GASTRIC CANCER TREATMENT IN GERMANY

In recent years gastric cancer has ranked among the most common malignant tumours. It is the second most common cancer worldwide, although the incidence varies considerably from country to country; high rates are seen in Japan, China, Chile and Iceland. The most common type of gastric cancer (up to 95% of cases) is adenocarcinoma, which develops from the glandular cells of the gastric mucosa. Localised gastric lymphomas occur less frequently.
The incidence increases with age: > 75% of patients are aged > 50 years.

Aetiology of gastric cancer

The aetiology of gastric cancer is regarded as multifactorial, and the important role of the bacterium Helicobacter pylori has been proven. Yet despite advances in cancer research, the causes of malignant transformation of gastric cells remain unclear. To date, only a group of risk factors has been identified which, under an unfavourable combination of circumstances, may trigger the disease. Risk factors also include autoimmune gastritis (autoimmune metaplastic atrophic gastritis) and various genetic factors that give rise to stromal tumours of the gastrointestinal tract. The role of dietary habits has not been fully studied.

Symptoms of gastric cancer

• dyspepsia (discomfort and pain in the epigastric region, early satiety, a feeling of heaviness in the stomach, a feeling of bloating in the epigastrium, nausea, heartburn, frequent belching;
• dysphagia at the level of the cardia (the passage of food from the oesophagus becomes difficult);
• weight loss and general weakness caused by reduced food intake;
• development of iron deficiency anaemia due to occult blood loss;
• in a number of cases the first symptoms are related to metastatic spread (in particular jaundice, ascites, bone fractures).

In its early stages gastric cancer usually has no clinical manifestations and is only rarely detected outside screening programmes. Screening is not widespread, except in countries with a very high incidence, such as Japan, Venezuela and Chile.

In most patients with gastric cancer, clinical manifestations are already present at the time of diagnosis, and the disease is progressive. In approximately 50% of patients the process has extended beyond the primary site, and only half of all patients are diagnosed with a locally advanced tumour in which radical resection is potentially possible.

Occult gastrointestinal bleeding accompanied by iron deficiency anaemia often develops, whereas overt bleeding (i.e. melaena - black, tarry stools - or vomiting of blood) is observed in less than 20% of cases. A palpable tumour usually indicates long-standing, advanced disease.

Approximately 25% of patients have a history of gastric ulcer. In every case of gastric ulcer, follow-up must be carried out until complete healing has occurred and, if healing does not take place, resection should be performed.

At first presentation patients may already have signs or symptoms of distant metastatic disease. The most frequent sites of metastasis in gastric cancer are the liver, the peritoneum and distant lymph nodes. Metastases arise less often in the ovaries, the central nervous system, the bones, the lungs or the soft tissues.

Paraneoplastic syndrome (PNS)

PNS is a group of pathological disorders that arise in malignant disease not through the direct action of the tumour on tissues and organs, but as a result of its possible influence on metabolic and other processes taking place in the body.

On the one hand, PNS in some cases makes it possible to diagnose a malignant neoplasm at an early stage; on the other hand, it masks the tumour process behind its own more striking manifestations, which leads to late identification of the true cause of the disease and therefore delays specific treatment.

Gastric cancer may give rise to skin manifestations: the sudden appearance of diffuse seborrhoeic keratoses (the Leser-Trelat sign) or acanthosis nigricans, which is characterised by velvety dark pigmented patches in the skin folds.

Other paraneoplastic changes that develop in gastric cancer include microangiopathic haemolytic anaemia, membranous nephropathy and hypercoagulable states (Trousseau syndrome). Polyarteritis nodosa has been described as the sole manifestation of early and curable stages of gastric cancer.

Diagnosis of gastric cancer

• endoscopic examination with biopsy;
• CT and endoscopic ultrasound are performed as the second step.

