Stomach cancer accounts for an estimated 27,600 cases and about 11,010 deaths in the US annually (1 General reference Etiology of stomach cancer is multifactorial, but Helicobacter pylori plays a significant role. Symptoms include early satiety, obstruction, and bleeding but tend to occur late in the... read more ). Gastric adenocarcinoma accounts for 95% of malignant tumors of the stomach; less common are localized gastric lymphomas Overview of Lymphoma Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems. The major types are Hodgkin lymphoma Non-Hodgkin lymphoma See table Comparison of Hodgkin... read more and leiomyosarcomas. Stomach cancer is the 2nd most common cancer worldwide, but the incidence varies widely; incidence is extremely high in Japan, China, Chile, and Iceland. In the US, incidence has declined in recent decades to the 7th most common cause of death from cancer. In the US, it is most common among blacks, Hispanics, and American Indians. Its incidence increases with age; > 75% of patients are > 50 years.
Etiology of Stomach Cancer
Risk factors for stomach cancer include the following:
Helicobacter pylori infection Helicobacter pylori Infection Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more (when it is associated with extensive gastric intestinal metaplasia)
Smoking (and people who smoke may have an impaired response to treatment)
Dietary factors are not proven causes; however, the World Health Organization (WHO) International Agency for Research on Cancer (IARC) has reported a positive association between consumption of processed meat and stomach cancer (1 Risk factor references Etiology of stomach cancer is multifactorial, but Helicobacter pylori plays a significant role. Symptoms include early satiety, obstruction, and bleeding but tend to occur late in the... read more ).
Gastric polyps can be precursors of cancer. Inflammatory polyps may develop in patients taking nonsteroidal anti-inflammatory drug (NSAIDs), and fundic foveolar polyps are common among patients taking proton pump inhibitors. Adenomatous polyps, particularly multiple ones, although rare, are the most likely to develop cancer. Cancer is particularly likely if an adenomatous polyp is > 2 cm in diameter or has a villous histology. Because malignant transformation cannot be detected by inspection, all polyps seen at endoscopy should be removed.
Various genetic factors are also risk factors. Hereditary diffuse gastric cancer is associated with a mutation in the cadherin 1 gene (CDH1) and has no precursor lesion. This mutation is an autosomal dominant trait with high penetrance. Affected patients usually develop gastric cancer at an early age (average age 38). Affected women are also at high risk of developing lobular breast cancer. Patients with personal or family history of diffuse gastric cancer and/or lobular breast cancer in multiple family members, especially if they were diagnosed before age 50, should be referred for genetic counseling and testing. Prophylactic gastrectomy should be offered to asymptomatic carriers of the CDH1 mutation between the ages of 20 and 40 (2 Risk factor references Etiology of stomach cancer is multifactorial, but Helicobacter pylori plays a significant role. Symptoms include early satiety, obstruction, and bleeding but tend to occur late in the... read more ). Breast cancer surveillance with annual breast MRI beginning at age 30 is also recommended for women with the CDH1 mutation (3 Risk factor references Etiology of stomach cancer is multifactorial, but Helicobacter pylori plays a significant role. Symptoms include early satiety, obstruction, and bleeding but tend to occur late in the... read more ). There are case reports of colorectal cancer in CDH1 mutation carriers. Data are insufficient to recommend colon cancer screening of all carriers or their families; however, if colon cancer has been diagnosed in a carrier, their family members should have colon cancer screening beginning at age 40 or at an age 10 years younger than when the youngest family member was diagnosed (3 Risk factor references Etiology of stomach cancer is multifactorial, but Helicobacter pylori plays a significant role. Symptoms include early satiety, obstruction, and bleeding but tend to occur late in the... read more ).
Risk factor references
1. Bouvard V, Loomis D, Guyton KZ, et al: Carcinogenicity of consumption of red and processed meat. Lancet Oncol 16(16): 1599–1600, 2015. doi: 10.1016/S1470-2045(15)00444-1
2. Shepard B, Yoder L, Holmes C: Prophylactic total gastrectomy for hereditary diffuse gastric cancer. ACG Case Rep J 3(4):e179, 2016. doi: 10.14309/crj.2016.152
3. van der Post RS, Vogelaar IP, Carneiro F, et al: Hereditary diffuse gastric cancer: Updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet 52(6):361–374, 2015. doi: 10.1136/jmedgenet-2015-103094
Pathophysiology of Stomach Cancer
Gastric adenocarcinomas can be classified by gross appearance:
Protruding: The tumor is polypoid or fungating.
Penetrating: The tumor is ulcerated.
Superficial spreading: The tumor spreads along the mucosa or infiltrates superficially within the wall of the stomach.
Linitis plastica: The tumor infiltrates the stomach wall with an associated fibrous reaction that causes a rigid “leather bottle” stomach.
Miscellaneous: The tumor shows characteristics of ≥ 2 of the other types; this classification is the largest.
Prognosis is better with protruding tumors than with spreading tumors because protruding tumors become symptomatic earlier.
Symptoms and Signs of Stomach Cancer
Initial symptoms of stomach cancer are nonspecific, often consisting of dyspepsia suggestive of peptic ulcer. Patients and physicians alike tend to dismiss symptoms or treat the patient for acid disease. Later, early satiety (fullness after ingesting a small amount of food) may occur if the cancer obstructs the pyloric region or if the stomach becomes nondistensible secondary to linitis plastica. Dysphagia Dysphagia Dysphagia is difficulty swallowing. The condition results from impeded transport of liquids, solids, or both from the pharynx to the stomach. Dysphagia should not be confused with globus sensation... read more may result if cancer in the cardiac region of the stomach obstructs the esophageal outlet. Loss of weight or strength, usually resulting from dietary restriction, is common. Massive hematemesis or melena is uncommon, but secondary anemia may follow occult blood loss. Occasionally, the first symptoms are caused by metastasis (eg, jaundice, ascites, fractures).
