Gastrointestinal, Hepatobiliary & Pancreatic Pathology Flashcards
What are the features of a Normal Oesophagus?
- 25cm long
- Mostly lined by stratified squamous epithelium
- Sphincter at upper end (cricopharyngeal) & lower end (gastro-oesophageal junction)
- Distal 1.5-2cm below diaphragm & lined by glandular (columnar) mucosa
- Squamo-columnar junction – 40cm from incisor teeth
Normal Oesophageal Histology
• Top mucosa- surfaced by stratified squamous epithelium
• Lamina propria- small blood vessels & lymphatics supplying epithelium
• Muscularis mucosae (muscle- seps mucosae from next level)
• Basal (stem cells) work their way up to surface (lamina propria above this)
What is Oesophagitis?
• Inflamm of oesophagus
• Classification; acute, chronic
• Aetiology;
o Infectious; bacterial, viral (HSV1 (herpes simplex), CMV), fungal (candida)) e.g. immunosuppressed patients, elderly
o Down endoscope; candida- white lining, herpes- ulcers down oesoph
o Chemical; ingestion of corrosive substances (children accidentally drunk e.g. kitchen cleaner, self-harming adults), reflux of gastric contents
What is Reflux Oesophagitis?
• Commonest form of oesophagitis
• Cause: gastric acid reflux (gastro-oesophageal reflux disease (GORD)) &/or bile (duodeno-gastric reflux)
• Creates inflamm response
• Risk factors;
o Defective lower oesophageal sphincter (around diaphragm area)
o Increased intra-abdominal pressure
o Increased gastric fluid vol due to gastric outflow stenosis (due to stenotic inflamm process or tumour)
o Hiatus hernia (abnormal bulging portion of stomach through diaphragm);
Sliding hiatus hernia= reflux symptoms (parts of gastric wall slipped up through diaphragm, so next to oesoph)
Para-oesophageal hernia= strangulation (pouch of stomach slid up- can become strangulated die)
• Leading clinical symptom: heartburn (differentiate between cardiac crushing central pain & heartburn buring pain in upper chest)
What is the Histology of Reflux Oesophagitis?
- Basal layer usually 1 or 2 layers thick
- Squamous epithelium- basal cell hyperplasia (can’t differentiate form other cells), papillae elongation, increased cell desquamation, inflamm
- Lamina propria- inflammatory cell infiltration (neutrophils, eosinophils, lymphocytes
What are the Complications of Reflux Oesophagitis?
- Ulceration (squamous lining eroded away- granulation tissue forms at base of ulcer)
- Haemorrhage (if erode into vessel at base of ulcer)
- Perforation
- Benign stricture (segmental narrowing- when fibrosis healing occurs)
- Barret’s Oesophagus (chronic reflux in lower portion of oesoph)
What is Barret’s Oesophagus?
Barret’s Oesophagus
• Cause: longstanding gastro-oesophageal reflux
• Risk factors: same as for reflux (male, Caucasian, overweight)
• Macroscopy: proximal extension of squamo-columnar junction (point epithelium transitions from squamous to clomnar has moved up to middle of oesoph)
• Histology: squamous mucosa replaced by columnar mucosa (glandular metaplasia)
• Premalignant condition with an increased risk of developing adenocarcinoma
• Regular endoscopic surveillance recommended for early detection (longer segment of BArrets oesoph- more freq endoscopies)
Types of Columnar Mucosa
• Gastric cardia type
• Gastric body type
• Intestinal type- the mucosa is the same as intestinal mucosa I.e it contains goblet cells which normally are only seen in the intestine and not in the oesophagus (specialised Barret’s mucosa)
Goblet cells- white spaces (commonly in small & large bowel)
Disease Progression
• Vast majority won’t progress down pathway (but proportion will)
• As go down pathway, nuclei more further up
• High grade- desmoplasia (invades into deeper lamina propria)
What is Oesophageal Carcinoma ?
• 8th most common cancer in the world
• 2 main histological types;
o Squamous cell carcinoma (from normal squamous cells)
o Adenocarcinoma (from metaplastic epithelium in Barret’s oesoph)
• Distrib varies around the world; UK= 30% squamous (more adeno), China/Japan= >95% squamous
What is Adenocarcinoma?
- Incidence dramatically risen in industrialised countries (more overwight ppl- get more reflux)
- Mainly lower oesophagus
- Higher incidence in men (male/female ratio: 7/1)
- Higher incidence amongst Caucasians
- Aetiology: develops from Barett’s oesophagus, (tobacco, obesity- relates to development without Barrets happening 1st)
What is Squamous Carcinoma?
• Wide geographical variation in incidence (high in Iran, China, South Africa, Southern Brazil)
• Risk factors;
o Tobacco (strong risk factor) & alcohol
o Nutrition (potential sources of nitrosamines)
o Thermal injury (hot beverages)
o Human Papilloma Virus (HPV)
o Male
o Ethnicity (black)
• Location; middle & lower 1/3rd oesophagus (<15% in upper 1/3rd of oesophagus)
• Preceded by squamous dysplasia (start with normal squamous then high grade dysplasia (haphazard nuclei which are variable shapes, bound by basement memb in tact) then invasive (broken through basement memb so invasive));
What is the Macroscopic Appearance of Oesophageal Cancer?
