GI cancers Flashcards
What is a neoplasm
an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue, and which persists even after the evoking stimulus (if known) is removed
How do GI cancers cos obstruction of luminca
Intussusception , where polyp causes the bowel to telescope and drags the blood vessels in the mesentery along with it causing ischemia
what are the cytological features of malignancy
- High nucleus/cytoplasm ratio ⇒ Suggests proliferation
- Hyperchromasia ⇒ Production of nuclear material in DNA
- Pleomorphism ⇒ Irregular appearances of different aspects of cells
How to diff adenocarcinoma with adenoma histologically
Abnormal glands invading the wall of the colon with a stromal reaction
Symptoms of GI Neoplasms
- Tiredness (anaemia)
- Bleeding
- Anorexia and vomiting
- Weight loss
- Pain caused by obstruction
- Dysphagia
- Alteration in bowel habit
What genes are involved in the A-C sequence
k-ras( activated oncogene), p53(inactivated TSG)
What is the APC protein
encoded by APC (TSG), negative regulator that controls beta-catenin concentrations and interacts with E-cadherin, whichareinvolved in cell adhesion → Deletion of the APC gene predisposes to cancer.
what genes cause early adenoma and then intermediate adenoma
APC, then KRAS
what does TMN staging show
how far the cancer has spread ( extent)
what are T1, 2, 3, and 4 respectively in colon
Ti is LP till submucosa, T2 has reached muscularis propria, T3 reaches serosa, T4 reaches nearby organs
Common Lymph node areas for oseophageal cancer
Bifrucation of trachea
Most common type of oesophageal cancer in the UK and which part of the oesophagus does it occur in
Common risk?
Adenocarcinoma, lower 1/3 oesophagus
Obesity , associated with reflux
Risk factors for squamous cell carcinoma of oesophagus
- Smoking is major factor ⇒Tobacco
- Alcohol
- Diet and very hot beverages
- Infection
What are the main symptoms and presentations for oesophageal cancer
- VERY FEW symptoms until late-difficulty swallowing ⇒ New, progressive dysphagia for solids first then liquids
- More likely in elderly
- May present with heartburn and increasing dysphagia
- May also have regurgitation and weight loss
- Advanced cancer may present with hoarse voice due to
- Left recurrent laryngeal nerve infiltrated in advanced tumour
Investigations and diagnosis fo oescophageal cancer
Endoscopy, then biopsy for diagnosis
- CT thorax and abdomen ⇒ Check for Metastases and Lymph Nodes around tumour
- May need more specialised testing like PET scanning
Endoscopic ultrasound to stage tumour ⇒ give info about depth of tumour
treatment for oeso cancer
If T3N1M0 for example, patient deemed fit for surgery and can have preoperative chemotherapy followed by surgery
Palliation if treatment nor possible
- Improve quality of life ⇒ swallowing ( using stent) and maintaining weight
- Re-establish connection between healthy bit of oesophagus and stomach
Is gastric cancer more common in males or females
More common in males
What germline mutations may contribute to gastric cancer
TP53, CDH 1 genes
Aetiology of gastric cancer
multifactorial: diet, H. pylori, bile reflux ⇒ Anything that causes chronic gastritis
Can gastric cancer cause melena
Yes, because of ulceration which can bleed
What are the two main histological patterns of gastric adenocarcinoma
Intestinal ( obvious gland formation) and diffuse (signet ring cells)
Which group of patients have higher risk of intestinal type gastric adenocarcinoma
Patients with FAP ( cancer predisposition syndrome)
Are females or males more likely to get diffuse gastric adenocarcinoma, and are patients likely to be younger or older
Younger, females.
What genes are more likely to cause diffuse gastric adenocarcinoma, and what appearance is likely on biopsy
e cadherin expression is lost in inactivation or mutation of CDH1
leather bottle stomach appearance ⇒ due to diffuse infiltration of gastric wall leading to distended stomach, rather than discrete
Where is adenocarcinoma in lower GI least likely?
