Gastric Tumours

90% Adenocarcinomas
4% lymphomas
3% carcinoids
2% sarcomas

Epidemiology
Western society
2.5 % of cancer mortalities
8/100 000 Males
4/100 000 Females
China and Japan x 5 higher risk

Symptoms
* Insidious and Non-specific
Weight loss
Pain
Anorexia
Vomiting
Altered bowel habit
Anaemia
Haemorrhage

Aetiology
Environmental
Nitrates (smoked/salted/pickled foods)
Absent fruit/veg
Smoking = x1.5-3 Risk
Host
H. Pylori infection (suggested)
Chronic gastritis / Autoimmune atrophic gastritis = x2-4 Risk

Ix
Pylorus/Antrum 50%
Cardia 25%
Body 25%
* lesser curve

Macro
Exophytic (nodular)
Flat (difficult to Dx)
Excavating (mimics PUD - h/e has heaped edge and necrotic centre)
If infiltrates stomach wall = rigid tube k.a. Linitis Plastica

Micro
In-situ - epithelium
Early - submucosa
Advanced - muscular wall

Histology
2 subtypes (Lauren Classification)

1) Intestinal-type Tumours
 - Resemble colonic AdCa
 - Cohesive front
 - *form glandular epithelium with mucin vacoule

2) Diffuse-type Tumours
 - Resemble gastric mucosa
 - Infiltrate as clusters & single cells
 - No glands
 - *signet ring cells

Prognosis
Relevant to depth of tumour invasion
Early Lesions
10-15% of Dx
5yr Survival = 90%
Advanced Lesions
5yr Survival = 15%
Average 5yr Survival = 20%

Invasion: Duodenum/Pancreas/Retroperitoneum
*Spread to supraclavicular nodes (Virchow's Node)

Peptic Ulcer Disease

Epidemology
Males: 10%, x3 duodenal
Female: 5%, more likely gastric

Symptoms
(NB not well correlated to actual endoscopic findings)
Relapsing, remitting
Epigastric pain
 - Worse at night & 1-3hrs post food
 - Improves with antacids & immediately post-food
 - Can radiate to chest/neck
also...
Nausea
Vomiting
Severe
Opiate-worthy pain
Haematemesis
Melaena
Weight loss
Anaemia
(the last few = ?malignancy)
Acute perforation
Peritonism
Shock

Aetiology
H. Pylori
 - 95% of Duodenal PUD
 - 75% of Gastric PUD
NSAIDs
Smoking
Alcohol
Hypercalcaemia
Zollinger-Ellison Sydrome

Pathogenesis
Imbalance b/w mucosal defences and effects of pepsin and acid
Pepsin potentiated by hyperacidity
Additive Aet Fx

Ix
98% of ulcers in duodenum (75%) & stomach (25% - * on lesser curve)
10-20% of those with gastric ulcer also have a duodenal ulcer
Other sites
GOJ
gastrojejunostomy sites
jejunum (Zollinger-Ellison syndrome)
Meckels diverticulum

Macro Dx
Solitary
<4cm
Round
Punched out mucosal defects
Vertical walls (NB heaping at edge = carcinoma)
Base = musc muc/vessels/omentum (if perforation)

Scarring 
puckered mucosa
radiating from central ulcer
*chronic gastritis in background (not common with acute erosive gastritis/stress ulcers)

Micro
Variable
Active necrosis/chronic ulceration/healing

Active ulceration
1) superficial fibrinoid necrosis with mucosal excavation
2) mixed inflammatory cell infiltrate within lamina propria
3) active granulation tissue
4) underlying fibrosis

Cx
Recurrent morbidity
Bleeding 15-20% (25% of ulcer deaths)
Perforation 5% (66% of ulcer deaths)
Obstruction 2%
Anaemia
Intractable pain
Malignancy (increased risk prob from underlying gastritis/malig. lesion mistaken as benign ulceration)

