Colorectal

Question 1

Peutz Jegher’s Syndrome

Answer 1

• Definition:
  
  • Autosomal dominant disorder in which hamartomatous polyps can occur throughout the gastrointestinal tract.
• Pathophysiology:
  
  • STK11 gene; chromosome 19,
  • Tumour suppressor gene
  • [St Kilda – luna park 1911]. 50% cases inherited and 50% sporadic
• Clinical manifestations:
  
  • mucocutaneous pigmentation, SB intussuception, colorectal polyps or bleed, malignant transformation
• Macroscopic features:
  
  • Large pedunculated polyps, ?cherry-red
• Microscopic features:
  
  • ​Non neoplastic hamartomas, connective tissue and smooth muscle covered by hyperplastic epithelium, Frond-like polyp with all three components of mucosa: (Muscosal epithelium (melanotic mucosa, goblet cells), Lamina propria, M. mucosae.)
• Investigations:
  
  • To get genetic testing (2 out of 3 needed)
    
    • GI hamartomatous Polyps
    • Pigmentation
    • Family history
• Risk of malignancy and surveillance:
  
  • GI malignancy 57%, baseline gas, colon, MRE age 8 or earlier, if polyps then 3 yearly if no polyps then start again age 18
  • Colorectal 39%
    
    • No prophylactic surgery
  • Breast: 45%
    
    • Consider bilateral mastectomy, age 30 annual imaging
  • Pancreas: 20%
    
    • 2 yearly MRCP or EUS age 35
  • Testicle/cervix:
    
    • Annual exam

Question 2

pseudomembranous colitis pathophysiology

Answer 2

• Organism:
  
  • Clostridium difficile
    
    • Spore forming anaerobic gram positive
• Pathophysiology
  
  • Antiobiotic therapy–> disruption of colonic microflora–> C difficile exposure and colonisation –> release of toxin A (enterotoxin) and B (cytotoxin) –> mucosal injury and inflammation
  • C Diff. Toxin A/B mediated ribosylation of small GTPases, leads to disruption of the epithelial cytoskeleton, tight junction barrier loss, cytokine release (IL-8,TNF), and apoptosis
• Pseudomembranes microscopic appearance
  
  • Bacteria
  • Fibrin
  • Mucus
  • Neutrophils
  • Crypt erosions

Question 3

Anatomy of the anal canal

Answer 3

• Definition
  
  • Begins at levator ani, opens to the anal verge
  • I.e. Anorectal junction (top of puborectalis) to the squamous mucocutaneous junction
  • 2.5-5cm in length, longer in men
• Columns of mogagni
  
  • Mucosal folds above the dentate line
  • In between the columns are the anal crypts into which drain the anal glands – site of cryptoglandular disease
• Embyrology
  
  • The lining of the upper part of the anal canal is embryologically derived from the cloaca, i.e. it is endodermal;
  • The lower part is from the proctodeum or anal pit and is ectodermal
  • The dividing line between these territories is usually considered to be at the pectinate (dentate) line (anal membrane remnant)
• Blood supply​
  
  • Arterial
    
    • Inferior anal canal
      
      • Inferior rectal artery (from the internal iliac artery pudendal artery)
    • Superior anal canal
      
      • Superior rectal or middle rectal artery if present
  • Venous
    
    • Drainage corresponds to the arteries
      
      • Upper anal canal IMV
      • Lower anal canal can drain to external iliac vein
• Lymphatic​
  
  • Upper portion drains to inferior mesenteric LN
  • Lower portion drains to superficial iliac LN
• Histology
  
  • Lacks a peritoneal covering
  • Three histologic types:
    
    • glandular (proximal)
    • transitional (also called intermediate, cloacogenic)
    • keratinized or nonkeratinized squamous (distal)
  • Notes: ganglion cells are normally absent 1 – 2 cm above dentate line (important for Hirschsprung’s disease biopsies)
  • Proximal colorectal zone:
    
    • Top of puborectalis to dentate line, 1 – 2 cm long
    • Rectal glandular mucosa (columnar)
    • Similar to rectal mucosa but with shorter more irregular crypts, more smooth muscle fibers in lamina propria
  • Anal transitional zone (ATZ):
    
    • 0.3 cm to 1.1 cm
    • Zone between uninterrupted columnar mucosa above and uninterrupted squamous epithelium below
    • Wrinkled, glistening appearance
    • Transitional epithelium resembles urothelium (small basal cells with nuclei perpendicular to basement membrane, columnar, cuboidal, polygonal or flat) with 4 – 9 cell layers, minimal mucin production
    • Contains anal glands in submucosa, also endocrine cells, rare melanocytes
  • Lower distal zone:
    
    • Dentate line to squamous mucocutaneous junction: nonkeratinizing squamous epithelium without skin appendages, without glands
    • Contains melanocytes
    • Anal papillae contain squamous mucosa that joins rectal mucosa
    • Squamous mucosa merges with perianal skin (with keratin, hair follicles and apocrine glands) at anal verge / anal margin
• Innervation
  
  • Pudenal nerve is important in rectal sensation (needed for rectal defaecation)

Question 4

Anatomy of anal sphincters

Answer 4

The outer longitudinal muscular fibres run between the internal and external anal sphincters

• Internal sphincter
  
  • Thickened extension of the inner circular smooth muscle layer
  • 5mm thick
  • mainly parasympathetic (pelvic splanchnic nerves), 75% of resting tone of the sphincter
• External sphincter
  
  • Continuation of the pubrectalis muscle which blends with the longitudinal muscular fibres (maybe)
  • In the middle posteriorly it is attached to the coxxyx and perineal body, anocoxygeal ligament
  • Extends below the internal sphincter
  • Skeletal muscle, pudenal nerve innervation, voluntarily control to defer defaecation

Question 5

Anatomy of the Pelvic Floor

Answer 5

• A combination of muscles (eg, levator ani, coccygeus) and fascia that support the pelvic organs of the lower abdominal cavity (eg, rectum, bladder, uterus). It separates the true pelvis from the perineum.
  
  • Levator ani (3 parts)
    
    • Puborectalis (U shaped sling around the anorectal junction)
    • Pubococcygeus muscle
    • iliococcygeus muscle
    • The muscles arise from the posterior aspect of the pubis, a white tendinous condensation of the obturator and the ischial spine and insert into the …
  • Coccygeus
    
    • Consider it the ischo-coccygeus
    • Origin ischial spine and insertion coccyx and lower sacrum
• Surface anatomy:
  
  • Urogenital triangle
    
    • Pubic symphysis anteriorly
    • Ischial tuberosity bilaterally
  • Anal triangle
    
    • Ischial tuberosity bilaterally
    • Coccyx posteriorly
  • Ischial spine is palpable on vaginal examination palpated at about a finger-length into the vagina, at 4 and 8 o’clock. They are felt as bony prominences.

Innervation:

• Perineal branches of S3-4
• Inferior rectal branch of the pudendal nerve (external sphincter)

Relevance to operations:

• Relevance in both APR, fistula in-ano and perianal sepsis

Question 6

Pudendal nerve

Answer 6

• S2-3-4 nerve roots
• Emerges from just deep to the ischial tuberosity inferior to the sacrospinous ligament)
• Supplies external anal sphincter

Question 7

Anatomy Ureter

Answer 7

• Definition:
  
  • Bilateral, 25cm long, retroperitoneal muscular tubes that carry urine from the kidney to the bladder
  • Narrows in 3 places: pelviureteric junction, pelvic brim and vesicoureteric junction
• Embryology:
  
  • The kidneys ascend from the pelvis to the lumbar region as the embryo lengthens, the ureter grows to length with them from the ureteric bud
  • The ureteric bud is derived from caudal mesonephric duct at the base of the urogenital sinus which will become the trigone of the bladder
  • Males (relation to vas)
    
    • The vas deferens is also derived from the caudal mesonephric duct but more medially and caudally (think about where prostate lies in relation to bladder)
    • As the kidney “ascends” along the posterior wall of the lumbar region, the gonads “descend” anteriorly and medial to the ureters
    • Thus the vas are draped over the insertion of the ureters into the trigone
• Surface anatomy:
  
  • The right ureter is found at the pelvic brim as it crosses the iliac artery bifurcation
• Surrounding structures and relations:
  
  • Course:
  • Arises from the renal pelvis and descends inferiorly towards the bladder/pelvis on the anterior surface of the psoas major muscle.
  • The ureters cross the pelvic brim then run posteroinferiorly on the lateral walls of the pelvis, and curve anteromedially to enter the posterior aspect of the bladder at the VUJ
  • The ureter is divided into abdominal and pelvic parts. The abdominal part lies retroperitoneal on the medial part of the psoas major muscle and is crossed by the gonadal vessles
  • It enters the pelvis by crossing the division of the common iliac vessels. The pelvic part runs downward on the lateral pelvic sidewall, along the anterior border of the sciatic notch. It lies anterior to the hypogastric artery?, and medial to the obturator nerve. It inclines medially to enter the bladder at the lateral angles of the trigone
  • In females the ureters pass under the uterine arteries (water under the bridge)
  • In males, the ureters pass under the vas deferens
  • Relations
    
    • Anterior
      
      • Right
        
        • Duodenum (D2)
        • R gonadal artery
        • R colic artery
        • Ileal mesentery, SMA
      • Left
        
        • L gonadal
        • L colic
        • Sigmoid mesentery
    • Posterior
      
      • Psoas muscle
      • Genitofemoral nerve
      • SI joint
      • Bifurcation of CIA
    • Medial
      
      • Right
        
        • IVC
• Arterial supply:
  
  • Segmental from the renal, gonadal, common iliac, vaginal, hypogastric and inferior vesicle
• Venous drainage:
• Innervation:
• Lymphatics:
• Structure within the organ and cell types:
• Relevance to operations:
  
  • Females
    
    • Looking from posteriorly (like laparoscopic) from top down (A->P) around the uterus
      
      • Bladder
      • Round ligament
      • Tubes draped over by broad ligament (which covers everything below)
      • Uterusligament of ovaryovarysuspensory ligament (of ovary) containing ovarian (gonadal) vessels
      • Cardinal ligament (transverse cervical ligament – containing uterine artery*)
      • Ureter
      • Uterosacral ligament
    • *At the midplane of the pelvis, the ureter is crossed superior by the uterine artery travelling from anterior to posterior (from proximal to distal/lateral to medial & relative to the ureter). Here it tunnels into the cardinal ligament, approximately 1.5 to 2.0 cm lateral to the cervix near the internal cervical os and vaginal fornices as it enters into the trigone of the bladder

Question 8

Innervation of the GIT

Answer 8

• The gut has dual innervation with intrinsic and extrinsic components
• It is able to function independently with the intrinsic enteric nervous system but is modulated by the extrinsic autonomic nervous system
• ANS synapses with the Enteric nervous system
• Enteric nervous system consists of myenteric and submucosa plexus
  
  • Myenteric plexus is situated between the outer longitudinal and middle circular layers, co-ordinates muscular contractions
  • Submucosal plexus, co-ordinates blood flow/secretion/absorption
• ANS Parasympathetic nerves
  
  • Generally stimulatory to GIT smooth muscle but inhibitory to sphincters
  • 2 different pathways (1 each for fore-midgut & hindgut)
  • Foregut/midgut receive preganglionic nerve fibres from the medulla (dorsal motor nucleus of vagus) which travel along the right vagus nerve, via the coeliac/(+/- SM) ganglion (actually the para aortic plexus – they don’t synapse in the ganglion) and blood vessels to synapse with the postganglionic neurons in the enteric plexus
  • Hindgut receive preganglionic nerve fibres from the IML (Intermediolateral nucleus) of the S2-4 spinal cord** which travel from anterior/ventral rami along **the pelvic splanchnic nerves (nervi ergentes) via the inferior hypogastric plexus (bilateral) to synapse with the enteric plexus, some fibres pass to the left colon via the superior hypogastric plexus
• ANS Sympathetic nerves
  