- Polypoidal growth in oesoph (difficulty swallowing)
- Lumen contric (difficulty swallowing)
- Ulcer (can’t differentiate from inflamm- need to biopsy to ensure not cancer) can lead to perforation or haemorrhage if it erodes through blood vessels
What is staging for cancer?
• Use TMN system
Just need to know what each stage is I.e M is metastasis don’t need to know the different numbers and what they stand for
• pT= depth of invasion of the primary tumour (don’t need to know details of individual stages)
o pT1: tumour invades lamina propria, muscularis mucosae or submucosa
o pT2: tumour invades muscularis propria
o pT3: tumour invades adventitia
o pT4: tumour invades adjacent strucs
• N= regional lymph nodes (whether lymph nodes involved & how many)
o pN0: no regional lymph node metastasis
o pN1: regional lymph node metastasis in 1 or 2 nodes
o pN2: regional lymph node metastatis in 3 to 6 nodes
o pN3: regional lymph node metastasis in 7 or more nodes
• M= distant metastasis
o M0: no distant metastasis
o M1: distant metastasis
What is Gastritis?
Normal • Balance of aggressive (acid) & defensive forces • Surface mucous • Bicarb secretion • Mucosal blod flow • Regenerative capacity • Prostogalndins Increased Aggression (affect equalib in stomach) • Excessive alcohol • Drugs (e.g. NSAIDs) • Heavy smoking • Corrosive • Radiation • Chemotherapy • Infection Impaired defences • Ischaemia (poor blood supply to sotomach more inflamm cells) • Shock • Delayed emptying (e.g. if mass or stricture) • Duodenal reflux • Impaired regulation of pepsin secretion (e.g. due to hormonal imbalances)
What is Acute Gastritis?
• Usually due to chemical injury
o Drugs e.g. NSAIDs (e.g. aspirin)
o Alcohol
o Initial response to Helicobacter pylori infec (has acute inflamm phase 1st before becomes chronic)
• Effects depend on the severity of injury (can get erosions, ulceration & if involves vessel- haemorrhage)
• Generally heal quickly (if insult removed)
What is Chronic Gastritis?
• Autoimmune- anti-parietal & anti-intrinsic factor antibodies against self leading to atrophy in gastric mucosa
• Number of glands in gastric mucosa reduced
• More blue dots (histology) - lymphocytes/ inflamm cells
• Bacterial infec (Helicobacter pylori);
o Majority have no disease
o 2-5% have gastric ulcers, 10-15% have duodenal ulcers
o Increased risk of gastric cancer & MALT (mucosal associated lymphoid tissue) lymphoma
• Chemical injury (NSAIDs, bile reflux into stomach, alcohol etc)- direct injury
What is H.pylori ?
Peptic Ulcer Disease • Localised defect extending at least into submucosa (undergoes granulation tissue process) • Major sites; o 1st part of duodenum o Junction of antral & body mucosa o Distal oesophagus (GOJ) • Main aetiological factors; o Hyperacidity o H.pylori infec o Dudeno-gastric reflux o Drugs (NSAIDs) o Smoking
Duodenal are mor common and occur at a younger age nearly all duodenal are due to H.pyloru but only 70% of gastric ulcers are due to h. Pylori
What is an Acute Gastric Ulcer?
Histology;
• Full-thickness coagulative necrosis of mucosa (or deep layers)
• Covered with ulcer slough (necrotic debris+ fibrin+ neutrophils)
• Redness- gone into vessel- bleeding (need to clip vessel)
• Granulation tissue at ulcer floor (trying to heal)
What is an Chronic Gastric Ulcer?
Histology;
• Clear-cut edges overhanging the base
• Extensive granulation (looks like crter in pic) & scar tissue at ulcer floor
• Scarring often through entire gastric wall with breaching of muscularis propria
• Bleeding
What are Complications of Peptic Ulcers?
- Haemorrhage (acute and/or chronic= anaemia)- can give rise to life-threatening bleeding
- Perforation (ulceration all the way through the wall- forms a hole)= peritonitis
- Penetration into an adjacent organ (liver, pancreas)- can get fistulae between organs
- Stricturing = hour-glass deformity (due to fibrosis form healing), causes vomiting & difficulty to keep food down)
What is Gastric Cancer? Which type is most common?
• Most frequently: adenocarcinoma (from gastric columnar cells)
• Less freq:
o Endocrine tumours (from endocrine cells in stomach)
o MALT lymphomas (from lymphoid tissue)
o Stromal tumours (GIST) (from stromal cells)
What is Gastric Adenocarcinoma?