Gastric Erosions & Ulceration

"pathological defects in the epithelial surfaces from acute/chronic mucosal damage"
Most common in stomach and duodenum (though it can occur anywhere in the GIT)


Erosions
Superficial mucosal defects
No breach of the muscularis mucosa
Most associated with acute gastritis

Ix
Macro
Small, flat, hyperaemic patches
Histology
Epithelial disruption
Acute inflammation of the lamina propria

Tx
Healing swift once stimulus removed


Ulcers
Breaches the muscularis mucosa to the submucosa/deeper

Acute Ulceration
Aetiology
NSAIDs
Severe physiological stresses (shock/sepsis/burns (Curling's ulcer))
Chemical poisoning
5-10% ITU admissions = acute ulceration

Ix
Multiple/small (<1cm)
Surrounding mucosa initially normal then inflammatory and haemorrhagic
No scarring
Micro

• Mucosal excavation
• Superficial fibrinoid necrosis
• Acute inflammation within mucosa
• Active granulation tissue

Healing within days to weeks

Chronic Ulceration

On background of sustained mucosal injury

Most commonly peptic (see PUD)

Chronic Gastritis

Characterised by:

• chronic inflammation of the gastric mucosa
• mucosal atrophy
• epithelial metaplasia.
• commonly without erosions

Symptoms
Episodic pain
Nausea
Vomiting

Cx
Anaemia
Peptic Ulcer Disease
Gastric Carcinoma

Aetiology
Autoimmune gastritis
Bacterial gastritis
Chemical gastritis
Misc (Crohn's, radiotherapy)


Autoimmune Gastritis

• < 10% of chronic gastritis
• Autoantibodies produced to gastric parietal cells (90%) and intrinsic factor (60%)
• 10% have pernicious anaemia (where decreased intrinsic factor and decreased gastric acid production = decreased vit B12 absorption)
• Autoimmune associations with Hashimoto's thyrioditis and Addison's disease

Pathology
Commonly occurs in the gastric body or fundus
Immune-mediated destruction of the gastric glands
Chronic inflammation
Mucosal atrophy


Bacterial Gastritis

• Helicobacter Pylori makes up 90% of chronic antral gastritis
• Gram-negative rod
• No mucosal invasion
• Instead adheres to surface epithelium & produces urease
• Urease converts urea to ammonia, which buffers local gastric acid
• Increases risk of PUD and gastric cancer

Aetiology
Arises from chronic gastric mucosal injury
Alcohol
Smoking
Bile reflux

Ix
Commonly found in antrum (less so in the body/fundus)
Early findings:
hyperaemic, course, boggy (similar to early malignancy)
Later findings:
mucosa flattened and thin, after long-standing atrophy
Micro
1) Inflammatory aggregates - lymphocytes and plasma cells within lamina propria
2) Intestinal metaplasia
3) Glandular atrophy
4) Neutrophils within glandular epithelium

 - H Pylori within syperficial mucosal layer
 - Not found in areas of intestinal metaplasia (Absent in BarO and duodenal/pyloric metaplasia)

Cx
Long-standing
Epithelial atypia & dysplasia (pastricularly with atrophic gastritis & pernicious anemia)
Increase risk of cancer

Acute Gastritis

Stomach inflammation
Triggered by damage to the gastric mucosa

Exists as acute/chronic

Acute Gastritis
Transient acute inflammatory response to damaged gastric mucosa
* superficial & self-limiting

Symptoms
Epigastric burning
Nausea
Vomiting
Severe:
Severe pain/Haematemesis/Melaena (partially digested blood)/Shock
a/w/ mucosal erosion/ulceration/haemorrhage/acute necrotising gastritis

Aetiology
Mainly chemicals
Alcohol
Smoking
NSAIDs
ChemoTx
Bile reflux

Stress
Hospital
Trauma
Burns

Infections
HSV
CMV

Pathology
Inflammation occurs from:

• Decreased gastric blood flow = compromised mucosal defences
• Decreased bicarbonate production = disrupted protective mucus layer
• Direct epithelium damage

Ix
Mucosa - normal/slightly erythematous
Micro
Oedema
Vascular congestion
Acute inflammatory cells in mucosa (neutrophil polymorphs)
Severe
Erosions
Ulceration
Haemorrhage

Erosions + Haemorrhage = acute erosive gastritis.

