Gastric cancer is the fourth most prevalent cancer and one of the leading causes of death worldwide. The disease arises from malignant cells in the lining of the stomach. There are numerous risk factors that contribute to the development of the disease.
Symptoms in early stages of the disease are usually vague and nonspecific. As the disease progresses the clinical picture will reflect this. The most frequent initial features at the time of presentation are weight loss and abdominal pain . Other common symptoms are anorexia, nausea, vomiting, indigestion, heartburn, early satiety, postprandial bloating, vomiting, and dysphagia. Furthermore, the epigastric pain is usually mild in the early stages but severe and persistent in advanced disease. Other late features include obstruction of the gastroesophageal junction, gastric outlet, or small intestine. Also, melena, hematemesis. peritoneal and pleural effusions and jaundice may develop.
The most common finding in advanced cases is palpable abdominal mass , which may be accompanied by succussion splash and hepatomegaly. Other possible signs of metastatic disease include left supraclavicular adenopathy (Virchow's node) , periumbilical node (Sister Mary Joseph nodule) , and an anterior axillary node (Irish node).
In cases with peritoneal involvement, a pelvic and rectal exam may reveal an enlarged ovary (Krukenberg's tumor) , or a retroperitoneal lesion known as Blumer's shelf. Also, peritoneal carcinomatosis produces ascites.
Jaundice and pallor may be apparent as well.
Patients presenting with clinical manifestations that are suggestive of gastric malignancy warrant a thorough assessment that consists of the personal and family history, a physical exam, and comprehensive testing.
Upper GI endoscopy is the initial diagnostic tool. Specifically, esophagogastroduodenoscopy (EGD) is very accurate in detecting GC as it provides visualization of the mass. It also allows the operator to obtain a biopsy of the lesion and the surrounding area as well. After establishing the diagnosis, an EUS is utilized to determine the tumor stage and to evaluate the GI tract and adjacent structures. Furthermore, computed tomography (CT) and magnetic resonance imaging (MRI) of the chest, abdomen, and pelvis are obtained to assess for potential metastases to the liver, lymph nodes, etc. A chest radiograph is also important for the same reason. Another modality, the positron emission tomography (PET), may be used to determine the presence of distant disease. Finally, a staging laparoscopy can be considered especially since imaging techniques may not detect small lesions less than 5mm in size.
A complete blood cell count (CBC) is important to determine the presence of anemia, which can occur due to GI bleeding, anorexia, or liver impairment. Additionally, electrolyte measurements and liver function tests (LFTs) will clarify the overall clinical picture.
The cancer marker, carcinoembryonic antigen (CEA), is elevated in up to 50% of all cases. Also, cancer antigen (CA) 19-9 is increased in approximately 20% of patients.
Immunohistochemical evaluation for HER2/neu is a crucial component of the workup in patients with metastatic disease  since there is a targeted agent for cancers that overexpress this receptor .
Patients with GC are managed by a team of specialists including gastroenterologists, surgical oncologists, medical oncologists, and radiation oncologists. They will conduct the preoperative assessment and collectively determine the best plan of care in conjunction with the patient's wishes.
According to the National Comprehensive Cancer Network (NCCN), the early stages of GC are treated with total or subtotal gastrectomy . Additionally, resection of D2 lymph nodes is also recommended. These include nodes of the following arteries: hepatic, left gastric, celiac, and splenic .
Various agents have been assessed in the neoadjuvant, adjuvant, and metastatic settings. Preoperative drugs may be used to debulk the tumor, which will render it easier for resection. This form of treatment can help evaluate the effect of chemotherapy, reduce relapse, and increase survival rates. One trial reported that perioperative treatment (before and after surgery) with the combination of epirubicin, cisplatin, and fluorouracil showed improvement in survival and shrinkage of tumor size versus the group who was treated with surgery alone . Furthermore, postoperative chemoradiotherapy was shown to prolong disease-free survival and increase overall survival in contrast to patients treated with only surgery . Other studies are comparing patients receiving preoperative and postoperative chemotherapy versus those who are managed with postoperative chemotherapy and radiation.
