Appendix to Anus Flashcards
Anatomy of the appendix
Midgut organ
Variable length 2-25cm
3 Taeniae coli coalesce to form a complete longitudinal muscle layer over appendix
Lined by colonic type columnar epithelium, neuroendocrine and mucin producing goblet cells
Blood supply from posterior caecal from ileocolic
Lymphatics to ileocolics
Appendicitis pathophysiology
Luminal obstruction
Increased intraluminal pressure from continued cellular mucus and bacterial gas production
Distension
Bacterial overgrowth
Venous stasis
Ischaemia
Perforation, either local or free
Bacteriology of appendicitis
Colonic flora- mixed anaerobic and anaerobic cultures
Aerobes
- E coli
- Enterococci
- pseudomonas
Anaerobes
- Bacteroides (fragilis)
- Bilophila wadsworthia
- peptostreptococci
List cystic lesions of the appendix
Non- Neoplastic
- Simple mucocoele (retention cyst)
Neoplastic
- Serrated Appendiceal polyps
- Low Grade Mucinous Neoplasms
- High Grade Mucinous Neoplasms
- Mucinous Adenocarcinoma
LAMN vs HAMN
Differentiated only by degree of dysplasia
HAMNs show high grade nuclear features: enlarged, pleomorphic, hyperchromatic. high mitotic activity
Neither invade the muscularis mucosa but both can have mucin forced into or through the wall or rupture the appendix and lead to PMP
LAMN staged as in situ disease
HAMN as invasive disease T1-T4
Appendiceal neuroendocrine neoplasms
Usually incidental/unexpected at appendicectomy
Most commonly submucosal in distal 3rd
Broadly grouped into
- Well differentiated (NETs)
- Divided into grades
- Low
- Intermediate
- High
- mutations in MEN1, DAXX and ATRX are entity defining
- Divided into grades
- Poorly differentiated
- Divided into
- small cell type
- large cell type
- TP53 or RB1
- Divided into
Major adverse prognostics
- Size >2cm
- Grade 3
List the primary appendiceal neoplasms
Epithelial derived
- LAMN
- HAMN
- Adenocarcinoma (mucinous, signet ring or intestinal)
- Goblet cell adenocarcinoma (mixed NET and adeno features- manage as adenoca)
Neuroendocrine derived
- NET (well vs poorly differentiated)
- MiNEN (mixed neuroendocrine-non neuroendrocrine) tumours (manage as poor diff. NET)
Borders of fore, mid and hindgut
Defined by vascular supply
Foregut
- Oesophagus to duodenal ampullla- Coeliac
Mid gut
- Ampulla to distal third of transverse colon- SMA
Hindgut
- Distal transverse to rectum- IMA
Colon lengths
Total colorectal length ~150cm
- Caecum 10cm
- Ascending 15cm
- Transverse 45cm
- Descending 25cm
- Sigmoid 40cm
- Rectum 15cm
Vertebral heights for the origins of the non paired visceral branches of the aorta
Coeliac T12
SMA L1
IMA L3
What is the arc of Riolan
Inconstant arterial communication between the proximal IMA and Proximal SMA
Flow may be in either direction
What is the relationship of the SMV to the SMA
The vein sits on the right of the artery and behind its arterial branches to the colon
What are the levels of the colonic lymph nodes
Epicolic- along bowel wall and in appendica epiploicae
Paracolic- Marginal artery
Intermediate- along main branches
Primary- SMA and IMA
Sympathetic supply of colon
T6-T12 preganganglionic sympathetics synapse in preaortic ganglia then travel with SMA branches to right and transverse colon
L1-L3 preganglionic sympathetics form preaortic ganglion above bifurcation then runs with IMA, lower fibers involved in inf. hypogastric plexus also
Parasympathetic supply of colon
Right (posterior) vagus supplies SMA distribution
Pelvic Splancnics S2,3,4 through inf hypogastric plexus to bowel to supply IMA distribution
Synapse at the organ
Primary energy source of the colonocyte
Short chain Fatty acids from bacterial fermentation of complex carbohydrate.
