Summary
The stomach is like a bag lined with muscle and glandular cells, and is the first place chewed food goes to after it has been chewed and swallowed. It produces acidic juices from its lining to start off the digestive process.
The vast majority of stomach cancers arise from this glandular lining of the stomach and are called adenocarcinomas. There are two broad types of stomach cancer: an intestinal type and a diffuse type. The former are like the usual adenocarcinomas found in the gut, whereas the latter have a very different appearance.
Causes
People who move from countries where stomach cancer is common to countries where it is rare become less likely to develop the disease. This means that there are risk factors that are environmental. These factors include:
- Diet – there are a number of foods that have an influence on the development of stomach cancer. A high intake of complex carbohydrates, nitrates or salt and a low intake of animal fat, protein and salads, fruit and vegetables all can increase the risk of the disease.
- Smoking – nearly one in five cancers of the stomach are caused by smoking. The risk of developing stomach cancer increases nearly 3 fold in smokers.
- Alcohol – There is not much evidence that alcohol consumption increases the risk.
- Gastric surgery – After gastric surgery the risk of stomach cancer is greatest 15 to 20 years later
- Epstein-Barr virus – The Epstein-Barr virus (EBV) may be associated with the development of some types of stomach cancer.
- Helicobacter pylori – This bacteria is now classified a definite cause of gastric cancer increasing the risk by a factor of 6.
There are other factors that seem to increase the risk of stomach cancer, unrelated to the environment.
- Blood group – Patients with a Blood Group A have a higher risk of developing gastric cancer
- Genetic factors – in some families there seems to be an inherited increased risk of the disease., the underlying genetic basis for the predisposition is not understood, while in others, certain risk factors have been identified.
- Gastric ulcers – Gastric ulcers are associated with stomach cancer, but they may be caused by similar factors, so as such may not be a direct cause.
- Pernicious anemia – Pernicious anemia is caused by a problem some people have in absorbing vitamin B12, is cause by the body ‘self-damaging’ the lining of the stomach through immune mechanisms. There is a 3 times increased risk of stomach cancer in this disease.
Incidence
Gastric cancer accounts for 6% of cancer deaths in the U.K. and there were 8500 cases in 2004. In most of the Western world its incidence is decreasing. However, the incidence varies dramatically across the globe and this cancer is the second commonest malignancy in Japan, Latin America and some parts of Northern Europe. For example, in Japan, the disease accounts for 60% of male cancer and 40% of female cancer incidence.
Symptoms & diagnosis: Stomach cancer (gastric cancer)
The commonest symptoms are non-deliberate weight loss and upper abdominal pain. Some may have difficulty swallowing if the tumour is near the top of the stomach. Another way patients are diagnosed with stomach cancer is if they are found to be anaemic, sometimes an endoscopy is done to check if there is a source of bleeding in the upper gastrointestinal tract. Occasionally the bleeding can be severe and patients have black tar like stools, as the blood passes though the gut. Gastric ulcers that are benign can produce the same type of bleeding.
Diagnosis
The doctor will refer the patient for gastroscopy where a flexible camera (a flexible fibre optic tube) is passed via the mouth into the stomach to directly view the lining and take samples, biopsies.
The alternative diagnostic test is a barium meal study, where the patient drinks some barium solution which shows up on a normal x-ray. This would only show an irregularity in the wall of the stomach rather than showing up the tumour itself. An endoscopy, however, is the usual first choice investigation.
Other tests done are designed to see if the tumour has spread: these include an endoscopic ultrasound, CT scan and occasionally a laparoscopy. A laparoscopy, done under general anaesthetic, is where a small camera is put into the abdominal cavity and allows a direct view of the lining of the abdomen and the bowels. it may show abnormalities that cannot be seen on the CT scan.
Stages
The ‘stage’ of any cancer is a description of its size, local spread and distant spread. Defining the stage is crucial in deciding the most appropriate treatment and whether it is possible to aim to cure the disease. Scans are the most important method of working out the stage of the disease. The most accurate stage however, is found by examining the specimen after an operation, if this is the right treatment.
Oncologist will use internationally recognised systems of staging, but the principles are to decide the following:
The main concern whether the growth is confined to the stomach or whether it has spread to other organs.