  • Generally inhibitory to GIT smooth muscle but stimulatory to sphincters
  • 2 different pathways (1 each for fore-midgut & hindgut)
  • Foregut/midgut receives preganglionic fibres from intermediate lateral horn of thoracolumbar spinal cord via sympathetic trunk and lesser splanchnic nerves which synapse with postganglionic splanchnic nerves in the coeliac/(+/- SM) ganglion whose fibres travel with blood vessels to synapse with the enteric plexus
  • Hindgut
    
    • Distribution of IMA blood vessels
      
      • Receives preganglionic fibres from the lumbar part of the sympathetic trunk via the lumbar splanchnic nerves which travel to the inferior mesenteric ganglion and post ganglionic fibres travel onward with the IMA to synapse with the enteric plexus
    • Distribution of middle rectal from internal iliac
      
      • Receives preganglionic fibres from the lumbar part (L1-3) of the sympathetic trunk which travel to the inferior hypogastric plexus (via superior hypogastric plexus - L & R pelvic nerves) post ganglionic fibres travel with the parasympathetic nervi ergentes

Question 9

Defaecation physiology

Answer 9

• Colonic mass movements and peristalsis move intestinal contents distally into the rectum
• Rectal filling activates mechanoreceptors in the rectal wall causing awareness of the need to defecate
  
  • As stool reaches the rectum, a small amount is allowed to pass through to the anal canal by an involuntary relaxation of the internal anal sphincter. This action, known as the rectoanal inhibitory reflex, is necessary for anal sampling, which is the process of determining if the rectal contents are of the gaseous, solid, or liquid form.
  • At this time, if defecation is not socially acceptable or convenient, the rectal wall relaxes (defer), and the need to defecate subsides temporarily.
• If it is a proper time to defecate, the person generally either sits or squats depending on their environment (When defecation is desired, the anorectal angle is voluntarily straightened (which is facilitated by squatting or sitting), and abdominal pressure is increased by straining)
  
  • Next, contraction of the abdominal muscles and performing the Valsalva maneuver while simultaneously relaxing the external anal sphincter and puborectalis muscle will expel feces from the body due to the pressure gradient generated between the rectum and anal canal.
• After fecal expulsion, the closing reflex occurs, which involves the external anal sphincter regaining its tone to maintain continence at rest

Question 10

A beautiful picture of splenic flexure mobilisation

Answer 10

Question 11

What is the rectum?

Answer 11

• Rectum
  
  • Starts from the:
    
    • 1. S3 (6cm distal to sacral promontory)
    • 2. Taenia coli fuse/coalesce into a continuous layer
    • 3. Absence of epiploic appendages
    • 4. No haustra/sacculations
    • 5. No intraperitoneal mesentery
    • And continues to the levator ani
• 15cm – final 3cm is anal canal
• Internal valves of Huston (3 semi lunar lateral curves)
  
  • Upper part to the right
  • Middle to the left
  • Lower to the right
• Peritoneal reflections
  
  • Proximal 1/3 anterolateral covered
  • Middle 1/3 anterior covered
  • Distal 1/3 extraperitoneal
• Mesorectum
  
  • Layer of fat around the outside of the rectum
  • Contained by the mesorectal fascia
  • Continuous with the sigmoid mesentery
  • Contains vessels and lymphatics
  • Tapers to finish at the levator muscles
• Waldeyes fascia
  
  • Posterior strong fascia that overlies the sacrum and the coccyx
• Denonvillers fascia
  
  • Anterior to the rectum in men and covers the seminal vesicles and prostate
• Lateral “ligament”
  
  • Middle rectal vessels

Question 12

Carcinogenesis of colorectal cancer

Answer 12

• 3 main known pathways
  
  • Chromosomal instability
    
    • 75% of cancers and those with FAP
    • Classic mucosa-adenoma-carcinoma pathway
    • Cumulation of mutations
      
      • Sporadic Inactivation of tumour suppressor genes APC and p53
      • Constitutive activation of oncogenes RAS and RAF
    • Adenomatous polyps (85%), sporadic and FAP
      
      • Multiple cumulative genetic changes happen that progress the adenoma into a carcinoma and onto metastatic
      • Inactivation in the APC gene, this causes early adenoma
      • KRAS mutation (50% of CRC will have this and can be targeted by epidermal growth factor inhibitors)-> progress early adenoma into intermediate adenoma
      • SMAD2-4 and CC mutation intermediate into late adenoma
      • TP53 mutation late adenoma into a carcinoma
    • Jevon Puckett “A KRASzy Disease Process”
      
      • APC
      • KRAS
      • DCC (deleted in colorectal cancer) or SMAD4
      • P53
  • Microsatellite instability & Hypermethylation/(CIMP) CpG Island Methylator Phenotype
    
    • 15% of cancers
    • Sporadic or familial mutation in DNA mismatch repair genes
    • BRAF mutation

Question 13

Pathology report CRC (RCPA)

Answer 13

• Macroscopic
  
  • Operative procedure
  • Specimen length
  • Tumour site
  • Tumour dimensions
  • Distance to the closest cut end
  • Perforation
  • Rectal
    
    • Distance to the non peritonealised circumferential margin
    • Relationship to the anterior peritoneal reflection
    • Specimen quality (Quirke grade)
      
      • Plane of mesorectal excision
        
        • N/A
        • 3 Mesorectal fascia (complete)
        • 2. Intramesorectal (near complete)
        • 1 Mucscularis propria (incomplete)
      • Plane of sphincteric excision
        
        • Extralevator – sphincteric – intersphincteric
      • Plane of mesocolic excision
        
        • Mesocolic plane – intramesocolic – muscularis propria
  • Peritoneum
    
    • Tumour invades to peritoneal surface
    • Discrete nodule along the serosal surface
• Microscopic features
  
  • ​Histological subtypes
    
    • Common:
      
      • Adenocarcinoma not otherwise specified
      • Medullary
        
        • Sheets of epithelioid neoplastic cells
        • Pushing border
        • Tumour infiltrating lymphocytes
        • Associated with lynch
        • Good prognosis
      • Signet ring cell adenocarcinoma
        
        • <1% of adenocarcinomas
        • At least 50% of tumour cells to show signet cell features
        • Poorly differentiated, high grade
        • Associated with lynch
      • Mucinous adenocarcinoma
        
        • 10% of adenocarcinomas
        • >50% tumour volume of extracellular mucin, if less than 50% then called a mucinous component
        • Poorly differentiated, high grade
    • Others:
      
      • Micropapillary
      • Serrated
      • Cribiform
      • Comedo
      • Adenosquamous
      • Spindle cell
      • Undifferentiated
• Histological tumour grade
  
  • Meaning gland formation differentiation (only used in adenocarcinoma NOS and mucinous adenocarcinoma)
    
    • Low grade >50%
    • High grade <50%
• Depth of invasion
  
  • T stage
  • Measurement of invasion beyond muscularis propria (T3 tumours)
  • Inflammatory cell infiltrate
• Lymphovascular (actually lymph and venous) invasion
  
  • Poor prognostic feature
  • Small (lymphatic, capillary or venular) vs large vessel (vein intra or extra mural)
• Perineural invasion
• Lymph node status
  
  • Number examined
  • Number involved
  • Apical node involvement
  • Ratio of involved to examined
• Discontinuous extramural deposits not associated with lymph nodes
• Tumour budding
  
  • For non-mucinous and non-signet
  • Tumour budding is defined as single cells or clusters of up to four tumour cells at the invasive front of carcinomas. It is considered to be the morphological manifestation of epithelial mesenchymal transition
  • Budding score
    
    • 1 low (0-4 buds)
    • 2 intermediate (5-9 buds)
    • 3 high (10+ buds)
  • Adverse prognostic feature
• Response to neoadjuvant (modified AJCC )
  
  • No treatment
  • Complete response (score 0)
  • Near complete response (score 1)
  • Partial response (score 2)
  • Poor or no response (score 3)
• Margins
  
  • Longitudinal
  • Circumferential
• Distant metastasis
• Co existent pathology
  
  • Polyps, synchromous carcinoma, other
• Microscopic residual tumour status (completeness of resection)
  
  • R0-R2
• Ancillary findings
  
  • BRAF V600E
    
    • Mutation common in sporadic MMR deficient tumours
    • Rare in Lynch
  • MLH1 promoter methylation testing
  • MMR status by MSI testing
    
    • MS, MSI low, MSI high
  • RAS
    
    • Mutated or wild type
    • Needed when metastatic disease
  • Neuroendocrine markers
• ———– below additional notes———

Patients with KRAS mutation - unlikely to benefit from anti EGFR therapy

Patients with BRAF mutation - unlikely to benefit from anti EGFR therapy

Patients with BRAF mutation - but would benefit from BRAF inhibitors

MSI high patients - likely to benefit from PD-1 inhibitor (pembrolizumab)

HER2 overexpressors- may benefit from targeted HER2 therapy (trastuzumab)

• CK20, CK7, CDX2, SATB2+ staining positive
• BRAF or KRAS mutation
  
  • BRAF
    
    • Familial lynch (wildtype) vs sporadic cancer (mutated from hypermethylation of MLH1 via serrated pathway)
  • KRAS – important because Cetuximab unable to used for EGFR if this is mutated in the setting of metastatic disease
• MSI histology
  
  • MMR immunohistochemistry MLH1 MSH2 MSH6 PMS2 proteins
  • if under age 70 and proteins missing then PCR test for MSI for germline testing (lynch)
  • Typically poorly differentiated
  • Crohns like inflammatory reaction
  • Lots of tumour infiltrating leukocytes (TILs)
  • No precursor lesion seen
  • Some subtypes such as mucinous/signet/medullary are MSI-H

Question 14

TNM staging colorectal

Answer 14

T; depth of tumour invasion

T1; into submucosa

T2; into muscularis propria

T3; through muscularis propria into surrounding pericolic tissues

T4a; penetrates through the adventitia (retroperitoneal) or visceral peritoneum/serosa (<-same thing)

T4b; into surrounding organs or structure

–

N0

N1; 1-3

N2; 4+

–

M0

M1; distant site or peritoneal surface

Question 15

Prognosis in CRC

Answer 15

Rectal cancer prognosis 5 year overall survival rates

• Stage1 92%
• Stage 2 84%
• Stage 3 64%
• Stage 4 11%
• Break into clinical, pathological, molecular, treatment
  
  • Clinical
    
    • Obstruction/perforation
    • High preoperative stage
    • High CEA >5ng/ml
  • Pathological
    
    • Right side worse than left
    • Stage
    • Poor differentiation
    • Extramural vascular/venous invasion
    • Prescence of mucin
    • <12 LN harvested
    • Absence of Peritumoral lymphocytes and crohns like aggregates (seen in MSI H tumours which have a better prognosis)
    • Residual tumour
    • Anterior location and low tumour position
    • CRM <1mm
  • Molecular
    
    • Mutations of KRAS BRAF (don’t respond to immunotherapy
    • dMMR MSI-H (better prognosis)
  • Treatment
    
    • Poor response to neoadjuvant
      
      • Modified Ryan Scale
        
        • 0 Complete response
        • 1 Near complete response
        • 2 Partial response
        • 3 Poor or no response
• MSI and BRAF mutation screening:
  
  • This approach would allow almost all cases to be categorized and managed appropriately
  • Lynch syndrome patients would need screening for other Lynch syndrome–associated malignancies and counselling of family members
  • Patients with sporadic MSI would be apprised of their superior prognosis and potential lack of response to 5-FU chemotherapy
  • MSS cases could plan for a poorer prognosis but could also potentially take advantage of 5-FU
• Circulating tumour DNA (ctDNA)
  
  • Big deal in prognosis

Question 16

Define TME

Answer 16

Enbloc resection of the mesorectum intact mesorectal fascia, removal of the regional LNs, decreases regional recurrence by 2/3s

Defintion of TME: a precise, sharp dissection between the visceral and parietal layers of the endopelvic fascia to ensure en bloc resection of the mesorectal envelope, lymphatics, and vascular/perineural tumor deposits with the primary rectal cancer

