Unless otherwise stated, the article below refers to gastric adenocarcinoma
- The second most common cancer worldwide (behind lung cancer)
- Most common in South America and Japan (due to diet)
- 8th most common cancer in the UK
- Male:female is 2:1
- Thought to be the result of the combination of genetic factors and nitrates in the diet, with increased risk on smokers and those with H pylori infection.
- Presentation can be non-specific and easily confused with other causes of dyspepsia (indigestion / reflux / GORD). Weight loss in the context dyspepsia symptoms should be investigated.
- Diagnosis is usually a combination a endoscopy (with biopsies) and CT +/-USS
- Staging is done using the TNM scale
- Gastric tumours are almost always an adenocarcinoma of the mucous secreting cells of gastric pits. The most common mutation is that of tumour suppressor gene p53. Some tumours (but not all) may ulcerate.
- Many cases present very late – 5 year survival in the UK is about 10%
- In cases suitable for curative treatment, then rejection of the stomach is usuallly the preferred choice +/- chemotherapy +/- radiotherapy
- Other types of tumours affecting the stomach include:
- Gastric lymphoma (MALT) – accounts for 1-2% of gastric carcinomas.H pylori is again a large precipitating factor. Presentation often similar to gastric adenina carcinoma and thus may be difficult to differentiate from GORD or gastric ulcer
- Oesophageal carcinoma – almost always occurs in the presence of Barrett’s oesophagus, and is basically just an adenocarcinoma of the new columnar epithelium – i.e. it is similar historically to gastric carcinoma. Likely to present with dysphagia
- Gastric lymphoma (MALT) – accounts for 1-2% of gastric carcinomas.
- Very common in Chine, South America, Scandinavia and Japan – because the diets of people in these regions tend to be high in nitrates. Less common in Britain, and not very common in the USA. The USA has similarly low rates in people of Chinese / Japanese ethnicity, and therefore we can deduce that environmental factors are very important.
- It is the second most common malignancy worldwide (behind lung cancer), and the third most common cause of cancer death worthwide.
- There is evidence to show that gastric carcinoma is correlated to infection rates with H. Pylori.
- M:F 2:1, and incidence rises sharply after the age of 50.
- It is the 8th most common cancer in the UK, and has an incidence of 12-15 per 100,000. Incidence around the world is falling.
- It is very rare in people under 30.
- Japan has an extremely good screening system (because the disease is so common there), and it has 5 year survival rates of about 80%. In the rest of the developed world, the 5 year survival rate is about 10%. This is because usually the cancer is asymptomatic in the early stages, and by the time it presents it has developed too far.
- The average age of presentation is 50 to 70.
- Diet (smoked fish, pickled foods, salt, nitrates) Foods known to have a beneficial effect are fresh fruit and vegetables, particularly those containing vitamin C and A.
- H. Pylori – it is thought that this is responsible for 60-70% of cases. You are at greater risk if you get the infection if you are young, and if you are one of the people who goes hypochlorohydric when they get it (~1% of people who are infected). H. Pylori will often cause inflammation, leading to gastritis, leading to gastric atrophy, which can lead to gastric carcinoma.
- Gastric polyps
- FAP (familial adenomatous polyposis)
- Genetic factors – e.g. HDC-1 mutations
- Resection of the stomach (e.g. form an old peptic ulcer – they don’t really use this treatment any more) is also a disposing factor. This is because resecting the stomach will ultimately reduce gastric acid secretion, which will lead to gastric atrophy, and gastric atrophy is a predisposing factor for gastric cancer.
- History of recent dyspepsia.(50%) This pain will be very similar to that of peptic ulcer disease, and can often be relieved by antacids.
- Loss of appetite / anorexia (35%)
- Bloating / fullness
- Weight loss (72%)
- Vomiting/nausea (40%)
- Iron-deficiency anaemia due to occult bleeding
- Dysphagia (22%)
- Melaena (20%)
- Mass (17%)
- Haematemesis is unusual
Sadly, patients who present with obvious physical signs on examination; such as palpable mass or lymph nodes almost certainly have incurable disease.
Red flag symptoms
Any patients with these symptoms should be referred for endoscopy immediately, and seen within 2 weeks.
Patients of any age with dyspepsia, AND:
- Chronic GI Bleeding
- Progressive weight loss
- Iron deficiency anaemia
- Persistent vomiting
- Epigastric mass
- Suspicious barium meal result
- Sudden onset dyspepsia (on its own)
Once patients have been referred, then an endoscopy should be done, and biopsies taken.
