Stomach cancer

Stomach cancer or gastric cancer, is when cancer develops from the lining of the stomach. Early symptoms may include: heartburn, upper abdominal pain, nausea, and loss of appetite. Later symptoms may include: weight loss, yellow skin, vomiting, difficulty swallowing, and blood in the stool among others. The cancer may spread from the stomach to other parts of the body, particularly the liver, lungs, bones, lining of the abdomen and lymph nodes.

The most common cause is infection by the bacteria Helicobacter pylori which accounts for more than 60% of cases. Certain type of H. pylori have greater risks than others. Other common causes include eating pickled vegetables, and smoking. About 10% of cases run in families and between 1% and 3% of cases are due to genetic syndromes inherited from a person's parents such as hereditary diffuse gastric cancer. Most cases of stomach cancers are gastric carcinomas. This type can be divided into a number of subtypes. Lymphomas and mesenchymal tumors may also develop within the stomach. Most of the time, stomach cancer develops through a number of stages over a number of years. Diagnosis is usually by biopsy done during endoscopy. This is than followed by medical imaging to determine if the disease has spread to other parts of the body. At least Japan and South Korea, two countries that have high rates of disease, screen for stomach cancer.

A Mediterranean diet lowers the risk of cancer as does the stopping of smoking. There is tentative evidence that treating H. pylori decreases the future risk. If cancer is treated early many cases can be cured. Treatments may include some combination of: surgery, chemotherapy, radiation therapy and targeted therapy. If treated late palliative care may be advised. Outcomes are often poor with a less than 10% 5-year survival rate globally. This is largely because most people with the condition present with advanced disease. In the United States 5-year survival is 28% while in South Korea it is over 65% partly due to screening efforts.

Globally stomach cancer is the fifth leading cause of cancer and the third leading cause of death from cancer making up 7% of cases and 9% of deaths. In 2012 it occurred in 950,000 people and caused 723,000 deaths. Before the 1930s in much of the world, including the United States and the United Kingdom, it was the most common cause of death from cancer. Rates of death have been decreasing in many areas of the world since then. This is believed to be due to the eating of less salted and pickled foods as a result of the development of refrigeration as a method of keeping food fresh. Stomach cancer occurs most commonly in East Asia and Eastern Europe and it occurs twice as often in males as in females.

Signs and symptoms
Stomach cancer is often either asymptomatic (producing no noticeable symptoms) or it may cause only nonspecific symptoms (symptoms which are specific not only to stomach cancer, but also to other related or unrelated disorders) in its early stages. By the time symptoms occur, the cancer has often reached an advanced stage (see below) and may have also metastasized (spread to other, perhaps distant, parts of the body), which is one of the main reasons for its relatively poor prognosis. Stomach cancer can cause the following signs and symptoms:

Early cancers may be associated with indigestion or a burning sensation (heartburn). However, less than 1 in every 50 people referred for endoscopy due to indigestion has cancer. Abdominal discomfort and loss of appetite, especially for meat, can occur.

Gastric cancers which have enlarged and invaded normal tissue can cause weakness, fatigue, bloating of the stomach after meals, abdominal pain in the upper abdomen, nausea and occasional vomiting, diarrhea or constipation. Further enlargement may cause weight loss, or bleeding with vomiting blood or having blood in the stool, the latter apparent as black discoloration (melena) and sometimes leading to anemia. Dysphagia suggests a tumor in the cardia or extension of the gastric tumor into the esophagus.

Note that these can be symptoms of other problems such as a stomach virus, gastric ulcer or tropical sprue.

Causes
Helicobacter pylori infection is the main risk factor in 65–80% of gastric cancers, but in only 2% of such infections. The mechanism by which H. pylori induces stomach cancer potentially involves chronic inflammation, or the action of H. pylori virulence factors such as CagA.

Smoking increases the risk of developing gastric cancer significantly, from 40% increased risk for current smokers to 82% increase for heavy smokers. Gastric cancers due to smoking mostly occur in the upper part of the stomach near the esophagus. Some studies show increased risk with alcohol consumption as well.

Dietary factors are not proven causes, but some foods including smoked foods, salt and salt-rich foods, red meat, processed meat, pickled vegetables, and bracken are associated with a higher risk of stomach cancer. Nitrates and nitrites in cured meats can be converted by certain bacteria, including H. pylori, into compounds that have been found to cause stomach cancer in animals. On the other hand, fresh fruit and vegetable intake, citrus fruit intake, and antioxidant intake are associated with a lower risk of stomach cancer. A Mediterranean diet is also associated with lower rates of stomach cancer, as is regular aspirin use.

There is a correlation between iodine deficiency and gastric cancer.

Gastric cancer shows a male predominance in its incidence as up to three males are affected for every female. Estrogen may protect women against the development of this cancer form.

Approximately 10% of cases show a genetic component. The International Cancer Genome Consortium is leading efforts to identify genomic changes involved in stomach cancer. A very small percentage of diffuse-type gastric cancers (see Histopathology below) arise from an inherited abnormal CDH1 gene. Hereditary diffuse gastric cancer (HDGC) has recently been identified and research is ongoing. Genetic testing and treatment options are already available for families at risk.