Incidence:
• 5th most common cancer in the world (951,594 new cases/yr)
• Wide geographical variation (high rates in Eastern Asia, Andean regions of South America, Eastern Europe)
• Steady decline over the past decades
Aetiology:
• Diet (smoked/ cured meat or fish, pickled veg)
• H.pylori infec
• Bile reflux (e.g. post Billroth II operation)
• Hypochlorhydria (hydrochloric acid absent/low)- allows bacterial growth
• 1% hereditary defect (in cadherin gene)
What is Carcinoma of GOJ (gastro-oesophageal junction)?
- (Similar to Barret’s adenocarcinomams in oesoph)
- White males
- Association with GO reflux
- No association with H.pylori/ diet
- Increased incidence in recent years
What is Carcinoma of gastric body/antrum?
- Association with H.pylori
- Association with diet (salt, low fruit & veg)
- No association with GO reflux
- Decreased incidence in recent years
What is Linitis plastica?
Macroscopic subtypes of Gastric Adenocarcinoma
Linitis plastica- entire stomach thickened & abnormal (no distinct mass)
What are the properties of microscopic Intestinal Gastric Adenocarcinomas?
• Intestinal type;
o Well/ moderately differentiated
o May undergo intestinal metaplasia & adenoma steps
o Rounded glandular tissue
What are the properties of microscopic Diffuse Gastric Adenocarcinomas?
o Poorly differentiated
o Scattered growth
o Cadherin loss/mutation
o Small groups of cells infiltrating into wall of stomach
o Linked to loss in cadherin gene (keeps cells stuck together)- so can infiltrate
o Linked to linctis plastic
What is Hereditary Diffuse Type Gastric Cancer (HDGC)?
Hereditary Diffuse Type Gastric Cancer (HDGC)
• Germline CDH1/E-cadherin mutation
• Precursor lesions?
• Surveillance? Prophylactic gastrectomy?
• Increased risk for other cancers
What is TNM Staging?
- pT1: intramucosal or submucosal
- pT2: into muscularis propria
- pT3: through muscularis propria into subserosa
- pT4: through serosa (peritoneum) or into adjacent organs
- pN0: no lymph node metastases
- pN1: 1 to 2 lymph node metastasis
- pN2: 3 to 6 lymph node metastasis
- pN3: more than 6 lymph node metastasis
- M0: no distant metastases
- M1: distant metastases present
What is Coeliac Disease?
- Also known as Coeliac sprue/ gluten sensitive enteropathy
- Immune mediated enteropathy (autoimmune- reac to glioden in gluten)
- Ingestion of gluten containing cereals (wheat, rye or barley)- genetically predisposed
- Fairley common, estimated prevalence 0.5% to 1% (in Western pops)
What is the pathogenesis of Coeliac Disease?
• Reaction to gliadin (in gluten)
o Alcohol soluble component of gluten
o Contains most of disease-producing components
o Induces epithelial cells to express IL-15 (interlukin 15)
• Increased CD8+ intraepithelial lymphocytes (IELs)
o IL15 made by epithelium CD8+ IELs activation/ prolif
o These are cytotoxic & kill erythrocytes
o CD8+ IELs (lymphocytes) don’t recognise gliadin directly
o Gliadin-induced IL15 secretion by epithelium is the mechanism
What is the diagnosis of Coeliac Disease?
• Commonly affects adults between 30 & 60yrs
• Diagnosis often difficult;
o Atypical presentations/ non specific symptoms
o Silent disease- +ve serology/ villous atrophy but no symptoms
o Latent disease- +ve serology but no villous atrophy (evidence of autoimm but no histological features)
o Symptomatic patients- anaemia, chronic diarrhoea, bloating or chronic fatigue
• Non-invasive serology tests before biopsy
• Most sensitive tests;
o IgA antibodies to tissue transglutaminase (TTG)
o IgA or IgG antibodies to deamidated gliadin
o Anti-endomysial antibodies- highly specific but less sensitive
• Tissue biopsy is diagnostic (2nd biopsy after GFD- should see resolution of pathological changes to small bowel mucosa)- see damage
What are the Clinical Features & Associations of Coeliac Disease?
• No gender preference
• Other disease associations
o Dermatitis herpetiformis (itchy rash)- 10% patients
o Lymphocytic gastritis & lymphocytic colitis (CD8+ lymphocytes in small & large bowel)
• Coeliac disease & cancer
o Enteropathy-associated T-cell lymphoma
o Small intestine adenocarcinoma
o BEWARE! Symptoms despite GFD (gluten free diet)- investigate to ensure haven’t got one of these complications
What is the treatment of Coeliac Disease?
Treatment
• Gluten-free diet= symptomatic improvement for most patients
• Reduces risk of long term complications e.g. anaemia, female infertility, cancer & osteopororsis
What is the morphology of Coeliac Disease?
Morphology of Coeliac Disease • Villous atrophy • Flattening of epithelium • Crypt elongation • Increased IELs • Increased lamina propria inflammation
What is Diverticulosis of the Colon?
