Incidence and treatment of gastric cancer

In Italy, there are large regional differences in the incidence of gastric cancer. Although the overall number of cases has decreased since World War II, mortality remains relatively high. This depends largely on the fact that this cancer is diagnosed when it is already at an advanced stage. Therefore early detection makes a big difference as with most cancers.

With modern endoscopic techniques, pre-cancerous lesions and some types of initial cancer can be treated effectively, but surgery has a fundamental role in locally-advanced stage. Increasingly, the integration of surgery with chemotherapy, radiotherapy, and the new biological therapies makes it possible to induce prolonged tumour remission in cases that up to ten years ago would not have been operable or would have relapsed early.

The importance of choosing the centre of care to ensure recovery from gastric tumors

It is essential that procedures and medical-surgical integrated therapies are performed in centres that can document a high number of patients treated per year, where the various groups of specialists involved in the process of diagnosis and treatment (endoscopist, radiologist, pathologist, surgeon oncologist, medical oncologist, nutritionist), work well together in association with other professionals who can make a significant contribution in particular cases (nuclear medicine, interventional radiologist, medical geneticist, clinical psychologist).

We have all this expertise at IEO, as well as an active partnership in optimising diagnosis and treatment plans. According to data from the Ministry of Health (AGENAS 2013), IEO ranks among the top 4 national centres and is in first place in Lombardy for the number of patients treated annually with surgery for gastric cancer.

Possible causes of stomach cancer

There is no targeted prevention because stomach cancer causes are not fully known. The reduction in incidence over the past 60 years seems to be linked to an improvement in the techniques of food preservation and a better overall quality of nutrition, with increased consumption of fresh foods and less salted and smoked meat.

A Mediterranean diet with plenty of fruit and vegetables and little grilled or smoked salted meat seems to have a protective effect. Avoiding cigarette smoking helps, a relationship having been shown between smoking and cancer formation in the stomach. There is a clear relationship between gastric infection with Helicobacter pylori and gastric cancer. In the event of symptoms and confirmed presence of the bacterium, it may be useful to prescribe specific antibiotic therapy.

However, there is also a type of gastric cancer that is not related to Helicobacter pylori. It tends to occur in the upper part of the stomach at the passage between the oesophagus and stomach, and its incidence is increasing (as opposed to the other type which is decreasing). This other type of gastric cancer is often related to gastroesophageal reflux disease, Barrett's oesophagus and obesity.

In rare cases, there is a familial predisposition. Some alterations in certain genes are the cause for the onset of cancers in the stomach and other organs. At IEO, study and research programmes have been active on this specific topic for years.

Nutritional prevention for stomach cancer

Based on careful evaluation of the results of scientific research, it has been possible to identify specific risk factors and protective nutritional factors for specific types of cancer. Experts have classified the results into four levels: "convincing evidence", "probable evidence", "limited evidence" and one last level that collects the effects for which evidence of association with the tumour is “highly unlikely." The following are probable and convincing evidence for the recommendations:

Risk Factors

• salt in food (probable evidence)
• preserved and processed foods rich in salt (probable evidence)

Protective factors

• fruits and vegetables (probable evidence)
• in particular, garlic, onion, shallots, leeks (probable evidence)

Gastrectomy and minimally-invasive interventions for the treatment of stomach cancer

In the case of early diagnosis, i.e. when the tumour is small and confined to the stomach, surgery alone may be sufficient. Depending on the location and extension of the disease the intervention may be limited only to subtotal gastrectomy  or total gastrectomy will be required, including removal of the lymph nodes adjacent to the tumour in both cases.

If conducted in accordance with the appropriate indications, the efficacy of partial gastrectomy on the tumour is comparable to that of total gastrectomy and allows better scope for postoperative nutritional adaptation. In forms at early stages, it is also possible to perform surgery with minimally-invasive techniques (laparoscopy, robot), with clinical benefit in terms of the post-operative recovery time.

After stomach removal, the possible negative effects on the nutritional and overall health are effectively prevented through recommendations and personalised diet plans, managed by qualified dietary staff on discharge and during successive follow-ups.

In some cases, it is appropriate to combine chemotherapy and/or radiotherapy with surgery to prevent tumour recurrence in cases at higher risk (adjuvant therapy), or as an alternative to surgery in order to eliminate cancer cells that may have spread around the tumour or in other parts of the body (through the blood and lymphatic circulation).

Clinical trials

Clinical trials in progress at IEO are aimed at: 

• earlier identification and increasingly reliable endoscopic diagnostic tools (such as Laser Confocal Endomicroscopy)
• defining the benefits of pre- and perioperative chemotherapy in locally-advanced tumours
• clarifying the role of lymph node removal in locally-advanced forms
• validating the use of new drugs for the treatment of metastases.

Confocal Laser Endomicroscopy for early diagnosis of oesophageal dysplasia

This study aims to clarify the diagnostic potential of Confocal Laser Endomicroscopy in the diagnosis of dysplasia associated with Barrett's oesophagus. The investigation consists of the so-called Seattle biopsy protocol.

