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Gastrointestinal > Neoplastic Disease of the GI Tract > Flashcards

Neoplastic Disease of the GI Tract Flashcards

1
Q

Describe the cancer mortality

A
  • The population of Scotland is around about 5.4 million.
  • 32 thousand new cancer diagnoses in 2017.
  • 30% of those deaths 2018 were due to cancer.
  • Incidents= rectal cancer is the third commonest type of cancer.
  • Colorectal above breast cancer in mortality to become the second commonest cause of cancer-related mortality in Scotland.
  • Oesophago-gastric third
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2
Q

What is hyperplasia?

A
  • Tissue growth due to increase in cell number

- Physiological response to hormones vs pathological

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3
Q

What is metaplasia?

A
  • Change from one fully differentiated cell types who are mature cell type to another fully differentiated cell type
  • Barrett’s oesophagus
  • Metaplasia represents a phenotypic shift in the stem cells present at the base of the epithelium (not a change in differentiation of mature cells).
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4
Q

What is neoplasia?

A

Uncontrolled cell growth

  • Abnormal mass of tissue growth exceeds and is not coordinated with that of the surrounding normal tissue.
  • Growth persists even after evoking stimulus removed.
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5
Q

What is dysplasia?

A
  • term used by pathologists to indicate pattern of disordered growth and differentiation, particularly applied to epithelial tissues where it’s most easy to understand.
  • Unlike metaplasia, neoplasia, it’s not a pathological process itself.
  • All it is is an appearance seemed like the microscope (abnormalities in the genetic control of tissue at a molecular level)
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6
Q

How do we classify dysplasia?

A
  • High-grade dysplasia and low-grade dysplasia
  • Based on the extent by which the growth pattern differs from that of the normal surrounding tissue. -Severe dysplasia as carcinoma in situ or intraepithelial neoplasia. =population of cells that possess most of the genetic characteristics of neoplasia but at that stage are unable to actually invade into the surrounding tissues.
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7
Q

What are the key features of dysplasia?

A

-Hyperchromatism
=Dark staining of nuclei reflecting an increase in DNA content (polyploidy, abnormal numbers of chromosomes)
-Nuclear pleomorphism
=Variation in nuclear shape and shape
-Loss of orientation
=Many normal epithelial cells show polarity (nucleus at one end)
-Cell crowding and stratification
=Reflects a loss of normal contact inhibition
-Increased and/or abnormal mitotic figures
=reflects increased cell proliferation

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8
Q

How are cancers named?

A
  • Epithelial= carcinoma (adenocarcinoma squamous cell carcinoma)
  • Soft tissue= sarcoma (osteosarcoma= bone chondrosarcoma= cartilage)
  • Haematological= lymphoma, leukaemia
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9
Q

Describe the aetiology of neoplasia

A
  • Chemical carcinogens
  • Physical agents (UV)
  • Infections (HPV)
  • Inherited susceptibility
  • Hormonal stimulation
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10
Q

What are the mechanisms of neoplasia?

A
  • Direct or indirect damage to DNA
  • Reduced ability to repair DNA damage
  • Increased stimulation to proliferate (oncogenes)
  • Reduced ability to inhibit growth (tumour suppressor)
  • Defects in apoptosis
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11
Q

Contrast benign and malignant neoplasms

A
  • Benign= well differentiated, usually slow growing, normal mitotic figures, no local invasion, no metastasis
  • Malignant= lack of differentiation, erratic or rapid growth, may be abnormal mitotic figures, local invasion, metastasis
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12
Q

What are the routes of metastasis?

A
  • Lymphatic
  • Vascular (veins>arteries)
  • Perineural and intraneural (pancreatic, bile duct and prostate cancers)
  • Spread across cavities (transcolonic)
  • Iatrogenic (needle track)
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13
Q

What are the effects of benign tumours?

A

-Bleeding= erosion and ulceration
-Space occupying lesions within skull
-Compression of adjacent structures
-Obstruction of lumina (intussusception in GI tract)
-Hormonal effects
=Increased production
=Decreased production

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14
Q

What does intussusception mean?

A
  • Polyp is propelled forward by waves of peristalsis, causing the bowl to telescope
  • Obstruction of the lumen and compresses the venous drainage= ischaemia and necrosis
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15
Q

What are borderline tumours?

A

-Uncertain malignant potential
=Tumours that show extensive local invasion but almost never metastasise. These are prone to local recurrence if incompletely excised
=Tumours that appear entirely benign at the time of diagnosis, but which can develop distant metastases, often presenting many years after the initial diagnosis

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16
Q

What are the symptoms of GI neoplasia?