Where the disease is localised then it may be possible to aim for a cure, otherwise palliation is the best approach.
Treatment & outcomes: Stomach cancer (gastric cancer)
The treatment of stomach cancer depends on the stage and the general fitness of the patient.
When the staging investigations suggest that cure is possible, and the patient is fit, it is now usual for chemotherapy to be offered before an operation.
Pre-operative chemotherapy is usually employed to downstage the primary and to ‘get in’ some treatment that goes around the body and reduces the chance of micrometastases taking root. For some time the 3 drug chemotherapy regime of epirubicin, oxaliplatin and either 5Fluorouracil of capecitabine (EOX) has been the first line therapy but recently the epirubicin has been repolaced by a taxane (TOF). Occasionally the gastric cancer is ‘driven’ by amplification of the HER-2 oncogene and (like HER-2 amplified breast cancer), HER-2 directed therapy is added to the chemotherapy in these cases. The operation then takes place after 2 months of such chemotherapy and usually the cancer has been down-staged and surgery is more likely to achieve complete resection.
However, an operation may be the first treatment if the tumour is obstructing the passage of food, or if the tumour is thought to be very small.
Otherwise, chemotherapy is used to shrink the tumour before the operation, and to start a treatment that covers the whole body sooner. Studies have shown that this approach improves the overall survival.
The operation that is done depends on where in the stomach the tumour is, usually a ‘total gastrectomy’ is done, where the whole stomach, along with the adjacent lymph nodes, are removed. If the tumour is in the lower part of the stomach, then a partial gastrectomy is done, which removes the lower half of the stomach, along with the lymph nodes.
After the operation, some oncologists recommend further chemotherapy, using the same drugs as were used preoperatively and assumoiimg that here was evidence of downstaging at the time of the operation (or on histological review of the operative specimen).
If there was incomplete histological resection (cancer at eh margins of surgical excision, the decision to deliver post-operative radiotherapy to the stomach ‘bed’ is taken
For cases where the cancer has spread to the liver or there are distant metastases to toher site in the body, clearly the emphasis of therapy is on Systemic treatment (i.e. treatment that goes around the body. The Three drug regime is usually first line therapy (as above). If there is no response to this then alternaive regimes are now available including the regime of the ‘smart’ drug : Ramucurumab and a taxane or combination therapy based on irinotecan. HER-2 directed therapoiesa re appropriate if the cancer is HER-2 positive fro amplification of this gene.
Outcomes
Early gastric caner is curable by surgery, backed up by neoadjuvant and adjuvant chemotherapy.
Sadly, the majority of late stage patients eventually relapse and die, largely due to liver relapse. The concentration of Oncology caer is on prolonging active life and the foregoing systemic therapies are important and can meaningfully prolong life in a large fraction of patients.
What to do if the [patient relapses despite the foregoing therapies?
Where the cancer relapses despite the foregoing therapies, alternative chemotherapy can help (e.g. mitomycin based chemotherapy) but any such remissions are shortlasting. New active chemotherapy agents are needed.
It is worth getting genomic analysis for any targetable genetic driving mutations. Although a minority chance, it is one which can be useful albeit in a small fraction of patients. This should be done a fresh tissue biopsy of the cancer or from cell-free DNA (cfDNA) from a blood draw. Most advanced gastric cancers release their fragmented DNA into the blood stream and next Generation Sequencing (NGS) of this or the fresh tissue biopsy can give the genomic information upon which to base decisions.
The NGS can be used to detect hyper-mutation (often as mismatch repair – MMR – deficiency) and this, if positive, predicts for repsonse to immunotherapy (especially with checkpoint inhibitors such as pembrolizumab and Nivolumab).
Credit: Dr. P. N. Plowman. MD, The Oncology Clinic, 20 Harley Street, London W1G 9PH. (Advanced Genomics). Tel: +44-207-631-1632
Screening
Screening for stomach cancer is routine in some countries where the incidence is very high, e.g. Japan and Chile. However in the rest of the world there is no screening programme in place for the general public. However, individuals with a strong family history or who have had a partial gastrectomy may benefit from individualised programmes of regular gastroscopies.