In the small intestine
Where can Nueroendocrine tumours be found and what kind of tumours are they
Epithelial tumours associated with the synthesis of hormones or neurotransmitters
What is a high grade, poorly differentiated NET
Small cell carcinoma
Is NET submucosa or mucosa based
NET is submucosa based
What kind of tumour is GIST, what cell type is it related to
gastrointestinal stromal tumour, soft tissue tumour (sarcoma) that can arise anywhere in the GI tract
Pacemaker cells in the muscularis propria
What mutation is common in GISTs
75-80% of GISTs have activating mutations in the KIT receptor tyrosine kinase gene
most common site of GIST
stomach
GIST histology patterns
epitheliod or spindle cell
what cancer is related to coeliacs
Enteropathy type T-cell lymphoma (EATL)
WHich colorectal cancer is more common in one gender
Rectal, in males
What familial syndromes are related with colorectal cancer
FAP, HNPCC
risk factors for colorectal cancer
- A diet high in redmeatsand processedmeats
- Cookingmeatsat very high temperatures (frying, broiling, or grilling) creates chemicals that might raise cancer risk
- Diet low in fibre
- Obesity
- Physical inactivity
- Smoking
- Alcohol excess in rectal carcinomas esp beer
- A family history of colorectalpolypsor colorectal cancer
- History ofinflammatory bowel disease ⇒ can create environment suitable for dysplasia
- Older age ⇒ More mutations escaping, less ability of TSG to stop suppression
- Occupational factors e.g. solvents
- Radiation ⇒ Radiotherapy
- Schistosomiasis ⇒ Infection - parasitic
- Excessive calories relative to requirement
- High intake of refined carbohydrates
- Low intake of protective micronutrients e.g. vitamins A, C, D and E
Which layer must adenocarcinoma of colon invade to be recognised as T1
submucosa
What genes are involved in first hit and second hit in adenoma carcinoma sequence, what happens after second hit
APC, then APC and B catenin
Second hit, becomes adenoma
What gene is involved in higher grade adenomas
Mutation of proto-oncogenes like KRAS
What pathways are FAP and HNPCC related to
APC/B catenin vs microsatelite instability
Is FAP or HNPCC related colorectal cancer more common
HNPCC more common
What genes are related to HNPCC
DNA mismatch repair genese like MSH 2, MLH1
Which part of the colon are sessile serrated lesions more common in and what gene is related. Are these more likely or less likely to progress to malignancy.
Right colon
BRAF or KRAS
More likely
Beter prognosis
Common presentation of colorectal cancer
May be bleeding from rectum for few weeks but not other symptoms, may have mild IDA
red flags for colorectal cancer
- Weight loss ⇒ Latest of the symptoms
- Rectal bleeding ⇒ NB: Haemorrhoids and local irritation can also cause bleeding
- Anaemia and thrombocytosis ⇒ Sign of inflammation and reactivity of bone marrow due to blood loss
- Persistent diarrhoea (lack of day-day variability) in R side colon cancers ( ascending colon and caecal tumours)
- Frequent nocturnal symptoms ⇒ eg. diarrhoea in middle of night
- New onset over 50 yrs
- FHx bowel cancer/
- PMHx IBD
Investigation for colon cancer
Colonoscopy to detect polyps of lesions
Can stage with CT scan or MRI
How to screen for colorectal cancer and who gets it
Routine and regular Quantitative Faecal Immunochemical Test (qFIT) in population over the age of 50 -74
Are more or less differentiated tumours more aggressive
less
What factors affect prognosis appart from stage and grade
- Presentation with obstruction or perforation (usually indicates advanced disease)
- Involvement of surgical resection margins ⇒ Likely to recur if on margin
- Extramural vascular invasion ⇒ Main route of metastasis
- Pattern of invasion and host response ⇒ Activate immune response- may have better prognosis
- ?Genetic markers ⇒ For prognosis and treatment
- KRAS- MAB targets receptors that KRAS is part of cascade of.
- If KRAS mutation present, drug may not work
Where are bowel cancer cases most common
Rectosigmoid area, then right colon
Are tubular or villous ademonas of a higher risk
Villous
What is the most important prognostic factor for oesophagus cancers
STAGE
What gastric cancer is most commonly associated with H pylori infection
Lymphoma
what polyps is most commonly assoicated with PPIs
Fundic gland polyps