A
  • Tiredness (anaemia as chronic low-grade blood loss)
  • Bleeding
  • Anorexia and vomiting
  • Weight loss
  • Pain caused by obstruction
  • Dysphagia
  • Alteration in bowel habit
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17
Q

Describe the epidemiology esophageal carcinoma

A 
-Adenocarcinoma
=Commonest time in UK
=Most associated with acid reflux and Barrett's oesophagus
=Tobacco and alcohol less important
-Squamous cell carcinoma
=90% worldwide
=80% developing
=variations in incidence within endemic regions
=aetiology uncertain
18
Q

Describe risk factors for oesophageal squamous cell carcinoma

A

-Tobacco and alcohol
-Diet
-Infection
=Fungal oesophagitis (Candida)
=Evidence for the role of HPV lacking
-Genetic

19
Q

What is the prognosis of esophageal carcinoma?

A
  • Tumour stage is most important prognostic factor for both types
  • Good prognosis for tumours confined to mucosa and early
  • Many tumours picked up late
  • 10-20% survival for adenocarcinoma involving deep, muscularis propria
20
Q

Describe the epidemiology of gastric adenocarcinomas

A

-Considerable geographical variations in incidence
-Highest rates in Japan and east Asia, eastern Europe and parts of South America
-Low rates in N America, N Europe and Africa
-Falling incidence and mortality worldwide
-Incidence increases with age
-Male> Females
-Often presents late
-Familial link in 10% cases
=small percentage have germline mutations (TP53, CDH1 for E cadherin so adhesion)

21
Q

Describe aetiology of gastric adenocarcinoma

A

-Diet
-H.pylori
-Bile reflux
=chronic gastritis

22
Q

What are the histological patterns observed in gastric adenocarcinomas?

A

-Intestinal (resembles those tumours)
-GLAND FORMATION, NECROTIC DEBRIS
=majority in high incidence areas
=Increased risk in patients with FAP
-Diffuse
-INDIVIDUAL CELLS SO LOST COHESION, SIGNET RING CELL= LARGE MUCIN VACUOLES
-DIFFUSE THICKENING OF GASTRIC WALL (LEATHER BOTTLE STOMACH)
=more common in low incidence areas
=younger
=female > male
=mutation or inactivation of CDH1 gene

23
Q

Describe the neoplasia of the small intestine

A 
-Uncommon
=Liquid so less contact with dietary carcinogens
-Adenocarcinomas present
-Neuroendocrine 
-GISTs
-Lymphoma
=Enteropathy type T-cell lymphoma in coeliac disease
=Others
24
Q

Describe neuroendocrine tumours

A
  • Epithelial tumours associated with the synthesis of hormone (gastrin/ insulin) or neurotransmitter-like substances (serotonin)
  • Range from well-differentiated benign tumours through to aggressive and poorly differentiated malignancies such as small cell carcinoma
  • Difficult to predict behaviour
  • Risk depends on size, site and grade (based on mitotic activity)
  • Yellow colouration
25
Q

Describe GISTs

A

-Gastrointestinal stromal tumours
-Soft tissue tumour that can arise anywhere in the GI tract
=related to pacemaker (coordinate waves of peristalsis) cells in muscularis propria
=malignant tumours are a type of sarcoma
=75-80% of GISTs have activating mutations in the KIT receptor tyrosine kinase gene (diagnostic)
-Stomach commonest site
-Can be difficult to predict behaviour
-Risk dependent on site, size, proliferative activity
=GIST is an example of a tumour where one of the diagnostic tests also highlights a therapeutic target – monoclonal antibody therapy

26
Q

What are the types of non-neoplastic colorectal polyps?

A

-Inflammatory= IBD, lymphoid
-Hamartomatous (normal elements in abnormal proportion)
=juvenile polyps and polyposis
=Peutz-Jegher Syndrome (associated with pigmentation of the lips)
-Hyperplastic (sigmoid and rectum)
-Lesions in submucosa (lipoma presenting as polyp)

27
Q

What are the types of neoplastic polyps?

A

-Adenomas
=Tubular (short crypts with lots of rounded crypt profiles)
=Tubulovillous
=Villous (more high-grade, long finger-like projections)
-Adenocarcinomas
-Lymphoid

28
Q

What are the shapes of polyps?

A
  • Sessile= broad attachment and flat based

- Pedunculated= long stalk

29
Q

Describe the epidemiology of colorectal adenocarcinomas

A
  • Peak incidence 60-79
  • No gender difference with exception of rectal cancer (M>F)
  • 55% tumours rectum and sigmoid colon
  • 22% tumours caecum/ ascending colon
  • Most sporadic
  • 5% associated with known familial syndrome (FAR, HNPCC= Lynch syndrome) or IBD
30
Q

What are the dietary risk factors for colorectal adenocarcinomas?