Question 17

Steps anterior resection

Answer 17

• Abdominal exploration
• Medial to lateral dissection
  
  • IMV high at inferior border of pancreas
  • Mobilisation splenic flexure and L colon for length
• IMA high
• Pelvic dissection TME
• 2cm distal to cancer margin (2cm fresh, 1cm fixed), >1mm CRF radial margin
• Tension free well vascularized anastomosis
• Diverting ileostomy (neoadjuvant, low or difficult, consider patient and bowel) – reversed at 6 weeks if well (check anastomosis with contrast enema)

Question 18

Dukes classification

Answer 18

A; limited to the muscular wall

B; through the muscular wall

C; involved lymph nodes

D; distant metastasis

Question 19

Liver metastasis (background stats, resectability)

Answer 19

Stats

• 20% of patients present with liver metastasis synchronously
• 2/3 of CRC patients develop distant metastasis
• Over half of colorectal patients will develop liver metastasis at some point
• Rectal cancer metastasis (liver 70%, Lung 50%, bone 12%, CNS 8%)
• Most recurrence occur within 3 years
• Most liver metastasis are not resectable (80-90%)

Resectability (patient, oncological & technical factors)

• Patient factors
  
  • Fitness for surgery (age, cardiopulmonary status)
  • Preference
• Oncological factors
  
  • Primary cancer
    
    • Resectable for cure
  • Extrahepatic disease
    
    • Limited extrahepatic disease amenable to surgical resection or long-term control with adjuvant therapies may be considered for a hepatic resection. (lung mets better than portal or retroperitoneal nodes)
  • Intrahepatic disease
• Technical factors
  
  • Old guidelines more strict (ESMO 2013 Steele et al)
  • Newer guidelines less conservative (SSO 2006, AHPBA 2013, NCCN 2021)
  • R0 resection achievable (aim >1mm MD Anderson study)
  • Adequate functional of future liver remnant (FLR)
    
    • 2 contiguous segments
    • Preserved vascular inflow & outflow, biliary drainage
    • FLR normal >20(27)%, chemotherapy injured 30%, cirrhosis 40%
    • If borderline; appropriate regenerative response post PVE

Question 20

Principles of screening test

Answer 20

• Important health problem
• Detectable in early stage
• Well understood biology
• Acceptable treatable for disease in the early stage
• Accurate screening method
• Better prognosis with early detection
• Non invasive method/acceptable to population
• Agreement on the screening population
• Affordable – screening should decrease total healthcare expenditure
• Continuous process

Question 21

FIT

Answer 21

• Tests directly for human globulin
• Positive predictive value (true test positive/total test positive) 16% = 1 in 6 for advanced adenoma or cancer
• Negative predictive value (true test negative/total test negative) 97.5% for advanced adenoma/cancer, cancer 0.1% or 1:1000 negative tests will actually have an invasive cancer
• The current NBCSP (iFOBT screening every 2 years) requires 56 colonoscopies to prevent one colorectal cancer death, assuming 100% adherence to screening recommendations

Question 22

FAP

Answer 22

Familial Adenomatous Polyposis syndrome

• Definition:
  
  • Autosomal dominant inherited condition
  • Characterized by multiple colonic polyps, high risk of colorectal and other cancers
  • – classically diagnosed as >100 colonic polyps – still useful because only 80% demonstrate APC gene mutation
  • Garners syndrome (polyps, epidermoid cysts, osteomas)
  • Turcotts (colonic polyps and brain tumours)
• Incidence/epidemiology:
  
  • <1% of all CRC
• Aetiology & risk factors:
  
  • 80% familial, 20% sporadic
• Pathophysiology:
  
  • Adenomatous Polyposis Coli (APC) gene mutation q5
  • Tumour suppressor gene
  • Deactivation of the protein which normally regulates b catenin-> increased b catenin which increases cellular growth processes->inappropriate cell growth-> polyps
  • Autosomal dominant
  • Can be sporadic
  • 3 phenotypes
    
    • Mutation Codon 157-1595 – 100% lifetime risk
    • (attenuated) mutation 5 prime and 3 prime ends – 70% risk of right colon cancer
    • Mutation 1309 codon mutation – 100% lifetime risk
• Clinical manifestations:
  
  • Polyposis syndromes should typically be considered in patients with
    
    • Greater than 20 lifetime adenomas, or
    • Desmoid tumour or other extracolonic manifestations of FAP, or
    • Family members of individuals with known FAP, AFAP, or MAP
  • Testing for: known family history, personal history polyps 10 under 30 or 20 any age
  • 3 phenotypes
    
    • 100-1000 colonic adenomas (culumulative)
    • 10-100
    • >1000 adenomas
• Macroscopic features:
  
  • Extracolonic polyps
    
    • Stomach
      
      • Fundic gland polyps (similar to PPI)
      • Rarely adenomas
    • Duodenum
      
      • Adenomatous
      • Premalignant
      • Form later in life
  • Extracolonic manifestations
    
    • Congenital hypertrophy of the retinal pigment epithelium (CHRPE)
      
      • 75% present
      • Bilateral
• Multiple osteomas
  
  • Mandible, skull, tibia
• Extracolonic cancers:
  
  • Duodenal
  • Desmoid tumours (20% will develop) – see own topic!
    
    • 2^nd greatest cause of death after CRC
    • Soft tissue tumours
    • Sites: SB mesentery, retroperitoneum and the abdominal wall
      
      • Intraabdominal 50%
      • Abdominal wall 45%
      • Trunk/extremities 5%
    • Rarely metastasis but can be invasive
    • Usually arises at site of trauma thus problem at prophylactic colectomy
  • Thyroid cancer
  • Hepatoblastoma
    
    • Young males
  • Extrahepatic biliary tree cancers
  • Adrenal tumours
    
    • Benign adenomas non functional
  • Brain tumours
    
    • Astroblastomas or gilalblastomas
  • Epidermoid inclusion cysts
• Multiple adenomatous polyps
  
  • Throughout colon and rectum
  • Childhood begins
• Microscopic features:
• Investigations:
  
  • Surveillance (eviQ guidelines check)
    
    • Gastroscopy
      
      • Spigelman Staging System
        
        • Rates duodenal polyps by number, max size, histology and dysplasia
        • Categories (points 1-3)
        • Number: 1-4, 5-20, >20
        • Max size: 1-4, 5-10, >10
        • Histology: tubular, tubulovillous, villous
        • Dysplasia: mild, mod, severe
        • Score >7 = high risk for invasive cancer (2%); particularly 9-12 points –> risk 36%.
        • Zero = scope 4 yearly
        • 1 = 3 years
        • 2 = 1-3 years
        • 3 = 6-12 months +/- EUS
        • 4 = EUS and consider surgery
        • Normal gastroscopy + side viewing scope to look at ampulla
    • Lower endoscopy
    • If known mutation
      
      • Flexi sigmoidoscopy annual from age of 10 years then change to colonoscopy once adenoma found (mean age 15 first polyps)
      • Colonoscopy 1 yearly until prophylactic colectomy
• Treatment:
  
  • Non operative
    
    • No role for chemoprevention
  • Operative
    
    • All FAP patients, 15-25 years old depending on phenotype and patient preferences
    • Consider leaving completion proctectomy until after family done, need to check rectal stump frequently

Question 23

MAP

Answer 23

MUTYH

-MAP (MUTYH-Associated Polyposis)

• Definition:
  
  • MUTYH-associated polyposis is a recessively inherited predisposition to adenomatous colorectal polyps and early onset colorectal cancer due to biallelic mutations in the MUTYH gene
  • Autosomal recessive- the only one
• Incidence/epidemiology:
  
  • 1-2% of the general population carry 1 gene mutation
  • Biallele expression of MUTYH mutation is <1% of CRC
• Aetiology & risk factors:
• Pathophysiology:
  
  • MUTYH gene mutation, gene responsible for base excision repair
  • Germline MUTYH mutations predispose to developing somatic APC and KRAS mutations
  • Prevents DNA repair development of polyps and cancers
  • Autosomal recessive
• Clinical manifestations:
  
  • Colonic polyps 20-100 but can have >100
  • If tested for FAP but no APC mutation found
  • Family history
  • Synchronous or early onset cancer (under 50)
• Macroscopic features:
  
  • Extracolonic cancers
    
    • Duodenal
    • ?Breast
  • Colonic
    
    • 10-100 cumulatively
    • Occurs older age
• Microscopic features:
  
  • Colonic
    
    • tubular or tubovillous adenomas
• Investigations:
  
  • Surveillance colonoscopy every 2 years from age of 18
• Treatment:
  
  • Non operative
    
    • Genetic testing if cumulatively more than 20 polyps
  • Operative
    
    • No prophylactic colectomy, unless unable to manage polyps endoscopically then ileorectal anastomosis with surveillance of rectum
• Prognosis:
  
  • CRC
    
    • 80% cancer risk
    • Later presentation
  • If monoallelic MUTYH mutations are present in 1 to 2% of the population and may confer, on average, a 1.5- to 2-fold increase in the risk of colorectal cancer

Question 24

Familial Juvenile Polyposis syndrome

Answer 24

• Definition:
  
  • Autosomal dominant inherited condition multiple hamartomatous polyps with histology characteristic of juvenile polyps occur in the gastrointestinal tract
  • • 5 juvenile polyps in the colorectum or juvenile polyps elsewhere in the gastrointestinal tract
  • Or any juvenile polyps with family history
• Incidence/epidemiology:
• Aetiology & risk factors:
• Pathophysiology:
  
  • 50% SMAD4 gene mutation, chromosome 10
  • BMPR1A mutation
  • TGFb signalling pathway
  • Can become adenomatous and therefore carcinoma risk
  • Associated with hereditary haemorrhagic telangectasia
  • Associated with other congenital problems including malrotation, hydrocephaly and cardiac problems
• Clinical manifestations:
  
  • Intussusception and bleeding
  • Rectal bleeding in child
  • Clubbing
• Macroscopic features:
  
  • 100s of polyps throughout GI tract, usually right colon
  • Cherry red
• Microscopic features:
  
  • Harmatomatous polyps
  • Inflammatory stromal tissue with mucus-filled cystic glands
• Investigations:
  
  • Screening colonoscopy from 12-15 years, annual if polyps found or 3 yearly until polyps found
  • Gastroscopy
• Treatment:
  
  • Non operative
  • Operative
    
    • Colectomy not indicated, unless unable to manage endoscopically
    • Total colectomy or proctocolectomy
• Prognosis:
  
  • Gastric duodenal and pancreatic cancer risk also
  • 30-40% lifetime CRC risk

Question 25

Serrated polyposis syndrome

Answer 25

• Definition:
  
  • Criteria
    
    • ≥ 5 serrated polyps ≥5mm proximal to the rectum, with ≥ 2 of these being >10mm
    • Any number of serrated polyps proximal to the sigmoid colon in an individual who has a first-degree relative with serrated polyposis syndrome
    • > 20 serrated polyps of any size, but distributed throughout the colon.
• Incidence/epidemiology:
• Aetiology & risk factors:
  
  • Unknown
  • Family history
• Pathophysiology:
  
  • Unknown mutation at the moment
• Clinical manifestations:
• Macroscopic features:
• Microscopic features:
• Investigations:
  
  • Colonoscopy every 1 to 3 years with the aim to remove all polyps ≥ 5mm.
  • Age 40 or 10 years younger than the youngest age of serrated polyposis syndrome diagnosis in the family, whichever comes first
• Treatment:
  
  • Non operative
  • Operative
  • if the number and size of polyps make it impossible endoscopically control, colectomy and ileorectal anastomosis should be considered
• Prognosis:
  
  • More polyps = more cancer

Question 26

PTEN

Answer 26

• Definition:
  
  • Autosomal dominant inherited mutation caused by PTEN mutation, multiple hamartomatous polyps and associated with colorectal, breast, endometrial and thyroid cancer
  • Cowden syndrome
  • Colorectal
• Incidence/epidemiology:
• Aetiology & risk factors:
• Pathophysiology:
  
  • Mutation in tumour suppressor gene chromosome 10
• Clinical manifestations:
  
  • Multiple hamartomatous polyps in stomach and colon
  • Extracolonic mucocutaneous lesions
  • Gylcogenic acanthosis of the oesophagus (if extensive, otherwise is probably benign)
• Macroscopic features:
  
  • Colonic polyps
  • Mucocutaneous lesions include trichilemmoma, acral keratosis and oral papilloma
  • Macrocephaly; dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos disease)
  • Breast fibroadenoma, fibrocysttic disease and carcinoma
  • Thyroid goiter
• Microscopic features:
  
  • Colon polyps: nondysplastic epithelium, dilated glands, expanded stroma; histologically similar to juvenile polyps; may also show intramucosal lipomas
• Investigations:
  
  • ?unclear how frequent colonoscopy
  • Cleveland clinic risk calculator to help determine genetic testing
• Treatment:
  
  • Non operative
  • Operative
• Prognosis:
  
  • 15-25% risk CRC
  • 30-50% breast cancer risk
  • 5% thyroid cancer (follicular)
  • CNS/cerebellar gangliocytoma
  • Endometrial cancer
  • Adenomas or MN goitre thyroid
  • Fibrocystic change in breast

Question 27

Revised Amsterdam criteria?