- Protrusions of mucosa & submucosa through bowel wall
- Diverticulum; congenital & acquired
- Commonly sigmoid colon
- Located between mesenteric & anti-mesenteric taenia coli (also between anti-mesenteric t.coli in 50% cases)
- Less commonly extend into proximal colon (e.g. Caecum- 15%)
- True congenital diverticulum or false pseudo diverticulum
What is the epidemiology Diverticulosis of the Colon?
• Common in developed Western world
• Rare in Africa, Asia, S. America
• Common in urban than rural areas (dietry factors contrib)
• Changing prevalence in migrant pops moving from low to high risk areas- their incidence matches where they moved (env element)
• Relationship with fibre content of diet
• Increases with age;
o <40 rare
o 40-60 10%
o >60 30%
o >90 50%
• Male= female
• Less common in vegetarians
• Muscularis propria thickened, get sacs of mucosa penetrating into bowel wall into fat
What is the pathogenesis of Diverticulosis of the Colon?
Pathogenesis
• Increased intra-luminal pressure in bowel
o Pushes mucosa out of bowel wall where gap in muscles (where vasa recta vessels go in)
o Irregular uncoordinated peristalsis (generates sealed compartments where pressure increases)
o Overlapping (valve like) semicircular arcs of bowel wall
• Points of relative weakness in bowel wall
o Penetration by nutrient arteries between mesenteric & antimesenteric taenia coli
o Age related changes in connective tissue (less collagen & elastin- weaken bowel wall so more susceptible to let pouches through)
What are the clinical features of Diverticulosis?
- Asymptomatic (90-99%)
- Cramping abdominal pain
- Alternating constipation & diarrhoea
- Acute & chronic complications (10-30%)
What are the complications of Diverticulosis?
• Acute (diverticulum inflamed- L iliac fossa pain);
o Diverticulitis/ peridiverticular abscess (20-25%) (if diverticulum bursts- have high WBC count)
o Perforation (in peritoneal surface release feaces into peritoneal cavity- acute faceal peritonitis)
o Haemorrhage (5%)
• Chronic;
o Intestinal obstruc (strictures: 5-10%) (repeat episodes scarring strictures, abdo pain)
o Fistula (sigmoid colon near urinary bladder (get neumaturia/ faecal matter in urine), vagina (fecal contents coming through vagina)- perforation drills hole into adherent bit of adjacent struc- communic with adjacent stuc)
o Diverticular colitis (segmental & granulomatous)- inflamm in surrounding mucosa
o Polypoid prolapsing mucosal fold- redundant folds of mucosa can cause bleeding & diaorrhoea
What is Colitis?
- Inflammation of colon
- Usually mucoasal inflamm (bowel lining) but occasionally transmural (across entire wall e.g. Crohns) or predominantly submucosal/ muscular (e.g. eosinophilic colitis)
- Divided into acute (days to a few wks) & chronic (months to years)
What is Acute colitis?
- Acute infective colitis e.g. campylobacter, shingella, salmonella, CMV
- Antibiotic associated colitis (including PMC)
- Drug induced colitis
- Acute ischaemic colitis (transient or gangrenous)
- Acute radiation colitis
- Neutropenic colitis
- Phlemonous colitis
What is Chronic colitis?
- Chronic idiopathic inflamm bowel disease
- Ischaemic colitis
- Diverticular colitis
- Microscopic colitis (collagenous & lymphocytic)
- Chronic infective colitis e.g. amoebic colitis & TB
- Diversion colitis
- Eosinophilc colitis
- Chronic radiation colitis
What is Idiopathic Inflammatory Bowel Disease?
- Ulcerative colitis (only recturm, colon, terminal ileum, appendix)
- Crohn’s disease (any part of GIT from mouth to anus)
- Unclassified & indeterminate colitis (10-15%)- clinically overlapping features between UC & Crohn’s
What is IBD Epidemiology ?
• UC 5-15 cases/ 100,000 p.a.
• CD 5-10 cases/ 100,000 p.a.
• Highest incidence in Scandinavia, UK, Northern Europe, USA
• Lower in Japan, Southern Europe, Africa
• Peak age incidence 20-40 yrs old
• CD more common in females (1.3:1)
• UC equally common in males & females
• UC incidence increased in urban areas
• Other risk factors;
o Cigarette smoking (UC 0.5x, CD 2x) at lower risk of developing UC (protective) but increases risk of Crohn’s (pre-disposes to it).
o Oral contraceptive (UC 1.4x, CD 1.6x)- increased risk of both
o Others e.g. childhood infecs, domestic hygiene, appendicetomy (protective against UC)
What is IBD-Familial Clustering ?
- Strong genetic component to both (stronger for Crohn’s)
- Genes linked to development of UC & Crohn’s
- Determined by env & b=genetic factors
What is Ulcerative Colitis?
Charcteristic sharp cut off between normal & inflamed large bowel
Granula inflamed mucosa- muscular wall left exposed
Colon and rectum affected
What is the Clinical presentation of Ulcerative Colitis ?
