We searched PubMed for articles published in English up to April 30, 2015. We used the search terms “gastric cancer”, “etiology”, “pathology”, “molecular pathogenesis”, “genetics”, “pathophysiology”, “diagnosis”, “chemotherapy”, “radiation”, “surgery”, and “targeted agent”. No other parameters were applied.
SeminarGastric cancer
Introduction
Gastric cancer is an important health problem, being the fourth most common cancer and the second leading cause of cancer death worldwide. More than 950 000 new diagnoses are made every year. An estimated 720 000 patients died from gastric cancer in 2012.1 Gastric cancer is separated anatomically into true gastric adenocarcinomas (non-cardia gastric cancers), of which there were 691 000 new cases in 2012, and gastro-oesophageal-junction adenocarcinomas (cardia gastric cancers), of which there were 260 000 new cases in that year.2 Despite a decline in incidence and mortality and despite important advances in the understanding of the epidemiology, pathology, molecular mechanisms, and therapeutic options and strategies, the burden remains high.
Gastric cancer is a main contributor to the global burden of disability-adjusted life-years from cancer in men and accounts for 20% of the total worldwide, following lung and liver cancers, which, respectively, account for 23% and 28%.3 The burden of gastric cancer remains very high in Asia, Latin America, and central and eastern Europe, whereas in North America and most western European countries, it is no longer a common cancer.4 Nevertheless, the decline in the incidence of gastric cancer has gradually lessened in some countries, particularly the USA. In other countries, such as France, mortality is predicted not to decrease further in the middle-aged population.4 This slowing of change is probably explained by long-term low and stable prevalence of Helicobacter pylori infection in these countries.4 By contrast, the incidence of gastro-oesophageal-junction adenocarcinomas is increasing sharply.5 In this Seminar we provide a comprehensive overview of the aetiology, pathological features, molecular pathogenesis, diagnosis, and treatment of gastric cancer.
Section snippets
Aetiology
H pylori infection is the most important cause of sporadic distal gastric cancer.6 During the chronic inflammation induced by H pylori infection and the subsequent carcinogenesis, various factors, including bacterial, host, and environmental factors, interact to facilitate damage repair. Altered cell proliferation, apoptosis, and some epigenetic modifications to the tumour suppressor genes might occur, which could eventually lead to inflammation-associated oncogenesis.7 Some patients with
Anatomical
Tumour classification on the basis of anatomical location is important because true gastric (non-cardia) and gastro-oesophageal-junction cancers (cardia) differ in terms of incidence, geographical distribution, causes, clinical disease course, and treatment. Gastro-oesophageal-junction cancers are widely categorised according to the Siewert classification:26 in true carcinomas of the cardia (Siewert type II) the tumour epicentre is located 1–2 cm below the gastro-oesophageal junction; in distal
Symptoms and diagnosis
Most patients with early-stage gastric cancer are asymptomatic and, therefore, diagnosis is frequently made when disease is at an advanced stage. The most common symptoms at diagnosis are anorexia, dyspepsia, weight loss, and abdominal pain. Patients with tumours at the gastro-oesophageal junction or proximal stomach might also present with dysphagia.
The diagnosis of gastric cancer relies on endoscopy and biopsy. Endoscopic ultrasonography and CT of the chest and abdomen are currently the
Surgical treatment
Adequate surgical resection is the only curative therapeutic option for gastric cancer.61, 62 Endoscopic resection might be suitable as an alternative to surgery for small well differentiated early-stage tumours (T1a),55, 63 Advances in technology and minimally invasive strategies have created new opportunities for surgery in gastric cancer. Minimally invasive procedures are associated with reduced surgical trauma and immunosuppression compared with conventional open surgery and, therefore,
Management of locally advanced disease
Adjuvant and neoadjuvant therapies are generally accepted to improve disease-free survival and overall survival in patients who have undergone adequate complete surgical resection (R0) of locally advanced gastric cancer by eradicating microscopic disease locoregionally and at a distance from the primary tumour. 5-year overall survival is increased by 10–15% with the addition of these treatments, but there is no global consensus about the optimum strategy. Perioperative chemotherapy additional
Management of metastatic disease
The outlook for patients with metastatic gastric cancer is very poor, with median survival ranging from 4 months when treated only with best supportive care to around 12 months when treated with combination cytotoxic chemotherapy.82, 83, 84 Studies have also shown improved quality of life. Patients with good performance status scores and with organ function should be offered the option to receive systemic chemotherapy for palliation and to improve survival.
Several cytotoxic agents are active
Conclusions
Progress has been made in understanding the pathogenesis and the molecular biology of gastric cancer and in optimising the available treatment options and modalities. However, in the future, the focus should be on further unravelling the taxonomy of gastric cancer, fine-tuning treatment strategies, and developing new drugs for patients with advanced gastric cancer.
