Gastric tumours Flashcards
what is gastric cancer?
uncontrollable growth of cells that start in the stomach
What are the different types of gastric cancers?
- Adenocarcinoma (from columnar glandular epithelium):
2 subtypes:
a. intestinal
b. diffuse
less common:
2. lymphoma (from lymphocytes)
3. carcinoid tumour (from G-cells in stomach)
4. Leiomyosarcoma (from stomach muscle cells)
What are the different regions of the stomach?
- Cardia (entrance of stomach below the esophagus)
- Fundus (top of the stomach)
- Body
- Pyloric antrum (lower or distal portion above the duodenum)
- Pyloric sphincter (muscular valve -closes while eating)
What are the layers of the gastric wall?
outer-> inner
1. Adventitia (serosa)
2. Muscular
3. Submucosa
4. Mucosa [direct contact w/ food]
What are the 3 layers of the mucosa lining the gastric wall?
innermost-> outer
1. Epithelial (absorbs/ secretes mucus + digestive enzymes)
2. Lamina propria (blood, lymph vessels, MALT (lymphocytes)
3. Muscularis mucosa (smooth muscle layer- helps break down food)
What cells make up the epithelial layer of the gastric wall?
- Foveolar cells:
- secretes mucus
- coats and protects epithelial cells - Parietal cells:
- secrete HCL
- Maintains acid pH - Chief cells:
- secrete pepsinogen - G cells:
- Secrete gastrin
- stimulate parietal cells
What are the 2 types of adenocarcinomas you can get with gastric cancer?
- Intestinal (well-differentiated)
- Diffuse (undifferentiated- much more aggressive)
What causes intestinal adenocarcinomas to develop?
- Caused by H. pylori infection
- H. Pylori releases virulence factors (cagA) which causes damage
- Immune system causes inflammatory response to this damage= gastritis (inflammation of gastric lining)
- chronic gastritis (lining is continuously damaged and repaired)
- Overtime stomach cells under change- begin to resemble intestinal epithelium (this is known as metaplasia)
- Metaplastic cells divide uncontrollably + accumulate mutations in tumour suppressor and proto-oncogenes
- Cells become malignant (invade & spread)
- This type of carcinoma typically appears on the lesser curvature of the antrum as large, irregular ulcers w/ heaped edges
- well- differentiated (resemble normal intestinal cells)
Describe lymphomas (gastric cancer)
- Lymphocytes in MALT are affected: role is recognising & responding to any pathogens that cross the peithelial layer
-appear as diffuse lymphocytes - chronic H. pylori infection can lead to excessive B cells proliferation
- accumulating mutations
- leading to lymphoma
What causes diffuse adenocarcinomas to develop?
- This type of adenocarcinoma can affect any part of the stomach
- Caused by mutations in CDH1 (a tumour suppressor gene that codes for a membrane adhesion molecule cells E-cadherin)
- E- cadherin normally helps cells stick together and controls cell cycle
- When mutated, cells begin to detach from one another and divide uncontrollably
= increased ability to spread & invade - results in thickening and increased rigidity of the stomach (gastric linitis)
- histologically: more signet ring cells (cells with large vacuoles that push the nucleus to the edge of the cell)
Describe carcinoid tumours (gastric cancer)
- Cancer of the neuroendocrine cells: G cells
- well-differentiated
- Change from mucosa to polyp
- polyps also found in intestine and pancreas
Describe leiomyosarcomas (gastric cancer)
- Cancer of the smooth muscle cells
- Extremely rare
- Look like spindle, epithelial or undifferentiated cells
What are some of the risk factors of gastric cancer?
- Smoked and processed foods, foods high in nitrosamines, high nitrates, high salt, pickling, low vitamin C
- Smoking
- Alcohol
- Helicobacter pylori infection
- Atrophic gastritis
- Pernicious anaemia
- Partial gastrectomy
- Gastric polyps
- Blood group A
- Obesity
- age
- male
- autoimmune gastritis
- achlorhydria
What are some protective factors against gastric cancer?