Butyrate is the most common
How much ileal effluent enters the caecum per 24 hours
1000-1500mL
How do antibiotics cause diarrhoea
Decreased colonic bacteria
Decreased fermentation
Decreased Butyrate production
Decreased active transport of sodium from lumen
What are the layers of the enteric nervous system
Subserosal, myenteric (Auerbach) plexuses
Submucusal (Meissner) plexuses
Mucosal plexuses
Normal bacteriology of the colon
Bacteroides most common (Anaerobe)
E. Coli most common aerobe
Pseudomonas
Enterococcus
Proteus
Klebsiella
Streptococci
What is used for bowel prep
- What are the benefits of this agent
Name some alternative agents
Polyethylene glycol and electrolyte solutions
- High molecular weight polymer and balanced electrolyte solution
- Isosmotic
- e.g Klean prep
- 4 sachets in 1L of water each
- Consume 250ml every 10 mins
- Does not injure the colonic mucosa
- Does not induce major fluid shifts (although this has been rarely reported anyway)
Alternatives
- All hyperosmotic
- Sodium picosulphate (picoprep)
- Sodium phosphate
- Magnesium citrate
Oral antibiotics for elective bowel surgery
Not used routinely in my institution but there is evidence from RCTs that shows reduced SSI rates and similar C. diff rates
Appropriate stoma siting
Consultation with stoma therapist is optimal
Away from creases
Visible
Easily accessible
Through Rectus
In a normal size patient usually below umbo and at the apex of the natural curvature if the abdomen
Delineate the Hinchey Classification
I- Localised pericolonic or mesenteric abscess
II- Pelvic walled off abscess
III- Purulent peritonitis
IV- Faeculent peritonitis
Causes of pseudoobstruction
Opiates
Neuroleptic meds
Retroperitoneal haematoma
Autonomic disruption (true Ogilvie’s)
DM
Severe metabolic illness
Electrolyte disturbance
Hyperparathyroidism
Parkinsonism
Scleroderma
Systemic lupus erythematosis
Uraemia
Pathophysiology of colonic pseudoobstruction
Signs and symptoms consistent with a large bowel obstruction without mechanical cause.
Multiple underlying aetiologies and often multifactorial.
Results ultimately from an imbalance of sympathetic and parasympathetic nervous supply to the colon.
Likely related to sympathetic overactivity vs parasympathetics.
Treatment of pseudoobstruction
First: Neostigmine
- 2.5mg IV over 3 mins
- Bradycardia- cardiac monitoring on and atropine ready
Second: Spinal epidural
- Block sympathetics- effective
Third: Colonoscopy
- Caution re: insufflation and perforation,
- Higher recurrence rates
Operate if needed or unable to resolve
Features of UC
Clinical features
- Bleeding and diarrhoea more prominent than Crohn’s
- Perianal disease rare
Microscopy
- Inflammation of mucosa and submucosa only
- Crypt abscesses (also seen in Crohn’s and infection)
Endoscopic
- Continuous
- Hyperaemic friable mucosa
- (ulceration is actually rare)
Features suggestive of malignancy in UC strictures
Prolonged UC (0%<10 years, 60%>20 years)
Proximal to splenic flexure
LBO
Extraintestinal Manifestations of IBD
Joints
- Arthritis
- Ankylosing Spondylitis
Skin
- Erythema Nodosum
- Pyoderma Gangrenosum
Eyes
- Primary
- episcleritis
- uveitis
- Secondary
- cataracts (steroid)
Hepatic
- Primary Sclerosing Cholangitis
Manifestations which may respond to surgical management of the affected bowel:
- Skin
- Eye
- Arthritis
Manifestations which do not respond to surgical management affected bowel:
- Ankylosing spondylitis
- PSC
- colitis often less severe with PSC associated phenotype but colon cancer risk is 5x that of UC alone
UC ECCO guidelines for UC management
Mild-moderate proctitis-
- 5ASA, topical,
- If resistant add oral 5ASA initially
More proximal involvement-
- enema and oral
Refractory- steroids, cyclosporin, biologics
Severe colitis-
- Steroid for 3 days-
- if no/inadequate response- either cyclospirin, infliximab or surgery
- if rescue therapy given then surgery if no/inadequate response by further 4-7 days
NB methotrexate is out
Truelove and Witts criteria for severe colitis in UC
(used by ECCO)
- Bloody diarrhoea at least 6x per day
AND any of:
- Pulse >90
- Temp> 37.8
- Hb <105
- ESR >30
- CRP>30
Indications for surgery in UC
Acute
- Toxic megacolon
- Non response to therapy
- Bleeding
Chronic
- Dysplasia
- Stricture (presume malignancy)
- Cancer
Risk factors for Crohn’s
Smoking
Jewish descent
Away from the equator (Scotland, Scandinavia)
Prev. Abx use
OCP
FHx
Mycobacterium paratuberculosis?
