Stomach cancer
From Wikipedia, the free encyclopedia
| Stomach cancer | |
|---|---|
A stomach ulcer that was diagnosed as cancer on biopsy and surgically removed.
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| Classification and external resources | |
| Specialty | Oncology |
| ICD-10 | C16 |
| ICD-9 | 151 |
| OMIM | 137215 |
| DiseasesDB | 12445 |
| MedlinePlus | 000223 |
| eMedicine | med/845 |
| MeSH | D013274 |
| GeneReviews | |
The most common cause is infection by the bacteria Helicobacter pylori, which accounts for more than 60% of cases.[4][5] Certain types 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.[5] Diagnosis is usually by biopsy done during endoscopy. This is then followed by medical imaging to determine if the disease has spread to other parts of the body.[2] Japan and South Korea, two countries that have high rates of disease, screen for stomach cancer.[5]
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.[5][6] If cancer is treated early, many cases can be cured.[5] Treatments may include some combination of surgery, chemotherapy, radiation therapy, and targeted therapy.[2] If treated late, palliative care may be advised.[5] 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.[7] In the United States 5-year survival is 28%[8] while in South Korea it is over 65% partly due to screening efforts.[5]
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.[9] In 2012 it occurred in 950,000 people and caused 723,000 deaths.[9] 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.[10][11][12] Rates of death have been decreasing in many areas of the world since then.[5] 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.[13] Stomach cancer occurs most commonly in East Asia and Eastern Europe and it occurs twice as often in males as in females.[5]
Contents
Signs and symptoms
Endoscopic image of linitis plastica, a type of stomach cancer where the entire stomach is invaded, leading to a leather bottle-like appearance with blood coming out of it.
Endoscopic images of the stomach cancer in early stage. Its histology was poorly differentiated adenocarcinoma with signet ring cells.Left above=Normal, right above=FICE, left low=acetate stained, right low= AIM stained
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.[15] Abdominal discomfort and loss of appetite, especially for meat, can occur.
Gastric cancers that 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 discolouration (melena) and sometimes leading to anemia. Dysphagia suggests a tumour in the cardia or extension of the gastric tumour into the esophagus.
Note that these can be symptoms of other problems such as a stomach virus, gastric ulcer, or tropical sprue.
Causes
Gastric cancer is a multifactorial disease.[16] Helicobacter pylori infection is an essential risk factor in 65–80% of gastric cancers, but in only 2% of such infections.[17][18] The mechanism by which H. pylori induces stomach cancer potentially involves chronic inflammation, or the action of H. pylori virulence factors such as CagA.[19] It was estimated that Epstein–Barr virus is responsible for 84,000 cases per year.[20]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.[21][22][23] Some studies show increased risk with alcohol consumption as well.[18][24]
Dietary factors are not proven causes,[25] but some foods including smoked foods,[26] salt and salt-rich foods, red meat, processed meat, pickled vegetables,[18] and bracken[27] 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.[18][21] A Mediterranean diet is also associated with lower rates of stomach cancer,[28] as is regular aspirin use.[18]
There is a correlation between iodine deficiency and gastric cancer.[29][30][31]
Sequence of 123-iodine human scintiscans after an intravenous injection,
(from left) after 30 minutes, 20 hours and 48 hours. A high and rapid
concentration of radio-iodine is evident in gastric mucosa of the
stomach, in salivary glands, oral mucosa and in the periencephalic and
cerebrospinal fluid (left). In the thyroid gland, I-concentration is
more progressive, also in the reservoir (from 1% after 30 minutes, to
5.8 % after 48 hours, of the total injected dose.[32]
Approximately 10% of cases show a genetic component.[36]
People may possess certain risk factors, such as those that are physical or genetic, that can alter their susceptibility for gastric cancer. Obesity is one such physical risk factor that has been found to increase the risk of gastric adenocarcinoma by contributing to the development of gastroesphageal reflux disease (GERD).[37] The exact mechanism by which obesity causes GERD is not completely known. Studies hypothesize that increased dietary fat leading to increased pressure on the stomach and the lower esophageal sphincter, due to excess adipose tissue, could play a role, yet no statistically significant data has been collected.[38] However, the risk of gastric cardia adenocarcinoma, with GERD present, has been found to increase more than 2 times for an obese person.[37] A genetic risk factor for gastric cancer is a genetic defect of the CDH1 gene known as hereditary diffuse gastric cancer (HDGC). The CDH1 gene, which codes for E-cadherin, lies on the 16th chromosome.[39] When the gene experiences a particular mutation, gastric cancer develops through a mechanism that is not fully understood.[39] This mutation is considered autosomal dominant meaning that half of a carrier’s children will likely experience the same mutation.[39] Diagnosis of hereditary diffuse gastric cancer usually takes place when at least two cases involving a family member, such as a parent or grandparent, are diagnosed, with at least one diagnosed before the age of 50.[39] The diagnosis can also be made if there are at least three cases in the family, in which case age is not considered.[39]
The International Cancer Genome Consortium is leading efforts to identify genomic changes involved in stomach cancer.[40][41] A very small percentage of diffuse-type gastric cancers (see Histopathology below) arise from an inherited abnormal CDH1 gene. Genetic testing and treatment options are available for families at risk.[42]
Other factors associated with increased risk are AIDS,[18] diabetes,[43] pernicious anemia,[24] chronic atrophic gastritis,[44] Menetrier's disease (hyperplastic, hypersecretory gastropathy),[45] and intestinal metaplasia.[46]
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 fibre optic camera into the stomach to visualise it.[24]
- 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 that is focal, eccentric and enhancing favours malignancy.[47]
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.[24]
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 visualise cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as optical coherence tomography are also being tested investigationally for similar applications.[50]
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.[51]
Various blood tests may be done including a complete blood count (CBC) to check for anaemia, and a fecal occult blood test to check for blood in the stool.