Physical findings may be unremarkable or limited to heme-positive stools. Late in the course, abnormalities include an epigastric mass; umbilical, left supraclavicular, or left axillary lymph nodes; hepatomegaly; and an ovarian or rectal mass. Pulmonary, central nervous system, and bone lesions may occur.
Diagnosis of Stomach Cancer
Endoscopy with biopsy
Then CT and endoscopic ultrasonography
Differential diagnosis of stomach cancer commonly includes peptic ulcer and its complications Complications A peptic ulcer is an erosion in a segment of the gastrointestinal mucosa, typically in the stomach (gastric ulcer) or the first few centimeters of the duodenum (duodenal ulcer), that penetrates... read more .
Patients suspected of having stomach cancer should have endoscopy with multiple biopsies and brush cytology. Occasionally, a biopsy limited to the mucosa misses tumor tissue in the submucosa. X-rays, particularly double-contrast barium studies, may show lesions but rarely obviate the need for subsequent endoscopy.
Patients in whom cancer is identified require CT of the chest and abdomen to determine extent of tumor spread. If CT is negative for metastasis, endoscopic ultrasonography should be done to determine the depth of the tumor and regional lymph node involvement. Findings guide therapy and help determine prognosis.
Basic blood tests, including complete blood count, electrolytes, and liver tests, should be done to assess anemia, hydration, general condition, and possible liver metastases. The carcinoembryonic antigen (CEA) level should be measured before and after surgery.
Screening with endoscopy is used in high-risk populations (eg, Japanese) but is not recommended in the US. Follow-up screening for recurrence in treated patients consists of endoscopy and CT of the chest, abdomen, and pelvis. If an elevated CEA level dropped after surgery, follow-up should include CEA levels; a rise signifies recurrence.
Prognosis for Stomach Cancer
Prognosis depends greatly on stage but overall is poor (5-year survival: < 5 to 15%) because most patients present with advanced disease. If the tumor is limited to the mucosa or submucosa, 5-year survival may be as high as 80%. For tumors involving local lymph nodes, survival is 20 to 40%. More widespread disease is almost always fatal within 1 year. Gastric lymphomas have a better prognosis ( see Mucosa-associated lymphoid tissue (MALT) lymphoma Mucosa-associated lymphoid tissue (MALT) lymphoma Gastritis is inflammation of the gastric mucosa caused by any of several conditions, including Helicobacter pylori infection, drugs (nonsteroidal anti-inflammatory drugs [NSAIDs], alcohol),... read more and see Non-Hodgkin Lymphomas Non-Hodgkin Lymphomas Non-Hodgkin lymphomas are a heterogeneous group of disorders involving malignant monoclonal proliferation of lymphoid cells in lymphoreticular sites, including lymph nodes, bone marrow, the... read more ).
Treatment of Stomach Cancer
Surgical resection, sometimes combined with chemotherapy, radiation, or both
(See also the National Comprehensive Cancer Network's guidelines on gastric cancer.)
Stomach cancer treatment decisions depend on tumor staging and the patient’s wishes (some may choose to forgo aggressive treatment— see Advance Directives Advance Directives Advance directives are legal documents that extend a person's control over health care decisions in the event that the person becomes incapacitated. They are called advance directives because... read more ).
Curative surgery involves removal of most or all of the stomach and adjacent lymph nodes and is reasonable in patients with disease limited to the stomach and perhaps the regional lymph nodes (< 50% of patients). Adjuvant chemotherapy or combined chemotherapy and radiation therapy after surgery may be beneficial if the tumor is resectable.
Resection of locally advanced regional disease results in a 10-month median survival (vs 3 to 4 months without resection).
Metastasis or extensive nodal involvement precludes curative surgery, and, at most, palliative procedures should be undertaken. However, the true extent of tumor spread often is not recognized until curative surgery is attempted. Palliative surgery typically consists of a gastroenterostomy to bypass a pyloric obstruction and should be done only if the patient’s quality of life can be improved. In patients not undergoing surgery, combination chemotherapy regimens (5-fluorouracil, capecitabine, doxorubicin, mitomycin, cisplatin, oxaliplatin, irinotecan, paclitaxel, docetaxel, or leucovorin in various combinations) may produce temporary response but little improvement in 5-year survival. In recent years, targeted therapies using trastuzumab for tumors that overexpress human epidermal growth factor receptor 2 (HER2+) tumors and ramucirumab (a vascular endothelial growth factor [VEGF] inhibitor) in conjunction with chemotherapy have been used in advanced cancer. Immunotherapy such as with pembrolizumab is approved for use in patients with programmed cell death ligand 1 (PD-L1)–positive advanced or metastatic gastric cancer. Programmed cell death receptor 1 inhibitors (eg, nivolumab) are approved for use outside the US for patients with advanced gastric cancer. Radiation therapy is of limited benefit.
Helicobacter pylori infection is a risk factor for some stomach cancers.
Initial symptoms are nonspecific and often resemble those of peptic ulcer disease.
Screening with endoscopy is used in high-risk populations (eg, Japanese) but is not recommended in the US.
Overall, survival is poor (5-year survival: 5 to 15%) because many patients present with advanced disease.
Curative surgery, perhaps with combined chemotherapy and radiation therapy, is reasonable in patients with disease limited to the stomach and perhaps the regional lymph nodes.
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