Oesophageal Tumours - Adenocarcinoma

Commonly Caucasian men in 50s

Risk Factors
Smoking
Alcohol
Barrett's Oesophagus

Aetiology
Commonly arises in areas of Barrett's Oesophagus
Associated with dysplastic epithelium
Progression from in-situ to invasive carcinoma less clear than SCC
Genetics: p53 gene mutation & chromosome 17p allele loss possibly involved tumour genesis

Ix
Distal oesophagus
Flat, ulcerating, infiltrative lesions
Classified as early/advanced tumours

Microscopy
Commonly intestinal-type differentiation
Less commonly gastric-type differentiation
* with mucus production

Clinical Course
* advanced at diagnosis, extending to surrounding structures, as tumours have to be large enough to produce dysphagia and local complications
Early Dx 5yr survivals = 75%
Overall 5yr survival = 5-10%

Oesophageal Tumours - Squamous Cell Carcinoma

Malignant oesophageal tumours = 5% of cancers.
Most common = squamous cell carcinomas & adenocarcinomas
SCC = 90% of oesophageal carcinomas
Higher incidence in China & Japan
Western world, however, AdCa = SCC

Both present with:
Dysphagia
Weight Loss
Anaemia

Squamous Cell Carcinoma

Commonly presents in 50s & males

Risk Factors
Environment:
Diet
Nitrates (smoked/pickled foods)
Smoking
Alcohol
Nutritional deficiencies

Host:
Long-standing oesophagitis
Achalasia
Plummer-Vinson Syndrome

Pathology
Ill-defined genetic associations
Epithelial dysplasia leads to carcinoma in-situ (intraepithelial neoplasia) leads to invasive carcinoma

Ix
80% in lower 2/3 of oesophagus
Endoscopy
protruding (60%)
flat (15%)
excavating (25%)

Microscopy
Early/advanced (invasion of submucosa) lesions
Poorly differentiated/Well differentiated (Squamous cells with keratinization and intercellular bridges)

Staging = TNM classification

Cx

Metastases occur early to:

LNs

Mediastinum

Liver

Bone

Barrett's Oesophagus

The word oesophagus reminds me of the muppet Snuffleupaguss.

Moving on.

Barrett's Oesophagus
aka Columnar-Lined Oseophagus aka CLO

Does exactly what it says on the tin. No, it doesn't sell shoes, silly, not that bit of the tin - the CLO bit.
Barrett's is the occurrence of metaplasia in the distal oesophagus, where its squamous epithelium is replaced by columnar epithelium, of the gastric/intestinal type.

Aetiology
It is a complication of chronic oesophagitis.and occurs in 10% of people with symptomatic GORD, and 40% of those with peptic oesophageal strictures.

Ix
Endoscopy!
 - abnormal red mucosa lies as islands or circumferential bands between the normal white squamous epithelium of the oesophagus and the normal gastric mucosa.
http://library.med.utah.edu/WebPath/GIHTML/GI416.html
.
Micro:
Sudden transition from squamous epithelium to columnar epithelium, proximal to GOJ.
Considered 'typical' Barrett's mucosa if it includes intestinal metaplasia i.e. goblet cells.
http://library.med.utah.edu/WebPath/GIHTML/GI171.html

Complications
x30/40 increased risk of adenocarcinoma of the oesophagus.
This can't be taken lightly, therefore CLO patients are required to undergo frequent endoscopy and biopsies.
The aim is to diagnose and treat and dysplastic changes when they occur, and treat any invasive disease ASAP.

