Gastrointestinal cancer Flashcards
What is cancer?
•A disease caused by an uncontrolled division of abnormal cells in a part of the body
What is primary?
•Arising directly from the cells in an organ
What is secondary/metastasis?
•Spread from another organ, directly or by other means (blood or lymph)
What are epithelial cells and cancers of GI tract?
squamous - squamous cell carcinoma (SCC)
“glandular epithelium” - adenocarcinoma
What are neuroendocrine cells and cancers of GI tract?
enterocendocrine cells - neuroendocrine tumours (NETs)
Intersittial cells of Canal - gastrointestinal stroll tumours (GISTs)
What are connective tissue and cancers of GI tract?
smooth muscle - leiomyoma/leiomyosarcomas
adipose tissue - liposarcomas
Where is squamous cell carcinoma?
- From normal oesophageal squamous epithelium
- Upper 2/3
- Acetaldehyde pathway
- Less developed world
Where is adenocarcinoma?
- From metaplastic columnar epithelium
- Lower 1/3 of oesophagus
- Related to acid reflux
- More developed world
What is the progress from reflux to cancer?
- Oesphagitis (inflammation) 30% of uk (GORD)
- Barretts (metaplasia) 5% of 30%
- Adenocarcinoma 0.5-1% barretta lifetime risk of cancer
- 30-100 fold risk of cancer
What is the progression to adenocarcinoma?
- Barrett’s oesophagus
- Dysplasia (low grade)
- Dysplasia (high grade)
What is Barrett’s surveillance?
BSG guidelines
• No dysplasia → Every 2-3 years
• LGD → every 6 months
• HGD → intervention
How is oesophageal cancer occurrence?
•Squamous- adenocarcinoma
•9th most common cancer
•Affects the elderly
Male/female (adeno 10:1)
What is survival of oesophageal cancer?
- Late presentation
- 65% palliative
- High morbidity & complex surgery
- Poor 5-year survival <20%
- Palliation- difficult
What is the management pathway for oesophageal cancer?
- Diagnosis: endoscopy-> biopsy
- Staging: Ct scan, Laparscopy, EUS< PET scan
- Treatment:
- Curative: Neo-ajuvant chemo -> radical surgery
- Palliative: chemo, DXT, Stent
- Oesophagectomy
- Two-stage Ivor Lewis approach
What is the prevalence 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
- Appendicitis is 8.6% M vs. 6.7% F
- Generally affect patients > 50 years (>90% of cases)
What is sporadic form of colorectal cancer?
•Absence of family history, older population, isolated lesion
What is familial form of colorectal cancer?
•Family history, higher risk if index case is young (<50years) and the relative is close (1st degree)
What is hereditary syndrome form of colorectal cancer?
•Family history, younger age of onset, specific gene defects
•e.g. Familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome)
-Hispathology: adenocarcinoma
What is the development?
- normal epithelium: APC mutation
- Hyper proliferative epithelium, aberramt cryptic foci (COX-2 over expression)
- Small adenoma (Kras mutation)
- Large adenoma (p53 mutation) (loss of 18q)
- Colon carcinoma
What are the history risk factors of colorectal cancer?
-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)
What is the diet/environmental risk factors of colorectal cancer?
- ?carcinogenic foods
- Smoking
- Obesity
- Socioeconomic status
What are the locations of the colorectal cancer?
- ⅔ in descending colon and rectum
* ½ in sigmoid colon and rectum (i.e. within reach of flexible sigmoidoscopy)
What happens in caecal and right sided cancer clinical presentation?
- Iron deficiency anaemia (most common)
- Change of bowel habit (diarrhoea)
- Distal ileum obstruction (late)
- Palpable mass (late)
What is a clinical presentation for left sided & sigmoid carcinoma?
- PR bleeding, mucus
- Thin stool (late)
- Bowel obstruction (late)
What is clinical presentation for Rectal carcinoma?
- PR bleeding, mucus
- Tenesmus
- Anal, perineal, sacral pain (late)
What is the clinical presentation for a late local invasion?
- Bladder symptoms
* Female genital tract symptoms
What is clinical presentation for late metastasis?
