Lecture 10.1: Common Gastrointestinal Malignancies Flashcards
How to Approach Tumours at any Site?
What is Barrett’s Oesophagus?
- Dysplasia of cells in oesophagus (can be seen via
hyperchromatic nuclei) - Columnar lined oesophagus instead of squamous
Why does Barrett’s Oesophagus occur?
As a result of Gastro-oesophageal reflux disease(GORD)
What is the complication associated with Barrett’s Oesophagus?
Increased incidence of adenocarcinoma compared to general populus
What is the common type of malignancy in the oesophagus? (1 overall, 2 subtypes)
Oesophageal Carcinoma:
* Adenocarcinoma
* Squamous Cell Carcinoma
What the other type of malignant tumours can be found in the oesophagus? (3)
- Lymphomas
- Melanomas
- Sarcomas
Where is Squamous Cell Carcinoma Oesophageal Cancer more commonly found?
Highest incidence seen in Asian oesophageal cancer belt (Turkey to Iran, Iraq and Khazakhistan to northern China)
Where is Adenocarcinoma Oesophageal Cancer more commonly found?
Increasing incidence in USA, UK and Europe
What Risk Factors of Squamous Cell Carcinoma Oesophageal Cancer? (8)
- Alcohol
- Tobacco
- Hot Drinks (tea)
- Less intake of fruits and vegetables
- Infections/Viruses (HPV)
- Genetic Factors
- Plummer Vinson Syndrome
- Associated with other head and neck malignancies
What Risk Factors of Adenocarcinoma Oesophageal Cancer? (7)
- GORD
- Obesity
- Smoking/Alcohol (lesser degree)
- Genetic Factors
- Zollinger Ellison Syndrome (too much gastric acid)
- Achalasia
- Scleroderma
What part of the Oesophagus is Adenocarcinoma found?
Distal Third
What part of the Oesophagus is Squamous Cell Carcinoma found?
- Rare in upper third
- Most common in the middle third
- Less frequent in lower third
Gross Appearance of Squamous Cell Carcinoma Oesophageal Cancer? (3)
- Exophytic
- Ulcerating Infiltrating
- Stricture
Gross Appearance of Adenocarcinoma Oesophageal Cancer? (3)
- Mostly ulcerating
- Stricturing
- Less likely to exophytic
How does a patient with Squamous Cell Carcinoma Oesophageal Cancer present? (2)
- Dysphagia
- Weight Loss
How does a patient with Adenocarcinoma Oesophageal Cancer present? (6)
- Long history of Dyspepsia
- Dysphagia
- Weight Loss
- Vomiting
- Anaemia
- Bleeding
Investigations for Oesophageal Cancers?
- Barium swallow
- Endoscopy
- Endoscopic Ultrasound (EUS)
- Staging purposes- CT, PET CT
- Biopsy
What is the 5 yr survival rate of early mucosa confined oesophageal tumours?
SCC: 70%
Adeno Ca: 80 -100%
Survival rates of oesophageal tumours when they invades the muscularis propria?
SCC: 50%
Adeno Ca: 10-20%
Treatments for Oesophageal Cancer (7)
- Oesophagectomy
- Endoscopic mucosal resection (EMR) and radioablation
for mucosa confined tumours - Neoadjuvant chemoradiotherapy
- Adjuvant chemotherapy for metastatic disease –
targeted treatments (trials), Her2 guiding treatment in
adenocarcinomas - Stenting to enable swallowing
- Palliative brachytherapy and radiotherapy
- Radiotherapy
What percentage of cancers worldwide does Gastric Cancer account for?
10%
What percentage of gastric cancers occur in patients before 45 years? Why?
- <10%
- Germline mutations of e-cadherin and also associated
with Helicobacter pylori infection
What part of stomach does cancer most commonly occur in?
- Most common site in the cardia
- Much smaller proportions in the pyloric antrum and
body of the stomach
Risk Factors for Gastric Cancer (8)
- Infection (H.pylori, EBV)
- Pernicious Anaemia
- Autoimmune Gastritis
- Gastric Ulcers
- Previous Gastric Surgery
- Low intake of fresh fruit and vegetables and high
intake of salt preserved foods or smoked foods (N-
nitroso compounds and benzopyrene) - Smoking
- Genetic factors
How can H.pylori can lead to development of gastric
carcinoma?