Answer 27

• Lynch
  
  • 3+ HNPCC associated family cancer:
    
    • CRC
    • Endometrium
    • SB
    • Upper urinary tract (ureter or renal pelvis)
  • 2 successive generations
  • 1 CRC needs to be <50
  • 0 FAP i.e needs to be excluded

Question 28

Mismatch repair genes?

Answer 28

• Autosomal dominant inherited MMR gene mutation 2p or 3p (MLH1, MSH2, MSH6, PMS2)
• MMR chromosome 2p or 3p or epCAM gene (MSH2 gene) mutation
• Tumour suppressor genes: DNA mismatch repair (MMR) gene.
• MMR corrects errors that spontaneously occur during DNA replication, such as single base mismatches or short insertions and deletions. The proteins involved in MMR correct polymerase errors by forming a complex that binds to the mismatched section of DNA, excises the error, and inserts the correct sequence in its place.
• Cells with abnormally functioning MMR are unable to correct errors that occur during DNA replication and consequently accumulate errors. This causes the creation of novel microsatellite fragments.
• NOT THE (Hypermethylation inactivation of promotor region of MLH ) pathway – they normally have BRAF

Question 29

CRC features of lynch, surveillance and treatment

Answer 29

• Loss of MMR, lymphocytic reaction, mucinous with medullary growth pattern, right sided, signet, R side, synchronous
• Surveillance
  
  • Annual colonoscopy from 25 or from 5 years younger than age of family member
  • Gastroscopy annual from 30 years
  • Urine analysis for cytology
  • Consider TAHSBO
• Treatment:
  
  • Non operative
    
    • Aspirin 75-100mg/day from 25 years of age for chemoprophylaxis
  • Operative
    
    • No prophylaxis unless multiple advanced adenoma (right side if elderly and total if young) – if doing segmental resection for cancer consider doing total colectomy [Europena guidelines – only for MLH1 & MSH2, MSH6 & PMS2 not necessarily]
    • TAHSBO
• Prognosis:
  
  • 80% risk of CRC
    
    • MSH6 or PMS2 20% risk
  • Endometrial cancer 33%
  • 9% ovarian
  • 6% gastric
  • <3 urothelial and SB tumours

Question 30

Operative indications for malignant polyps

Answer 30

• Indications for resection
  
  • Haggit 4, SM2-3
  • Poorly differentiated
  • Incomplete margin <1mm
  • Piecemeal removal
  • LVI
  • Tumour budding
  • St Mark’s LN risk calculator
  • Patient factors
• Low-risk malignant polyps have all of the following features:
  
  • Superficial submucosal invasion (<1000 microns i.e. 1mm)
  • Moderate or well differentiated histology
  • No lymphovascular invasion
  • Clear margins
  • No other risk features:
    
    • Malignant invasion depth >2mm
    • Invasion width >3mm
    • Tumour budding and cribriform architecture
• In these cases, where the endoscopist is certain that the lesion has been completely removed, then the neoplasm should be considered cured by endoscopic polypectomy.

Question 31

Risk of lymph node metastasis in malignant colorectal polyp

Answer 31

• Haggit classification
  
  • Level of invasion into a pedunculated polyp
  • Sessile polyps are level 4
  • Risk of LN metastasis
    
    • Level1-3: very low
    • Level 4 only: 12-25% (need resection)
• Kikuchi level (see diagram below)
  
  • Used for sessile polyps
  • Submucosa divided up into thirds (sm1,2,3)
    
    • SM1: 2%
    • SM2: 8%
    • SM3: 28%
  • Note above [2 + 8 = 28] for Kikuchi & Level 4 is the same as Kikuchi, so it depends, but is up to 28%

Question 32

Hamartomatous polyps

Answer 32

• Juvenile & Hamartoma
  
  • Associated with
    
    • Peutz Jaghers disease
    • Familial juvenile polyposis
    • Cowdens syndrome or PTEN syndrome
  • Rounded, pedunculated, abnormal colour (cherry-red)
  • Connective tissue, smooth muscle, lamina propria, inflammatory cells
  • Anywhere throughout the GI tract (SB intussuception)
  • Autosomal dominant

Question 33

Demoid tumours

Answer 33

• Definition:
  
  • Well differentiated mesenchymal (myofibroblasts) tumour that is locally invasive
  • Also known as aggressive fibromatosis
• Incidence/epidemiology:
  
  • Rare 0.5 per 100,000
  • Peak age 30-40
  • 10% associated with FAP, note 20% of FAP will develop
• Aetiology & risk factors:
  
  • FAP
  • High oestrogen states
  • Trauma
• Pathophysiology:
  
  • Genetic mutation
    
    • 85% have a mutation in the CTNNB1 encoding beta-catenin pathway
    • FAP APC mutation
  • Cause displacement/obstruction i.e. hydroureter, SBO
  • Desmoid tumours are a type of soft-tissue tumor that come from fibrous tissue. They are related to connective tissue cancers called sarcomas, but desmoid tumors are not cancer because they do not spread to other parts of the body.
• Clinical manifestations:
  
  • Abdominal wall
    
    • Enlarging mass, smooth
  • Intra-abdominal
    
    • SB obstruction
    • Hydroureter
  • Extra-abdominal
    
    • Mass
• Macroscopic features:
  
  • Firm, rubbery, ill-defined, infiltrative masses
• Microscopic features:
  
  • Differentiated fibroblasts and myofibroblasts within collagenous stroma
  • Uniform spindle cells resembling myofibroblast
  • Histology: long, sweeping fascicles with thin walled vessels and microhaemorrhages; bland cells with mild to moderate cellularity and minimal atypia
    
    • Immunohistochemistry: SMA+ (smooth muscle actin) and nuclear beta catenin+
    • Molecular: CTNNB1 and APC mutations may be seen
  • Spindle, beta-catenin
• Investigations:
  
  • Imaging
    
    • MRI & CT
  • Endoscopy for ?FAP
  • Biopsy
• Staging of Desmoids
  
  • Size, doubling rate, location
  • 0 = minimal lesion, doubling rate unknown
  • 1 = <5cm, >24m doubling rate, extra-abdominal
  • 2 = 5-10cm, 12-24m doubling, abdo wall
  • 3 = 10-20cm, 6-12m doubling, mesentery without obstruction
  • 4 = >20cm, 1-6m doubling, mesentery with obstruction.
• Treatment: (this area is super difficult)
  
  • Operative
    
    • Surgical resection
      
      • May need SB transplant
      • Abdominal wall reconstruction
      • Complex..
  • Non operative
    
    • NSAID
    • SERM (tamoxifen)
    • Cytotoxic (chemotherapy)
    • Targeted (Tyrosine Kinase Inhibitors)
      
      • Sorafenib (multiple targets)
      • Imatinib (c kit)
• Prognosis:
  
  • 2^nd leading cause of death for FAP patients
  • Locally recurrent but do not metastasize
  • 10% will spontaneously regress

Question 34

Causes of appendiceal neoplasm, mucocele and PMP

Answer 34

• Neoplasm by cell lineage [epithelial vs neuroendocrine]
  
  • Epithelial
    
    • Mucinous
      
      • Low-grade appendiceal mucinous neoplasm (LAMN) (also called cyst adenoma)
      • High-grade appendiceal mucinous neoplasm (HAMN)
      • Serrated polyp
      • Mucinous adenocarcinoma
    • Non mucinous
      
      • Adenoma
      • Adenocarcinoma
    • Goblet cell adenocarcinoma*? Are these neuroendocrine?
  • Non epithelial
    
    • Neuroendocrine
      
      • Well differentiated neuroendocrine tumours (previously called carcinoid)
      • Poorly differentiated neuroendocrine carcinoma
    • Lymphoma
    • Sarcoma
• Mucocele causes [non neoplastic vs neoplastic]
  
  • Non neoplastic
    
    • Simple mucocele/retention cyst
  • Neoplastic
    
    • Serrated polyp
    • Low-grade appendiceal mucinous neoplasm (LAMN)
    • High-grade appendiceal mucinous neoplasm (HAMN)
    • Mucinous adenocarcinoma
• Pseudomyxoma peritonei (PMP)
  
  • LAMN
  • HAMN
  • Mucinous adenocarcinoma
  • Ovarian mucinous neoplasm (rare)

Question 35

PMP pathophysiology

Answer 35

• As the lesion grows and occludes the lumen, mucus accumulates and the appendix ruptures or the mucin dissection of mucin through periappendiceal connective tissues onto the serosal surface with/without atypical epithelium.
• The peritoneum is then seeded with mucus-producing cells, which continue to proliferate and produce mucus.
• The progressive accumulation of copious amounts of mucinous fluid gradually fills the peritoneal cavity, resulting in the characteristic “jelly belly”.
• Inevitably, this condition progresses to intestinal obstruction, which is fatal without treatment.
• A distinctive feature of PMP is the redistribution phenomenon. The mucus and the cells it contains follow the normal flow of peritoneal fluid and are “redistributed” within the peritoneal cavity to sites of fluid absorption through lymphatic lacunae and lymphoid aggregates. Consequently, the tumor tends to spare mobile loops of small intestine but accumulates in other sites such as the pelvis, paracolic gutters, omentum, and liver capsule. Bulky accumulations can form as the mucus is absorbed and epithelial cells “filtered out” and concentrated. Peristalsis and mobility of the SB excludes it till later.
• Omentum has lots of phagocytic cells that trap the tumour cells, thus preferentially involved with omental caking

Question 36

histo features neuroendocrine appendix

Answer 36

• • Poorly differentiated neuroendocrine carcinoma
    * High grade (G3): > 20 mitoses / 2 mm2 or > 20% Ki67 index
    * Note that 10 HPF is eqivolent to 2mm2 these days but not previously when HPF meant x40 magnification
    Well differentiated neuroendocrine tumour
    
    • Stains: serotonin, chromogranin A, synap-to-physin
    • Nests surrounded by palisading cells on the periphery and separated by trabecula
    • Stippled/salt & pepper chromatin, nucleoli small
    • Grading systems for neuroendocrine tumors of the midgut (jejunum, ileum, appendix and cecum):
      
      • Low grade (G1): < 2 mitoses / 2 mm2 and < 3% Ki67 index
      • Intermediate grade (G2): 2 - 20 mitoses / 2 mm2 or 3 - 20% Ki67 index

Question 37

LAMN/HAMN TNM staging

Answer 37

• LAMNs that are confined to the appendiceal wall without invasion or loss of the muscularis propria are classified as Tis(LAMN)
• This is to reflect the excellent outcome for confined LAMNs. The T1 and T2 stages are not used for LAMNs (but are for HAMN).
• LAMNs that demonstrate involvement with either acellular mucin or mucinous epithelium of the subserosa or serosa are classified as T3 or T4a, respectively.
• Acellular mucin involving the appendiceal serosa or mesoappendix is classified as T4a, while mucin involvement of distant peritoneal sites is classified as M1.
• In order to address the improved outcome for cases in which peritoneal dissemination is limited to acellular mucin only, these cases are classified as M1a. Other metastatic categories are M1b, which refers to metastases confined to the peritoneum only, and M1c, which refers to metastases outside the peritoneum.