Mechanism of action of Infliximab
Anti TNF-a
Clostridioides Difficile risk factors
Antibiotic use (esp Clinda)
Hospitalisation
Age
Comorbid illness
Acid suppression
IBD
Cirrhosis
GI surgery
Immunosuppression
Obesity
Clostridioides difficile microbiology
Gram positive spore forming, toxin producing anaerobic bacillus
Pathophysiology of C. Diff
Interruption of normal flora
Colonisation
Toxin production
- Toxin A (enterotoxin) and B (cytotoxin) enter colonocytes and interrupt Rho GTPases
- Toxin A also direct neutrophil recruitment and activation of macrophages
Colonocyte death and direct toxin A effects lead to inflammation
- mediated by IL-1,6,8, TNF, substance p causing:
Further colitis and colonocyte death.
Toxin B is a potent cytotoxin, ? necessary to pathogenesis
Classification of ischaemic colitis
By depth and cause
Partial thickness
- transient
- stricturing
Full thickness with gangrene
Occlusive
Non occlusive
The adenoma-carcinoma pathway
Normal Colonocyte
- APC/Beta-catenin (tumour suppressor)
Tumour Initiation (abnormal crypt foci and early adenoma)
- KRAS
Adenoma formation and growth
- DCC/SMAD4/SMAD2
Late adenoma
- p53
Carcinoma
What is the APC gene
Tumour suppressor gene
Chromosome 5q21
APC mutation leads to increased intracytoplasmic pool of Beta Catenin and Wnt signalling pathway disruption
It is the underlying genetic mutation in FAP and the initial mutation in the sporadic adenoma-carcinoma pathway in 80%
Gardner syndrome
Original description is FAP with extraintestinal manifestations
- Mandibular osteomas
- Desmoids
- Periampullary neoplasms
More recently recognised associations
- papillary thyroid cancer
- medulloblastoma
- gastric fundic gland polyps
MYH associated polyposis (MAP)
Autosomal recessive polyposis and cancer
Mutation in MYH gene encodes oxidative repair of DNA genes
Mutation promotes APC mutation
MAP phenotype is variable
p53
Tumour Supressor gene
Induces either:
- Apoptosis or:
- G1 cell cycle arrest allowing DNA repair-
in response to cellular injury
HNPCC
Lynch syndrome
Autosomal dominant, 80% penetrance
Accounts for 3% of colon cancers
Mutation in DNA MMR genes
- MLH1, PMS2, MSH2, MSH6, EPCAM
- MLH1 and MSH2 account for 90% of detected known mutations
50% of clinical Lynch syndrome (on family history) will not have an identifiable genetic mutation
MMR defects induce microsatellite instability
- Errors in S phase of DNA replication- resulting in vast increase in rate of mutation
Associated malignancies-
- Classically
- Colon
- ovarian
- endometrial
- urothelial
- gastric.