Adenocarcinoma identified on biopsy
http://library.med.utah.edu/WebPath/GIHTML/GI406.html

Gastro-Oesophageal Reflux Disease, Ulcerations & Strictures, oh my!

GORD!!! Can you believe it?! GORD!!!
Enough of that.

Gastro-duodenal contents can enter the lower oesophagus, just for the hell of it, and a small amount of reflux, as it is known, can be perfectly normal. When abnormal reflux causes oesophagitis, however, this is known as Gastro-Oesophageal Reflux Disease.
Only a % of these actually have symptoms, though.

Symptoms:
Dysphagia

Regurgitation

Nocturnal asthma

Aetiology
Increased abdominal pressure

(pregnancy/obesity/trauma/vomiting)
Lower oesophageal sphincter incompetence
(smoking/alcohol/hiatus hernia/systemic sclerosis)
Decreased muscosal protection
(NSAIDs)

Ix
Endoscopy
 - normal/erythema
Biopsy +/- Barium Swallow

Histology
NB there is a poor correlation between symptom severity and the actual histological findings.
There are 3 diagnostic histological features in biopsies:

1. Epithelial Hyperplasia
2. Congestion of the lamina propria
3. Chronic inflammatory cells within muscosa

Neutrophils are suggestive of ulceration

Complications

• Mucosal erosions
• Ulceration
• Lower oesophageal stricture
• Bleeding
• Barrett's Oesophagus

Erosive & Ulcerative Oesophagitis
Well visualised at endoscopy.
Similar to those found in PUD.


Benign Strictures
Occur when recurrent/persistent ulceration leads to oesophageal fibrosis
These can be focal/circumferential = stenosis & dysphagia

Tx
Underlying causes/Sx

Oesophagitis

Oesophageal inflammation.
Affects 5% of the adult Western population.

Symptoms:
Retro-sternal burning (heartburn)
 - worse with leaning forward, or drinking hot liquids
Severe Presentation:
Dysphagia/Bleeding/Haematemesis/Melaena

Pathology:
Occurs due to damage to the oesophageal mucosa

Aetiology:
Risk factors include -
*GORD
Infection (candida/herpes/CMV/bacteria)
Chemicals (NSAIDS/toxins)
Radiotherapy
Crohn's

Acute Oesophagitis
http://library.med.utah.edu/WebPath/GIHTML/GI002.html
Neutrophils infiltrate the submucosa and squamous mucosa

Normal Oesophagus
http://library.med.utah.edu/WebPath/GIHTML/GI209.html

Hiatus Hernia

Definition:
"partial or total herniation of the stomach/gastro-oesophageal junction (GOJ) through the diaphragmatic hiatus, into the thoracic cavity"

Presentation:
Common, mostly > 50yrs
Can be asymptomatic/symptoms of reflux oesophagitis

Aetiology
Increased abdo pressure
Low residue diet
Laxity of diaphragmatic hiatus or peri-oesophageal attachments

Classification:
There are two main types of hiatus hernia:

• Sliding (most common)

In this, the GOJ is pulled up through the diaphragmatic hiatus (DH) +/- the stomach

• Para-oesophageal (5%)

In this, a part of stomach (*greater curve), slides up through the hiatus, between the oesophagus & the diaphragm. The GOJ remains secure.
It is x 4 more common in females.
Extreme cases - "upside down stomach" when the entire stomach herniates into the thoracic cavity.

Complications
Similar to reflux oesophagitis:

• mucosal erosions
• ulceration
• lower oesophageal stricture
• bleeding
• Barrett's Oesophagus

Congenital Abnormalities of the Oesophagus

These include:

Absent Oesophagus
Short Oesophagus
Tracheo-oesophageal fistulae
Oesophageal Atresia
Diverticulae
Congenital Stenosis