Question 38

Management of appendiceal lesions

Answer 38

Mucocele - depends on underlying pathology

• Adenocarcinoma = right hemicolectomy
• LAMN/HAMN = appendicectomy +/- caecectomy, mucin cytology, PCI calculation and washout - referral to peritonectomy unit for discussion on surveillance
• Neuroendocrine tumour
  
  • Criteria to encourage formal oncological right hemicolectomy
    
    • R1
    • G3
    • Base (opposed to tip or middle)
    • Mesoappendix invasion >3mm
    • Size >2cm (definite)
    • Size 1-2cm with high risk features
      
      • R1
      • G2
      • LVI
  • For appendiceal NETs ≤2 cm without high-risk features (nodal metastases, lymphovascular invasion, mesoappendiceal invasion, intermediate- or high-grade or mixed histology) that are confined to the appendix and treated with simple appendectomy, we do not recommend routine follow-up

Question 39

Where does anal cancer occur?

Answer 39

• Primary malignancy of the anal canal or perianal skin, arising from glandular, transitional or squamous cells
• Relatively uncommon, vast majority are squamous cell carcinoma
• AJCC definition: “Anus begins where the rectum enters the puborectalis sling at the apex of the anal sphincter complex (palpable as the anorectal ring) and ends at the squamous mucosa blending with the perianal skin.”

Question 40

Anal SCC pathophysiology

Answer 40

• Arising from the squamous epithelium of the mucosa of the anal canal
• SCC arise from precursor lesion anal intraepithelial neoplasia
• HPV infection type 16 & 18
  
  • Infects the basal epithelial cells, preferably transformational zone, cellular proliferation in the mucosa - dysplasia in the transformational zone
  • Chronic infection leads to gene dysregulation and cell growth and progression to precancerous lesions - invasive carcinoma
  • P53 and Rb genes (tumour suppressors) inhibited by HPV E6 and E7 oncoproteins
  • Anal Intraepithelial Neoplasia (AIN)
    
    • Grading 1-3 based on depth of affected mucosa (depth in thirds)
    • Grade 3 = carcinoma in-situ
  • AIN now replaced in terminology low & high grade squamous intraepithelial lesion (LSIL & HSIL)
    
    • LSIL (AIN 1)
    • HSIL (AIN 2-3)
• Principal sites of distant metastases are the liver, lung, para-aortic nodes and bones. However, metastases have been described in the kidneys, adrenals and brain.

Question 41

Anal cancer macroscopic

Answer 41

• AIN = plaque, raised, scaly, sometimes pigmented
• Cancer = Ulcerated lesion with rolled indurated everted edges
• Palpable inguinal/femoral and perirectal lymph nodes
• Other anorectal pathology may coexist, confusing the picture.

Question 42

Staging anal SCC

Answer 42

• EUA and biopsy, (should also do full colonoscopy?)
  
  • High resolution anoscopy with magnification
  • Anal canal vs perianal (can you see the edge when the cheeks are spread)
• Staging CT chest/abdo/pelvis
• Locoregional staging with MRI
• PET scan
• Testing for HIV and cervical pap smear for women
• FNA of suspicious groin nodes

Question 43

Treatment anal scc

Answer 43

• Non operative
  
  • AIN
    
    • LSIL (grade 1 AIN)
      
      • Surveillance
        
        • Low risk – GP clinical exam?
        • High risk – EUA in 12 months + biopsy of suspicious lesions, anal mapping in clock face, biopsy of acetic acid lesions
    • HSIL (grade 2-3 AIN)
      
      • Ablation (CO2 laser), coagulation
      • Excision
      • Topical
        
        • Good for widespread mutifocal field change
        • 5FU; antimetabolite that interferes with DNA synthesis, daily for 16 weeks
        • Imiquimod/aldara cream – immune response modifier, 3x per week for 16 weeks – local inflammatory reaction)
      • HPV vaccination
  • Primary chemoradiation is the modality of choice for nearly all anal SCC
    
    • Modified Nigro protocol
    • Mitomycin-c and 5-FU (radiosensitiser) + 50Gy (28 fractions) of RTx (75% cure) including inguinal node exposure even if not involved
      
      • Similar survival to APR
      • 6 weekly EUA – can take 6 months for response to be complete
      • 30% will have local failure and need APR
      • Complications
        
        • Early: Diarrhoea, myelosuppression, skin erythema
        • Late anal stenosis or fistula
      • May need defunctioning stoma
        
        • Indication
          
          • Obstructing
          • Incontinence
          • Perianal fistulas
          • Tenesmus or pain
    • Salvage APR
  • Adenocarcinoma treated like rectal adenocarcinoma (surgical)
• Operative
  
  • If small <1-2cm and fully visible (perianal) with no compromise of the sphincter can do WLE with chemoradiation – need 5mm margins – recurrence rate is high
  • APR
    
    • Indications
      
      • Complications of radiotherapy: radionecrosis, incontinence, fistula
      • Failure of primary chemoradiotherapy
      • If recurrence after chemoradiation
      • Contraindication to chemoradiotherapy
    • Needs myocutaneous flap as previous radiotherapy, will have wound break down

Question 44

Manifestations of Crohns Disease

Answer 44

• Gastrointestinal
  
  • Abdominal pain
  • Diarrhoea
    
    • Malabsorption
    • Bile salt malabsorption
    • Short bowel if previous resection
    • SB bacterial overgrowth
  • Rectal bleeding
  • Perianal disease
  • Intraabdominal fistulas
  • Strictures
  • Terminal ileitis
  • 3-5% CRC adenocarcinoma
• Systemic
  
  • Fever
  • Weight loss (anorexia, food fear, diarrhoea, malabsorption)
  • Fat soluble vitamin deficiency (particularly in ileal disease with loss of bile salt malabsorption loss of absorption of fat soluble vitamins A D E K
  • Osteomalacia (vitamin D)
  • Bleeding (vitamin K)
  • Cholesterol stone formation
  • Steatorrhea (oxilate  renal stones)
• Extraintestinal manifestations
  
  • 50%
  • Skin
    
    • Aphthous ulcers
    • Erythema nodosum
    • Pyoderma gangrenosum
  • MSK
    
    • Arthropathy
    • Sacroiliitis
    • Ankylosing spondylitis
  • CNS
    
    • Eye complications
    • Amyloidosis
  • Biliary
    
    • PSC
    • Hepatitis
    • Cirrhosis
  • Renal and gallstones

Question 45

Microscopic and macroscopic appearence of Crohns

Answer 45

• Transmural inflammation and lymphocytic infiltrate, fissuring, non caseating granuloma, fibromuscular obliteration and nerve fibre hyperplasia in the submucosa
• 3 diagnostic hallmarks
  
  • Non caseating granulomas
  • Intralymphatic granulomas
  • Granulomatous vasculitis
• UC VS CD:
  
  • CD normal goblet cells (depleted in UC)
  • CD less crypt abscesses (more common in UC)
  • Glandular architecture maintained in CD (atrophic in UC)
  • Lymphocytic infiltrate patchy in CD but uniformly heavy in UC
  • Granulomas in CD not in UC,
  • Muscularis propria is thickened in UC but not in CD
  • Heavy subserosal inflammation in CD not in UC

Question 46

goals in crohns management

Answer 46

• Goals
  
  • Not curative
  • Treat acute disease
  • Improve QoL
  • Correct nutritional deficiencies
  • Steroid free remission
  • Minimize hospitalizations and surgery
  • Maintain SB length

Question 47

TPMT

Answer 47

thiopurine methyltransferase

Absence leads to high levelsof 6TGN which has hepatotoxic and myelosuppresion

Question 48

Indications for surgery in crohns

Answer 48

• Indications
  
  • Failed medical management
    
    • Ongoing symptoms despite medical therapy
    • Poor compliance/poor response/adverse side effects
  • Complicated disease
    
    • Acute
      
      • Abscess
      • Perforation
      • Haemorrhage
      • Obstruction (particularly fibrotic)
      • Toxic megacolon
    • Chronic
      
      • Obstructive
      • Fistula
      • Growth retardation in children
      • Neoplastic disease

Question 49

Colonoscopy in IBD

Answer 49

• 8 years after the symptoms of IBD colonoscopy surveillance
• chromendocopy preferable
• Random biopsies less good, 2-4 bx every 10cm

Question 50

Management of Crohns complications

Answer 50

• Strictures
  
  • Inflammatory or fibrotic
  • Endoscopic dilation (<5cm, 50% will avoid surgery after 5 years), 5% risk of bleeding or perforation
  • If long, inaccessible, refractory then surgery
  • Bypass (duodenal or distal gastric)
  • Resection with 2cm margin normal bowel
    
    • End-end (easier to dilate) vs side-side (wider)
  • Plasty
    
    • SB strictures
      
      • Contraindicated in fistula, sepsis, cancer
    • Colonic strictures are treated with resection and reanastomosis (stricturoplasty contraindicated)
    • Types
      
      • [stupid way of remembering these stupid eponymous names
        
        • Heineke-miculicz; easiest to do, hardest to say
        • Finney; fin, end, blind ended
        • McLassey; side to side SS spooning
      • Heineke-miculicz
        
        • <5cm
        • Incise antemesenteric side of bowel 1cm proximal and distal, close transersely
      • Finney
        
        • 10-20cm
        • Incise antemesenteric
        • Fold in half and close in two layers i.e. side to side anastomosis
      • McLassey
        
        • >20cm
      • If >20cm then probably do resection (leak rate 2%)
• Abscess
  
  • Perc drain and IVABx (1/3 will fail)
  • Surgery
• Perforation
  
  • Resection of the disease segment and either end stoma or diverted anastomosis
• Haemorrhage
  
  • Typically from SB mucosal ulceration, can be managed with angiography
  • Laparotomy
• Fistula disease (intraabdominal)
  
  • Perforation/obstruction/phlegmon
  • Remove the disease segment of bowel (or both bits of disease bowel if enteroenteric) and the secondarily involved organ will resolve with primary closure
  • If fistula is going to the duodenum then may require a patch or a roux repair as the primary repair may breakdown
• Colonic crohns
  
  • Extent, symptoms, systemic wellness
  • Segmental resection vs subtotal/end ileostomy
    
    • [CH] If one segment then do segment, if 2+ then subtotal
  • If doing a proctectomy then don’t need to do TME resection and therefore will avoid the pelvic nerves
  • Pelvic pouch
• Perianal disease
• Non operative
  
  • Best to avoid operative intervention
  • Multidiscipinary approach due to the complexity
  • Best medical management
    
    • Inflixamab therapy – monoclonal AB TNFa
  • Fissures
    
    • Don’t respond that well to botox, diltizem or lateral sphincterotomy
  • Skin tags
    
    • Don’t excise them because they reoccur – can be removed for diagnostic purposes (30% have granulomas of CD)
• • Operative
    
    • Draining sepsis
      
      • Incision and drainage
      • Vessel loop for fistula
      • May need mushroom drain/malecot if deep cavity
      • Give antibiotics, ciprofloxacin and metronidazole
    • Preserve sphincter function
    • Fistula
      
      • Seton
      • If active disease then need to do medical management
      • For me, if they aren’t responding with draining seton I would be refering them to a colorectal surgeon for more definitive surgery
      • Options surgically
        
        • Fistulotomy
        • Fibrin glue and plug
        • Endorectal advancement flap
        • Ligation of Intersphincteric Flap LIFT
        • Faecal diversion (high likelihood this would be permanent)
        • Proctectomy

Question 51

Exraintestinal UC manifestations

Answer 51

• Extraintestinal (20% of patients)
  
  • MSK manifestations
    
    • Spondylitis
  • Hepatobiliary
    
    • Primary sclerosing cholangitis
      
      • Idiopathic, chronic, progressive fibrotic disorder
      • Stricturing inflammation and fibrosis of intra and extrahepatic bile ducts
      • PSC + UC = increased risk of primary liver cancer
  • Dermatological
    
    • Erythema nodosum
      
      • Red inflamed nodules on shins
    • Pyoderma gangrenosum
      
      • Pustule plaques that break down into ulcerated areas
      • Usually on legs and can be anywhere (peristomal)
  • Thromboembolic
    
    • DVT, PE
    • Cerebral venous/sinus thrombosis – stroke
  • Ophthalmological
    
    • Uveitis
    • Episcleritis
    • Scleritis
    • Visual impairment

Question 52

UC microscopic

Answer 52

• Mucosal inflammation, ulcers and atrophy
• Goblet cell absence (GC maintained in CD)
• Crypt distortion
• Vascular congestion
• Neutrophils in the epithelium of the crypt and forming crypt abscesses
• Infiltration of the lamina propria with neutrophils, plasma cells and lymphocytes
• Pseudo polyps with granulation over the exposed lamina propria
• Intact muscularis and all inflammation confined to the mucosa
• NOT CD (i.e. transmural inflammation and lymphocytic infiltrate, fissuring, non caseating granuloma, Fibromuscular obliteration and nerve fibre hyperplasia in the submucosa)

Question 53

UC vs crohns antibodies

Answer 53

CD: ASCA

UC: ANCA

Question 54

Acute severe colitis severity?

