Stomach ( Gastric ) cancer
Stomach is lined with a mucous membrane made of columnar epithelial cells and glands- these are prone to inflammation ie gastritis leading to ulcers which can turn into gastric cancer GCs is a multifactorial disease where both environmental and genetic factors play a role GCa is the result of accumulation of multiple epi / genetic changes during the patient’s lifetime which results in oncogenic activation and / or tumour suppressor pathways inactivation 95 % of GCa’s are epithelial in origin and are adenocarcinomas , followed by primary gastric lymphoma Adenocarcinoma histologically can be differentiated ( intestinal ) or undifferentiated ( diffuse ) Intestinal ( differentiated ) type is more common -develops slowly and seen more in older males whereas diffuse type is seen more in females , younger age ( < 50 ) and carries a worse prognosis as a delay in diagnosis is common Adenocarcinomas based on location can be cardia and non-cardia , this distinction is important as there is evidence that the two entities have different etiologies Oesophago-gastric cancers account for 6 % of all UK cancers with 2/3rd being men and 92 % of cases happen in those aged > 55
Fifth most common neoplasm and 3rd leading cause of cancer deaths worldwide
Incidence related to geography with highest rates in Eastern Asia such as Korea, Japan and China , Eastern Europe , Central and South
Seen more commonly in men and incidence rises progressively with age , median age at diagnosis is 70 yrs but about 10 % are found in people < 45 America
Gastric cancer rates are declining worldwide but 2018 GLOBOCAN data shows that every 1 in 12 of deaths due to cancer is attributable to gastric cancer
Risk factors –Gastro-esophageal reflux Pernicious anaemia- up to 6 fold increased risk of intestinal type gastric cancer Low socioeconomic status Occupational exposure to rubber manufacturing , tin mining , metal processing and coal Type A blood group Radiation – for e.g childhood cancer survivors are at increased risk N-nitroso compounds Partial gastrectomy Menetrier’s disease
Diet-Salt is known to erode the mucosal barrier of the stomach and cause inflammation Salt also known to increase carcinogenic effects of known gastric carcinogens as N methyl-N-nitrosoguanidine ( MNNG ) Regions as Japan where diet is rich in salt and pickled food have higher rates of GCa High temp drinking habits Diet high in meat and low in fruits and vegetables Higher intake of fresh fruits and vegetable has protective effect and reduces the risk of GCa by as much as 37 %
EBV -About 5-10 % of GCa’s are associated with EBV EBV related GCa’s more common in men Exact role of EBV in GCa development is is still not clear.
Lifestyle -Smoking has been linked to risk of cardia gastric cancers in developed countries It is now estimated that 11 % of global stomach cancers and 17 % of cases in Europe are due to smoking Hookas and opium use are also risk factors for gastric cancer Alcohol- erodes and irritates the stomach lining leading to gastritis which is precursor for stomach cancer Heavy drinkers show a higher risk of GCa Obesity- strong predisposing factor
Helicobacter pylori-Gram negative bacterium ,known class 1 carcinogen Up to 80 % of GC are lefd by H Pylori infection H Pylori is known to increase the odds ratio of GCa by 5.9 x within 10 yrs of infection Oncogenesis by 2 main mechanisms -indirect inflammatory reaction to H pylori infection on the gastric mucosa and a direct epigenetic outcome of H pylori on gastric epithelial cells – impairs the gastric tissue microenvironment promoting epithelial -mesenchymal transition ( EMT ) and further GCa progression H Pylori promotes non-cardia gastritis ( protects against cardia ) H pylori eradication may reduce the risk of developing GCa Barry Marshall and Robin Warren received Nobel price in 2005 for the discovery of bacterium in 1985.
Familial -Most GCa are sporadic but about 10 % have familial clustering and about 1-3 % are hereditary Inherited GCa’s with a Mendelian inheritance beset < than 3 % of GCa’s Risk of GCa in someone with a family history is around 3 fold higher than others Strongest association is noticed with hereditary diffuse gastric cancer CDH1 syndrome in which about 80 % of patients develop gastric cancer HDGC is an autosomal dominant inherited condition -malignant cells promulgate below the stomach lining and subsequently metastasize Others with a lower risk include - Lynch syndrome - Hereditary breast and ovarian cancer ( BRCA ) - Li-Fraumeni - Familial adenomatous polyposis - Peutz-Jeghers syndromes
Assessment -Features can be non specific and early GCa will have minimal or no symptoms Dyspepsia /nausea / Vomiting Dyspepsia may affect up to 40 % of the population Early satiety Anorexia Dysphagia -proximal or gastro-oesophageal junction tumours ( late stages) Persistent abdominal pain Weight loss Iron deficiency anaemia Haematemesis ( emergency presentation ) Advanced disease may present with ascites , fatigue , gastric outlet obstruction Paraneoplastic manifestations can - skin related as diffuse seborrhoeic keratosis or acanthosis nigricans - haematological as microangiopathic hemolytic anaemia and hypercoagulable state - renal membranous nephropathy - autoimmune polyarteritis nodosa Common sites of gastric cancer metastases include lungs , liver and bones.
Examination -a mass may be palpable in advanced disease metastatic lymphatic spread may manifest as Virchow’s triad i,e ◘ left supraclavicular adenopathy ◘ peri umbilical nodule ◘ left axillary node an ovarian mass can happen if the cancer spreads directly to the peritoneum ascites hepatomegaly.