Histopathology
Poor to moderately differentiated adenocarcinoma of the stomach. H&E stain.
Gastric signet ring cell carcinoma. H&E stain.
Adenocarcinoma of the stomach and intestinal metaplasia. H&E stain.
- Gastric adenocarcinoma is a malignant epithelial tumour, originating from glandular epithelium of the gastric mucosa. Stomach cancers are overwhelmingly adenocarcinomas (90%).[52] 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 tumour cells describe irregular tubular structures, harbouring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Often, it associates intestinal metaplasia in neighbouring 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) tumour 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 tumour cell, it pushes the nucleus to the periphery: "signet-ring cell".
- Around 5% of gastric malignancies are lymphomas (MALTomas, or MALT lymphoma).[53]
- Carcinoid and stromal tumors may also occur.
Staging
T stages of stomach cancer
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:[55][56]
- 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.
Stomach cancer metastasized to the lungs
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.[58] A Minnesota population was diagnosed 10% in Stage I, 13% in Stage II, and 18% in Stage III.[59] 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.[60]
Prevention
Getting rid of H. pylori in those who are infected decreases the risk of stomach cancer, at least in those who are Asian.[61] Low doses of vitamins, especially from a healthy diet, decrease the risk of stomach cancer.[62] A previous review of supplementation did not find supporting evidence and possibly worse outcomes.[63][64]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.[65] Treatment for stomach cancer may include surgery,[66] chemotherapy, and/or radiation therapy.[67] New treatment approaches such as biological therapy and improved ways of using current methods are being studied in clinical trials.[68]Surgery
Anatomy before Roux-en-y surgery to resect stomach cancer.
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.[7][69]
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.[70] 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.[7] Recently, a targeted treatment called trastuzumab has become available for use with chemotherapy for the treatment of those overexpressing the HER2 gene in their tumor cells.[7]Radiation
Radiation therapy (also called radiotherapy) may also be used to treat stomach cancer, often as an adjuvant to chemotherapy and/or surgery.[7]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.[71] The 5-year survival rate for stomach cancer is reported to be less than 10%.[7]Epidemiology
Age-standardized death from stomach cancer per 100,000 inhabitants in 2004.[72]
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no data
<3.5
3.5–8
8–12.5
12.5–17
17–21.5
21.5–26
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26–30.5
30.5–35
35–40
40–45
45–50
>50
|
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.[78]
In 2011, stomach cancer accounted for 0.64% of deaths (13,230 cases) in the United States.[79] In China, stomach cancer accounted for 3.99% of all deaths (354,829 cases).[80] The mortality rate was highest in the Maldives, stomach cancer accounting for 8.92% of all deaths.[81]
Stomach cancer is the fifteenth most common cancer in the UK (around 7,100 people were diagnosed with stomach cancer in 2011), and it is the tenth most common cause of cancer death (around 4,800 people died in 2012).[82]
Incidence and mortality rates of gastric cancer vary greatly in Africa. The GLOBOCAN system is currently the most widely used method to compare these rates between countries, but African incidence and mortality rates are seen to differ among countries possibly due to the lack of universal access to a registry system for all countries.[83] Variation as drastic as estimated rates from 0.3/100000 in Mali to 20.3/100000 in Botswana have been observed.[83] In Uganda, the incidence of gastric cancer has increased from the 1960s measurement of 0.8/100000 to 5.6/100000.[83] Gastric cancer, though present, is relatively low when compared to countries with high incidence like Japan or China. One suspected cause of the variation within Africa and between other countries is due to different strains of the Helicobacter pylori bacteria. The trend commonly seen is that H. pylori infection increases the risk for gastric cancer, however this is not the case in Africa giving this phenomenon the name the “African enigma.”[84] Although this bacteria is found in Africa, evidence has supported that different strains with mutations in the bacterial genotype may contribute to the difference in cancer development between African countries and others outside of the continent.[84] But, increasing access to health care and treatment measures have been commonly associated with the rising incidence, particularly in Uganda. [83]
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