- Bloody diarrhoea (>66%) with urgency/ tenesmus
- Constipation (2%)
- Rectal bleeding (>90%)
- Abdo pian (30-60%)
- Anorexia
- Weight loss (15-40%)
- Anaemia
What are the Complications of Ulcerative Colitis ?
- Toxic megacolon (formanant colitis- transverse colon becomes so dilated & thin can perforate) & perforation
- Haemorrhage (ulcers can erode into arteries & veins- bleeding into bowel lumen)
- Stricture (rare)- suspect malignancy
- Carcinoma (if have stricture in UC may have cancer)
What is Crohn’s Disease ?
Distrib
• Ileocolic (terminal ileum & cacecum) 30-55%
• Small bowel 25-35%
• Colonic (hard to distinguish from UC) 15-25%
• Peri-anal/ ano-rectal 2-3%
• Gastro-duodenal (oesoph & duodenum) 1-2%
• UC always affects rectum then spreads contiunually around bowel, but Crohn’s patchy regions (areas of diseased & normal bowels)
• Crohn’s- look likes cobbled stone path
• Granuloma seen in Crohn’s (50-60%) but NOT UC
What is the Clinical presentation of Crohn’s Disease ?
Clinical Features • Chronic relapsing disease (like UC) • Affects all levels of GIT (from mouth to anus) • Diarrhoea (may be bloody) • Colicky abdo pain • Palpable abdo mass- inflamm tansmural so entire thickness of bowel (can feel it through abdo wall, unlike in UC where only mucosa layer affected) • Weight loss/ failure to thrive • Anorexia • Fever • Oral ulcers • Peri-anal disease • Anaemia
What are the Complications of Crohn’s Disease ?
- Toxic megacolon
- Perforation
- Fistula (as goes through whole bowel wall)- not in UC
- Stricture (common- as transmural so thickens bowel wall)
- Haemorrhage
- Carcinoma (risk of cancer similar to that of UC)
- Short bowel syndrome (repeated resection- bowel removed)- if too much bowel removed can’t get enough nutrition
What are Extra-Intestinal Manifestations of IBD?
Hepatic • Fatty change in granulomas • PSC & bile duct carcinoma Osteo-articular • Polyarthritis • Sacro-ileitis & ankylosing spondylitis Muco-cutaneous • Oral ulcers • Pyoderma gangrenosum & erythema nodosum Ocular • Uvenitis & retinitis Systemic • Amyloidosis • Thrombo-embolic disease
What are the Risk Factors for CRC in UC?
- Early age of onset (in children)
- Disease duration >8-10yrs (increases in incidence after 10yrs)
- Total extensive coitis (if disease extends beyond splenic flexure (extensive colitis)- worry about cancer)
- PSC- inflamm of bile duct
- Fam history of CRC
- Severity of inflamm (pseudopolyps)
- Presence of dysplasia
- Overall prevalence 3.7%
- Prevalence in pancolitis 5.4%
- Risk of CRC at 10 yrs 2%, 20 yrs 8%, 30 yrs 18%
- Risk increases the longer you have an inflamed colon
Inflamm= mutations=low grade dysplasia = severe atypia etc =CRC
What is Ischaemic colitis?
- Colonic injury 2ndry to acute, intermittent/ chronic reduc in blood flow
- May be occlusive or non-occlusive (NOMI- reduced blood flow)
- Usually multifactorial & associated with other vascular diseases e.g. hypertension, peripheral vascular disease, coronary artery disease, diabetes mellitus, chronic renal failure, IBS, COPD
- Patchy distrib of ischaemia- usually affect L colon, cases on R more severe
- Splenic flexure usually involved- as is a watershed area (2 blood supplies converge- poorly supplied with blood)
• In majority symptoms improve within 48hrs
• Complete recovery within 1-2wks
20% need surgery for colonic infarction
What are the forms of Ischaemic colitis?
• 3 clinical forms;
o Transient or evanescent (>80%)- mild form, spontaneously heals
o Chronic segmental ulcerating (ischaemic stricture)- scarring develop obstruction
o Acute fulminant & gangrenous (10-20%)- seevre obstruc, bowel wall necrosis (colon infarction)- SURGICAL EMERGENCY!!!
• Transient form- acute onset cramping abdo pains; urge to defaecate, bloody diarrhoea/ rectal bleeding
What is Mesenteric Ischaemia ?
Causes;
• Arterial embolism (40-50%)- esp. cardiac e.g. MI, AF, endocarditis
• Arterial thrombosis (25-30%)- esp. SMA origin supplying large bowel
• Non-occlusive mesenteric ischaemia (20%)- low cardiac output with mesenteric vasoconstric (low flow state) e.g. MI, CCF, major surgery & trauma
What are Colorectal Polyps ?
• Mucosal protrusion • Solitary or multiple (polyposis) • Pedunculated, sessile or flat • Small or large • Due to mucosal/ submucosal pathology/ lesion deeper in bowel wall • Classification; o Neoplastic, hamartomatous, imflammatory or reactive o Benign or malignant o Epithelial or mesenchymal
What are Non-Neoplastic Polyps in Colo-Rectum?