For advanced unresectable disease, standard chemotherapy regimens can be given. Additionally, there are alternative treatments that are directed at specific characteristics of the tumor. In the U.S., two drugs have been approved as targeted therapies. Trastuzumab is a monoclonal antibody that inhibits HER2 . Studies have demonstrated that overall survival was improved in patients receiving trastuzumab with standard chemotherapeutic agents versus those who received the latter only . Hence, the HER2 positive disease can be treated with trastuzumab in conjunction with cisplatin and either 5-fluorouracil or capecitabine for individuals who have not received prior therapy for metastatic disease.
Another targeted treatment, ramucirumab, is a monoclonal antibody directed at vascular endothelial growth factor receptors 2 (VEGFR2). This is the first biologic agent that exhibited survival in patients with advanced stages of GC when administered alone . It can be used in advanced cancer following standard chemotherapy.
The prognostic factors for GC are lymph node involvement and depth of the tumor . With regards to patient outcome, localized distal disease represents the best prognosis as more than half of these cases can be cured with surgical resection. In contrast, localized proximal cancer has a 5-year survival rate of 10% to 15%. Furthermore, the disseminated disease has a 5-year survival rate of zero. Unfortunately, the majority of patients are diagnosed with advanced cancer. Note that this cancer exhibits a high rate of recurrence.
The cause of GC is mostly multifactorial in origin as it is composed of genetic and environmental interplay . For example, a diet rich in pickled foods, salty fish, smoked meat , red meat, and fat  is associated with this cancer. Also, smoking was found to increase the risk of GC by 1.5 to 1.6 times . Very importantly, H. pylori are the primary carcinogen for GC and hence the strongest risk factor .
Other risk factors include a history of previous gastric surgery, adenomatous polyps, pernicious anemia, gastric ulcers , chronic atrophic gastritis, obesity, radiation exposure, and possibly Epstein-Barr virus (EBV). In contrast, fruit, vegetables, and vitamin C are considered protective factors .
GC is the fourth most common cancer worldwide and the third deadliest cancer in men and fifth in women . There are approximately 990,000 new diagnoses annually across the globe . According to the World Health Organization (WHO), GC was responsible for 723,000 worldwide deaths in 2012 . Hence, this cancer represents one of the highest cancer burdens .
This type of cancer is most prevalent in regions such as East Asia, Eastern Europe, and South America . For example, its incidence in Korea is 65.9 in 100,000 . In contrast, GC occurs the least in North America and Africa . Specifically, the incidence of GC in the U.S. is 7.8 per population of 100,000 in white non-Hispanic males and 3.5 per 100,000 in white non-Hispanic females . Furthermore, it is the 15th most prevalent cancer in the U.S. .
With regards to patient demographics, there is a racial preference. Moreover, GC in U.S. Hispanics is much higher than in white individuals . Additionally, the Maoris in New Zealand as well as the Inuit community exhibit elevated rates . As for gender, males are affected 2 to 3 times as much as females .
Tumors can arise in various parts of the stomach, which is divided into the cardia (uppermost portion), fundus (middle), and the pylorus (distal stomach). Most GCs occur in the non-cardia segments. Additionally, 10% will affect more than one portion.
There are two main histological variants of GC, which are diffuse and intestinal . Diffuse cancer is typified by tumor extension and liver metastasis . It usually results from genetic abnormalities  such as in hereditary diffuse gastric carcinoma (HDGC). Note that the diffuse type is more common in women and patients below the age of 50 .
The intestinal form is characterized by infiltrative growth and dissemination to the peritoneum . Non-cardia intestinal cancer is associated with H. pylori infection. A series of consecutive precancerous lesions known as Correa's cascade describes the malignant process that transforms chronic non-atrophic gastritis to atrophic gastritis, then intestinal metaplasia, and eventually dysplasia. One study demonstrated a correlation between the progression of the cascade and the risk of developing cancer . Note that the intestinal type is more prevalent in elderly males.
