GI Cancers Flashcards
Define cancer
CANCER = • A term for diseases in which abnormal cells divide without control and can invade nearby tissues.
What are the two types of neuroendocrine cancers of GI tract?
neuroendocrine tumours (NETs) and gastrointestinal stromal tumours (GISTs)
What is the most common GI cancer in western society?
Colorectal cancer
Colorectal cancer usually affects people above what age?
50
Outline the Wilson and Jungner criteria (7)
1.The condition sought should be an important health problem2. There should be an accepted treatment for patients with recognised disease3. Facilities for diagnosis and treatment should be available4. There should be a recognisable latent or early symptomatic stage5. There should be a suitable test or examination6. The test should be acceptable to the population7. The natural history of the condition, including development from latent to declared disease, should be adequately understood
What are the three forms of colorectal cancer?
Sporadic, familial and hereditary syndrome
What are the two types of epithelial cell GI cancer?
Squamous cell carcinoma
Adenocarcinoma
what are the two types of neuroendocrine GI cancer?
Neuroendocrine tumours (NETs) and Gastrointestinal stromal tumours
What are the three connective tissue GI cancer?
Leiomyoma, leiomyosarcomas, liposarcomas
What are the characteristics of sporadic colorectal cancer?
Absence of family history, older population, isolated lesion
What are the characteristics of familial colorectal cancer?
Family history, higher risk if index case is young (<50years) and the relative is close
What are the characteristics of hereditary syndrome 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)
What is the histopathology of colorectal cancer?
Adenocarcinoma
Outline the pathophysiology of colorectal cancer:
normal epithelium + (aspirin and other NSAIDS, folate, calcium) + APC mutation ->
hyper proliferation epithelium with aberrant cryptic foci, small adenoma, large adenoma, colon carcinoma
Outline the risk factors of colorectal cancers
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
What is the clinical presentation of colorectal cancer dependent on?
Location
What percentage of colon cancer are in the descending colon and rectum vs. In the sigmoid colon and rectum?
2/3 descending colon and rectum
1/3 sigmoid colon and rectum
What does the term mural indicate?
Can be across any layer of the oesophagus
What are the characteristics of caecel and right sided cancer?
iron deficiency anaemia, change of bowel habits, distal ileum obstruction, palpable mass (last 2 r late stage)
What are the characteristics of left sided and sigmoid cancer?
PR bleeding, mucus and thin stool (late)
What are the characteristics of rectal carcinoma?
PR bleeding, mucus, tenesmus, anal/perineal/sacral pain (late)
What are the metastases of colorectal cancer usually?
Liver, lung, regional lymph nodes, peritioneum
What is the name of the nodule seen in the metastases of colorectal cancer to the peritoneum?
Sister Marie Joseph nodule
What are the signs of primary colorectal cancer?
abdominal mass, DRE > 12cm dentate and reached by examining finger, rigid sigmoidoscopy, abdominal tenderness and distension – large bowel obstruction
What are the signs of metastases and complications of colorectal cancer?
Hepatomegaly, monophonic wheeze, bone pain
What investigations are made in suspected colorectal cancer?
Faecel occult blood - henoccult or FIT, full blood test - anaemia, haematinics (low ferritin)
Tumour markers: CEA which is useful for monitoring - NOT a diagnostic tool
Colonoscopy
CT colonoscopy/ colonography
What other imaging tests are done for suspected colorectal cancer?
MRI pelvis - rectal cancer
CT chest/abdo/pelvis
What are the differences between a colonoscopy and a CT colonoscopy?
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 is the primary management option for colon cancer?
Surgery
What is the treatment plan for a obstructing colon carcinoma in the right side and transverse colon?
Resection and primary anastomosis
What are the treatment options for an obstructing colon carcinoma in the left side colon?
Hartman’s procedure. Primary anastomosis, palliative stent
What is the aetiology of 70-90% of primary liver cancer?
70-90% have underlying cirrhosis
What is the optimal treatment for primary liver cancer?
Surgical excision with curative intent
In the treatment of primary liver cancer via surgical excision with curative intent, what is the 5 year survival rate and how does this compare to the survival rate without this treatment?
5yr survival >30%, without surgical excision is <5%
What is another name for primary liver cancer?
Hepatocellular carcinoma
What is the underlying aetiology of gallbladder cancer?