Essentially all you need to do is a gastroscopy, and routine FBC and LFT’s.
- Most gastric carcinoma’s are adenocarcinoma (carcinoma of glandular tissue) derived from mucous secreting cells.
- The most common genetic factor is loss of the tumour suppressor gene p53, which occurs in about 70% of gastric cancers.
- Early gastric cancers are confined to the mucosa and submucosa, whilst more advanced cancers can penetrate the muscularis proporia, and may become ulcerating. Prognosis for early gastric cancer is very good (~90%).
- Virtually all gastric cancers are adenocarcinomas of the mucous secreting cells in the base of the gastric pits.
- The cancers can be described as either intestinal or diffuse. Intestinal ones have histology representative of intestinal epithelium, whilst diffuse ones arise from normal gastric mucosa. Diffuse cancers tend to occur in younger patients. Intestinal carcinoma cells are well differentiated (i.e. they are more like the ‘normal’ cells they originally grew from) and as a result these cancers have a better prognosis.
- Intestinal tumours account for most of the tumours in high-incidence countries, and are associated with H. Pylori infection. Diffuse tumours account for most of the tumours in low-incidence countries, and are probably more associated with genetic factors.
- Many of the abnormalities in gastric cancer are the same as those in colon cancer.
- First degree relatives of those with gastric cancer have a 2-3x greater chance of developing the disease.
- Ulcers cannot develop into cancer (benign ulcers), however, some cancers can cause ulceration (malignant ulcers). Benign ulcers cannot turn into malignant ulcers. It can be very different to distinguish between these benign and malignant ulcers, and even the malignant ones can show some signs of healing with triple therapy.
- In the western world, tumours are becoming more common in the proximal regions of the stomach, and less common in the distal regions.
- In the west, over 80% of the population present with advanced gastric cancer (i.e. it has spread deeper than the submucosa)
- Early gastric cancer is often asymptomatic and may only be discovered upon endoscopy for investigation of dyspepsia.
Course of the disease
- Basically, the disease follows a pattern in its development. Initially there will be chronic gastritis leading to atrophy, then onto metaplasia, and premalignant dysplasia, finally ending up at malignancy.
- A gastric adenocarcinoma can be classed as early, even if it has spread to lymph nodes if it has not penetrated the muscularis mucosae.
- The carcinoma can spread lymphatically to Virchow’s node, and can spread via venous blood to the liver and ovaries (Krukenburg tumours). Spread also occurs directly to the pancreas, depending on the initial tumour location, and can also spread to the spleen and transverse colon, perhaps by fistulation.
Staging in extremely important as it provides the basis for future treatment. In gastric cancer, histological staging in not very useful, and so pathological staging is used.
To stage effectively, you will probably need to carry out a CT and USS, and more recently, and endoscopic ultrasound is also performed.
- CT – this will show liver metastasis, but not lymph node involvement. Will also show gastric wall thickening.
- USS – will show gastric wall thickening and masses
- Endoscopy – shows whether the tumour is resectable or not
- Endoscopic ultrasound – will show how far the tumour has progressed through the gastric wall and lymph node involvement. Biopsies – these are a bit hit and miss. Samples from the same tumour will have cells of early stage and cells of late stage – if the tumour is late stage. SO it is a bit hit and miss. To fully diagnose late stage you would have to thoroughly take many sample from the whole tumour – which isn’t practical, and that is what pathological staging is used.
The tumours are staged using TNM, or UICC score.
No nodes involved
1-6 nodes involved
7-15 nodes involved
15+ nodes involved
Tumour is mucosa / submucosa
Tumour in muscularis propria
Tumour through serosa
Tumour invading other structures
No distant metastasis
UICC score gives a value of 1-4 as shown in the table below.
5 Year survival
T1 N0 M0
T2 N0 M0
T1-4 M1-3 M0
T4 N3 M0-1
The majority of cancers in the western world present as stage III-IV. The screening system in Japan is able to pick up many at level I-II.
‘Early cancer’ is technically level I.
Surgery is the best form of treatment if the patient is operable. However, there are many situations that mean the patient may be inoperable, such as when the tumour is tethered; e.g. to the aorta, or if there is such wide spread that surgical removal of the primary tumour would have little therapeutic effect.