- Others
- HPB
- gliomas
- sebaceous skin cancers
- Breast cancers
- in some studies but this finding is variable
Define invasive colon cancer
Breach of the muscularis mucosae
Haggitt Classification for Malignant polyps
Kikuchi
Paris Polyp Classification
Kudo Pit Pattern
Tattooing in colonoscopy
Use pure carbon black
Polyps >1cm- 1 spot
Worrisome polyp (suspect malignancy)- 3 spots
Cancer- 3 spots
Not usually caecum/ascending (caecum is reliable endoscopic landmark) or rectum
Risk Factors to consider in malignant polyps:
ACPGBI 2013
Malignant polyp risk factors
Haggit 4
SM2-3
Positive margin
LVI +
Width of cancer >4mm
Depth of cancer >2mm
Tumour budding
Cribriform
Poor differentiation
FAP expression and clinical outcomes
100% penetrance
Autosomal Dominant
Average age of presentation with new diagnosis 29
Average age of Malignancy 39
FAP UGI Surveillance recommendations
No firm guidelines, initial endoscopy at ~30 years
Suggest endoscopy based on Spigleman stage
- Stage 0: Every four years
- Stage I: Every two to three years
- Stage II: Every one to three years
- Stage III: Every 6 to 12 months
- Stage IV: In the absence of surgery (duodenectomy), surveillance every six months
Muir-Torre syndrome
Rare
Autosomal dominant
Phenotypic variant of HNPCC
At least:
- 1 sebaceous skin tumour and:
- 1 visceral tumour
- colon
- endometrial
- urothelial
- ovarian
Same Mutations as HNPCC
- MLH1
- PMS2
- MSH2
- MSH6
Sporadic MSI in colon cancer
Results from hypermethylation of MLH1 promoter region and is strongly associated with the BRAF V600E mutation.
- Detection of BRAF V600E almost completely excludes lynch syndrome
MSI status prognosis and management
True Lynch have favourable stage for stage prognosis
MSI high (MMR deficient) cancers are resistant to 5-FU based chemotherapy and there is no or little survival advantage
MSI high cancers may be sensitive to irinotecan, mytomycin and checkpoint inhibitors e.g pembrolizumab
Peutz-Jeghers syndrome
Rare autosomal dominant syndrome
Congenital hamartomatous polyposis of GI tract and hyperpigmentation of buccal mucosa, lips and digits
STK11 tumour supressorgene
2-10% GI cancer risk (panenteric)
Associated cancers
- GI
- Breast
- Cervix
- Testicle
- Ovary
- Pancreas
Juvenile polyposis syndrome
Rare
Autosomal dominant
High penetrance
SMAD4 tumour suppressor
Variable phenotype
Predominantly hamartomas but also adenomas and increased colorectal cancer risk
Colonic and extraintestinal cancers
Syncronous Colorectal cancer rate
3%
Dukes staging
Colorectal Staging:
Tumour (overview)
T1: tumor invades submucosa
T2: tumor invades muscularis propria
T3: tumor invades through the muscularis propria into the pericolorectal tissues
T4:
- T4a: tumor invades through the visceral peritoneum
- including gross perforation of the bowel through tumor
- T4b: tumor directly invades or adheres to other adjacent organs or structures
Non TNM prognostic variables in colorectal cancer
- CEA
- MSI
- Tumour deposits
- Satellite deposits (? obliterated LN’s)
- Tumour regression grade
- CRM
- Resection margin
- Perineural invasion
Assessing neoadjuvant response in colorectal cancer
Multiple scoring systems, AJCC advocates/uses the:
- Modified Ryan tumour regression score
- 0- No viable tumour cells (complete response)
- 1- Single cells or rare small groups of cells (near complete response
- 2- Residual cancer with evident regression (desmoplastic response)
- 3- No evident response
5 year survival by stage in colorectal cancer
From SEER 1998-2005
I- 90%
II- 75%
III- 50%
IV- <5%
One suspects outcomes have improved from these though
Surveillance post colorectal cancer
Adjuvant chemotherapy in colorectal adenocarcinoma
Stage 2 and above with at least 1 poor prognostic factor should be considered
- Treatments are 5F-U based
- Either infusiional 5-FU or capecitabine
- Capecitabine may infact be superior as it is activated by an enzyme universally overexpressed by tumour cells
- Either infusiional 5-FU or capecitabine
- addition of Oxaliplatin (FOLFOX) or Irinitecan (FOLFIRI) or both (FOLFIRINOX) is beneficial in stage III and IV disease
- possibly in stage II also
Consider MoABs
- Bevacizumab- VEGF inhibitor
- Cetuximab- EGFR inhibitor
- Not in RAS gene mutations
- Not in BRAF mutations
Checkpoint inhibitors
- Pembrulizumab, nivolumab
- Only in dMMd/MSI-h cancers
What is the appropriate distal margin in rectal cancer
Heald et al descrided tumour deposits 4cm distal to the cancer, more contemporary series show 3cm.