Endoscopic examination of the upper gastrointestinal tract is the most reliable and most informative method of diagnosing various lesions of the stomach, oesophagus and duodenum. If gastric cancer is suspected, endoscopy with multiple biopsies and brush cytology must be performed. In some cases a biopsy confined to the mucosa fails to detect a tumour with a submucosal location, in the so-called «linitis plastica». X-ray examination, especially with double contrast, is informative in the diagnosis of tumours, but as a rule subsequent endoscopy is then required. Endoscopic examinations are carried out exclusively in certified endoscopy centres by expert-level physicians, using state-of-the-art equipment. Early endoscopic examination of patients with gastrointestinal complaints helps to detect gastric cancer at an early stage.

Once a diagnosis of gastric cancer has been established, CT of the chest and abdomen is indicated in order to determine the extent of the disease. If CT reveals no metastases, endoscopic ultrasound should be performed to determine the depth of invasion of the gastric wall and the involvement of regional lymph nodes. The findings determine the treatment plan and the prognosis of the disease.

Basic blood tests are performed – a full blood count, assessment of electrolyte levels and liver function tests – in order to evaluate the patient's general condition, the presence of anaemia, any water and electrolyte imbalance, and signs of metastatic involvement of the liver. Carcinoembryonic antigen (CEA) levels in the blood are measured before and after surgical treatment.

The diagnosis of particularly aggressive diffuse-type gastric cancer, the so-called «linitis plastica», may be difficult at endoscopic examination. Because these tumours tend to infiltrate the submucosa and the muscularis propria, a superficial biopsy may give false-negative results. For this reason a combination of snare biopsy and «bite» biopsy techniques is used when diffuse-type gastric cancer is suspected. Poor distensibility of the stomach or the classic appearance on a barium study (resembling a leather bottle) makes it possible to suspect this disease.

Barium studies can reveal both malignant gastric ulcers and infiltrating lesions and, in some cases, gastric cancer can be seen at an early stage. However, the rate of false-negative results with this examination reaches 50% of cases. This problem is of particular importance in the early stages of gastric cancer, where the sensitivity of the barium study may not exceed 14%. Thus, in most cases endoscopic examination of the upper gastrointestinal tract is the preferred method of initial diagnosis for patients with suspected gastric cancer. The only situation in which a barium study may have advantages over endoscopy is in patients with linitis plastica.

Contrast-enhanced computed tomography of the chest, abdomen and pelvis makes it possible to assess the regional lymph node basins and the spread of the tumour to adjacent organs and tissues, and to rule out distant metastases.

Treatment of gastric cancer

Surgery – resection, in a number of cases – in combination with radiotherapy, chemotherapy or both.

The choice of treatment strategy depends on the stage of the tumour and on the wishes of the patient (many prefer more aggressive treatment

Radical treatment involves subtotal resection of the stomach or gastrectomy with removal of the regional lymph nodes; this approach is justified when there are no signs of tumour spread beyond the stomach, while the presence of metastases in the regional lymph nodes is permissible (this category accounts for < 50% of patients). Adjuvant chemotherapy or a combination of chemotherapy and radiotherapy after surgery improves treatment outcomes (if the tumour is resectable).

After resection of a late-stage tumour with local spread, life expectancy averages 10 months (in the absence of resection – 3–4 months).

In the presence of metastases or extensive involvement of the regional lymph nodes, radical operations are not indicated and, as a rule, palliative procedures are carried out. The true extent of tumour spread can be difficult to assess before radical surgery is attempted. Palliative operations usually involve the creation of a gastrointestinal anastomosis in case of gastric outlet obstruction; the procedure is performed only if an improvement in the patient's quality of life is expected. In patients who have not undergone surgical treatment, combination chemotherapy (5-fluorouracil, doxorubicin, mitomycin, cisplatin and leucovorin in various combinations) may lead to temporary improvement, but increases 5-year survival only marginally. The efficacy of radiotherapy is limited.

Operations on the stomach are performed via both an open and a laparoscopic approach, with the same extent of lymph node dissection.

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