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Editors

RaijaRistamäki
ArtoKokkola

Gastric Cancer

Essentials

  • The most common symptoms are upper abdominal complaints, anaemia and weight loss, but in the majority of cases gastric cancer is asymptomatic in its early stages.
  • Gastroscopy is the investigation of choice.
  • Surgical resection with adjuvant chemotherapy has improved prognosis.

Frequency

  • Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer death http://www.who.int/news-room/fact-sheets/detail/cancer.
  • The incidence of gastric cancer has declined over the last few decades. However, the proportion of gastric cardia carcinomas has increased.
  • Geographic variation exists in the incidence of gastric cancer, the rates being highest in Asia, Central and Eastern Europe and parts of South America and lowest in North America, Northern Europe and Africa. Worldwide, there were about 1.03 million new cases in 2018, about 86% of them in the high or very high human development countries, with about 780 000 deathshttp://gco.iarc.fr/today/fact-sheets-cancers.

Aetiology

  • Environmental factors are thought to play a central role in the development of gastric cancer. Helicobacter pylori infection is the most important environmental factor.
  • Infection by Helicobacter causes inflammation of the gastric mucosa which, in some patients, results in chronic atrophic gastritis. Atrophic mucosa is more likely to undergo changes that lead to cancer.
  • Gastro-oesophageal reflux disease Gastro-Oesophageal Reflux Disease and Barrett's oesophagus are often present in gastric cardia carcinomas.
  • Smoking and excessive salt intake increase the risk of gastric cancer.
  • Consumption of fresh vegetables and fruits decreases the risk of gastric cancer.

Histology

  • Over 90% of cases are adenocarcinomas
    • Intestinal carcinoma
      • This type is the end-result of a carcinogenic cascade, i.e. cancer develops slowly through precursor stages.
      • More common among elderly patients.
      • Spreads by forming distinct tumours.
      • Typically spreads to the lymph nodes and, haematogenously, to the liver.
      • Expression and amplification of the HER2 cancer gene is encountered in about 20% of patients (influences the choice of treatment in advanced disease).
    • Diffuse carcinoma
      • No clearly defined precursor stages.
      • More common in younger patients and in some of them familially.
      • Spreads by infiltration.
      • Typically spreads to the lymph nodes and the peritoneal space.
  • Rare tumour types include neuroendocrine carcinomas Rare Endocrine Tumours, lymphomas and GIST tumours.

Symptoms

Findings

  • Clinical findings are usually only present in advanced disease.
  • Alarming findings
    • Anaemia
    • Upper abdominal mass
  • Other possible findings
    • Ovarian tumour (metastasis)
    • Ascites
    • A palpable lymph node in the clavicular fossa

Diagnosis and staging

  • Gastroscopy and biopsies
    • Should always be carried out if the patient has alarming symptoms Dyspepsia, and in patients over 55 years presenting with a new upper abdominal complaint
  • Staging is based on a whole body CT scan (and endoscopic ultrasound)
  • The findings of an upper abdominal ultrasound that was prompted by symptoms may potentially include ascites or liver metastasis.
  • No specific laboratory tests are available. It is recommended that basic blood count with platelets and liver function tests (ALT, ALP) are checked.

Treatment

Curative surgery

  • Distal tumours: > resection; other tumours: total gastrectomy
  • Level 1 lymph nodes should always be removed from the tissues surrounding the stomach during the surgery (D1 gastrectomy).
  • If the excision of level 2 lymph nodes is possible without adding to the complications, their removal during surgery is also recommended (D2 gastrectomy).
  • At least 15 lymph nodes from the surgical tissue sample should undergo analysis.
  • Splenectomy should only be performed if there is a high probability that the patient has lymph node metastases in the hilum of the spleen or if the tumour directly infiltrates the spleen.
  • Certain early-stage tumours may be managed with a more minor procedure, such as endoscopic mucosal resection.
  • After total gastrectomy, the patient will require lifelong vitamin B12 replacement therapy.
  • Pneumococcal, meningococcal and haemophilus vaccinations are indicated after splenectomy.

Oncological treatment combined with curative surgery

  • Perioperative cytotoxic chemotherapy
    • Perioperative cytotoxic chemotherapy (pre- and postoperatively) can be given in an attempt to improve the prognosis of gastric cancer.
    • The aim of preoperative treatment is to reduce the tumour mass, increase the radical resection rate and thus improve prognosis.
    • Chemotherapy is also better tolerated before the surgery.
    • Usually a combination therapy with epirubicin, cisplatin or oxaliplatin together with 5-fluorouracil or capecitabine is used.
    • A combination of docetaxel, oxaliplatin, leucovorin (calcium folinate) and 5-fluorouracil has proven to be more effective thatn the aforementioned combination.
  • Adjuvant chemotherapy
    • The benefit of adjuvant chemotherapy has not been shown in individual western studies.
    • Meta-analyses have shown it to slightly reduce mortality.
  • Adjuvant chemoradiotherapy
    • Postoperative chemoradiotherapy is mainly reserved for patients whose disease has spread beyond the surgical margins.

Palliative treatment Chemotherapy for Advanced Gastric Cancer

  • Chemotherapy improves survival compared with best symptomatic treatment.
  • In metastatic disease, the median life expectancy of a patient treated with chemotherapy is 12 months.
  • In HER2 positive disease, the addition of the anti-HER2 antibody trastuzumab to the chemotherapy regimen significantly increases survival.
  • Obstruction
    • Palliative resection if possible (better than bypass or stenting)
    • Gastrojejunostomy
    • Endoscopic stenting
  • Haemorrhage
    • Resection if possible
    • The role of resection in metastatic disease with no major symptoms is unclear.

Prognosis

  • About 50% of gastric cancers are not diagnosed until the disease has advanced, and prognosis is therefore poor.
  • The 5-year survival rate is generally 25% and after curative treatment 50%.

Follow-up

  • Intensive follow-up regimens have not been shown to improve prognosis.
  • A follow-up regimen aims to
    • detect possible nutritional deficits resulting from the surgery
      • Weight, bowel function, basic blood count with platelets, electrolytes, creatinine, vitamin B12 annually
      • If necessary, the patient may be referred to the care of a dietitian or a specialist physician.
    • identify recurrences which may be treated curatively (rarely).
      • Endoscopy after subtotal gastrectomy every few years
      • Imaging studies or a referral for specialist care as guided by symptoms, for example, the emergence of eating difficulties, weight loss or abdominal pain.
  • Need for replacement therapy
    • Iron deficiency is the most common cause of anaemia after gastric surgery. It can usually be corrected by oral iron products.
    • Megaloblastic anaemia resulting from vitamin B12 deficiency is also common. After total gastrectomy, vitamin B12 is normally administered through injections every 3 months, but also oral B12 substitution may be tried.
    • Also folate deficiency is possible after gastrectomy.
    • The risk of osteoporosis is increased after gastrectomy, and calcium and vitamin D supplementation is therefore recommended.
    • Use of a pancreatic enzyme product may be tried in severe steatorrhoea and weight loss.

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Evidence Summaries