- Liver (hepatic pain, jaundice)
- Lung (cough)
- Regional lymph nodes
- Peritoneum
- Sister Marie Joseph nodule
What are signs of primary cancer?
- Abdominal mass
- DRE: most <12cm dentate and reached by examining finger
- Rigid sigmoidoscopy
- Abdominal tenderness and distension – large bowel obstruction
What are signs of metastasis and complications?
- Hepatomegaly (mets)
- Monophonic wheeze
- Bone pain
What is a faecal occult blood test?
- 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
What blood test do you do?
- FBC: anaemia, haematinics – low ferritin
- Tumour markers: CEA which is useful for monitoring
- NOT diagnostic tool
What is a Double contrast barium enema
for an investigation for colorectal cancer?
- Does not require sedation
- Decreased risk of perforation
- More limited in detecting small lesions
- All lesions need to be confirmed by colonoscopy and biopsy
- Historic interest only
What is colonoscopy for investigation of colorectal cancer?
- Can visualize lesions < 5mm
- Small polyps can be removed
- Reduced cancer incidence
- Usually performed under sedation
How is CT colonoscopy/colonography used for investigation of colorectal cancer?
- Can visualize lesions > 5mm
- No need for sedation
- Less invasive, better tolerated
- If lesions identified patient needs colonoscopy for diagnosis
How is an MRI of pelvis used for colorectal cancer?
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?
Why is CT used in colorectal cancer?
CT Chest/Abdo/Pelvis
•Staging prior to treatment
How would you manage colorectal cancer?
- 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
What is the epideimeology of pancreatic caner?
-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%
-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 incidence of pancreatic cancer like?
•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 risk factors for pancreatic cancer?
- 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 syndromes increase your risk for pancreatic cancer?
- Hereditary pancreatitis
- Familial atypical multiple mole melanoma
- Familial breast-ovarian syndrome
- Peutz-Jegers syndrome
- HNPCC (Lynch syndrome)
- FAP
Describe the pathogenesis of pancreatic cancer?
-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
-Normal, PannIN 1A, 1B, , 3
Where do PDAs usually arrive?
Carcinoma of the head of the pancreas
•At least two-thirds of PDAs arise in the head
When is jaundice a clinical presentation of pancreatic cancer?
Jaundice >90% due to either invasion or compression of CBD
- often painless
- palpable gallbladder (Courvoisier’s sign)
When is weight loss a clinical presentation of pancreatic cancer?
Weight loss
- anorexia
- malabsorption (secondary to exocrine insufficiency)
- diabetes.
When is pain a clinical presentation of pancreatic cancer?
Pain 70% at the time of diagnosis
- epigastrium
- radiates to back in 25%
- back pain usually indicates posterior capsule invasion and irresectability.
What are other clinical presentations of pancreatic cancers?
• 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 for 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
What tumour marker investigations can be done for pancreatic cancer?
•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\
What ultrasonography for pancreatic cancer?
-Ultrasonography
- can identify pancreatic tumours
- dilated bile ducts
- liver metastases
How is dual phase CT used in pancreatic cancer?
-Dual-phase CT accurately predicts resectability in 80–90% of cases
- contiguous organ invasion
- vascular invasion (coeliac axis & SMA)
- distant metastases
What investigations can be done with 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
What other investigations can be done with pancreatic cancer?
•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
What are different liver cancers?
- HCC
- ChCA
- CRC
- GB CA
What is HCC?
Primary Liver Cancer (Hepatocellular Carcinoma [HCC])
•Aetiology
- 70-90% have underlying cirrhosis
- Aflatoxin
• Median survival without Rx 4-6 m
• 5yr survival <5%
• Systemic chemotherapy ineffective (RR <20%)
• Other effective Rx options
- OLTx
- TACE
- RFA
• Optimal Rx surgical excision with curative intent
- 5yr survival >30%
• 5-15% suitable for surgery
What is gallbladder cancer?
•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% • <15% suitable for surgery
What is ChCA?
Cholangiocarcinoma (ChCA)
•Aetiology
- PSC & UC
- 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
What is CRC?
Secondary liver metastases (CRC) •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
