gastrointestinal cancers Flashcards
what type of cancers are most commonly found in the GI tract?
adenocarcinoma - cancers of the glandular epithelium
but there are also: squamous cell carcinoma neuroendocrine tumours gastrointestinal stromal tumours leiomyoma/leiomyosarcomas liposarcomas
what are the two types of oesophageal cancers?
Squamous Cell Carcinoma:
From normal oesophageal squamous epithelium
Upper 2/3
Acetaldehyde pathway (related to alcohol)
more common in the Less developed world
Adenocarcinoma: From metaplastic columnar epithelium Lower 1/3 of oesophagus Related to acid reflux More developed world
what is the progression from reflux to cancer like?
Oesophagitis (Inflammation) - 30% of UK population has GORD
->
Barrett’s (metaplasia) - 5% of GORD populn → Barrett’s
->
Adenocarcinoma (neoplasia) - Barrett’s lifetime risk of cancer - 0.5-1%/ year.
what is the progression of barrett’s oesophagus like and how is each stage surveyed?
barrets oesophagus -> dysplasia (low grade) -> dysplasia (high grade) -> adenocarcinoma
Barrett’s surveillance BSG guidelines: No dysplasia → Every 2-3 years LGD → every 6 months HGD → intervention
what is the epidemiology of oesophageal cancer?
squamous and adenocarcinoma combined
9th most common cancer
affects the elderly
more common in men than women (10:1)
what are some facts about presentation and prognosis of oesophageal cancer?
Late presentation
- dysphagia & wt loss
65% palliative
High morbidity & complex surgery
Poor 5-year survival <20%
Palliation- difficult
what is the management pathway of oesophageal cancer?
diagnosis:
endoscopy -> biopsy
staging: CT laparoscopy EUS (endoscopic ultrasound) for some PET scan for some
treatment plan:
curative - (for adenocarcinoma) neoadjuvant chemo -> radical surgery
(squamous cell carcinoma is pretty effectively treated with radiotherapy)
also two stage ivor lewis approach surgery (oesophagectomy around the cancer)
palliative - chemo, DXT (radiotherapy), stent
what is the epidemiology of colorectal cancer?
Most common GI cancer in Western Societies
Third most common cancer death in men & women
Lifetime risk:
1 in 10 for men
1 in 14 for women
Generally affects patients > 50 years (>90% of cases)
what are the different forms of colorectal cancer?
Sporadic:
Absence of family history, older population, isolated lesion
Familial:
Family history, higher risk if index case is young (<50years) and the relative is close (1st degree)
Hereditary syndrome:
Family history, younger age of onset, specific gene defects
e.g. Familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome)
Histopathology - pretty much all Adenocarcinoma
how does colorectal cancer develop?
normal epithelium - cause APC mutation
->
hyperproliferative epithelium
->
small adenoma
->
large adenoma (K-ras mutation)
->
colon carcinoma (p53 mutation) this one can metastasise)
aspirin and NSAIDs may stop this progression
what are the risk factors for colorectal cancer?
Past history:
Colorectal cancer
Adenoma, ulcerative colitis, past radiotherapy has a big effect on the bowels
Family history:
1st degree relative < 55 yrs
Relatives with identified genetic predisposition
(e.g. FAP, HNPCC, Peutz-Jegher’s syndrome)
Diet/Environmental: ?carcinogenic foods Smoking Obesity Socioeconomic status
what is the clinical presentation of colorectal cancer?
Depends on location of cancer
Locations:
⅔ occur in descending colon and rectum
½ in sigmoid colon and rectum (i.e. within reach of flexible sigmoidoscopy)
Caecal & right sided: cancer Iron deficiency anaemia (most common) Change of bowel habit (diarrhoea) Distal ileum obstruction (late) Palpable mass (late)
Left sided & sigmoid carcinoma:
PR bleeding, mucus
Thin stool (late)
Rectal carcinoma:
PR bleeding, mucus
Tenesmus (cant get poo out)
Anal, perineal, sacral pain (late)
Bowel obstruction (late)
how do local invasion and metastasis of colorectal cancer present clinically?
Local invasion (late):
Bladder symptoms
Female genital tract symptoms
Metastasis (late):
Liver (hepatic pain (rare), jaundice (also rare))
Lung (cough)
Regional lymph nodes
Peritoneum
Sister Mary Joseph nodule (belly button bump)
what are the signs of colorectal cancer on examination?
Signs of primary cancer:
Abdominal mass
DRE (digital rectal examination): most <12cm dentate and reached by examining finger
Rigid sigmoidoscopy
Abdominal tenderness and distension – large bowel obstruction
Signs of metastasis and complications:
Hepatomegaly (mets)
Monophonic wheeze
Bone pain
what investigations are done for colorectal cancer?
Faecal occult blood:
Guaiac test (Hemoccult) – based on pseudoperoxidase activity of haematin
Sensitivity of 40-80%; Specificity of 98%
Dietary restrictions – avoid red meat, melons, horse-radish, vitamin C & NSAIDs for 3 days before test
FIT (Faecal Immunochemical Test) - detects minute amounts of blood in faeces (faecal occult blood).