- Produces urease which converts urea into ammonia
which neutralises stomach acid - Allow bacteria to proliferate
- Adheres to gastric mucosa epithelial cells via the outer
membrane protein and injects CagA into host cells - This causes Chronic Inflammation
- Leads to gastritis
- Leads to dysplasia
- Leads to neoplasia
- Carcinoma
What are Macroscopic Features of Gastric Cancer? (3)
- Fungating
- Ulcerating
- Infiltrative (linitis plastica)
What are Microscopic Features of Gastric Cancer? (2)
- Intestinal variable degree of gland formation
(commonly associated with H pylori) - Diffuse single cells and small groups, signet ring cells
(common in younger age group and EBV infection)
Symptoms of Gastric Cancer (4)
- Symptoms often Vague
- Epigastric Pain
- Vomiting
- Weight Loss
Investigations for Gastric Cancer (3)
- Endoscopy
- Biopsy
- Barium Studies
What is the 5-year survival rate for Gastric Cancer that is confined to mucosa/sub-mucosa?
65%
What is the 5-year survival rate for late Gastric Cancer?
- 10%
- But with curative surgery 50%
Where does Gastric Cancer commonly spread? (4)
- Adjacent Organs (pancreas, liver, spleen, transverse
colon, greater omentum) - Lymphatic Spread (supraclavicular lymph node
involvement- Virchow’s node) - Haematogenous Spread (liver, lung, peritoneum,
adrenals, ovary) - Transcoelomic (peritoneum, ovaries [Krukenberg
tumours])
Treatment of Gastric Cancer (3)
- Surgery
- Chemotherapy
- Herceptin
What infection is Gastric Lymphoma (MALT Lymphoma) strongly associated with?
- Strong association with H. pylori
- Eradication of H. pylori may lead to regression of
tumour
Where are Gastrointestinal Stromal Tumours derived from?
Interstitial Cells of Cajal
Gastrointestinal Stromal Tumours are uncommon, but where are they most commonly found (percentages)? (3)
- 60% Stomach
- 30% Small Intestine
- 10% Other
How are Gastrointestinal Stromal Tumours Treated?
Specific Targeted Treatment: Imatinib
What protien/oncogene is found on the surface of Gastrointestinal Stromal Tumours?
- C-KIT
- CD117
Gastrointestinal Stromal Tumours are unpredictable, what factors can be used to predict the Behaviour of these lesions? (4)
- Site
- Size
- Mitoses
- Necrosis
What Type of Malignancies are found in the Small Intestine?
- Lymphomas
- Neuroendocrine Tumours
- GIST are tumours that are encountered in this site and
have a higher risk of malignancy
Where in the Body do Neuroendocrine Tumours occur?
70% in GI Tract
Where in the GI Tract do Neuroendocrine Tumours occur? (5)
- Small Intestine(38%)
- Rectum (34%)
- Colon (16%)
- Stomach (10%)
- Rare in the Oesophagus and Anus
Clinical Presentation of Small Intestine Cancers (6)
- Incidental finding during evaluation of non specific
symptoms - Symptoms due to local mass effect
- Symptoms due to substances secreted by tumour
- Symptoms as a result of tumour fibrosis
- Primary tumour can be silent and present later with
metastasis - Carcinoid Syndrome
What is Carcinoid Syndrome?
- Occurs when a carcinoid tumour secretes certain
chemicals into your bloodstream - Cutaneous Flushing
- Diarrhoea
- Restrictive Cardiomyopathy
3 Stages of Evolving Cancer
1) Initiation
2) Promotion
3) Progression
What Cancers are found in the Large Intestine? (2)
- Adenomas
- Adenocarcinoma
What is Familial Adenomatous Polyposis? (4)
- Autosomal Dominant
- Chromosome 5
- Thousands of adenomas by 20 yrs
- High risk of cancer
What is Lynch Syndrome?
- Also known as hereditary non-polyposis colorectal
cancer (HNPCC) - Is the most common cause of hereditary colorectal
(colon) cancer - R-sided colonic tumours
What is Gardner’s Syndrome?
- Phenotypic variant of familial adenomatous polyposis.
- Autosomal Dominant
- Characterised by numerous adenomatous polyps
lining the intestinal mucosal surface with a high
potential for malignancy - Bone and Soft Tissue Tumours
Are Adenomas Cancerous?
No they are Premalignant
What are the Types of Adenomas? (3)
- Tubular adenoma
- Tubulovillous adenoma (>20% villous)
- Villous adenoma (> 80% villous)- high risk of
malignancy
What is Risk of Malignancy (carcinoma arising within a polyp) based on? (4)
- Type
- Dysplasia (Malignancy rate increases to 27% if high
grade dysplasia) - Polyp size (Polyps>20mm higher incidence of invasive
carcinomas 35% to 53%) - Number of polyps
Who is the Bowel Cancer Screening (2006) aimed at?