5cm is consider the appropriate distal margin
Muscles of levator ani
Pubococcygeus
Ileococcygeus
Puborectalis
Components of anorectal physiology testing
Anal resting and squeeze pressures
- Manometry
Anal reflexes
Pudendal nerve conduction velocities
electromyographic muscle fibre recruitment
Risk factors for rectal propapse
Age
Female gender (6:1)
Chronic constipation
More common in young institutionalised psychiatric men also
Parity deserves a mention but may not actually be that important (35% nulliparous)
Macroscopic features differentiating rectal prolapse from prolapsed haemorrhoids
Concentric mucosal rings vs deep radial grooves
Abdominal vs perineal rectal prolapse repairs
Solitary rectal ulcer syndrome
Anteriorly based 4-12cm from anal verge
1/3 related to fullthickness rectal prolapse
- Respond well to surgery
If related to mucosal prolapse- less well
Topical 5ASA, pelvic floor physio and dietary management resolve most episodes
Chagas Disease
Rare
Protozoan parasite disease
Trypanosoma Cruzi
South america
Denervation of both myenteric (Auerbach) and submucosal (Meissner) plexuses secondary to immune mediated cross reactivity
Oesophageal (differential for Achalasia) and colonic (progressive dilatation, megacolon and slow transit) are the most common manifestations of the gut
Also causes cardiomyopathy
Biopsies for Hirschprungs
Suction or punch biopsy
3cm (in adults) above the dentate line (below this is usually aganglionic anyway)
Histology by ACh shows an increased number of large brown nerve fibres
Musculature and innervation of the anal canal
4cm in length, variable shorter in multiparity
Tube within a cone
- External sphincter continuous with levator ani
- Skeletal muscle
- S2, Pudendal, somatic innervation
- Internal sphincter continuous thickened portion of internal circular muscular layer of colon
- Visceral smooth muscle
- Sympathetic fibres maintain contraction (pelvic plexus L1,2)
- Parasympathetics relax (pelvic sphlancnic)
Lining of the anal canal
divided by the dentate (pectinate line) approx 1/3 from anorectal margin and intersphincteric groove inferiorly
- Above dentate line:
- GRADUAL transition between columnar rectal mucosa and stratified squamous epithelium
- up to 12 anal columns
- at the base of these are the anal valves transversely which constitute the visual dentate line
- Anal sinuses above valves, between columns
- Anal glands open into sinuses
- Pecten extends from dentate line to intersphincteric groove
- stratified squamous epithelium
- Non keratinising
- No follicles or sweat glands
- stratified squamous epithelium
- Below intersphincteric groove is histologically typical skin
- keratinizing squamous epithelium
- sebaceous, sweat glands and hair follicles present
Blood and lymphatic supply of the anus
Arterial
- Upper part from superior rectal artery from IMA
- lower part from inferior rectal artery from internal pudendal from internal iliac
Venous
- correspond to arteries but partake in the rectal venous plexus (which is actually anal)
- Internal venous plexus form cusions at 3,7,11
- Contributes to continence and development of haemorrhoids
Watershed “as per the vascular supply” in lasts but not totally correct
- Upper part usually drains with the internal pudendal supply to the internal iliacs
- lower part via anastomoses with superficial external pudental (from femoral) to the medial superficial inguinal group
Factors contributing to anal continence
Pressure differential between rectum and anus
- anus ~90cm H2O
Haemorrhoidal cushions
Anorectal angle
- 75-90º at rest
- Angle opens out with relaxation of puborectalis
Management of anal incontinence
Medical
- Konsyl D- Bulking
- Loperamide- Decrease transit
Physiotherapy
- Pelvic floor physiotherapy
- Biofeedback training
Surgery
- Sphincter repair
- Prostheses-
- Bulking (collagen, silicone)
- Artificial sphincter
- Sacral nerve stimulation
- Diversion
- Dynamic graciloplasty
Internal haemorrhoid grading
Rectocoele definition
2cm anterior to the anterior line of the anal canal on DPG
Haemorrhoid management
Lifestyle
- Water supplementation
- Fibre supplimentation
Office procedures (best suited for grade 1-2, consider in 3)
- Banding
- Failure predicted by >4 bandings
- Sclerotherapy
Surgery
- Open (Milligan-Morgan)
- Closed (Fergusson)
- Use of an energy device probably decreases post operative pain.