Blood tests:
FBC: anaemia, haematinics – low ferritin
Tumour markers: CEA which is useful for monitoring (NOT diagnostic tool)
Colonoscopy: Can visualize lesions < 5mm Small polyps can be removed Reduced cancer incidence Usually performed under sedation
CT colonoscopy/colonography: Can visualize lesions > 5mm No need for sedation Less invasive, better tolerated If lesions identified patient needs colonoscopy for diagnosis
what are imaging tests used in colorectal cancer?
CT colonoscopy/colonography: Can visualize lesions > 5mm No need for sedation Less invasive, better tolerated If lesions identified patient needs colonoscopy for diagnosis
MRI pelvis – Rectal Cancer:
Depth of invasion, mesorectal lymph node involvement
No bowel prep or sedation required
Help choose between preoperative chemoradiotherapy or straight to surgery
CT Chest/Abdo/Pelvis:
Staging prior to treatment
how is colorectal cancer managed?
Colon cancer is primarily managed by surgery
? Stent/Radiotherapy/Chemotherapy
Obstructing colon carcinoma: Right & transverse colon – resection and primary anastomosis Left sided obstruction - Hartmann’s procedure Proximal end colostomy (LIF) \+/- Reversal in 6 months Primary anastomosis Intraoperative bowel lavage with primary anastomosis (10% leak) Defunctioning ileostomy Palliative stent
how common is pancreatic cancer and what is the prognosis like?
Relatively common & highly lethal:
Commonest form of panc CA is pancreatic ductal adenocarcinoma (PDA)
80-85% have late presentation
Overall median survival <6 months
5-year survival 10-15%
15-20% have resectable disease
Median survival 11-20 months
5-year survival 20–25%
Virtually all pts dead within 7 years of surgery
what is the epidemiology of pancreatic cancer?
Incidence ↑er in Western/industrialised countries
Rare before 45 years, 80% occur between 60 & 80 years of age
Men > women (1.5 - 2:1)
UK & USA annual incidence panc CA 100 per million popn
4th commonest cause of cancer death
Incidence & mortality roughly equivalent – UK in 2015
9,921 new cases of PDA
9263 deaths from PDA
2nd commonest cause of cancer death – in USA 2030
- 48,000 deaths
what are the risk factors for pancreatic cancer?
Chronic pancreatitis → 18-fold increased risk
Type II diabetes mellitus → relative risk 1.8
Cholelithiasis, previous gastric surgery & pernicious anaemia – WEAK
Diet (↑fat & protein, ↓fruit & veg, coffee & EtOH) - WEAK
Occupation (insecticides, aluminium, nickel & acrylamide)
Cigarette smoking → causes 25-30% PDAs
7-10% have a family history
Relative risk of PDA increased by: 2, 6 & 30-fold
with: 1, 2 & 3 affected first degree relatives
what inherited syndromes are associated with an increased risk of pancreatic cancer?
hereditary pancreatitis (40% lifetime risk of PDA)
familial atypical multiple mole melanoma (10-17%)
familial breast-ovarian cancer syndrome (5%)
peutz-jeghers syndrome (11-36%)
HNPCC (lynch syndrome) (3.7%)
all involve mutations in tumour supressor genes
what is the pathogenesis of pancreatic cancer?
commonest
Pancreatic Intraepithelial Neoplasias (PanIN):
PDAs evolve through non-invasive neoplastic precursor lesions
PanINs are microscopic (<5 mm diameter) & not visible by pancreatic imaging
Acquire clonally selected genetic & epigenetic alterations along the way
progression from PanIN-1 to PanIN-3
this is the stage before pancreatic cancer
they are similar to polyps
what is the clinical presentation of pancreatic cancer - head of pancreas?
Carcinoma of the head of the pancreas:
At least two-thirds of PDAs arise in the head
• Jaundice >90% due to either invasion or compression of CBD
- often painless
- palpable gallbladder (Courvoisier’s sign)
• Weight loss
- anorexia
- malabsorption (secondary to exocrine insufficiency)
- diabetes.
• Pain 70% at the time of diagnosis
- epigastrium
- radiates to back in 25%
- back pain usually indicates posterior capsule invasion and irresectability.
• 5% atypical attack of acute pancreatitis.
• In advanced cases, duodenal obstruction results in persistent vomiting.
• Gastrointestinal bleeding
- duodenal invasion or varices secondary to portal or splenic vein occlusion.
what is the clinical presentation of pancreatic cancer - body and tail?
Carcinoma of the body & tail of pancreas:
Develop insidiously and are asymptomatic in early stages
At diagnosis they are often more advanced than lesions located in the head
There is marked weight loss with back pain in 60% of patients.
Jaundice is uncommon
Vomiting sometimes occurs at a late stage from invasion of the DJ flexure
Most unresectable at the time of diagnosis