Unknown
What is the median survival rate for gallbladder cancer without Rx?
5-8mnths
Is systemic chemotherapy effective against gallbladder cancer or hepatocellular carcinoma?
Neither
What is the optimal treatment for gallbladder cancer and how many patients are suitable for this?
Surgical excision , <15%
What are the risk factors that cause cholangiocarcinoma?
PSC and UC, liver fluke, choledochal cyst
What is the median survival for cholangiocarcinoma without Rx?
<6 months
What is the optimal treatment option for cholangiocarcinoma? what is the 5 year survival following this compared to before?
Surgical excision with curative intent
5 yr survival 20-40% in comparison to <5%
How many cholangiocarcinoma patients are suitable for surgery?
20-30%
What is the median survival rate for secondary liver metastases without Rx?
<1 year
Other than systemic chemotherapy what are the other effective Rx options for secondary liver metastases?
RFA and SIRT, optimal treatment is surgical excision with curative intent
What is the most common form of pancreatic cancer?
Pancreatic ductal adenocarcinoma
What percentage of people with pancreatic cancer do not present till a late stage?
80-85%
What percentage of pancreatic cancer patients have resectable disease? What is the 5 and 7 year survival rate following this
15-20%
5 year survival = 20-25%, virtually all patients die within 7yrs
Are men or women more likely to have pancreatic cancer?
Women
What are the risk factors for developing pancreatic cancer?
Chronic pancreatitis
T2DM
Cholelithiasis, previous gastric surgery and pernicious anaemia
High fat, high protein, high coffee, high EtOH diet
What percentage of pancreatic cancer patients have a family history of the disease?
7-10%
Cigarette smoking is said to cause what percentage of pancreatic cancers?
25-30%
What three genes are associated with hereditary pancreatitis and what lifetime risk for PDA does this carry?
PRSS1, SPINK1, CFTR
40% risk
What gene is associated with familial atypical multiple mole melanoma and what lifetime risk for PDA does this carry?
CDKN2A, 10-17%
What genes are associated with familial breast-ovarian cancer syndrome and what lifetime risk for PDA does this carry?
BRAC1, BRAC1, PALB2
3-5%
What gene is associated with Peutz-Jeghers syndrome and what lifetime risk for PDA does this carry?
STK11
11-36%
What genes are associated with HNPCC (lynch syndrome) and what lifetime risk for PDA does this carry?
MLH1, MSH2, MSH6, PMS2
4%
What gene is associated with FAP and what lifetime risk for PDA does this carry?
APC
5%
Outline the pathogenesis behind pancreatic intraepithelial neoplasias (PanIN)
PDAs evolve through non-invasive neoplastic precursor lesions
PanINs are microscopic and not visible via pancreatic imaging
They acquire clonally selected genetic and epigenetic alterations along the way
What percentage of PDAs occur in the head of the pancreas?
At least two thirds
Jaundice is seen in ______% of pancreatic cancer patients, why is this? what sign is observed
Seen in more than 90% of pancreatic cancer patients due to either invasion or compression of the common bile duct, is often painless and shows a palpable gallbladder (Courvoisiers sign)
Back pain as a feature of pancreatic cancer usually indicates what?
Posterior capsule invasion and irresectability
In advanced pancreatic cancer cases, duodenal obstruction results in what?
Persistent vomiting
What causes GI bleeding seen in pancreatic cancer?
Duodenal invasion or varices secondary to portal or splenic vein occlusion
how does a carcinoma of the body and tail of the pancreas develop?
insidiously and are asymptomatic in early stages
At the time of diagnosis of a carcinoma of the body and tail of pancreas, what are the surgical treatment options?
most are unresectable at time of diagnosis
T or F: jaundice is a feature of carcinoma of the body and tail of the pancreas?
False. it is uncommon
in the late stages of a carcinoma of the body and tail of the pancreas, why is vomiting often a feature?
from invasion of the DJ flexure
60% of patients with a carcinoma of the body and tail of the pancreas experience what?
marked weight loss with back pain
what tumour marker is an indicator of pancreatic cancer and what other conditions give a false elevation of this marker?
CA19-9
falsely elevated in pancreatitis, hepatic dysfunction and obstructive jaundice
when investigating pancreatic cancer, what three things is an ultrasonography useful for?
can identify pancreatic tumours
- dilated bile ducts
- liver metastases
what imaging method can be used to accurately predict resectability in 80-90% of cases of pancreatic cancer?