- Stapled
- Increased recurrence rate
Risks post haemorrhoidectomy
Urinary retention 30%
Faecal incontinence 2%
Infection 1%
Haemorrhage 1%
Stricture 1%
Anal fissure differentials
Consider esp if atypical position (non midline)
TB
Crohns
HIV
Syphillis
Carcinoma
Classification of fistula in ano
Parks Classification
- intersphincteric
- Trans-sphincteric
- suprasphincteric
- extrasphincteric
Percentage risk of fistula in ano after abscess.
What can be done to reduce this risk
up to 40%
Am. J. Surg. 2019 metanalysis showed reduction in fistula from 25% to 16% with an oral 5-10 day post operative antibiotic course but that study was pretty shit, a retrospective cohirt study was included and the 2 RCTS actually showed quite different outcomes and the better one trended toward harm
Goodsalls rule
Risk factors for pilonidal disease
Male sex
Ages 18-45
Obesity
Trauma
Sedentary lifestyle
Deep natal cleft
Hirsuit
Family history
Evidence based pilonidal abscess management
deroofing and curretage is superior to simple excision
Pit excision is not beneficial
Depilation decreases recurrence and number of procedures with laser, wax, creams- razor may increase recurrence
Evidence based pilonidal surgery
Secondary intention has long healing times but lower recurrence rates
For primary closure, off midline procedures are superior to midline
Thats pretty much it
Surgical options for pilonidal repair
Simple excision with primary or secondary intention healing
Bascome 1 (pit picking)
Bascome cleft lift
Rhomboid flap (inferiorly based)
Karydakis flap
AJCC anatomic regions in perianal neoplasia
Anal canal
- Not visible externally or incompletely with light external traction
Perianal
- completely visible, arising within5cm of the anal opening
Skin
- >5cm from the anus
HPV viral subtype pathologic predilections
Benign condyloma
- HPV-6, HPV-11
Dysplasia and increased cancer risk
- HPV-16, HPV-18
Anal and genital tract squamous intraepithelial neoplasia nomenclature
AJCC recommends the use of Squamous Intraepithelial Lesion (SIL) rather than Anal Intraepithelial neoplasia (AIN)
- Low-grade squamous intraepithelial lesions (LSIL)
- AIN I, low grade
- High-grade squamous intraepothelial lesions (HSIL)
- AIN II, moderate grade
- AIN III, high grade
Management of AIN
LSIL
- May spontaneously regress
- HSIL may be found but likely arises seperately
- Biopsy anything concerning or excise for symptoms (e.g condylomata) but does not specifically need treatment
- Follow up every 6/12
HSIL
- Recommend treatment
- Unlikely to regress
- ablate the tissue somehow
- cautery, excision, imiquimod, 5-FU
- Surveillance required- high recurrence rate
Buschke-Lowenstien tumour AKA
Giant condylomata accumenatum
Verrucous carcinoma
Anal SCC risks
Anal canal 5x more common than perianal disease
Risk factors include:
- HPV
- HSIL
- HIV
- Receptive anal intercourse
- Smoking
- Lifetime number of sexual partners
List perianal and anal canal neoplasms
Squamous derived
- Benign
- Condylomata accumenatum
- Premalignant
- LSIL/HSIL
- Malignant
- SCC
- BCC
- Melanoma
- Extramammary Paget’s disease
Columnar derived
- Adenocarcinoma
Soft tissue
- Sarcoma
Anal SCC staging
CT CAP
MRI Pelvis
CT PET for T2 (2cm) or greater or node positive disease
Anal SCC management
Definitive chemorads
- 5-FU and Mitomycion C.