Answer 54

• Truelove & Whitt
  
  • Mild
    
    • BM<4
    • No blood
    • No systemic toxicity
  • Severe
    
    • >6 bloody BM
    • Systemic toxicitiy
    • Anaemia
    • ESR >30
• Montreal
  
  • Extent and severity
  • Extent
    
    • E1 proctis
    • E2 left sided disease (distal to SF)
    • E3 extensive colitis (proximal to SF)
  • Severity
    
    • S0 clinical remission
    • S1 Mild UC:
      
      • <4BM/day +/- blood
      • no systemic illness,
      • normal inflammatory markers
    • S2 moderate disease:
      
      • 4+ BM,
      • minimal systemic features
    • S3 severe:
      
      • 6+ bloody BM,
        
        • systemic toxicity
          
          • (HR>90, T37.5, Hb<105, ESR 30+)

Question 55

pentasa

Answer 55

• Aminosalicylates (5 ASA)
  
  • Mesalazine (pentasa) or sulfasalazine (salazopyrin)
  • Used more in UC than CD, maintenance
  • MOA not fully understood
    
    • Decreased COX inflammatory mediators inhibition of prostaglandin and leukotriene synthesis
    • Inhibition of cytokines
    • Inhibits both T-cell proliferation and subsequent activation and differentiation
    • Impairment of white cell adhesion and function
  • Can be enema or oral
  • First line in mild-moderate disease

Question 56

• Corticosteroids in IBD

Answer 56

• Budesonide (enteric coated) or IV
• MOA: inhibit the transcription and development of proinflammatory mediators and inhibition of phospholipase A2 (production of inflammatory mediators)
• Used in both UC and CD for induction and acute flares
• Complications
  
  • Weight gain, osteonecrosis, immunosuppression, acne, facial hair, HTN, mood and sleep disturbance, cataracts, osteoporosis

Question 57

Immunomodulators in IBD

Answer 57

• Thiopurines
  
  • Azathiopurine and 6 metcaptopurine (6 MP)
• Maintenance, take 3-4 months to work
• MOA: purine analogues, inhibit cell proliferation, inhibit cytotoxic t cells and NK cells
• Check for thiopurine methyltransferase, if they don’t have this then they can’t metabolise thiopurine and will get bone marrow suppression
• Side effects; pancreatitis, hepatitis, fevers, rashes, bone marrow suppression
• To minimise the risk of infection and adverse effects; screening and vaccination before starting an immunomodulatory drug are important

Question 58

Methotrexate IBD

Answer 58

• Methotrexate
  
  • 6MP and azathioprine are used more commonly
  • MOA: Folic acid antagonist, inhibits t cell activation, downregulates B cells, inhibits methyltransferase
  • Side effects: hepatotoxicity, ulcerative stomatitis, bone marrow suppression, fatigue, pneumonitis, pulmonary fibrosis, renal failure, teratonogenic (beware pregnancy)

Question 59

Biologics in IBD

Answer 59

• Biologics
  
  • TNFa inhibitors
    
    • Infliximab (Remicade) infusion
    • Adalinimab (humeria) subcut injection
    • Measure serum anti TNF levels for dosing
  • Anti integrin therapy
    
    • Vedalizumab
    • Prevents lymphocyte migration into intestinal tissue, slower onset
  • MABs against cytokines
    
    • IL-12 and IL-23
    • Usatakinuzmab (also used for psoriasis)
    • Complications: immunosuppression, malignancy, lymphoma, immunogenicity (psoriasis) paradoxical autoimmune conditions
  • Moderate-severe IBD where other therapy has failed
  • Complicated perianal Crohn’s

Question 60

Stepup approach UC

Answer 60

• Rectal disease
  
  • Foam or suppository enemas
    
    • Mesalazine or steroids (colifoam)
    • 4-6 weeks to work
  • Oral ASA or steroids if they don’t want enema or not responding
• Mild-moderate disease
  
  • Oral sulfasalazine or oral steroids
• Moderate disease
  
  • AZA or 6MP
  • 3 months for maximal effect
  • Consider infliximab
• Severe fulminant colitis
  
  • IV steroids
  • Broad spectrum Abx
  • IV cyclosporin
  • IV infliximab

If not improving on maximal management then consider surgery

Question 61

Toxic Mega Colon criteria

Answer 61

• Criteria:
  
  • Radiographic evidence of TC >6cm
  • 1 of the following
    
    • Fever
    • Tachycardia
    • WCC or anaemia
  • 1 of the following
    
    • Dehydration
    • Altered GCS
    • Electrolyte abnormalities
    • Hypotension

Question 62

TMC pathophysiology (of dilation)

Answer 62

• Inflammation decreased smooth muscle contraction ?nitrous oxide relateddilatation
• As inflammation continues neutrophils secrete proteolytic enzymes and inflammatory cytokines…
• Ischaemia of myenteric plexus

Question 63

Aetiology of diverticular disease

Answer 63

• Pathophysiology:
  
  • Stool size/fibre intake/transit time (Burkitt et al 1972)
  • High pressure from slow transit (Painter et al 1965), sigmoid narrowest part therefore highest pressure according to la places law
  • Meta analysis, not pressure related (Bissett et al 2017)
  • [Frank F]
    
    • Diverticulosis related to aging/collagen & genetics weak points in the muscularis propria where the vasorecta penetrate the bowel wall
    • Diverticulitis related to microbiome & diet/environmental factors
  • Related to aging in the elastin/collagen properties of the colon
    
    • Genetics
    • Connective tissue disorders
      
      • Ehlers Danlos
      • Marfans
    • Race
    • Migrant studies
      
      • Increase in diverticulitis but not diverticulosis
    • Change in collagen/elastin with age
      
      • Increasing elastin with age
      • Increase in type 3 collage
      • Increased cross links between collagen leads to rigidity
  • Dysbiosis – higher rates of Bifidobacterium
  • Diverticulitis is commonly believed to be caused by obstruction of a diverticulum, leading to stasis, ischemia, microperforation, and local infection
  • Inflammatory diverticular colitis, similar to inflammatory bowel, abnormal immune response to gut flora

Question 64

Location of diverticulae within the bowel wall

Answer 64

• 4 defined sites around the bowel wall, all on the mesenteric side (see diagram)

Question 65

Modified Hinchey classification of diverticulitis

Answer 65

Class

CT findings

Stage 0

Mild clinical diverticulitis

Stage Ia

Confined pericolic inflammation/phlegmon

Stage Ib

Confined pericolic abscess (within sigmoid mesocolon)

Stage II

Pelvic, distant intra-abdominal or intraperitoneal abscess

Stage III

Generalized purulent peritonitis

Stage IV

Faecal peritonitis

Question 66

Diverticulitis prognosis (risk recurrent disease)

Answer 66

• If you have diverticulosis your risk of diverticulitis is 5% (?1:20)
• If you have uncomplicated diverticulitis
  
  • Risk of single recurrence 20%
  • Risk of recurrent recurrence 5%
  • 75% no recurrence
• Recurrent disease gets less likely with each attack
• Recurrent disease doesn’t affect survival
• Two types of recurrence
  
  • If early recurrence within 18 months, probably in the same location and more likely to be complicated disease (would benefit from surgery)
  • If late recurrence (>18 months), probably in different location, less severe, avoid operating on
• Complicated disease is most common in the 1 or 2^nd episode
• Following diverticular abscess (managed non operatively)
  
  • @ 12 months
    
    • 50% “successful”
    • 30% failed NOM
    • 15% have elective resection
• Young patients under 50 years have 7.5% chance of needing emergency surgery after single episode of diverticulitis
• Perforated diverticulitis occurs in 1% of patients
• Mortality from free perforated diverticulitis is 15%

Question 67

Appendicitis Alvarado score - mneumonic

Answer 67

MANTRELS

Question 68

Non operative management appendicitis

Answer 68

• Indications
  
  • Fit well patient with no faecolith (instead of surgery) or
  • Abscess needing percutaneous drain (then interval appendicectomy)
• Contraindications
  
  • Sick
  • Peritonitic
  • Moderate free fluid
  • Cancer
  • Immunosuppression
  • Pregnancy
• Failure of NOM
  
  • 10% 48hrs
  • 20% 30 day
  • 30% 90 day (higher faecolith)
  • 40% 1 year
  • 50% 4 years…
  • • others had recurrence but no surgery..
• Risks of conservative management
  
  • Higher complication rate
  • Higher unplanned ICU stay
  • Intrabdominal abscess and perc drainage 2.5 vs 0.5%
  • Antibiotic complications (but not c diff)
  • Higher perforation rate 33 vs16% if failed NOM and needed appendicectomy
• Risk of cancer?
  
  • NOM of periappendicular abscess = 20% cancers in interval appendicectomy and 29% over the age of 40
  • Otherwise uncomplicated <1%
• Follow up
  
  • Complicated appendicitis (perforated, phlegmon, abscess)
    
    • Age 40+
      
      • CT
      • Colonoscopy
      • Interval appendicectomy (3-17% risk of malignancy)
    • Age <40 (WJES 2020)
      
      • No interval appendicectomy unless recurrent symptoms

Question 69

Radiation proctitis pathophys and management

Answer 69

• Acute; mucosal injury
• Chronic; epithelial atrophy, fibrosis, ischaemia, vasculitis (in reverse)
  
  • Chronic radiation proctitis results from progressive epithelial atrophy and fibrosis associated with obliterative endarteritis and chronic mucosal ischemia
• Acute
  
  • Hydration
  • Antidiarrhoeals
  • Butyrate enema
• Chronic
  
  • Sucralfate enema
  • APC
  • Formalin (controversial, APC better)

Question 70

Pseudomembranous colitis management

Answer 70

• Non operative
  
  • Resuscitation
  • Contact isolation
  • Correct fluid and electrolytes
  • Cease the causative antibiotics if C diff
  • 1^st line metronidazole (oral) 400mg TDS for 14 days
  • 2^nd line vancomycin (oral) 125-250mg QID 10 days
  • If severe/ileus; vancomycin can be given IV or retention enema
  • Probiotics
  • Cholestyramine to bind the toxin
  • Faecal transplant?
• Operative
  
  • Indications
    
    • TMC, perforation, bleeding
  • Subtotal abdominal colectomy with end ileostomy

Question 71

Rfs ischaemic colitis

Answer 71

• Age
• Cardiovascular risk factors (HTN, lipids, IHD, diabetes)
• AF
• COPD
• Smoking
• Constipation
• Younger
  
  • Hypercoagulable states
  • Vascular disease
  • Long distance runners
  • Constipation
  • OCP
  • Digoxin
  • Diuretics
  • Calcium channel blockers
  • Cocaine

Question 72

Pruitis ani causes

Answer 72

• 75% of cases coexisting underlying cause
• Faecal incontinence or seepage
• Excessive cleaning or topical creams
• Malignancy
  
  • Rectal cancer or rectal adenomas, anal scc, melanaoma, extramammary pagets
• Inflammation
  
  • Haemorrhoids, fissures, fistulas, rectal prolapse, radiation proctitis and UC
  • Dermatitis, lichen simplex, lichen planus, lichen atrophicus
• Infectious
  
  • Condylomata, candida, syphilis, HSV, anal pinworm

Question 73

Surgical sieve for differential diagnosis

Answer 73

VINDICATE

Question 74

Treatment pruitis ani

Answer 74

• Principle
  
  • Treat the underlying cause
• Avoid high fibre diet to reduce flatuance
• Anal hygiene
  
  • Wash with water only
  • Dab dry (don’t rub)
  • Protection of the perianal skin with zinc oxide
• 1 percent hydrocortisone cream BD (<2 weeks due to skin atrophy
• Nocturnal symptoms an antihistamine
• Topical capsaicin
• Anal tattoo with methylene blue..