• Hyperplastic polyps (reactive, neoplastic)
• Hamartomatous polyps
o Peutz-jeghers polyps
o Juvenile polyps
• Polyps related to mucosal prolapse (imflamm cloacogenic polyp, inflammatory cap polyp, inflammatory myoglandular polyp, polypoid prolapsing mucosal fold)
• Post-inflammatory polyps (pseudopolyps)- mucosa regenrates & creatses a polyp
• Inflammatory fibroid polyp
• Benign lymphoid polyp
What are Hyperplastic Polyps?
- Common
- 1-5mm
- Often multiple
- In rectum & sigmoid colon
- Small distal HPs have NO malignant potential
- (Some large R sided do have malignant potential- ‘hyperplastic polyps’ (sessile serrated lesions) may give rise to microsatellite unstable carcinoma (10-15% all colorectal cancer)).
What are Juvenile Polyps?
- Often spherical & pedunculated
- 10-30mm
- Commonest polyp type in children
- Typically in rectuem & distal colon
- Sporadic polyps (when in isolation)- NO malignant potnetial
- (Rare genetic condition- inherit Juvenille polyposis associated with increased risk of colorectal & gastric cancer)
What is Peutz-Jeghers Syndrome?
- Autosomal dominant condition (mutation in STK11 gene on chromosome 19)- heerditary
- Prevalence: 1 in 50,000- 1 in 120,000 births
- Present clinically in teens or 20s- abdo [ian (intussusception), GI bleeding & anaemia; increased cancer risk (e.g. breast etc)
- Multiple GIY polyps (predominantly small bowel)
- Mucocutaneous pigmantation (brown freckling)- 1-5mm macules peri-oral, lips, buccal mucosa, fingers & toes)
What are Benign Neoplastic Polyps?
- Adenoma (benign glandular neoplasm)
- Lipoma
- Leiomyoma
- Haemangioma
- Neurofibroma
- Ganglioneuroma
What are Malignant Neoplastic Polyps?
- Carcinoma
- Carcinoid
- Leiomyosarcoma
- GIST
- Lymphoma
- Metastatic tumour
What is an adenoma?
Benign Neoplastic Polyp
• Benign epithelial tumours
• Commonly polypoid but may be ‘flat’
• Precursor of colorectal cancer (at least 80%)
• Present 25-35% pop >50yrs
• Multiple in 20-30% patients
• Evenly distributed around colon BUT larger in recto-sigmoid & caecum
• Macroscopic apperance: pedunculated (on stalks), sessile (broad base) or flat
• Architectural type: villous, tubulo-villous or tubular (smooth surface)
• Histological grade: high v. low grade dysplasia
• Adenoma showing low grade dysplasia enlarged nuclei, crypt showing dysplasia
• The adnoma carcinoma sequence; a small % of adenomas slow progression to adenocarcinoma over avergae of 10-15yrs
• Adenoma carcinoma sequence (common way of getting cancer in large bowel- adenoma becomes cancerous)
What are the risk factors for adenomas to become malignant?
Features that make adenomas high risk to become malignant;
• Flat adenomas
• Size (bigger it is greater risk, most malignant polyps >10mm)
• Villous & tubulo-villous
• Severe high grade dysplasia
• Lynch syndrome associated adenomas
What is CRC?
- 2nd (women) or 3rd (males) commonest cancer (mortality) after bronchus, breast & prostate
- Lifetime risk 1/18 to 1/20
- Estimated prevalence in UK 77,000
- UK incidence 35,300
- UK mortality 16,220
- Group of pateints have fam risk
- Genetic single gene disroder- lynch syndrome & FAP (high risk of developing bowel cancer)
What are CRC risk factors
- Diet; dietray fibre (protective), fat, red meat, folate (protective), calcium (protective)
- NSAIDs & aspirin (protective)
- Obesity/ reduced physical activity
- Alcohol
- HRT (hormone replacement therapy & oral contraceptives
- Schistosomiasis
- Pelvic radiation (radiotherapy for other cancers- affects rectum, increases rectal cancer risk)
- UC & Crohn’s disease
What Is FAP?
- > 1% all colorectal cancer
- Autosomal domiannt
- 100% lifetime risk of large bowel cancer (clasical); <100% attenuated FAP (100% chance of developing 1 or more large bowel cancers, if have it removed- increased gastric/duodenal cancer risk)
- Associated with multiple benign adenomatous polyps in colon
- Due to mutation in APC tumour suppressor gene
- FAP- assocated with development in teens of multiple benign adenomatous polyps (coats colonic mucosa)
What Is Lynch Syndrome ?
