GI Cancers Flashcards
Cancer
A disease caused by uncontrolled division of abnormal cells in a part of the body
Primary vs secondary cancers
Primary arisss from cells in an organ
Secondary is spread to another organ directly or by other means
What are GI tract squamous cell cancers called?
Squamous cell carcinoma (SCC)
What are GI tract glandular epithelium cell cancers called
Adenocarcinoma
What are GI tract enteroendocrine cell cancers called?
Neuroendocrine tumours
What are GI tract interstitial cells of Cajal cancers called?
Gastrointestinal stromal tumours (GISTs)
What are GI tract smooth muscle cell cancers called
Leiomyoma/leiomyosarcoma
What are GI tract adipose tissue cell cancers called?
Liposarcoma
Colorectal cancer prevalence
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)
Forms of colorectal cancer
Forms
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 - Adenocarcinoma
How does colorectal cancer
Normal epithelium becomes hyperproliferative epithelium, aberrant cryptic foci.
Hyperproliferatife epithelium and abherrant cryptic foci become small adenoma (cox over expression)
Small adenoma becomes a larger adenoma
Large adenoma becomes colon carcinoma
NSAIDS ,ASPIRIN,FOLATE,CALCIUM have protective affects
Normal epithelium-hyperproliferative epithelium and aberrant cryptic foci-small adenoma-large adenoma-colon carcinoma
What mutations occur in colorectal cancer
APC mutation between normal epithelium and hyperproliferative epithelium
COX2 overexpression at hyperproliferative epithelium stage
K ras mutation from small to large adenoma
P53 mutation from large adenoma to colon carcinoma
Loss of 18q in between large and colon carcinoma
Colorectal cancer risk factors
Risk factors
Past history
Colorectal cancer
Adenoma, ulcerative colitis, radiotherapy
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
Colorectal cancer presentation for caecal and right sided cancer
Depends on location of cancer
Iron deficiency anaemia (most common)
Change of bowel habit (diarrhoea)
Distal ileum obstruction (late)
Palpable mass (late)
Common locations for colorectal cancer
⅔ in descending colon and rectum
½ in sigmoid colon and rectum (i.e. within reach of flexible sigmoidoscopy)
Presentation for left sided sigmoid carcinoma
PR bleeding,mucus
Thin stool (late)
Presentation for rectal carcinoma
PR bleeding mucus
Tenesmus (feeling like you need to open bowel)
Anal Perineural and sacral pain
What are late presentations for colorectal cancer
Bowel obstruction
Local invasion:bladder symptoms,female genital tract symptoms
Metastasis’s:
Liver (hepatic pain jaundice)
Lung (cough)
Regional lymph nodes
Peritoneum
Sister Marie joesph nodule
Signs of primary cancer (colorectal)
Abdominal mass
DRE (digital rectum exam) <12cm dentate and reached by examining finger
Abdominal tenderness and distension (large bowel obstruction)
Signs of mestasis and complications for colorectal cancerous
Hepatomegaly
Monophonic wheeze
Bone pain
Colorectal cancer investigations
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
Colonoscopy
Can visualize lesions < 5mm
Small polyps can be removed
Reduced cancer incidence
Usually performed under sedation
Colonography
Used for elderly or more frail patients as colonoscopy can dehydrate the pt
CT colonoscopy/colonography
Can visualize lesions > 5mm
No need for sedation
Less invasive, better tolerated
If lesions identified patient needs colonoscopy for diagnosis
Other imaging done for colorectal
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
Is the CRM threatened?
CT Chest/Abdo/Pelvis
Staging prior to treatment
Colorectal cancer management
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
Primary liver cancer;hepatocellular carcinoma aetiology and survival rate and optimal treatment
Aetiology
- 70-90% have underlying cirrhosis
- Aflatoxin (toxin made by certain fungi)
Median survival without Rx 4-6 m
5yr survival <5%
Systemic chemotherapy ineffective (RR <20%)
Other effective Rx options
- OLTx:liver transplant if you have less than 3 cancers in liver and they’re <3cm
- TACE:transarterial chemo embolisation (put small catheter in blood dull,T of tumour then embolism blood supply
- RFA:radio frequency ablation, stick a needle into tumour and burn it
Optimal Rx surgical excision with curative intent
- 5yr survival >30%
5-15% suitable for surgery
Gallbladder cancer aetiology survival and treatment
Aetiology unknown
- GS
- porcelain GB
- chronic typhoid infection
Median survival without Rx 5-8 m
5yr survival <5%
Systemic chemotherapy ineffective
No other effective Rx options
Optimal Rx surgical excision with curative intent
- 5yr survival: stage II 64%; stage III 44%; stage IV 8%
Stage II-transmural invasion of cancer going through mucosa to muscle we can remove some liver and lymph nodes
Stage III-begins to invade liver
Stage IV-invaded liver >2cm and distal metastasis
<15% suitable for surgery
Cholangiocarcinoma aetiology survival and treatment
Aetiology
- Primary sclerosing cholangitis& Ulcerative colitis
- liver fluke (clonorchis sinesis)
- choledochal cyst
Median survival (depends on site) without Rx <6 m
5yr survival <5%
Systemic chemotherapy ineffective
GEMCIS - median overall survival 11.7 months*
No other effective Rx options (OLTx)
Optimal Rx surgical excision with curative intent
- 5yr survival 20-40%