Question 75

Stoma dietary advice

Answer 75

• Aim:
  
  • Maintain nutrition, hydration and electrolytes
  • Avoid mechanical obstruction
  • Avoid skin irritation
  • Avoid excess flatus
• Nutrition
  
  • Full fat milk and cheese
  • Double cream (add to soup, mashed potato and puddings)
  • Snack on biscuits and cakes
  • Foods high in protein each day such as fish, tender meat and eggs
• Mechnical blockages - avoid
  
  • Nuts
  • Coconut
  • Celery
  • Mushrooms
  • Sweetcorn
  • Raw fruit skins
  • Bean sprouts and bamboo shoots
  • Dried fruit such as currants and raisins
  • Pith, pips and stones
  • Popcorn
• Flatus - avoid
  
  • Cabbage
  • Beans/lentils/pulses
  • Cauliflower
  • Sprouts
  • Spicy foods
  • Onions
  • Fizzy drinks
  • Chewing gum
  • Leafy green vegetables can cause more wind in the early days. Try root vegetables such as carrots, parsnips and sweet potatoes.
  • Avoid talking and drinking whilst eating and keep your mouth closed whilst chewing
  • Avoid drinking with a straw
  • Eat regularly and avoid long gaps between meals
  • Allow fizzy drinks to go flat
  • Try drinking peppermint drinks such as cordial or tea
  • Eat live yoghurt – 1 carton per day. The natural kind seems more effective
  • Keep mobile
  • Avoid smoking and chewing gum
• If needing to thicken stoma output
  
  • Starchy foods such as:
  • white rice, pasta, white bread and potatoes
  • Very ripe banana
  • Marshmallows or jelly babies
  • Live yoghurt
  • Cheese
  • Noodles
  • Tapioca and other milk puddings
  • Smooth peanut butter
• Hydration
  
  • 2L a day
  • Maintain salt
  • Flat soft drinks or isotonic sports drinks
  • Enerlyte sachets
    
    • Sodium Chloride BP 0.47g
    • Potassium Chloride BP 0.30g
    • Sodium acid citrate BP 0.53g
    • Glucose BP3.56g
  • restrict both hypotonic (eg, tea, coffee, water, reduced sugar fruit juices/squash) and hypertonic (fruit juices, coca cola, sip feeds) fluids to 1 liter per day

Question 76

Definition of lower GI bleed

Answer 76

Bleeding that originates distal to the ligament of treitz

Question 77

What is a polyp (colorectal)?

Answer 77

• A polyp is a growth that arises from an epithelial surface
• Circumscribed mass that protrudes above the surrounding epithelium of the colon
• Intramucosal glandular neoplasm of the colon or rectum
• A malignant polyp (MP) is polyp in which neoplastic cells have invaded through the muscularis mucosa into the submucosa. It is therefore a colorectal cancer, and such invasion is associated with the possibility of spread to locoregional lymph nodes and distant organs

Question 78

How to categorise polyp aetiology?

Answer 78

• Neoplastic
• Non Neoplastic

Question 79

Polyp risk factors for malignancy (macroscopic - pre resection)

Answer 79

• Location L>R
• Size
  
  • 1cm = 10%
  • 2cm = 20%
• Sessile
• Friable/bleeding
• NICE cat 3 and Kudo pit pattern 5 (disrupted pits or vessels, heterogenous)
• Ulceration, Paris classification 0-II or 0-III (depressed)
• Not lifting
• Distortion of surrounding colonic folds

Question 80

Factors predicting difficult polypectomy (colorectal)

Answer 80

• flat
• >3cm,
• >1/3 of lumen,
• covering 3 haustral folds
• close to appendiceal orifice

Question 81

Factors predicting LN metastasis in colorectal polyp

Answer 81

• Haggit 4
  
  • 28%
• SM3
  
  • SM1 2%, SM2 8%, SM3 28%
• >2mm SMI
• LV or perineural invasion
• positive or close margin (<1mm)
• Poorly differentiated
• Mucinous
• Tumour budding

Use St Marks LN risk calculator

Question 82

Lynch surveillance

Answer 82

• Annual colonoscopy from 25 or from 5 years younger than age of family member
• Gastroscopy annual from 30 years
• Urine analysis for cytology
• Consider TAHSBO

Question 83

Scoring tool for severity of lower GI bleed

Answer 83

Oakland score

Recommended by the british gastro and colorectal surgeons

Question 84

Definition and causes of LBO

Answer 84

• Definition:
  
  • Narrowing of the colorectal lumen that restricts passage of the stool and gas
• Aetiology:
  
  • Structured answer
    
    • Mechanical obstruction vs pseudo-obstruction
    • Mechanical causes
      
      • Luminal, mural, extramural
        
        • Benign vs malignant
          
          • Structures/layers possible
          • Underlying aetiology (inflammatory, neoplastic…)
  • Mechanical causes
    
    • Intraluminal
      
      • FB
      • Gallstone
      • Constipation
      • Intussception
    • Mural
      
      • Colorectal cancer
      • Stricture
        
        • Inflammatory (diverticular, Crohn’s)
        • Ischaemic (post operative, radiation)
        • Neoplastic (colorectal cancer or metastasis)
        • Anastomosis post operative
        • Congenital Hirschprung’s Disease
    • Extramural
      
      • Benign
        
        • Volvulus
        • Haematoma
        • Post partum uterus
        • Parastomal hernia
      • Malignant
        
        • Pelvic malignancy (prostate, uterine, cervical)
        • Carcinomatosis

Question 85

Why is it that the caecum dilates the most in LBO?

Answer 85

• 3 components
  
  • 1 Pascal’s Principle (PP)
  • 2 Laplace’s Law (LL)
  • 3 Caecal is already had the greatest radius
  • 4 Stretched colon - perforation
• Pascal’s Principle = Pressure is transmitted undiminished in an enclosed static fluid. Meaning that there must be equal application of pressure throughout the colon (there isn’t higher pressure in the caecum – it is equal throughout). Example hydraulic jack
• Laplace’s Law = within a tubular structure the change in pressure required to cause distension is proportional to the surface wall tension and inversely proportional to its radius. In other words, a structure with a larger radius and low surface tension requires minimal change in pressure to cause further dilatation however one with a smaller radius and high surface tension requires a significant amount of pressure. Example balloon animal

Question 86

Positioning stoma

Answer 86

• Stoma nurse
• Landing and lying flat
• Can see, within the rectus sheath, room for the plates away from creases, bony prominence and incision
• The site should be 5 cm away from skin folds, prior scars or bony prominences, and the patient’s belt line.
• Difficult stoma (immobility or long distance)
  
  • Obese = place high on the abdo
  • 1. Take IMA(proximal to the left colic
  • 2. Take IMV
  • 3. Mobilise splenic flexure
  • Immobility = score the mesentery
  • Immobility = get it to the fascia and let it fistula

Question 87

Considerations of operation in LBO

Answer 87

• Immediate vs urgent
• Laparoscopic vs open
  
  • Open preferred
    
    • Poor insufflation
    • Dilated bowel
    • Friable bowel under pressure
    • Haemodynamically instability
• Oncological resection
  
  • Assume malignancy
• State of the caecum
• Location of the lesion
  
  • Proximal to splenic flexure
    
    • (extended) Right hemicolectomy with primary anastomosis (+/- loop) or end ileostomy
  • Distal to splenic flexure
    
    • Hartmanns (sigmoid colectomy + end colostomy)
      
      • For unwell patient
      • Traditional 3 stage
        
        • Stages
          
          • Loop stoma brought out
          • Tumour resected
          • Reversal of stoma
        • Only indication now for that traditional 3 stage would be low rectal cancer if wanting to do neoadjuvant
    • Resection with primary anastomosis
      
      • Options to try and mitigate risk
        
        • Loop ileostomy
        • On table lavage
    • Subtotal colectomy
      
      • Ileosigmoid/rectal/anal anastomosis
        
        • Need to consider sphincter continence
        • For high risk colon (prophylactic colectomy) or dodgy caecum
      • End ileostomy
  • Low rectal (not perforated or threatened caecum)
    
    • USA (uptodate) loop right transverse colostomy
    • UK (colorectal companion series) doesn’t cover it
    • Europe (WJES guidelines) loop right transverse
    • Australia (loop ileostomy or ..
• Patient/colon risk factors
  
  • Patient factors
    
    • Underlying patient comorbidities (ASA3)
    • Elderly (over 70 years)
    • Steroid use
    • Stability haemodynamically
    • Previous irradiation
    • Nutritional status
  • Colon factors
    
    • Peritoneal contamination
    • Vascularity/viability of the bowel
    • If it is even technically possible (length)
    • Large proximal faecal load
  • Tumour factors
    
    • Need for adjuvant treatment (delays if leak)
    • Metastatic or peritoneal disease
    • Location of tumour (low anastomosis)

Question 88

Pseudoobstruction

Answer 88

• Definition:
  
  • Acute dilatation of the colon in the absence of an anatomic lesion that obstructs the flow of intestinal contents
  • (also called Ogilvie’s syndrome)
• Incidence/epidemiology:
• Aetiology & risk factors:
  
  • Precipitating factors:
    
    • Medical
      
      • Cardiovascular
        
        • MI
      • Respiratory
        
        • PE
      • Neurological
        
        • PD
        • Stroke
        • Institutionalised patients
      • Sepsis
      • Metabolic
        
        • Electrolyte abnormalities
        • Diabetes
        • Alcohol
        • Hypothyroidism
    • Medication
      
      • Anticholinergic drugs (inhibiting parasympathetic)
      • Antidepressants
      • Opiates
      • Anti Parkinson drugs
      • Benzodiazepines
      • Chemotherapy agents
      • Calcium channel blockers
      • Clonidine
    • Surgical
      
      • Post operative
        
        • Ortho high risk, hip
        • Abdominal surgery
        • Pelvic/gynae surgery
        • CABG
      • Trauma
      • Pancreatitis
• Pathophysiology:
  
  • Functional problem with the colonic motility
  • Imbalance in the autonomic nervous system
    
    • Sympathetic (inhibitory)
    • Parasympathetic (stimulates)
  • Increasing colonic diameter accelerates the rise in tension on the colonic wall, increasing the risk of colonic ischemia and perforation. The risk of colonic perforation increases when cecal diameter exceeds 10 to 12 cm and when the distention has been present for greater than six days. The duration of dilation is probably more important than the absolute diameter of the colon
• • Clinical manifestations:
    
    • Same as LBO (see above)
    • Differential
      
      • Mechanical obstruction
      • Toxic Mega Colon
• Investigations:
  
  • Radiological
    
    • CT with rectal contrast
      
      • Degree of distension
  • Bloods
    
    • TFT
    • Electrolytes
      
      • Hypokalaemia
      • Hypocalcaemia
      • Hypomagnesaemia
      • • Stool
    • C Diff
• Principles
  
  • Supportive care
  • Endoscopic
  • Neostigmine
  • Surgery
• Supportive care
  
  • CcRISP
  • Metabolic disturbances (potassium, magnesium, check thyroid?)
  • Optimise underlying comorbidities and cause of current admission
  • Mobilise the patient ++
  • Serial abdominal examination and daily AXR
• Decompression
  
  • Endoscopic decompression (minimal insufflation, use CO2)
  • Flatus tube
  • Fleet enemas
  • Laxatives
• Neostigmine
  
  • In patients with caecal diameter >12 cm or failure of 48 to 72 hours of conservative therapy, we administer neostigmine (2 mg IV over 3-5 minutes), may need repeat dose every few hours
    
    • Acetylcholinesterase inhibitors that stop the enzymatic breakdown of acetylcholine in the nerve junction, increasing parasympathetic stimulation
    • Cardiac monitoring for bradycardia, hypotension and bronchoconstriction
    • Atropine is reversal agent
• Operative
  
  • Indications
    
    • Peritonitis
    • Ischaemia
    • Failure to progress despite medical and endoscopic management
  • Options
    
    • Cecostomy
    • Colectomy
      
      • Same as obstruction
      • Subtotal with end ileostomy

Question 89

What maintains faecal continence?