Other factors associated with increased risk are AIDS, diabetes, pernicious anemia, chronic atrophic gastritis, Menetrier's disease (hyperplastic, hypersecretory gastropathy), and intestinal metaplasia.

Diagnosis
To find the cause of symptoms, the doctor asks about the patient's medical history, does a physical exam, and may order laboratory studies. The patient may also have one or all of the following exams:
 * Gastroscopic exam is the diagnostic method of choice. This involves insertion of a fiber optic camera into the stomach to visualize it.
 * Upper GI series (may be called barium roentgenogram).
 * Computed tomography or CT scanning of the abdomen may reveal gastric cancer, but is more useful to determine invasion into adjacent tissues, or the presence of spread to local lymph nodes. Wall thickening of more than 1 cm which is focal, eccentric and enhancing favors malignancy.

In 2013, Chinese and Israeli scientists reported a successful pilot study of a breathalyzer-style breath test intended to diagnose stomach cancer by analyzing exhaled chemicals without the need for an intrusive endoscopy. A larger-scale clinical trial is now underway.

Abnormal tissue seen in a gastroscope examination will be biopsied by the surgeon or gastroenterologist. This tissue is then sent to a pathologist for histological examination under a microscope to check for the presence of cancerous cells. A biopsy, with subsequent histological analysis, is the only sure way to confirm the presence of cancer cells.

Various gastroscopic modalities have been developed to increase yield of detected mucosa with a dye that accentuates the cell structure and can identify areas of dysplasia. Endocytoscopy involves ultra-high magnification to visualize cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as optical coherence tomography are also being tested investigationally for similar applications.

A number of cutaneous conditions are associated with gastric cancer. A condition of darkened hyperplasia of the skin, frequently of the axilla and groin, known as acanthosis nigricans, is associated with intra-abdominal cancers such as gastric cancer. Other cutaneous manifestations of gastric cancer include tripe palms (a similar darkening hyperplasia of the skin of the palms) and the Leser-Trelat sign, which is the rapid development of skin lesions known as seborrheic keratoses.

Various blood tests may be done including a complete blood count (CBC) to check for anemia, and a fecal occult blood test to check for blood in the stool.

Histopathology



 * Gastric adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the gastric mucosa. Stomach cancers are overwhelmingly adenocarcinomas (90%). Histologically, there are two major types of gastric adenocarcinoma (Lauren classification): intestinal type or diffuse type. Adenocarcinomas tend to aggressively invade the gastric wall, infiltrating the muscularis mucosae, the submucosa, and thence the muscularis propria. Intestinal type adenocarcinoma tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Often, it associates intestinal metaplasia in neighboring mucosa. Depending on glandular architecture, cellular pleomorphism and mucosecretion, adenocarcinoma may present 3 degrees of differentiation: well, moderate and poorly differentiated. Diffuse type adenocarcinoma (mucinous, colloid, linitis plastica, leather-bottle stomach) tumor cells are discohesive and secrete mucus which is delivered in the interstitium, producing large pools of mucus/colloid (optically "empty" spaces). It is poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus to the periphery: "signet-ring cell".
 * Around 5% of gastric malignancies are lymphomas (MALTomas, or MALT lymphoma).
 * Carcinoid and stromal tumors may also occur.

Staging
If cancer cells are found in the tissue sample, the next step is to stage, or find out the extent of the disease. Various tests determine whether the cancer has spread and, if so, what parts of the body are affected. Because stomach cancer can spread to the liver, the pancreas, and other organs near the stomach as well as to the lungs, the doctor may order a CT scan, a PET scan, an endoscopic ultrasound exam, or other tests to check these areas. Blood tests for tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) may be ordered, as their levels correlate to extent of metastasis, especially to the liver, and the cure rate.

Staging may not be complete until after surgery. The surgeon removes nearby lymph nodes and possibly samples of tissue from other areas in the abdomen for examination by a pathologist.

The clinical stages of stomach cancer are:


 * Stage 0. Limited to the inner lining of the stomach. Treatable by endoscopic mucosal resection when found very early (in routine screenings); otherwise by gastrectomy and lymphadenectomy without need for chemotherapy or radiation.
 * Stage I. Penetration to the second or third layers of the stomach (Stage 1A) or to the second layer and nearby lymph nodes (Stage 1B). Stage 1A is treated by surgery, including removal of the omentum.  Stage 1B may be treated with chemotherapy (5-fluorouracil) and radiation therapy.
 * Stage II. Penetration to the second layer and more distant lymph nodes, or the third layer and only nearby lymph nodes, or all four layers but not the lymph nodes. Treated as for Stage I, sometimes with additional neoadjuvant chemotherapy.
 * Stage III. Penetration to the third layer and more distant lymph nodes, or penetration to the fourth layer and either nearby tissues or nearby or more distant lymph nodes. Treated as for Stage II; a cure is still possible in some cases.
 * Stage IV. Cancer has spread to nearby tissues and more distant lymph nodes, or has metastatized to other organs. A cure is very rarely possible at this stage.  Some other techniques to prolong life or improve symptoms are used, including laser treatment, surgery, and/or stents to keep the digestive tract open, and chemotherapy by drugs such as 5-fluorouracil, cisplatin, epirubicin, etoposide, docetaxel, oxaliplatin, capecitabine, or irinotecan.