Search strategy and selection criteria
References (120)
- et al.
Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012
Eur J Cancer
(2013) - et al.
Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions
Lancet
(2012) - et al.
Worldwide trends in gastric cancer mortality (1980-2011), with predictions to 2015, and incidence by subtype
Eur J Cancer
(2014) - et al.
Helicobacter pylori-induced gastric inflammation and gastric cancer
Cancer Lett
(2014) - et al.
Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial
Lancet
(2008) - et al.
Epstein-Barr virus-associated gastric carcinomas: relation to H. pylori infection and genetic alterations
Gastroenterology
(2000) - et al.
Familial gastric cancer: genetic susceptibility, pathology, and implications for management
Lancet Oncol
(2015) - et al.
Hereditary. Hereditary diffuse gastric cancer: diagnosis and management
Clin Gastroenterol Hepatol
(2006) - et al.
Overweight, obesity and gastric cancer risk: results from a meta-analysis of cohort studies
Eur J Cancer
(2009) - et al.
The dichotomy in carcinogenesis of the distal esophagus and esophagogastric junction: intestinal-type vs cardiac-type mucosa-associated adenocarcinoma
Mod Pathol
(2011)
Classification of gastric carcinomas
Curr Diagn Pathol
Microsatellite instability in gastric cancer is associated with better prognosis in only stage II cancers
Surgery
HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target
Ann Oncol
Amplification of HER-2 in gastric carcinoma: association with topoisomerase IIα gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab
Ann Oncol
Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial
Lancet
Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil
Gastroenterology
Gastric cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up
Ann Oncol
Expert opinion on management of gastric and gastro-oesophageal junction adenocarcinoma on behalf of the European Organisation for Research and Treatment of Cancer (EORTC)-gastrointestinal cancer group
Eur J Cancer
The diagnosis and management of gastric cancer: expert discussion and recommendations from the 12th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2010
Ann Oncol
Highlights of the EORTC St. Gallen international expert consensus on the primary therapy of gastric, gastroesophageal and oesophageal cancer—differential treatment strategies for subtypes of early gastroesophageal cancer
Eur J Cancer
Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial
Lancet Oncol
Unmet needs and challenges in gastric cancer: the way forward
Cancer Treat Rev
Left thoracoabdominal approach versus abdominal-transhiatal approach for gastric cancer of the cardia or subcardia: a randomised controlled trial
Lancet Oncol
Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of randomized trials
Eur J Surg Oncol
Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial
Lancet
Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer
Ann Oncol
A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer
Ann Oncol
S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial
Lancet Oncol
Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study
Lancet Oncol
Global patterns of cardia and non-cardia gastric cancer incidence in 2012
Gut
Esophageal adenocarcinoma incidence: are we reaching the peak?
Cancer Epidemiol Biomarkers Prev
H. pylori infection is a key risk factor for proximal gastric cancer
Dig Dis Sci
A human model of gastric carcinogenesis
Cancer Res
Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication
Gut
Helicobacter pylori eradication and gastric preneoplastic conditions: a randomized, double-blind, placebo-controlled trial
Cancer Epidemiol Biomarkers Prev
Long term follow up of patients treated for Helicobacter pylori infection
Gut
Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions
J Natl Cancer Inst
Clinical prevention of gastric cancer by Helicobacter pylori eradication therapy: a systematic review
J Gastroenterol
Lymphoepithelioma-like carcinoma of the stomach: a subset of gastric carcinoma with distinct clinicopathological features and high prevalence of Epstein-Barr virus infection
Hepatogastroenterology
Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families
Gastroenterology
Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer
JAMA
Chromoendoscopic surveillance in hereditary diffuse gastric cancer: an alternative to prophylactic gastrectomy?
Gut
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome
Gut
Fruit and vegetable consumption and gastric cancer by location and histological type: case-control and meta-analysis
Eur J Cancer Prev
Smoking and gastric cancer: systematic review and meta-analysis of cohort studies
Cancer Causes Control
Classification of adenocarcinoma of the oesophagogastric junction
Br J Surg
The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification
Acta Pathol Microbiol Scand
Gastric carcinoma
Comprehensive molecular characterization of gastric adenocarcinoma
Nature
Cited by (1600)
Oleuropein induces apoptosis in gastric cancer cell lines by regulating mir-34a, mir-21, and related genes: An experimental and bioinformatic study
2024, International Journal of Biological MacromoleculesPotent antitumor activity of anti-HER2 antibody-topoisomerase I inhibitor conjugate based on self-immolative dendritic dimeric-linker
2024, Journal of Controlled ReleaseUpdate on gastric cancer
2024, Medicine (Spain)