squamous cancers, or other rare types.
a. Histologic classification (Lauren): Diffuse (scattered solitary or small clusters of small cells in the submucosa), intestinal (polarized columnar large cells with inflammatory infiltrates localized in areas of atrophic gastritis or intestinal metaplasia), and mixed types. Studies have shown that “diffuse” histology affects younger patients, with slight predominance among women. Diffuse histology occurred in 50% of all cases and in 55% of unresectable cases. Intestinal type predominates in high-risk regions of the world and among older people and affects more men than women.
b. Clinical classification. Macroscopic classification for early noninvasive carcinoma is based on the absence of progression to either the muscularis propria or serosa irrespective of lymph node metastases. Early ACS can be classified as one of three basic types:
1. Protruded Type. 2. Superficial Type. There are three subgroups. IIa is the elevated and superficial type, which is characterized by sessile mucosal elevations of a plateau-like or flower-bed pattern. The height of the elevation is no more than twice the thickness of the surrounding mucosa. IIb is the flat and superficial type, which has discoloration or a slight unevenness of the gastric mucosa. These lesions usually are minute. IIc is the depressed superficial type, which has slightly depressed and macroscopically eroded areas.
3. Evacuated Type. These ulcerated carcinomas are the most common, representing up to 68% of early cancers. They appear on inspection or radiographic examination to be quite similar to a benign peptic ulcer.
c. Japanese Endoscopic Society (JES) classification. Type I (polypoid or masslike), type II (flat, minimally elevated, or depressed), and type III (cancer associated with true ulcer)
2. Location of cancers: a. Distal location: 40%; b. Proximal: 35%; c. Body: 25%.
B. Clinical course. About 18% of gastric cancer patients are long-term survivors in the
C. Associated paraneoplastic syndromes: 1. Acanthosis nigricans (55% of cases that occur in malignancy are associated with gastric carcinoma). 2. Polymyositis, dermatomyositis; 3. Circinate erythemas, pemphigoid; 4. Dementia, cerebellar ataxia;5. Idiopathic venous thrombosis; 6. Ectopic Cushing’s syndrome or carcinoid syndrome (rare); 7. Leser-Trelat sign.
III. Diagnosis
A. Symptoms and signs. Gastric cancer often progresses to an advanced stage before symptoms and signs develop. Symptoms of advanced disease include anorexia, early satiety, distaste for meat, weakness, and dysphagia. Abdominal pain is present in about 60% of patients, weight loss in 50%, nausea and vomiting in 40%, anemia in 40%, and a palpable abdominal mass in 30%. The abdominal pain is similar to ulcer pain, is gnawing iature, and may respond initially to antacid treatment but remains unremitting. Hematemesis or melena occurs in 25% and, when present, is seen more often with gastric sarcomas.
B. Diagnostic studies
1. Preliminary studies include CBC, LFTs, esophagogastroduodenoscopy (EGD) or upper GI barium studies, and chest radiographs.
2. CT of the abdomen is useful for assessing the extent of disease. At laparotomy, however, half of patients are found to have more extensive disease than predicted by CT. 3. EUS is up to six times more accurate in staging the primary gastric tumors than CT, but differentiation between benign and malignant changes in the wall is often difficult. 4. Endoscopy. The combination of flexible upper GI endoscopy with biopsy of visible lesions, exfoliative cytology, and brush biopsy is able to detect more than 95% of gastric cancers. Biopsy of a stomach lesion alone is accurate in only 80% of cases. C. Differential diagnosis and gastric polyps. The differential diagnosis of gastric cancer includes peptic gastric polyps, ulcer, leiomyoma, leiomyoblastoma, glomus tumor, malignant lymphoma (and pseudolymphoma), granulocytic sarcoma, carcinoid tumors, lipoma, fibrous histiocytoma and metastatic carcinoma. Gastric polyps rarely undergo malignant transforation (3% after 7 years), but many contain independent carcinoma.
1. Inflammatory gastric polyps are not true neoplasms. 2. Hyperplastic gastric polyps (Menetrier’s polyadenome polypeux) are the most common polyps (75%). Randomly distributed throughout the stomach, these polyps are usually small and multiple. Coexisting carcinoma is present in 8% of cases. 3. Adenomatous polyps are usually located in the antrum of the stomach and are frequently single and large. Coexisting carcinoma is present in 40% to 60% of patients. 4. Villous adenomas rarely occur in the stomach but are more often malignant. 5. Polyposis syndromes: a. Familial gastric polyposis presents with multiple gastric polyps but no skin or bone tumors. The gastric wall is usually invaded with atypical carcinoma; b. Familial adenomatous polyposis (FAP) is associated with gastric involvement in more than half of patients. The gastric polyps are adenomatous, hyperplastic, or of the fundic gland hyperplasia type.
IV. Staging and prognostic factors
TNM Staging of Gastric Cancer
T Primary tumor
Tx Primary tumor cannot by assessed
T0 No evidence of primary tumor
Tis Noninvasive carcinoma in situ
T1 Extension to submucosa
T2 Extension to serosa
T3 Extension through serosa
T4 Invasion of adjacent organs
N Regional lymph nodes
Nx Regional nodes cannot be assessed
N0 No regional nodal metastases
N1 Metastases in 1 to 6 regional lymph nodes
N2 Metastases in 7 to 15 regional lymph nodes
N3 Metastases in more than 15 regional lymph nodes
M Distant metastases
Mx Distant metastases cannot be assessed
M0 No distant metastases
M1 Distant metastases present
B. Prognostic factors. Previously, data using three grave prognostic signs (serosal involvement, nodal involvement, and tumor at the line of resection) have shown that if none of these signs is present, the 5-year survival rate is 60%, and if all are present, the 5-year survival rate is less than 5%.