The TNM staging system is also used.

In a study of open-access endoscopy in Scotland, patients were diagnosed 7% in Stage I 17% in Stage II, and 28% in Stage III. A Minnesota population was diagnosed 10% in Stage I, 13% in Stage II, and 18% in Stage III. However in a high-risk population in the Valdivia Province of southern Chile, only 5% of patients were diagnosed in the first two stages and 10% in stage III.

Prevention
Getting rid of H. pylori in those who are infected decreases the risk of stomach cancer, at least in those who are Asian.

Management
Cancer of the stomach is difficult to cure unless it is found at an early stage (before it has begun to spread). Unfortunately, because early stomach cancer causes few symptoms, the disease is usually advanced when the diagnosis is made. Treatment for stomach cancer may include surgery, chemotherapy, and/or radiation therapy. New treatment approaches such as biological therapy and improved ways of using current methods are being studied in clinical trials.

Surgery
Surgery remains the only curative therapy for stomach cancer. Of the different surgical techniques, endoscopic mucosal resection (EMR) is a treatment for early gastric cancer (tumor only involves the mucosa) that has been pioneered in Japan, but is also available in the United States at some centers. In this procedure, the tumor, together with the inner lining of stomach (mucosa), is removed from the wall of the stomach using an electrical wire loop through the endoscope. The advantage is that it is a much smaller operation than removing the stomach. Endoscopic submucosal dissection (ESD) is a similar technique pioneered in Japan, used to resect a large area of mucosa in one piece. If the pathologic examination of the resected specimen shows incomplete resection or deep invasion by tumor, the patient would need a formal stomach resection.

Those with metastatic disease at the time of presentation may receive palliative surgery and while it remains controversial, due to the possibility of complications from the surgery itself and the fact that it may delay chemotherapy the data so far is mostly positive, with improved survival rates being seen in those treated with this approach.

Chemotherapy
The use of chemotherapy to treat stomach cancer has no firmly established standard of care. Unfortunately, stomach cancer has not been particularly sensitive to these drugs, and chemotherapy, if used, has usually served to palliatively reduce the size of the tumor, relieve symptoms of the disease and increase survival time. Some drugs used in stomach cancer treatment have included: 5-FU (fluorouracil) or its analog capecitabine, BCNU (carmustine), methyl-CCNU (semustine) and doxorubicin (Adriamycin), as well as mitomycin C, and more recently cisplatin and taxotere, often using drugs in various combinations. The relative benefits of these different drugs, alone and in combination, are unclear. Clinical researchers have explored the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells. Recently, a targeted treatment called trastuzumab has become available for the treatment of those overexpressing the HER2 gene in their tumor cells.

Radiation
Radiation therapy (also called radiotherapy) may also be used to treat stomach cancer, often as an adjuvant to chemotherapy and/or surgery.

Prognosis
The prognosis of stomach cancer is generally poor, due to the fact the tumour has often metastasised by the time of discovery and the fact that most people with the condition are elderly (median age is between 70 and 75 years) at presentation. The 5-year survival rate for stomach cancer is reported to be less than 10%.

Epidemiology
Stomach cancer is the fourth most common cancer worldwide with 930,000 cases diagnosed in 2002. It is more common in men and in developing countries. In 2012, it represented 8.5% of cancer cases in men, making it the fourth most common cancer in men. In 2012 number of deaths were 700,000 having decreased slightly from 774,000 in 1990 making it the third leading cause of cancer death after lung cancer and liver cancer.

Less than 5% of stomach cancers occur in people under 40 years of age with 81.1% of that 5% in the age-group of 30 to 39 and 18.9% in the age-group of 20 to 29.

In 2011, stomach cancer accounted for 0.64% of deaths (13,230 cases) in the United States. In China, stomach cancer accounted for 3.99% of all deaths (354,829 cases). The mortality rate was highest in the Maldives, stomach cancer accounting for 8.92% of all deaths.

Other animals
The stomach is a muscular organ of the gastrointestinal tract that holds food and begins the digestive process by secreting gastric juice. The most common cancers of the stomach are adenocarcinomas but other histological types have been reported. Signs vary but may include vomiting (especially if blood is present), weight loss, anemia, and lack of appetite. Bowel movements may be dark and tarry in nature. In order to determine whether cancer is present in the stomach, special X-rays and/or abdominal ultrasound may be performed. Gastroscopy, a test using an instrument called endoscope to examine the stomach, is a useful diagnostic tool that can also take samples of the suspected mass for histopathological analysis to confirm or rule out cancer. The most definitive method of cancer diagnosis is through open surgical biopsy. Most stomach tumors are malignant with evidence of spread to lymph nodes or liver, making treatment difficult. Except for lymphoma, surgery is the most frequent treatment option for stomach cancers but it is associated with significant risks.