- 45Gy initially, up to 59 if needed as second dose or in high risk disease
- Continued response for 6 months, therefore:
- Initial assessment at 10 weeks
- Complete response
- Monitor every 3-6 months for 2 years then less frequent
- Partial response
- Monitor out to 6 months then salvage if persistent disease beyind that
- Progressive disease
- Get histological confirmation before considering salvage
- Complete response
- Initial assessment at 10 weeks
- Salvage is with APR
Anal melanoma
Rare
Very poor prognosis
Often amelanotic
Manage by obtaining R0 resection, more aggressive surgery i.e APR doesn’t seem to improve survival
Colorectal cancer screening
NZ uses Faecal Immunochemical Test
- Age 60-75
- Single test (c/w Guaic acid-3 days)- highest uptake
- every 2 years
Screening has been shown in RCTs to decrease mortality
Most international guidelines recommend screening from age 50
Other screening options range from stool based tests to CTC, to flex sig to colonoscopy
Main risks are psychological and related to colonoscopy
Melanosis coli
Benign
Pigmentation of colon (and small bowel) caused by lipofuscin deposition in macrophages
Associated with long term laxative use/abuse
Incidental finding of crohns with normal appendix at laparoscopy
ESMO guidelines recommend not resecting either the small bowel or appendix
High rates of abscess and fistula from appendicectomy
small bowel can be treated medically if crohns but the differential would still be broad.
Interval appendicectomy for perforated appendicitis
JAMA surg paper 2019 RCT of interval appendicectomy vs MRI surveillance showed 20% rate of neoplasm in patients managed with perc drain for perforated appendicitis.
The study was terminated early and all patients offered interval appendicectomy
33% of the MRI group had already required interval appendicectomy for recurrence
Antibiotics after perianal abscess drainage
2019 meta-analysis showed of 5 days of cipro/metronidazole or Augmentin reduced the risk of fistula from 24% to 16%
The studies included were at some risk of bias
Management of appendiceal NETs
Colorectal Staging:
N1
N1: metastasis in 1 - 3 regional lymph nodes
- N1a: metastasis in 1 regional lymph node
- N1b: metastasis in 2 - 3 regional lymph nodes
- N1c: no regional lymph nodes are positive but there are tumor deposits in the subserosa, mesentery or nonperitonealized pericolic or perirectal / mesorectal tissues
Colorectal cancer staging:
N2
Metastasis in 4 or more regional lymph nodes
- N2a: metastasis in 4 - 6 regional lymph nodes
- N2b: metastasis in 7 or more regional lymph nodes
There is no N3 for colorectal cancer
Colorectal cancer staging:
T1
Tumour invades submucosa
Colorectal cancer staging:
T2
Tumor invades muscularis propria
Colorectal cancer staging:
T3
Tumor invades through the muscularis propria into the pericolorectal tissues
Colorectal cancer staging:
T4
T4a
- tumor invades through the visceral peritoneum
- including gross perforation of the bowel through tumor
T4b
- tumor directly invades or adheres to other adjacent organs or structures
What is the optimal timing for colonoscopy prep
Optimal preprocedural preparation depends on timing of procedure
- Morning procedures should have split dosing
- Improved rates of adequate prep, adenoma detection and patient tolerance
- Afternoon procedures single dose appears to be better
Clear fluids should be ceased at least 2 hours prior to procedure to facilitate sedation
Predictors of poor preparation in colonoscopy
- Prior inadequate preparation
- History of constipation
- Use of medications associated with constipation
- e.g tricyclic antidepressants and opioids
- Dementia or Parkinson disease
- Male sex
- Low health literacy of cognitive function
- Low patient engagement
- Obesity
- Diabetes mellitus
- Cirrhosis
Effect on colonoscopy outcomes due to poor prep
- Increase the risk of adverse events related to the procedure
- Lengthen the insertion time and overall procedure time
- Necessitate reducing the interval between procedures
- Lower caecal intubation rates
- Lower adenoma detection rates
Colorectal cancer genetic changes can be broadly grouped into which 3 pathways
- What are their relative frequencies in CRC
MSI-high phenotype
- 15-20% of CRCs
- loss of DNA mismatch repair genes
- Sporadic (BRAF associated)
- HNPCC (~3%)
Chromosomal instability (CIN)
- 70-85% of CRCs
- Wnt/beta-catenin pathways
- Most frequently APC
Global genomic hypermethylation
- inactivation of tumour suppressor genes
- CpG island methylator phenotype (CIMP)
- Often results in MLH1 mutation leading to dMMR
- Frequently associated with serrated polyps
- progress to MSI-h sporadic CRC (BRAF V600E associated)
- CpG island methylator phenotype (CIMP)
Hyperplastic polyps
- What are the recommendations for colonoscopy surveillance if identified?