20-30% suitable for surgery
Secondary liver metastases aetiology survival treatment
15-20% synchronous, 25% metachronous
median survival without Rx <1yr
5yr survival 0%
Systemic chemotherapy improving
Other effective Rx options (RFA & SIRT)
Optimal Rx surgical excision with curative intent
- 5yr survival rates of 25-50%
25% suitable for surgery
Secondary liver metastases
Best supportive care 4-6 months
5-FU/LV 12-14 months
IFL OR FOLFIRI 15-16 months
5 FU/LV and bevacuzimab 18.3 months
FOLFOX4 or CAPEOX 19-20 months
IFL AND BEVACIZUMAB 20.3 months
FOLFOX6 20.6
IFL+BV to OX 25.1 months
Pancreatic cancer epidemiology
IRelatively 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 0.4 - 5%
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
15-20% have resectable disease
Median survival 11-20 months
5-year survival 20–25%
Virtually all pts dead within 7 years of surgery
Pancreatic cancer risk factors
Chronic pancreatitis → 18-fold ↑er 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 syndrome cause an increased risk of pancreatic cancer
Heridatery pancreatitis (genes PRSS1,SPINK1,CFTR) genes cause cationic trypsinogen,panc secretory trypsin inhibitors,CFTR prtone
Familial atypical mutltiple mole melanoma (gene CDKN2A) which is a tumour suppressor
Familial breast ovarian syndrome (BRAC1,BRACW,PALB2) are tumiur suppressors
Peutz jeghers syndrome (STK11) tumiur suppressor
HNPCC (lynch syndrome) and FAP mismatch repair and tumour support (MLH1,MSH2,MSH6,PMS2)APC
Pancreatic cancer Pathogenesis
Pancreatic Intraepithelial Neoplasias (PanIN) are precancerous lesions found in pancreatic ducts
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
What is the Pathogenesis of pancreatic cancer (stages) PanIn progression model
Normal
PANIN-1A
(ERBB2 KRAS MUTATION)
PANIN-1B
PANIN-2
(CDKN2A)
OANIN-3
(TP53,SMAD4,BRCA2)
Minimal changes in 1 to moderate dysplasia
Pancreatic cancer presentation
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.
Carcinoma of body and 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
Pancreatic cancer investigations
Tumour marker CA19-9
- falsely elevated in pancreatitis, hepatic dysfunction & obstructive jaundice.
- concentrations > 200 U/ml confer 90% sensitivity
- concentrations in the thousands associated with high specificity
• Ultrasonography
- can identify pancreatic tumours
- dilated bile ducts
- liver metastases
• Dual-phase CT accurately predicts resectability in 80–90% of cases
- contiguous organ invasion
- vascular invasion (coeliac axis & SMA)
- distant metastases
Other investigations for pancreatic cancer
MRI imaging detects and predicts resectability with accuracies similar to CT
MRCP provides ductal images without complications of ERCP
• ERCP
- confirms the typical ‘double duct’ sign
- aspiration/brushing of the bile-duct system
- therapeutic modality → biliary stenting to relieve jaundice
EUS
- highly sensitive in the detection of small tumours
- assessing vascular invasion
- FNA
• Laparoscopy & laparoscopic ultrasound
- detect radiologically occult metastatic lesions of liver & peritoneal cavity
PET mainly used for demonstrating occult metastases
Neuroendocrine tumiurs
Arise from the gastroenteropancreatic (GEP) tract (or bronchopulmonary system)
Diverse group of tumours
Regarded as common entity as arise from secretory cells of the neuroendocrine system
Sporadic tumours in 75%
Associated with a genetic syndrome in 25%
Multiple Endocrine NeoplasiaType 1 (MEN1)
Parathyroidtumours
Pancreatic tumours
Pituitarytumours
NETS presentation
Most NETs are asymptomatic & incidental findings
Secretion of hormones & their metabolites in 40%
serotonin, tachykinins (substance P) & other vasoactive peptides
< 10% of NETs produce symptoms
Can result in a variety of debilitating effects
Carcinoid syndrome
Vasodilatation
Bronchoconstriction
↑ed intestinal motility
Endocardial fibrosis (PR & TR)
Nets clinical features
Pancreatic:
Insulinoma-hypoglycaemua,whipples triad
Glucagonoma-diabetes mellitus,necrolytic migratory erythema
Pancreatic/duodenal:
Gastrinoma-zollinger ellison syndrome
Entire GIT
VIPoma-vernor morrison syndrome,watery diarrhea
Somatostatinima-gallstones,diabetes,steatorrhea
Midgut-most are non functioning some may develop carcinoid syndrome
Hindgut-usually non functioning
NET diagnosis
Biochemical Assessment
Chromogranin A is a secretory product of NETs
Other gut hormones: insulin, gastrin, somatostatin, PPY
Measured in fasting state
Other screening: Calcium, PTH, prolactin, GH
24 hr urinary 5-HIAA (serotonin metabolite)
Imaging
Cross-sectional imaging (CT and/or MRI)
Bowel imaging (endoscopy, barium follow through, capsule endoscopy)
Endoscopic ultrasound
Somatostatin receptor scintigraphy
68Ga-DOTATATE PET/CT most sensitive
Grading of GEP-NETS
G1-mitosis <2-10 HPF, ki67 <=2
G2-mitosis 2-20 HPF,ki67 3-20%
G3->20/10 HPF ki67 >20%
High grade (poorly differentiated)Neuroendocrine carcinoma
Treatment for NETS
Curative resection (R0)
Cytoreductive resection (R1/R2)
Liver transplantation (OLTx)
RFA, microwave ablation
Embolisation (TAE), chemoembolisation (TACE)
Selective Internal RadioTherapy (SIRT)
90Y-Microspheres
Somatostatin receptor radionucleotide therapy
90Y-DOTA
177 Lu-DOTA
Medical therapy, targeted therapy, biotherapy
Octreotide, Lanreotide, SOM203
PK-inhibitors, mTOR-inhibitors
⍺-Interferon
