COLORECTAL

Question 1

What is the difference between a hyperplastic, traditional serrated adenoma (TSA) and a sessile serrated adenoma (SSA)?

Answer 1

all 3 are serrated polyps which have varying malignant potential

hyperplastic = normal cell architecture, no dysplasia, rectosigmoid

TSA = have dysplasia, rectosigmoid

SSA = lack classic dysplasia but may have mild cytologic atypia. Located more proximally.

Question 2

How do you do diagnose sessile serrated polyposis syndrome?

Answer 2

Use WHO criteria (number and/or size of polyps)

Number

• >20 + any location

or

• >5 + proximal to sigmoid

Question 3

what is the cause of adenomatous polyps?

Answer 3

genetic mutations = MMR pathway, APC pathway

enviromental = reduced fibre, increased fat (more associative rather than causative

Question 4

what is the Vogelstein hypothesis?

Answer 4

• mutations are required for malignant transformation,
• the accumulation of multiple genetic mutations rather than their sequence determines the biological behavior of the tumor

Question 5

What are the mismatch repair genes?

Answer 5

MLH1, MSH2, MSH6, PMS2

Question 6

what is meant by RAS? (e.g. K-RAS)

Answer 6

Types

• RAS = oncogene with 3 subtypes (K-RAS, H-RAS, N-RAS)
• K-RAS most frequently mutated

Function

• one-way switch for the transmission of extracellular growth signals to the nucleus

K-RAS mutations

• constitutively active GTP-bound protein and a continuous growth stimulus

Question 7

How is finding a K-RAS mutation clinically relevant?

Answer 7

epidermal growth factor receptor (EGFR) such as cetuximab less effective

Question 8

What is meant by CIMP?

Answer 8

CpG Island hyperMethylation Phenotype pathway (CIMP+)

• Methylation of CpG islands inactivates genes
• May result in hypermethylation of the promoter region of MMR enzymes such as MLH1 and silencing of gene expression (­ accumulation of errors similar to MMR pathway)

Question 9

what is the Amsterdam criteria?

Answer 9

(Modified) Amsterdam criteria (3,2,1 rule)

• 3 relatives with a HNPCC cancer (colorectal, endometrium, small bowel, urothelium)
• 2 successive generations
• 1 affected individual is <50

Question 10

what is the Bethesda criteria?

Answer 10

Bethesda criteria

• BET
• Histopathology – resembles MSI pathology in patients <60 years (LAMPS)
• Extracolonic cancers – endometrium, small bowel, urothelium
• Single – 1st degree relative < 50
• Double 1st/2nd degree relative HNPCC cancer
• Age < 50

Question 11

What are the pathological features that suggest Lynch?

Answer 11

LAMPS

Tumour infiltrating lymphocytes, Crohn’s like lymphocytic reaction

associted extracolonic features (endometrium, stomach, ovary, small bowel)

Metachranous, mucinous

Proximal (right sided), poorly differentiated

signet ring,

Question 12

Pathophysiology of C diff

Answer 12

Anerobic Gram-positive spore forming and toxin producing organism

Antibiotics = disruption of colonic flora = C difficile spores ingested = toxins released

TOXINS

Toxin A (enterotoxin)

• Neutrophil chemotaxis causes inflammation, mucosal injury, fluid secretion mediated by cytokines IL-1, TNF-a

Toxin B (cytotoxin)

• 10 times more virulent than toxin A
• is the clinically important toxin; no CDAD due to toxin A alone has been reported.

Once intracellular, toxins A + B inhibit regulatory pathways leading to apoptosis and disrupt intercellular tight junctions.

A minority of C. difficile strains (10 to 30 percent) are non-toxigenic and do not produce toxins; these strains can colonize the gastrointestinal tract and grow normally in culture media but are not pathogenic

Question 13

What are the risk factors for anal cancer?

Answer 13

immunosuppressed - HIV, transplant, steroids

MSM -

AIN (especially high grade)

Question 14

what HPV subtypes cause anal warts and anal intra-epithelial neoplasia (AIN)

Answer 14

AIN = HPV 16 + 18

warts = HPV 6 + 11

Question 15

What is the Nigro protocol?

Answer 15

Definitive chemodradiation using Nigro protocol

• Infusion of 5-FU (days 1-4 and 29-32)
• Mitomycin C (Day 1)
• 30 Gy radiotherapy over 3 weeks

Question 16

Managment principles

Answer 16

“CARESS”

Cause

• primary (cryptoglandular)
• secondary (crohn’s, cancer, radiation, trauma)

Anatomy

• define anatomy. Park’s classification.

Risk (simple vs. complex)

• Simple = intersphincteric/low transphincteric.
• Complex = recurrent, high, horshoe, Crohn’s, anterior in women)

Eradicate

• eradicate as much fistula tract as possible
• identify both ends (internal and external)

Sepsis

• Drain sepsis
• obvious internal opening = seton
• if not obvious = leave alone as can cause iatrogenic fistula

Sphincters

• preserve as much as possible
• document

Question 17

What is the cryptoglandular theory?

Answer 17

blocked anal gland becomes infected. pus follows the path of least resistance and results in fistula formation

Question 18

What is the difference between internal and external haemorrhoids?

Answer 18

internal

• above dentate line
• superior haemorrhoidal cushion
• epithelium = columnar
• visecerally innervated – insensitive to pain/touch/temperature

external

• below dentate line
• inferior haemorrhoidal plexus
• epithelium = modified squamous
• somatically innervated - painful

Question 19

Pathogenesis

Answer 19

Primary – usually posterior midline

• Trauma – forceful tearing of anal canal (hard formed stools/constipation, anal sex)
• Anodermal ischaemia (of posterior midline anal canal) – end arteries susceptible to ischaemia
• Hypertonicity of IAS - Increased resting anal pressures from sustained resting hypertonia

Secondary - Usually lateral

• AIDS/HIV
• TB
• Crohn’s disease, Cancer
• STDiseases (sexually transmitted) – syphilis

Question 20

What are the theories of pilonidal disease development?