Lymphadenectomy in gastric cancer

We analysed data of 114 patients taken from the IEO Cancer Registry, who underwent gastrectomy and lymphadenectomy for N0 adenocarcinoma of the stomach between 2000 and 2005. Since an extended lymphadenectomy has shown survival benefit, we concluded that a lymphadenectomy comprising at least 15 lymph nodes should be conducted in all cases of gastric carcinoma. An article was published in the Eur J Surg Oncol 2011 Apr, 37 (4) :305-11, and a new study is being planned on a larger number of cases.

Metastatic gastric tumour

HER2 positive tumours. We are studying whether pertuzumab will improve the results of trastuzumab (JACOB international randomised clinical trial). In patients who have already used trastuzumab and/or pertuzumab, with the tumour further increasing, we are evaluating the safety and efficacy of a new biological drug that inhibits PI3K/mTOR, as part of a phase I study (in collaboration with the early clinical trials division).

HER2 negative tumours. We are comparing two different polychemotherapy regimens made up of 3 drugs (GISCAD trial: low TOX vs EOX). In collaboration with the early clinical trials division, patients who received “standard” therapies and are affected by a further increasing tumour may be assessed for a Phase Ib study with two oral biological drugs, which inhibit FGFR1 and PI3K.

Diffused hereditary gastric carcinoma

In collaboration with the Division of Cancer Prevention and Genetics, we are conducting a study for researching into the germinal mutation in the CDH-1 gene in patients under 45 with gastric carcinoma with diffuse isotype.

Gastric cancer quite frequently shows equivocal symptoms, resembling those of gastritis or peptic ulcer: nausea, difficult digestion, loss of appetite or difficulty to eat a large amount of food. If these symptoms persist, a gastroscopy is advisable, thus obtaining a direct evaluation of the inner mucosal layer.

Prevention is based on the preferential use of fresh foods, and stopping tobacco smoking. There are at least 3 cases of gastric cancer in a family – even in successive generations -  a genetic investigation could be useful. Initially there will be an interview, and a family pedigree reconstruction by specialised personnel with a specific expertise in hereditary tumours. Appropriate genetic tests will be performed in selected cases. This tumour can be successfully cured through minimally-invasive techniques at the early stages. When diagnosed at advanced stages, many effective treatments are still possible, thanks to the integration of techniques and professional expertise available in advanced oncology Centres.

Clinical nutrition for patients with stomach cancer

A state of malnutrition is often found in patients with stomach and oesophageal cancer. This may be related to dysphagia (difficulty with sensation or obstruction of the passage of food through the mouth, pharynx or oesophagus), cachexia associated with the disease (syndrome characterised by loss of fat and muscle mass) and chemotherapy. In addition to the causes of malnutrition common to all cancer patients, there are the nutritional alterations resulting from surgical treatments.

Nutritional alterations resulting from surgical treatment for stomach cancer

During surgery for oesophageal or gastric resection, a small probe can be positioned (nutritional jejunostomy) to ensure physiological nutrition in the postoperative period (through the use of Enteral Nutrition - NE) as well as the required amount of nourishment when its introduction through the mouth is poor or inadequate compared to the need. The nutritional jejunostomy is left in place at the time of discharge, and is used in cases where the patient is unable to maintain a proper diet to cover nutritional requirements.

After gastrectomy, the early symptoms include small stomach syndrome (early satiety and gastric distension) and dumping syndrome (occurring after taking the meal and include hypotension, tachycardia, dizziness, tiredness, fainting, feeling cold and profuse sweating are found. Diarrhoea may also be experienced and bilious vomiting may occur in patients who have undergone partial gastrectomy with gastro-jejunal reconstruction.

The later issues include anaemia and malabsorption of calcium. It is necessary to carry out blood tests to assess any possible supplements.

Following oesophagectomy, patients may experience a reduced ability to intake large volumes of food and in some patients dumping syndrome may occur.

Information for the diet of patients operated for gastric cancer

Dietary guidelines focus on the consumption of small, frequent meals throughout the day, separating liquids from solids. Eating small bites and chewing well are recommended in order to facilitate swallowing and digestion. For the nutritional management of dumping syndrome, simple sugars have to be limited.

In the presence of diarrhoea, it is advisable to limit simple sugars and drink liquids in small sips. As regards the possible presence of bilious vomiting after intervention for subtotal gastrectomy, treatment is essentially surgical, but in this condition the patient may also benefit from a partition of the diet into small and frequent meals.

Following oesophagectomy, sticky foods, foods that are fermented and carbonated soft drinks should all be avoided. It is also important that the patient remains sitting for 30-60 minutes after taking the meal and at least 2 hours before going to bed.

For patients who have undergone gastric or oesophageal resection, short and long term follow-ups are of crucial importance in order to immediately adapt to the more appropriate dietary pattern, correct any errors present in the diet, prevent weight loss and identify any late symptoms.