Differentials -Gastro-esophageal reflux disease Peptic ulcer Acute / chronic gastritis Bacterial gastroenteritis Cancer of the oesophagus Oesophageal stricture Non-Hodgkin’s lymphoma.
Management principles -In cases where early diagnosis is achieved surgery is the only curative treatment with excellent survival outcome Endoscopic resection is now considered curative option for early gastric neoplasm ◘ total gastrectomy is when the entire stomach is removed with GEJ , and omentum with subsequent intestinal restoration using a Roux-en Y reconstruction ◘ subtotal gastrectomy involves resection of about 80 % of the stomach leaving only a small portion of the proximal stomach Best surgical window is often missed as most patients have advanced disease at diagnosis Adjuvant therapy with chemotherapy , chemoradiotherapy or perioperative chemotherapy can enhance survival Surgery is not considered a treatment option when there is evidence of peritoneal involvement , distant metastases , or locally advanced disease including invasion of major blood vessels Biomarkers as microsatellite instability ( MSI ) , programmed cell death ligand ( PD-L1 ) , human epidermal growth factor receptor 2 ( HER2 ) , tumour mutation burden and EBV offer hope to improve outcome by identifying populations most likely to benefit from immunotherapy and targeted therapy HER2 is the only current biomarker which is screened for prognostic and therapeutic purposes to identify patients who may benefit with treatments as trastuzunamab Metastatic disease -chemotherapy or chemoradiation
Prognosis-Diagnostic delay is common due to non specific symptoms and up to 70 % of patients are diagnosed with stages III or IV disease In England patients with oesophago-gastric cancers have some of the poorest outcomes and longest intervals between referral and commencement of treatment ( NHS England Implementing a timed oseophago-gastric cancer diagnostic pathway 2019 ) Survival as in most cancers depends on the stage of diagnosis ◘ stages 1A and 1B the 5 yr survival following surgical treatment is 94 % and 88 % ◘ stage 3 tumours treated with surgery have a 5 yr survival rate of 18 % Presentation as emergency is associated with higher stage disease and is an independent In UK currently there are no screening tests available for oesophago-gastric cancers Worldwide the incidence of gastric cancer ( non-cardia ) has declined due to factors as ◘ H pylori eradication ◘ changes in food preservation ◘ greater availability of fresh fruits and vegetables Cardia cancers incidence has increased in US and most European countries due to growing incidence of gastroesophageal reflux and rising obesity.
Diagnosis -FBC , Basic metabolic profile , LFT Diagnosis is via endoscopy and biopsy CT abdomen , thorax and pelvis for staging Endoscopic ultrasound to help detect the proximal and distal extent of tumour and further T and N staging Laparoscopy to exclude metastatic disease PET may improve detection of occult metastatic disease in some cases
- Recio-Boiles A, Babiker HM. Gastric Cancer. [Updated 2020 Dec 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459142/
- Sitarz, Robert et al. “Gastric cancer: epidemiology, prevention, classification, and treatment.” Cancer management and research vol. 10 239-248. 7 Feb. 2018, doi:10.2147/CMAR.S149619
- Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies. Int J Mol Sci. 2020 Jun 4;21(11):4012. doi: 10.3390/ijms21114012. PMID: 32512697; PMCID: PMC7312039.
- Kamiya S, Rouvelas I, Lindblad M, Nilsson M. Current trends in gastric cancer treatment in Europe. J Cancer Metastasis Treat 2018;4:35. http://dx.doi.org/10.20517/2394-4722.2017.76
- Casamayor Montserrat, Morlock Robert, Maeda Hiroshi, Ajani Jaffer (2018) Targeted literature review of the global burden of gastric cancer ecancer 12 883
- Chen-Yu Kuo, Yee Chao, Chung-Pin Li, Update on treatment of gastric cancer, Journal of the Chinese Medical Association,
Volume 77, Issue 7,2014, Pages 345-353,ISSN 1726-4901,https://doi.org/10.1016/j.jcma.2014.04.006.
- Rawla, Prashanth, and Adam Barsouk. “Epidemiology of gastric cancer: global trends, risk factors and prevention.” Przeglad gastroenterologiczny vol. 14,1 (2019): 26-38. doi:10.5114/pg.2018.80001
- Figueiredo, C., Costa, S., Karameris, A. and Machado, J.C. (2015), Pathogenesis of Gastric Cancer. Helicobacter, 20: 30-35. https://doi.org/10.1111/hel.12254
- Suspected Cancer : recognition and referral NICE Guideline NG 12 June 2015 1 Recommendations organised by site of cancer | Suspected cancer: recognition and referral | Guidance | NICE
- Carcas, Lauren Peirce. “Gastric cancer review.” Journal of carcinogenesis vol. 13 14. 19 Dec. 2014, doi:10.4103/1477-3163.146506
- Quadri, Humair S et al. “Gastric Adenocarcinoma: A Multimodal Approach.” Frontiers in surgery vol. 4 42. 3 Aug. 2017, doi:10.3389/fsurg.2017.00042
- Vasas, P., Wiggins, T., Chaudry, A. et al. Emergency presentation of the gastric cancer; prognosis and implications for service planning. World J Emerg Surg 7, 31 (2012). https://doi.org/10.1186/1749-7922-7-31
- Implementing a timed oesophago-gastric cancer diagnostic pathway NHS England implementing-a-timed-oesophago-gastric-cancer-pathway.pdf (england.nhs.uk)