JES classification. Survival is better with type II (flat) than with type III (associated with ulcer) tumors and worst with type I (polypoid) tumors.
Grade. Tumors with high histologic grade have a poor prognosis.
Nature and extent of resection. Survival is better with curative resection (a resection with uninvolved margins, or R-2 resection) versus palliative resection, distal gastrectomy versus proximal gastrectomy, and subtotal gastrectomy versus total gastrectomy.
V. Screening and early detection. Early detection of gastric cancers is clearly improved with relentless investigation of persistent upper GI symptoms. In
VI. Management. A. Surgery
1. Curative resection. A potentially curative operation (R0) is defined as complete removal of all gross disease with a negative margin of resection. An R1 resection is one performed with residual microscopic disease such as a positive luminal or radial margin. An R2 resection is one in which gross residual disease is left behind such as peritoneal or hepatic metastases. Clearly, patients with localized disease are most likely to benefit from surgery, and the patients most likely to be long-term survivors are those who undergo resection. The goal of a potentially curative operation is to remove all visible disease en bloc. Although the impact of nodal metastasis is clearly important, there are many patients with gastric cancer who are cured of disease by surgery alone.The various types of procedure to achieve gastrectomy include (1) subtotal gastrectomy (used for a tumor of the antrum or distal body), (2) total gastrectomy, and (3) proximal subtotal gastrectomy or esophagogastrectomy performed either with a transperitoneal approach or combined with a transthoracic approach. For proximal tumors, controversy concerning the benefits of a proximal subtotal versus a total gastrectomy notwithstanding, most data suggest that a total gastrectomy is the operation of choice. In most series that examine the relative survivals of patients undergoing an R0 resection, survival has been better for patients who have had a total gastrectomy. One possible explanation for this would be the complete removal of lesser curvature nodes. The goals of the luminal resection for gastric cancer include a negative margin while maintaining as much function as possible. Early and sometimes advanced cancer may be cured by surgery alone with an en bloc resection. Subtotal gastrectomy may be used for cancer of the pylorus and body. Whereas total gastrectomy is used for most other tumors, proximal subtotal gastrectomy and esophagectomy transperitoneally or transthoracically are used for cancer of the cardia. Widespread or infiltrating tumors may require total gastrectomy. Some recommend extensive mapping with frozen sections for lesions associated with intestinal metaplasia, severe atrophy, or dysplasia before undertaking a subtotal gastrectomy to avoid leaving behind an early cancer in the gastric stump. The macroscopic and histologic boundaries of cancer are different. Two centimeters beyond the macroscopic margin of a superficial cancer, more than
Lymph Node Dissection. There has been a change in the nomenclature for the description of both the type of gastric resection and the extent of nodal dissection. Previously, the description for the type of lymph node dissection was R; however, the designation of R now refers to the type of resection. An R0 resection is a potentially curative resection, and R1 is a resection that has a microscopic positive margin, and an R2 resection leaves gross residual disease behind. The designation for the type of lymph node dissection is D. A D1 dissection is only nodes adjacent to the tumor; a D2 dissection includes the nodes along the stomach as well as nodes along the celiac, splenic, and hepatic arteries; and D3 and D4 include these nodes plus nodes along the porta hepatis and along the aorta and vena cava as far down as the inferior mesenteric artery. Lymph nodes also reside in the splenic hilum and removal of these nodes has been advocated; however, this can only be achieved by performing a splenectomy.
2. Palliative resections are performed to rid patients of infected, bleeding, obstructed, necrotic, or ulcerated polypoid gastric lesions. For these purposes, a limited gastric resection may suffice. Palliative resections succeed in ameliorating symptoms about half the time.
3. Vitamin B12 deficiency develops in all patients who undergo total gastrectomy within 6 years and in 20% of patients who undergo subtotal gastrectomy within 10 years unless parenteral B12 injections are administered.
B. Chemotherapy
Neoadjuvant chemotherapy. Nearly all trials involving 5-FU in combination with other agents (doxorubicin, epirubicin, mitomycin, or cytarabine) as adjuvant therapy have failed to show any benefit.
Intraperitoneal cisplatin and 5-FU followed by systemic 5-FU or 5-FU and mitomycin is being evaluated. Side effects are mainly neutropenia and sclerosing encapsulating peritonitis (are toxicity).
Chemotherapy for advanced disease. Single agents produce low response rates. Combination regimens produce higher response rates but are more toxic and more costly. Cisplatin has been increasingly used iew combinations that also yield higher response rates, but the incidence of important toxic events exceeds 10%. The reported response rates are about 20% for 5-FU alone and 10% to 50% for combination chemotherapy; the median survival times range from 5 to 11 months. After nearly two decades of using combination chemotherapy, including mitomycin, doxorubicin, epidoxorubicin, etoposide, methotrexate, nitrosoureas, irinotecan, or cisplatin, there is no regimen considered standard in the setting of advanced disease.
C. RT
1. Localized disease. RT alone has not proved useful for treating gastric cancer. RT (4000 cGy in 4 weeks) in combination with 5-FU (15 mg/kg IV on the first 3 days of RT), however, appears to improve survival over RT alone in patients with localized but unresectable cancers. Intraoperative radiation (IORT) allows high doses of radiation to the tumor bed or residual disease while permitting the exclusion of mobile radiosensitive normal tissues from the area irradiated.
2. Advanced disease. Gastric adenocarcinoma is relatively radioresistant and requires high doses of radiation with attendant toxic effects to surrounding organs. RT may be useful for palliating pain, vomiting due to obstruction, gastric hemorrhage, and metastases to bone and brain.
Prepared by:
Prof. G.S. Moroz, and
Prof. I.Y. Galaychuk