Answer 20

Simple = hairs either block or cause trauma/foreign body reaction

Bascom’s theory (Blockage theory)

• Hair follicles become distended with keratin causing obstruction and secondary abscess formation.
• Abscess ruptures into subcutaneous tissue causing sinus

Karydarkis’ theory (foreign body reaction)

• Hair roots with chisel like ends insert into the natal cleft causing foreign body tissue reaction and infection.

Question 21

what are the microscopic features of UC?

Answer 21

• Submucosal/mucosal layer only
• crypt abscess
• goblet cell depletion
• no (non-caseating) granulomas

Question 22

What are the findings of UC on colonscopy?

Answer 22

• Loss of vascularity
• mucosal oedema
• contact bleeding
• ulceration
• pseudopolyps

Question 23

What is the Truelove and Witts criteria for determining the severity of UC?

Answer 23

HITTS

Severe UC

• Haemoglobin <105
• Inflammatory markers - CRP>30
• Tachycardia - >90
• Temperature >37.8
• Stools (bloody) - >6/day

Question 24

What are the key components of medically managing acute UC?

Answer 24

Resuscitation

• fluids, electrolytes
• nutrition
• Hb > 100

Medications

• stop - ones that increase toxic dilatation (NSAIDs, antidirrahoeal, anti-cholinergic)
• start - hydrocortisone 100 mg TDS (maximum 5 days)

If fails, then 2 options

• surgery (3 stage - subtotal colectomy + ileostomy, completion proctectomy, ileostomy reversal)

or

• immune therapy (infliximab, tacrolimus)

Question 25

What medications are not safe in pregant IBD patients?

Answer 25

Methotrexate * stop before (ie trying to conceive) * during pregnancy (teratogenic) Sulfasalazine * can be used but impairs folic acid synthesis * must be given with folate remainder (steroids, biologics, antibiotics, immunomodulators) safe in low doses

Question 26

What is the mechanism of stone formation (gallstones, kidney stones) in IBD?

Answer 26

Gallstones: * Common in Crohn’s because TI disease → ↓ bile salt pool → **lack of enough bile salts to solubilize the cholesterol in bile** Kidney stones: * oxalate stones mechanism: due to ileal disease, non-absorbed fatty acids bind to calcium in the intestinal lumen, allowing free oxalate (which would usu bind to Ca) to be absorbed from the colon

Question 27

Which type of antibodies are found in IBD?

Answer 27

Crohn's = ASCA UC = P-ANCA

Question 28

What are the indications for TEMS?

Answer 28

* T1 if Haggit 1-3 * mobile tumour \< 3cm in diameter * well differentiated * no LVI * no nodal metastasis

Question 29

When do you offere surveillance colonoscopy for patients with 1. adenomas 2. genetic syndromes 3. IBD

Answer 29

**Adenomas** * high risk adenoma (\> 3 adenomas, villous/TV/HGD, measuring \>1 cm) = 3 yearly * low risk adenoma = 5 yearly **Genetic syndromes** * FAP = 1-2 yearly colonoscopy at 12-15 (gastroscopy at 30). Prophylactic colectomy in teens * Lynch = 2 yearly from 25 **IBD** yearly if * active disease * complicated disease (stricture, inflammatory polyps) * DALMs (LGD) * PSC * FHx of CRC in first degree relative \<50 3 yearly if * stable disease (ie none of above factors) 5 yearly if * last two scopes were normal macroscopically and histologically

Question 30

How do you manage dysplasia in UC?

Answer 30

confirm diagnosis with 2nd pathologist HGD or multifocal LGD or DALM in raised lesion = colectomy not above = surveillance (preferably with chromendoscopy. If not possible then random 4 quadrant biopsies every 10 cm)

Question 31

Which patients with CRC do you give chemotherapy to?

Answer 31

Stage I * none Stage II * Controversial but consider if high risk features (T4, LNC\>12, obstructing/perforating cancer, LVI, positive/close margins) Stage III * FOLFOX (based on MOSAIC trial - NEJM 2004) for 6 months Stage IV * Multiple protocols but main are either FOLFOX, FOLFIRI or FOLFOXIRI * Add cetuximab if K-RAS wild-type * Consider adding bevacizumab

Question 32

How do you treat neutropenic enterocolitis?

Answer 32

Management is primarily medical * bowel rest * broad-spectrum antimicrobials for hospital-acquired infections (including fungal pathogens) * intravenous fluid resuscitation * correction of neutropenia with granulocyte colony stimulating factors. * **Colonoscopy has no role in the diagnosis or treatment of NE.** Surgical intervention if * gastrointestinal bleeding not responsive to blood component therapy * free intra-abdominal perforation * clinical deterioration with uncontrolled sepsis * other intra-abdominal pathology not associated with neutropenia.

Question 33

When does neutropenic enterocolitis typically occur clinically?

Answer 33

* It typically occurs with the nadir in neutrophil count 10–14 days after chemotherapy.

Question 34

What is the typical CT finding of neutropenic enterocolitis?

Answer 34

* The radiographic finding of pneumatosis intestinalis lacks sensitivity but is very specific for NE.

Question 35

What are the clinical manifestations of FAP?

Answer 35

Intestinal * Colonic = multiple polyps (\>100) * UGI = duodenal polyps Gardner's syndrome * sebaceous cyst * desmoid * osteomas * **thyroid cancers** * **CHRPE (congenital hypertrophy of retinal pigment epithelium)** Other UGI = duodenal/gastric polyps