- 60-69 year old men and women
- Phased out to 70-75 (2010)
- From April 2021 start rolling out to >50 years
What test is used in Bowel Cancer Screening?
- Faecal Occult Blood
- FIT(Faecal Immunochemical Testing)
Who is the Bowel Scope Screening Programme aimed at?
Men and Women aged 55
BUT THIS IS DISCONTINUED FROM APRIL 2020
What test is used in the Bowel Scope Screening Programme?
Flexible Sigmoidoscopy
BUT THIS IS DISCONTINUED FROM APRIL 2020
How common are Colorectal Adenocarcinomas?
Fourth most common cancer with respect to incidence in developed countries (2018)
Is Rectal Cancer more common in men or women?
Men
What percentage of of colon cancers are hereditary?
5-10%
How aggressive is Colorectal Adenocarcinoma?
- Disease has slow progression
- 20% present at A&E
- 55% not diagnosed until disease has spread to lymph
nodes or elsewhere
Risk Factors for Colorectal Adenocarcinoma (4)
- Low residue diet
- Slow transit time
- High fat intake
- Genetic predisposition
Investigations for Colorectal Adenocarcinoma (6)
- Blood Tests (CEA marker, FBC, LTFs)
- Colonic Examination
- Colonoscopy with Biopsy
- CT Colonography
- Barium Enema
- Radiology
What parts of the Large Intestine does Colorectal Adenocarcinoma occur (percentages)?
- About 50% occur in rectum
- 30% in sigmoid colon
- Rest are equally distributed in other parts of colon
How do Rectal Lesions in Colorectal Carcinoma present?
Ulceration present as rectal bleeding
How do Left Sided Lesions in Colorectal Carcinoma present?
Stenosing lesions and as such present with obstruction (alteration of bowel habit colicky abdominal pain)
relatively early
How do Right Sided Tumours in Colorectal Carcinoma present?
- Polypoidal and fungating
- Present as anaemia due to recurrent occult bleeding
- Often late presentation (due to more distensibility of
the right side and the fluid nature of the faeces)
Macroscopic Characteristics of Colorectal Adenocarcinoma (3)
- 60-70% rectosigmoid
- Fungating (esp right side)
- Stenotic (esp left side)
Microscopic Characteristics of Colorectal Adenocarcinoma (3)
- Adenocarcinoma
- Mucinous (often right sided tumours and associated
with microsastellite instability) - Signet Ring Cell Type
How can Colorectal Adenocarcinomas spread? (3 routes)
- Direct through bowel wall to adjacent organs
- Via lymphatics to mesenteric lymph nodes
- Via blood stream – liver, lung
What used to be used instead of TNM to Stage Colorectal Adenocarcinoma?
Dukes’ Staging
Colorectal Cancer Staging (T1-T4)
T1: Cancer is no deeper than submucosa
T2: Cancer is no deeper than muscularis propria
T3: Cancer is no deeper than subserosa
T4: Cancer has spread outside of the serosa
Involvement of muscularis propria in Colorectal Cancer increases risk of metastasis by …?
12%
Percentage of 5-year survival if 1 lymph node invaded in Colorectal Cancer?
63.6%
Percentage of 5-year survival if 2-5 lymph nodes invaded in Colorectal Cancer?
36.1%
Percentage of 5-year survival if 6-10 lymph nodes invaded in Colorectal Cancer?
21.9%
Percentage of 5-year survival if >10 lymph nodes invaded in Colorectal Cancer?
2.1%
Management of Colorectal Cancer (7)
- Surgical resection with curative intent
- +/- Neoadjuvanttherapy in rectal tumours
- Stenting in obstructive tumours in a palliative setting
- Palliative chemotherapy and surgery
- Metatstectomy-liver and lung resections
- Post operative chemoradiotherapy
- Targeted therapy
Targeted Therapy/Personalised Medicine for Colorectal Adenocarcinoma
- Kras
- Mismatch Repair Genes
Why Kras relevant?
- When there is metastatic colorectal disease, if
the patient has a mutated form of Kras the patient
does NOT respond to EGFR inhibitors such as
cetuximab, and other forms of treatment are
required - However, if the patient has the “wild type Kras” EGFR
treatment is an option
Why are Mismatch Repair Protein’s (MRRP’s) relevant?
- Because in MSI (Microsatellite Instability) CRC there is
a loss of MMR proteins - This means MSI CRC do not respond to 5FU based
chemotherapy - But responds to specific forms of immunotherapy
- This knowledge can help improve prognosis/outcomes