- fruits/ veg
- fiber
- folate
Summarise the epidemiology of gastric cancer
- COMMON cause of cancer death worldwide
- Highest incidence in JAPAN (and Asia in general)
- 6th most common cancer in the UK
- Usual age of presentation: > 50 yrs
What symptoms of gastric cancer can be found in the history?
- Often asymptomatic early
- malaise
- Early satiety (feeling full after eating small amount)
- Epigastric discomfort
- Haematemesis, melaena, symptoms of anaemia (Anaemia can be due to blood loss from ulcer or of chronic disease)
- Systemic symptoms: weight loss, anorexia, nausea/vomiting
- Dysphagia (in tumours of the gastric cardia)
- Dyspepsia/ indigestion
- Symptoms of metastases (e.g. ascites, jaundice)
What signs of gastric cancer can be found on physical examination?
- May be normal
- Epigastric mass
- Abdominal tenderness
- Ascites
- Signs of anaemia
- Virchow’s Node (aka Troisier’s sign) – lymphadenopathy in left supraclavicular fossa
- Sister Mary Joseph’s Nodule (metastatic node on the umbilicus)
- Krukenberg’s Tumour (ovarian metastases)
- Acanthosis nigricans
- leser trelat sign (brown spots on skin)
What investigations are used to monitor and diagnose gastric cancer?
- Upper GI endoscopy – with biopsy of all gastric ulcers
- X-ray w/ barium contrast
- Bloods - FBC (check for anaemia), LFTs
- Abdominopelvic CT/MRI - for staging
- Endoscopic USS - assess depth of gastric invasion and lymph node involvement
- Liver ultrasound and bone scan – for tumour staging
- Laparoscopy may be needed to determine if tumour resectable
- Oesophago-gastro-duodenoscopy OGD and biopsy for advanced cancer
How are gastric cancers treated?
- Surgery: Surgical resection as the sole treatment modality is recommended in early-localised disease (T1b-T2, N0). However, in more advanced disease (T2 or higher, and any N), preoperative treatment or adjuvant treatment in addition to gastrectomy is advised.
- Chemoradiation: Patients with pathological stage II-IIIC or any T, N+ disease or R1 resection should receive postoperative radiation with adjuvant fluorouracil chemotherapy, as this regimen has been shown to improve overall survival
- Preoperative chemoradiation may be offered as it potentially downstages the cancer and increases resect ability
- Perioperative chemotherapy with ECF (epirubicin, cisplatin, and fluorouracil) has been shown to improve overall survival in patients with stage II or higher disease compared with surgery alone
- Metastatic disease : Chemotherapy and/or immunotherapy with or without radiation - Palliative gastrectomy : May improve symptoms such as bleeding and obstruction.
What are possible complications that can be caused by surgical treatment of gastric cancer?
- Gastroparesis, dumping syndrome, anastomotic leak, wound infection, postoperative cardiopulmonary complications, and malnutrition
- Postoperative cardiac and pulmonary complications, such as myocardial infarction and pneumonia.
- Osteopenia
- Diarrhoea
- Nutritional deficiency
- Indigestion
- Gastric obstruction
- Gastrointestinal bleeding
- Gastric perforation
- Small bowel obstruction
- Postoperative dumping syndrome
What are possible complications that can be caused by chemotherapy of gastric cancer?
- Febrile neutropenia, thrombocytopenia, nausea, and fatigue.
- Radiation
- Anorexia, thrombocytopenia, and nausea
- A feeding tube in patients receiving upper abdominal radiation for nutrition may be considered.
Describe the prognosis of gastric cancer
- POOR: v. low survival (usually diagnosed at later stage)
Describe the pathophysiology of gastric cancer
Several events at the molecular level have been implicated in the development and progression of gastric cancers. Gastric cancer can involve loss of the tumour suppression gene, p53
Several proto-oncogenes, such as ras, c-myc, and erbB2 (HER2/neu), have been shown to be over-expressed in gastric cancers. Helicobacter pylori has been associated with molecular events that could lead to gastric cancer, such as an increase in p53 mutations. Causes inflammatory response = damage mucosa = chronic gastritis. Epithelium undergo metaplasia.