Oncogenic pathways such as the proliferation/stem cell, Wnt/beta-catenin, and NF-kappaβ have been implicated in more than 70% of GCs. These findings may have an impact on the use of targeted therapies and patient survival .
GC can extend to the liver, peritoneum, and distant lymph nodes. Distribution to other sites such as the ovaries, lungs, bone, soft tissue, and the central nervous system is less common. Dissemination occurs through the hematogenous and lymphatic routes. The former method uses the extensive vascular supply of the stomach, which is perfused by the celiac artery, its branches, and sub-branches. The tumor can also spread through the stomach's complex drainage system. Specifically, the celiac lymph nodes represent the primary mode of drainage. Further drainage occurs from other gastrointestinal nodes.
The preventative strategies address the known risk factors. For example, the World Health Assembly recommends dietary modifications such as reducing consumption of salty foods and red meat while increasing the intake of fruits and vegetables. Also, smoking cessation is key since smoking is the greatest avoidable risk for cancer in general. Furthermore, prevention, treatment, and eradication of H. pylori are also important approaches. Finally, countries with high prevalence of GC such as Japan, Korea, Chile, and Venezuela have instituted early mass screening programs for the detection of this cancer.
Gastric cancer (GC) is the fourth most common cancer in the world and is among the most fatal . It results from the combination of genetic predisposition and environmental components. The latter includes Helicobacter pylori infection, salty diets, smoking, and other risk factors. This cancer has a higher occurrence in certain parts of the world such as Eastern Asian countries. Furthermore, the incidence of GC has significantly declined in many developed countries in the past decades. This is likely attributed to an increased consumption of fresh fruits and vegetables and reduced intake of salt. Additionally, infections with H. pylori have decreased due to better hygiene, antibiotic treatment, and screening.
The clinical manifestations of the early disease are usually vague and nonspecific such as weight loss, anorexia, nausea, and indigestion. As the disease progresses, patients experience emesis, abdominal pain, dysphagia, postprandial fullness, etc. Complications include GI obstruction, jaundice, peritoneal effusions, and other features as well.
Patients suspected to have GC should be evaluated thoroughly by a personal and family history, a detailed physical exam, and the appropriate studies. In order to understand the overall clinical picture, it is important to perform a comprehensive preoperative assessment that consists of imaging, pathologic analysis of the biopsy, and blood analysis. Imaging tools include upper gastrointestinal (GI) endoscopy, endoscopic ultrasound (EUS), and other relevant modalities.
The prognosis is better for patients whose cancer is detected early. Hence, aggressive surgery should be performed promptly for resectable tumors. In addition to surgery, there are various treatment regimens that have been studied or are currently being investigated. Management may include a combination of surgery, chemotherapy, radiation, and/or targeted agents.
Preventative strategies have been recommended and implemented worldwide. Lifestyle modifications such as diet adjustment, smoking cessation, and eradication of H. pylori are some of the key approaches.
What is Gastric Cancer?
This also known as stomach cancer, which develops when cancer cells form and grow in the stomach's lining. This cancer is much more common in East Asia, Eastern Europe, and South America than it is in North America. It is also more common in men. It is much less common in the U.S. since people are eating less salty food.
What are the causes?
There are genetic and environmental components that increase the risk of developing gastric cancer. The risk factors include:
What are the signs and symptoms?
Early symptoms are vague. They include:
As the disease progresses and the tumor grows, patients may develop:
How is it diagnosed?
Patients with a presentation that resembles gastric cancer should be evaluated with a personal and family history, a physical exam, and imaging tests such as:
How is it treated?
The medical team will decide the best treatment for the patient based on the size of the tumor, the stage of cancer, and the patient's wishes. The following may be options:
If the tumor can be resected, a combination of chemotherapy and radiation may be given as a combination after surgery. Also, chemotherapy may be used before surgery.
Can it be prevented?
There are preventative strategies that address the factors that increase the risk of developing this cancer. The following are the key approaches:
What is the prognosis?
If detected in the early stages, gastric cancer can be cured although it may recur. Advanced stages of gastric cancer have a poor prognosis.