Answer 89

• Relevant anatomy/physiology of continence (4 parts: anatomy, sensation, compliance, stool)
  
  • Mechanical/anatomical (3 components)
    
    • Anal sphincter
      
      • Internal
      • External
    • Anal mucosal folds and vascular cushions
    • Anorectal angle (90 degrees)
  • Anorectal sensation
  • Rectal compliance
  • Stool consistency

Question 90

Pathophysiology fistula in ano

Answer 90

• Primary
  
  • Cryptoglandular hypothesis (see perianal abscess)
    
    • Consequence of perianal sepsis
    • 10-30% of abscess result in fistula
    • Pathological process that affects the anal glands at the dentate line, blockage, infection, abscess, tissue disruption and tracks in the planes to the skin, track forms which can become chronic and epithelialize
• Secondary
  
  • Crohn’s disease
  • Malignancy
  • Tuberculosis
  • Trauma or post surgical (haemorrhoidectomy, episiptomy)
  • Radiation
  • Hiadrenitis supprutiva

Question 91

Hydradenitis suppurativa - classification and management

Answer 91

The Hurley system, the most widely used assessment tool, describes three clinical stages.

Stage I: solitary or multiple isolated abscess formation without sinus tracts or scarring.

Stage II: Recurrent abscesses, single or multiple widely spaced lesions, with sinus tract formation.

Stage III: Diffuse involvement of an area with multiple interconnected sinus tracts and abscesses.

• Patients with inflammatory lesions without skin tunnels or scarring (Hurley stage I disease):
  
  • Initial therapy
    
    • Topical clindamycin
  • Failure of initial therapy
    
    • Oral doxycycline
    • Antiandrogenic drugs
    • Metformin
  • Refractory disease
    
    • Clindamycin and rifampicin ombination therapy
    • Aciretin
    • Dapsone
• Patients with inflammatory lesions with skin tunnels or scarring (Hurley stage II or III disease):
  
  • Initial therapy
    
    • Topical clindamycin
  • Failure of initial therapy
    
    • Oral doxycycline
    • Antiandrogenic drugs
    • Metformin
  • Refractory disease
    
    • Clindamycin and rifampicin ombination therapy
    • Aciretin
    • Dapsone
    • Adalimumab
    • Inflixmab
• Surgical management
  
  • WLE – double v-y advancement flaps

Question 92

Fistula in ano classification

Answer 92

Question 93

Pathogenesis of haemorrhoids

Answer 93

• Risk factors
  
  • Increased venous pressure
    
    • Cirrhosis
    • Ascites
    • Pregnancy
    • Constipation
    • Prolonged standing
    • Collagen vascular abnormalities
    • Pelvic floor dysfunction
    • Obesity
    • Sedentary lifestyle
• Internal haemorrhoids, the supportive connective tissues that keeps the haemorrhoids above the anal canal deteriorate allowing the haemorrhoids to slide down the anal canal which leads to imeded venous drainage, progressive engorgement, local stasis and transuation of fluid
• Prolpase, blocking the venous outflow, leading to a cycle of more engorgement

Question 94

Essential principals of ERAS

Answer 94

Question 95

Hereditary CRC syndromes

Answer 95

Familial Adenomatous Polyposis

• >100 colonic polyps
• APC mutation
• AD
• APC tumour suppressor gene, B-catenin
• 100% lifetime risk CRC
• Extracolonic manifestations
  
  • Ectodermal
    
    • Epidermoid cyst
    • CNS tumours
    • CHRPE
  • Mesodermal
    
    • ConTissue: Desmoids
    • Bone: Osteoma
    • Teeth: extra teeth
  • Endodermal
    
    • Adenoma/carcinoma
    • Duodenum stomach
    • SB biliary tract
    • Thyroid
    • Adrenal cortex
    • Fundic gland polyps
    • Hepatoblastoma
• Surveillance (colonic)
  
  • Flexi age 10+
  • Colonoscopy annual from 1^st polyps
• Management (colonic)
  
  • Colectomy 15-25
  • Consider staged proctectomy after family
• Extracolonic surveillance
  
  • Spigelman gastroscopy surveillance
    
    • (#/size/histo/dysplasia)
    • Duodenectomy?
  • Desmoids 2^nd cause of death after CRC
    
    • Invasive growth/rare mets
      
      • Intraabdominal (SB mesentery) or abdo wall
    • Management
      
      • Observation
      • Resection
      • Tamoxifen
      • Radiation
      • Chemotherapy
      • Imatinib (cKIT +’ve)

MUTYH Associated Polyposis

• Found on genetic testing for FAP
• AR
• Biallelic mutation in MUTYH
• Base excision repair gene
• Develop somatic APC mutation
• 20-100 polyps or >100
• 80% risk of CRC, later onset than FAP
• Microscopic
  
  • Adenomas, tubular or tubovillous
• Extracolonic
  
  • Duodenal adenoma and carcinoma
  • Breast cancer risk 18%
• Colonic surveillance
  
  • Colonoscopy every 2 years from age of 18
  • No prophylactic colectomy, unless unable to manage polyps endoscopically then ileorectal anastomosis with surveillance of rectum
• Extracolonic surveillance
  
  • Age 35 spigelman gastroscopy surveillance
  • (#/size/histo/dysplasia)
  • Breast screening as per population

Peutz Jeghers

• To get genetic testing
  
  • 2 of 3 GI hamartomatous polyps, pigmentation, family history
• AD
• STK11 (stick 11 or luna park 1911)
• Tumour suppressor
• Polyps throughout the GI tract
• SB intussusception in childhood
• 57% lifetime risk of GIT cancer
• 39% lifetime risk of CRC
• Microscopic
  
  • (Non neoplastic) hamartomas: CT, SM covered by hyperplastic epithelium
  • Frond-like polyp all 3 layers of mucosa
• Extracolonic disease
  
  • Mucosal pigmentation (around mouth, hands, feet, genitalia and anus)
  • Breast cancer is 45% (similar to BRCA)
  • Gynae cancer 18% (ovarian, cervical and fallopian)
  • 20% risk of pancreatic cancer
  • Thyroid, testicular, bile duct cancers
• Colonic surveillance
  
  • Age 8 or younger
  • Annual Hb +
  • Baseline MRE or capsule endoscopy then from age 18 gas/colon every 3 years + MRE
• Extracolonic surveillance
  
  • Breast screening from 30 years, consider bilateral mastectomy
  • Gynae: Annual abdominal/pelvic examination
  • Testicles:
    
    • Birth – teenage years Gynaecomastia and testicle exam

Familial Juvenile Polyposis

• 5 juvenile polyps in large bowel or any elsewhere in GI tract
  
  • Or juvenile polyp with family history
• AD
• SMAD4 gene
  
  • TGFb signalling pathway
• Cherry red
• 100s of polyps usually right colon
• Intussception bleeding child
• 40% CRC risk
• Microscopic appearance
  
  • Hamartomatous polyps,
  • Cystic dilation of glands + Inflammatory cells
• Extracolonic manifestations
  
  • Gastric, duodenal and pancreatic cancer risk 20%
  • Clubbing
  • Hereditary haemorrhagic telangectasia
• Colonic surveillance
  
  • 2 yearly from age 15 colonoscopy, annual if polyps
  • Colectomy if unable to manage poly burden
• Extracolonic surveillance
  
  • 2 yearly gastroscopy from age 25, annual if polyps
  • ?Gastrectomy

Serrated polyposis

• WHO criteria
  
  • ≥ 5 serrated polyps proximal to sigmoid with ≥ 2 being >10mm OR
  • Any serrated polyps proximal to sigmoid with 1^st degree relative with syndrome OR
  • > 20 serrated polyps of any size, anywhere colon.
• Mutation
  
  • Unknown
• ?
• Colonic surveillance
  
  • Colonoscopy every 1-3 years with the aim to remove all polyps ≥ 5mm
  • Age 40 or 10 years younger than the youngest age of family diagnosis

PTEN tumour syndrome

• 2 major, 1 major and 2 minor or 3 minor criteria
• AD
• pTEN
• Tumour suppressor gene
• Multiple polyps in stomach and colon
• 15-25% CRC
• Microscopic
  
  • Hamartomatous Polyps
• Extracolonic
  
  • Macrocephaly
  • Breast cancer >30%
  • Thyroid cancer
  • Endometrial cancer
  • Renal cancer
  • mucocutaneous lesions (trichileommoma)
  • acanthosis of the oesophagus
• Colonic surveillance
  
  • Colonoscopy from age 35 baseline then 5 yearly
• Extracolonic surveillance
  
  • Breast screening age 30, consider mastectomy
  • Hysterectomy once childbearing done
  • Thyroid annual examination from age 5
  • Renal 2 yearly USS from 40 years

Lynch/ Hereditary Non Polyposis Colorectal Cancer

• Revised Amsterdam:
  
  • 3 HNPCC cancers
  • 2 generations
  • 1 <50years
  • 0 exclude FAP
• AD
• MMR gene then 2^nd hit
  
  • MSI
    
    • MLH1
    • MSH2
    • MSH6
    • PMS2
  • EPCAM
• Right sided cancer 45-60 years
• Higher risk of synchronous
• CRC 80% risk
• Loss of MMR, lymphocytic reaction, mucinous with medullary growth pattern, right sided, signet, R side, synchronous
• Extracolonic manifestations
  
  • Endometrial cancer 33%
  • 9% ovarian
  • 6% gastric
  • <3 urothelial and SB tumours
• Colonic management
  
  • Aspirin from 25 years of age for chemoprophylaxis
  • Annual colonoscopy from 25 or from 5 years younger than age of family member
  • No prophylaxis unless multiple advanced adenoma (right side if elderly and total if young) – if doing segmental resection for cancer consider doing total colectomy
• Extracolonic surveillance
  
  • Urine analysis for cytology
  • Gastroscopy annual from 30 years
  • Consider TAHSBO

AD: autosomal dominant

AR: autosomal recessive* only one

APC: Adenomatous Polyposis Coli

Note 7 total; 1 serrated, 1 cancer, 2 adenomatous, 3 hamartomatous

Note Li-fraumeni 25% lifetime risk of cancer, usual onset is before age 40, recommend colonoscopy from 25 years

Question 96

Colonoscopy surveillance interval for polyp

Answer 96

Adenoma

• 1 year:
  
  • +10 adenoma
• 3 year;
  
  • 5-9 adenoma
  • HGD or TVA
  • +10mm size
• 5 year;
  
  • 3-4 adenoma
• 10 year;
  
  • 1-2 adenoma

Serrated

• 1 year:
  
  • SPS
    
    • ≥5 serrated polyps ≥5mm proximal to rectum with 2x≥10mm
    • 20+ serrated colorectal polyps of any size, but ≥5 proximal to rectum
• 3 year:
  
  • ≥5 polyps
  • ≥10mm size
  • SSL with dysplasia
  • Traditional serrated adenoma
• 5 year:
  
  • 1-4 polyps

If piecemeal resection of high risk polyp then repeat scope 2-6 months