- 1-2% all colorectal cancer
- Autosomal dominant (inherited)
- 50-70% lifetime risk of large bowel cancer
- Inreased risk of endometrial (60-80%), ovarian, gastric, small bowel, urinary tract & biliary tract cancer
- Due to mutations in DNA mismatch repair genes (can’t repair genetic errors- accumul mutations)
- 2/3rds are distal to splenic flexure
What is the grading of CRC?
• Well differentiated 10-20% (resemble normal glandualr epithelium)
• Moderatley well differentated 60-80%
• Poorly differentiated 10-20%
Reflects biologicla aggressivness- less differentated, more aggressive (prognostic factor)
What is the route of spread of CRC?
- Direct invasion of adjacent tissues
- Lymphatic metastasis (spreads to lymph nodes)
- Haematogenous metastasis (typically to liver & lung)
- Transcoelomic (peritoneal) metastasis (perforates into peritoneal cavity)
- Iatrogenic spread e.g. needle track recurrence (spread along length of biopsy needle), port site recurrence
What is the staging of CRC?
• Dukes stage;
o Stage A: adenocarcinoma confined to bowel wall with no lymph node metastasis
o Stage B: adenocarcinoma invading through bowel wall with no lymph node metastasis
o Stage C: adenocarcinoma with regional lymph node metastasis regardless of depth of invasion
o Satge D: distant metastasis present
• TNM stage;
o T1- invades into submucosa
o T2- invades into muscle wall (but not through)
o T3- invades through muscle wall
o T4- involves peritoneal surface, invades adjacent struc, tumour that is perforated
o N0- no nodes involved
o N1- 1-3 nodes involved
o N2- 4 or more nodes involved
• May be clinical (imaging) or pathological (based on histopathology)
• Describes extent of local & distant tumour spread
• Tumour stage, either TMN or Dukes, predicts probability of cure with surgery, liklihood of tumour recurrence & site of recurrence & determines selection of patients for adjuvant therapy e.g. at C stage (reduces recurrance by 10%)
What are the GIT sterile and non sterile sites?
• GIT sterile sites; o Peritoneal space o Pancreas o Gall bladder o Liver
• GIT non-sterile sites (bacteria throughout); o Mouth o Oesophagus o Stomach o Small bowel o Large bowel
How do you name bacteria?
- 1st give genus name then species name e.g. Escheria (genus) coli (species)
- Give full bacterial name in italics
- May have clues in names e.g. E. coli mainly found in colon (coli), Enterococcus found in enteric tract & are cocci (round bacteria).
What is normal flora?
- Will have Haemophilus spp but doesn’t mean you’ll have pneumonia
- If have intra-abdominal abcess- if know what bacteria in bowel- can help you decide which drugs you need to choose
What is Angular Cheilitis ?
• Lesions at side of mouth- acute/ chronic inflamm of skin & contagious labial mucosa at lateral comissures of mouth
• Typically presents; erythema, maceration, scaling & fissuring at corners of mouth
• Lesions often bilateral & may be painful
• Cause: excessive moisture & maceration from saliva & 2ndry infec with C. abicans (or less commonly S. aureus)
• Candida & S.aureua part of normal mouth flora, travelled from mouth to skin- e.g. damage to skin at that site
• Occurs at any age but especially common in older individuals wearing dentures
• No sex preference
• Predisposing local factors;
o Wearing orthodontic appliances/ ill-fitting dentures
o Sicca symptoms (dry mouth)
o Intrsoral fungal infec
o Age-related anatomic changes of mouth e.g. older individuals alveolar ridges causes loss of vertical dimension of mouth, edentulous state leads to drooping of corners of mouth, drooling & saliva retention in creases
o In young children- drooling, thumb sucking & lip licking freq causes
o Less common causes in adults & children; nutritional deficiencies, type 2 diabetes, immunodeficiency, irritant/ allergic reactions to oral hygiene products/ denture materials & medications causing dryness & xerostomia
• Cheilitis- acute/chronic inflamm of lips, usually involves lip vermilion & vermilion border but surrounding skin & oral mucosa may also be affected
• Common symptoms; erythema dryness, scaling, fissuring, oedema, itching & burning
• Treatment: topical antifungals/ antibiotics
What is Hairy Leucoplakia?
- Caused by Epstein Barr virus (can give you glandular fever)
- Seen in HIV patients
- Well-demarcated white plaques on lateral aspects of tongue- cleared with oral acyclovir
- Treatment: immune retroviral therapy
What are common Dentoalveolar infections?
• Caries (need filling)
o Bacterial plaques form on tooth surface
o Acid made by bacteria (Streptococcus mutans & Lactobacillus spp)- erodes enamel & bone (dentin) so bacteria can move inside tooth
o When bacteria within pulp (vascular nervous supply- here feel pain)- cause inflamm swelling & acute pain
• Pulpitis- inflamm of pulp(need root canal)
• Periapical abscess- when down to base
• Not sure which bacteria cause pulpitis & peripheral abscess but likely to be oral commensals e.g. Streptococci & anaerobes
• Dental x-rays (less dense area- loss of bone) & examination aid diagnosis
What are common Periodontal infections?