A

-Excessive calories relative to requirement
-Low fibre
-High intake of refined carbohydrates
-High intake of red meat
-Low intake of protective micronutrient (vitamin A, C, D and E)
-Exact mechanisms unclear
=Production of reactive oxygen species by intestinal bacteria?

31
Q

What are other risk factors for colorectal adenocarcinomas?

A
  • First degree relative with CRC
  • Inherited syndromes (FAP, HNPCC)
  • Alcohol in rectal carcinomas
  • Smoking
  • Inflammatory bowel disease
  • Occupational factors (solvents)
  • Radiation
  • Schistosomiasis (parasitic infection)
32
Q

What are the genetic pathways involved in colorectal carcinomas?

A

-APC/ Beta-catenin
=Inactivation of APC (Adenomatous Polyposis Coli) tumour suppressor gene seen in 80% of colorectal carcinomas
=Genetic basis of inherited condition FAP
=Early event in adenoma-carcinoma sequence
=Subsequent accumulation of multiple mutations and chromosomal instability
= APC involved in the degradation of the beta-catenin transcription factor. Patients with FAP have an inherited mutation in one copy of the APC tumour suppressor gene.

33
Q

Describe the adenoma-carcinoma sequence in terms of genetic events and the typical genes involved

A
  • Inherited or acquired mutation in tumour suppressor genes (first hit)= APC
  • Inactivation of normal allele (second hit)= APC, Beta-catenin
  • Mutation of proto-oncogenes= KRAS
  • Homozygous inactivation of other tumour suppressor genes, over-expression of COX-2= TP53, SMAD2, SMAD4
  • Additional mutations and gross chromosomal alterations= Telomerase, multiple genes
34
Q

Describe the microsatellite instability pathway

A

-10-15% of sporadic colorectal carcinomas (R>L)
-Inactivation of DNA mismatch repair genes
=MSH2, MLH1 (90% of cases involve one of these)
=Others include MSH6, PMS1, PMS2
-Inherited mutation in one of these genes is the basis of Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC) syndrome (Lynch syndrome)
-Loss of one of these genes increases mutation rate by up to 1000-fold
-Not associated with typical adenoma-carcinoma sequence
-MSI-H tumours more commonly seen in the right side of the colon.
-Inactivation of MMR genes may be caused by methylation of the gene promoter rather than mutation of the gene itself.
-Microsatellite are regions of DNA containing repeated short sequences of several bases. These are prone to replication errors due to “slippage” of the replication machinery.

35
Q

Describe the serrated neoplasia pathway

A
  • More recently identified pathway
  • Associated with distinctive precursor lesions showing similarities to hyperplastic polyps (sessile serrated lesions)
  • More common in the right colon
  • Thought to have a more rapid progression to malignancy
  • Typically have a mutation in either BRAF or KRAS proto-oncogenes
  • Can also show microsatellite instability, often due to methylation of mismatch repair gene promoter regions rather than actual mutation
  • A proportion of “interval cancers” in the bowel screening programme may be accounted for by this type of tumour
36
Q

Why might we miss sessile serrated lesions in colonoscopy?

A
  • Flat
  • Covered in mucus cap
  • Can be highlighted by blue dye (chromo-endoscopy)
37
Q

Describe Familial colorectal carcinomas

A
  • About 1% of colorectal carcinomas are associated with FAP
  • Up to 5% associated with HNPCC

-Of sporadic carcinomas, ≥30% may be associated with an inherited defect
-Having a 1st degree relative with CRC increases risk by up to 8-fold over the general population
=Shared genetic pool?
=Shared environmental factors?
=Both?

38
Q

What are the prognostic factors for colorectal carcinomas?

A
  • STAGE: Higher = reduced survival
  • GRADE: Poorly differentiated tumours more aggressive
  • Presentation with obstruction or perforation (usually indicates advanced disease)
  • Involvement of surgical resection margins
  • Extramural vascular invasion
  • Pattern of invasion and host response
  • ?Genetic markers= can predict response to certain chemotherapy drugs
39
Q

Describe colorectal carcinoma screening

A
  • Screening for colorectal carcinoma now established UK-wide
  • In Scotland, offered to all aged 50-74 years
  • Uses faecal occult blood test (FOBt) or faecal immunochemical test (qFIT), with referral for colonoscopy if positive result
  • England and Wales= can’t request screening kit after 69 years
40
Q

Describe the TNM system for colorectal cancer?

A
  • Don’t recognise intramucosal adenocarcinoma in colon and rectum so must invade submucosa
  • M stage dependent on where metastatic disease is
  • More stages

Gastrointestinal (48 decks)

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