Better staging in recent years has meant fewer patients being operated on, and thus the operative survival rate has increased to about 30%.
Of those operations that are undergone for the reason of a total cure (i.e. at the time of doing the operation they think a total cure is possible) the 5-year survival is 50%.
Surgery will involve a partial or total resection of the stomach, and removal of varying amounts of the surrounding lymph nodes. There has been serious debate as to whether removing the lymph nodes makes much difference. In Japan, often they do very long operations (perhaps >6 hours) and meticulously dissect and remove many lymph nodes, although there is little evidence to support an increased prognosis in this situation.
This type of surgery has 2-3% mortality and 20-30% chance of serious complications.
In some rare cases (or in about 50% in japan!), treatment is possible by endoscopy. In these early type I tumours, the tumours are completely removed in endoscopy.
For those who cannot undergo surgery, then palliative care, pain relief and counselling are the only treatments available.
Complications of surgery
- Usual cardiac, respiratory and wound complications seen after any abdominal surgery;
- Wound infection
- Lung infection as a result of aspiration as a result of intubation during the operation
- Cardiac failure
- Leakage at the point of anastomosis, particularly if it was a total gastrectomy, and the oesophagus is joined straight onto the jejunum.
- Fluid collection and abscesses around areas of lymph node dissection
- Acute pancreatitis if lymph nodes from this region have been removed.
- Nasogastic drainage / vomiting if the jejunum doesn’t drain well after the operation.
These are normally due to physiological changes in the upper GI tract. Most of these symptoms will appear within a few months after the surgery, but then disappear within a year.
- Reflux gastritis due to loss of the pyloris and reflux of biliary contents into the stomach. Most patients who have surgery will have endoscopic evidence of gastritis, but only a small percentage will have significant symptoms.
- Dumping – is a term used to refer to many symptoms that are attributed to rapid gastric emptying. These symptoms include:
- Vasomotor symptoms – i.e. the symptoms affecting the level of dilatation of the blood vessels. These are due to rapid fluid shifts into the bowel lumen, and are similar to the symptoms of hypovolaemia. Hypovolaemia is a decreased blood volume.
- Late dumping – this is due to an insulin surge soon after a meal followed by reactive hypoglycaemia.
- Dumping is treated by controlling the diet. Patient’s should eat lots of small meals, keep dry food and liquids separate, and avoid simple sugars. The symptoms of dumping will lessen over time.
- Weight loss – Patients who have a total gastrectomy will lose about 10% of their body weight, whilst those who have a partial gastrectomy will only lose about 5%. This is due to a combination of factors, including, symptoms of dumping, change in diet, gastritis, and possibly due to continuing cancer progression.
- Anaemia – very common as a result of loss of intrinsic factor due to the fact you have removed the parietal cells in the stomach! Another factor will also be that iron remains in its insoluble ferric form, as there may not be enough acid to convert it to ferrous. After a total gastrectomy, patients have to have vitamin B12 injections.
- Increased risk of osteoporosis and osteomalacia – it is not entirely clear why this is the case, but it is possibly to do with reduced calcium / vitamin D absorption.
Chemotherapy may be offered to some people, and for a significant proportion is does have beneficial effects, however the 5-year survival rate does not significantly improve. There is little research in this area, and more needs to be done.
- One of the most common indications for this is a gastric outlet obstruction from a stenosing distal gastric cancer, but there are many others. In this particular example, placing a stent gives just as good, if not better care than surgical removal of the tumour.
- The median life expectancy for somebody just diagnosed with incurable gastric cancer is 4-6 months. It is very important that a palliative plan is put in place as soon as possible after diagnosis.
- This accounts for 2-5% of all gastric neoplasms.
- Gastric lymphomas account for 60% of all GI primary lymphomas.
- They occur in mucosa associated lymphoid tissue (MALT). This type of tissue appears in the stomach as a result of chronic inflammation, which is though to be a result of H. pylori infection. MALT tissue is not normally present in the stomach.
- The lymphomas are usually B cell derived (although T cell ones do sometimes occur)
- These tumours can be classed as high grade or low grade. Low grade tumours are treated with H. pylori eradication treatment, and this will also result in healing of the tumour in 70-100% of cases. High grade tumours are treated with chemoradiotherapy. Surgery is generally only used when there are complications, such as haemorrhaging.
- The presentation is similar to that of gastric cancer, and the tumour will appear as a polypoid or ulcerating mass.