Alveolar bone= thickened ridge of bone that contains tooth sockets (dental alveoli) on bones that hold teeth)
• Plaque beneath gingival margin
o Gingivitis –
Early stage of infec, inflamm of gums (red & swollen gingival tissue- easily bleeds when floss & brush) – treat with improved oral hygiene
Presents with red swollen painful bleeding gums, halitosis
Is a clinical diagnosis
o Periodontitis –
Gingival inflamm with accompanying loss of supportive connective tissues including alveolar bone (pockets >5mm)
Progression of gingivitis with progressive loss of dental support struc function
May need antibiotics in addition to cleaning
o Periodontal abscess-
May be focal or diffuse
Present as red fluctuant swelling of gingiva (extremely tender to palpation)
Abscesses always communic with a periodontal pocket- pus can be readily expressed after probing
Needs surgical drainage
o Periodontal infec can progress to an acute condition called Vincent’s angina or infec can spread to soft tissues in mouth which can lead to deep neck infecs
o Acute necrotizing ulcerative gingivitis (Vincent’s angina- necrotising trench mouth)-
Sudden onset pain in gingiva & tissue appears eroded with superficial grayish pseudomembranes
Other manifeststaions; halitosis, altered taste sensation, fever, malaise, lymphadenopathy.
Need antibiotics
o May progress to orofacial space infecs
o Associated with increased detection on anaerobic bacteria
• Inadequate oral hygiene- no interdental cleaning= bacterial infec of gingival margin (gum-bone interface)= gingivitis which can progress to periodontitis
• These infecs can spread to other spaces
What is Peritonsillar abscess (quinsy)?
Deep Neck Space Infecs
can cause airway obstruction
o Swollen tonsil becomes abscess that needs draining (usually pus filled pocket near one of tonsils)
o Unilateral swellings of the tonsil
o Normally caused by Streptococcus pyogenes (group A streptococcus)
o Symptoms: painful swallowing, unilateral sore throat & ear ache
o Signs: muffled voice, trismus (lock jaw), unilateral deviation of uvula towards unaffected side & soft palate fullness/ oedema
o Oral airway might be compromised & may be drooling
o Surgical drainage & antibiotic management
What is Acute suppurative parotitis ?
Deep Neck Space Infecs
can cause airway obstruction
Acute suppurative parotitis (non mumps)-
o Parotid glands (normally secrets saliva)- if poor oral care/ dehydration flow of saliva decreased so bacteria can’t flow out (swelling on side of face (may also be meningitis))
o Mostly caused by staphylococcus aureus
o Normally 1 side affected
o Sudden onset of swelling from cheek to angle of jaw & bacterima may result (patient may be systemically un well)
o Consider surgical drainage & antibiotics
What is Ludwig’s angina?
Deep Neck Space Infecs
can cause airway obstruction
Submandibular space infections- Ludwig’s angina
o Bilateral infec of submandibular space
o Aggressive, rpidly spreading cellulitis without lymphadenopathy
o Potential for airway obstruct, needs careful monitoring & rapid intervention for prevention of asphyxia and aspiration pneumonia
o If abscesses form- need surgical drainage
o Antibiotic s
What is Pretracheal space infection?
Deep Neck Space Infecs
can cause airway obstruction
• Pretracheal space infecs (infecs around trachea);
o Common consequence of anterior oesophageal wall perforation
o Occasionally through contaiguous extension from a retropharyngeal space infec/ consequence of prolonged tracheostomy
o Clinical presentation; hoarseness, severe dyspnoea, difficulty swallowing, fluids regurgitated through nose
o Always serious- impending airway obstruc & possible extension into meduiastinum
o Prompt surgical drainage to prevent complications
What is Prevertebral space infection?
Deep Neck Space Infecs
can cause airway obstruction
Prevertebral space infecs-
o Spread of infec to bone e.g. vertibritis
o Usually originate from contiguous spread of a cervical spine infec (e.g. discitis/ vertebral osteomyelitis), local instrumentation of trachea/ oesoph, or by haematogenous seeding
What is Parapharyngeal space infection?
Deep Neck Space Infecs
can cause airway obstruction
o Potentially life threatening- possibility of carotid sheath involvement & it’s contents (e.g. common carotid artery, internal juguar vein, vagus nerve
o Inclination for airway impingment & bacteremic dissemination
o Suppurative jugular thrombophlembitis (also known as lemierre’s syndrome)- infec of jugular vein (thrombus infected with fusobacteria (normal bacteria in bloodstream))- suspected in patients with antecedent pharyngitis
o Clinical presentation may be dominated by primary source of infecs symptoms & signs- so diagnosis often delayed
o Infec of parapharyngeal space may arise from diff sources throughout neck- dental infecs common underlying cause
o Cardinal clinical features: trismus, induration & swelling below angle of mandible, medial bulging of pharyngeal wall & systemic toxicity with fever & rigors
o Complications: carotid sheath involvement- carotid artery erosion & suppurative jugular thrombophlebitis