Dual phase CT
other than predicting resectability of pancreatic cancer, what else is dual-phase CT useful for seeing?
- contiguous organ invasion
- vascular invasion (coeliac axis & SMA)
- distant metastases
what imaging method used to investigate pancreatic cancer can provide ductal images without the complications an ERCP would have?
MRCP
in investigating pancreatic cancer, what is ERCP used for?
confirms the typical ‘double duct’ sign
- aspiration/brushing of the bile-duct system
- therapeutic modality → biliary stenting to relieve jaundice
in investigating pancreatic cancer, what is an EUs useful for?
highly sensitive in the detection of small tumours
- assessing vascular invasion
- FNA
what is an FNA?
fine-needle aspiration biopsy
The removal of fluid, cells, or tissue with a thin needle for examination under a microscope.
in investigating pancreatic cancer, what is a Laparoscopy & laparoscopic ultrasound useful for?
detect radiologically occult metastatic lesions of liver & peritoneal cavity
in investigating pancreatic cancer, what is PET useful for?
mainly used for demonstrating occult metastases
from where in the gastrointestinal system do NETs arise?
gastroenteropancreatic (GEP) tract (or bronchopulmonary system)
what percentage of NETs are sporadic tumors
75%
what percentage of NETs are associated with a genetic syndrome?
25%
what percentage of NETs produce symptoms?
<10%
NETs can result in a variety of debilitating effects, what are the most common ones?
Carcinoid syndrome
Vasodilatation
Bronchoconstriction
↑ed intestinal motility
Endocardial fibrosis (PR & TR)
carcinoid tumours can release hormones such as ___________, causing symptoms such as __________
Carcinoid tumours can release hormones such as serotonin, tachykinins (eg substance P) and other vasoactive peptides, causing carcinoid syndrome which commonly presents with symptoms of flushing, diarrhoea, wheeze and bronchoconstriction.
where is serotonin that has been released into portal circulation metabolised? what knock on effect does this have?
the liver
Therefore carcinoid syndrome seldom occurs in the absence of metastatic liver deposits.
in the absence of hepatic metastases, which type of carcinoid tumours can present with carcinoid syndrome?
carcinoid tumours that directly release hormones into the systemic circulation (eg bronchial carcinoids) can present with carcinoid syndrome in the absence of hepatic metastases.
serotonin directly causes endocardial fibrosis, what does this lead to?
predominantly right-sided valvular lesions such as pulmonary and tricuspid incompetence (carcinoid heart disease)
what are the clinical features of a pancreatic insulinoma and what cell type does this effect?
hypoglycaemia, Whipples triad, beta-cell type
what are the clinical features of a pancreatic glucagonoma and what cell type does this affect?
diabetes, necrolytic migratory erythema. alpha-cell type
what is Whipples triad?
(1) symptoms of hypoglycemia, (2) hypoglycemia (blood glucose level <50 mg/dL), and (3) relief of symptoms following ingestion of glucose
what are the clinical features associated with a pancreatic/duodenal gastrinoma and what cell type does this affect?
Zollingere-Ellison syndrome, G cells
what are the clinical features associated with a pancreatic/duodenal gastrinoma and what cell type does this affect?
Zollingere-Ellison syndrome, G cells
what are the clinical features associated with a pancreatic/duodenal gastrinoma and what cell type does this affect?
Zollingere-Ellison syndrome, G cells
what are the clinical features associated with a VIPoma and what cells does this affect?
Verner-Morrison syndrome, watery diarrhoea
vasoactive intestinal peptide cells
What are the clinical features associated with a somatostatinoma and what cell type does this affect?
Gallstones, diabetes mellitus, steatorrhoea
D cells
what are the clinical features of NETs in the midgut?
Most are non-functioning, 40% develop carcinoid syndrome
what are the clinical features associated with NETs of the hindgut?
usually non-functioning
what biochemical assessments are made for suspected NETs?
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)
what imaging is done to investigate suspected NETs?
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
what are the treatment modalities for NETs?
Curative resection (R0)
Cytoreductive resection (R1/R2)
Liver transplantation
Embolisation (TAE), chemoembolisation (TACE)
Selective Internal RadioTherapy (SIRT)
Somatostatin receptor radionucleotide therapy
Medical therapy, targeted therapy, biotherapy