Most common non neoplastic polyp of the colon
- Most common in rectum and rectosigmoid
- Unclear if associated with increased risk of more proximal neoplasia
- Guidelines
- consensus of US multidisciplinary taskforce Am J gastro 2020 recommends colonoscopy in
- 10 years for:
- <20 polyps in rectum and sigmoid all <10mm
- <20 polyps proximal to rectosigmoid all <10mm
- 3-5 years for
- >10mm
- 1 year for
- serrated polyposis syndrome
- diagnosis requires both of:
- >20 sessile polyps distributed throughout the colon
- > at least 5 proximal to the rectum of which 2 or more are >10mm
- diagnosis requires both of:
- serrated polyposis syndrome
- 10 years for:
- NZ and Aus just say return to baseline screening if hyperplastic polyps
- No further delineation of risk (both NZGG and Australian Cancer Council)
- consensus of US multidisciplinary taskforce Am J gastro 2020 recommends colonoscopy in
Serrated polyposis syndrome
Rare syndrome (formerly called hyperplastic polyp syndrome)
Genetic testing not recommended due to unknown genetics and heterogeneity
Diagnosis is endoscopic (use carmine blue!)
- requires both of (WHO):
- >20 sessile polyps distributed throughout the colon
- > at least 5 proximal to the rectum of which 2 or more are >10mm
Lifetime risk of cancer is ~50%
Features to encourage formal right hemicolectomy in appendiceal NETs
- R1
- G3
- Mesoappendiceal invasion >3mm
- Size >2cm (definate)
- Size 1-2cm (if high risk features)
- Tumour at base of appendix (even R0)
- LVI
- G2
What is the rate of appendicitis in pregnancy
~1 in 1000 pregnancies
- It is unclear if appendicitis is more or less common in pregnancy, if anything it is probably less common
- Appendiceal rupture occurs more frequently in pregnant women especially in the third trimester
What is the recommended management of appendicitis in pregnancy
Operative
- this is considered the standard of care in appendicitis and there is insufficient data to support non operative management in pregnant patients
- A higher negative appendicectomy rate in pregnant women is generally accepted
How should appendicitis with abscess or inflammatory mass be managed
This is usually from late or missed appendicitis
- management depends on the clinical condition of the patient primarily
- well patient
- drainable- drain
- not drainable- antibiotics only
- the role of interval appendicectomy should be considered especially in those over 40 as there is a risk of rare but clinically important diagnoses such as NETS
- Overall this risk and the risk of relapse are low
- in some series the risk or relapse is up to 40%
- Overall this risk and the risk of relapse are low
- unwell patient
- operate on initial presentation
- well patient
Familial risk in colon cancer; recommendations on colonoscopy
Category 1
Familial risk in colon cancer; recommendations on colonoscopy
Category 2
Familial risk in colon cancer; recommendations on colonoscopy
Category 3
KPI in colonoscopy:
Adenoma detection rate
20% in women
30% in men
Adenoma detection rates correlate with the risk of interval colorectal cancer
Recent paper in the gastroenterology literature suggests that overall polyp detection rate may be a reasonable surrogate marker for ADR
Outcome numbers in bowel screening with FIT testing
50/1000 will obtain a positive result
- 35/1000 will have adenomatous polyps
- 3-4/1000 will have colorectal cancer
In Lynch syndrome what are the major associated risks other than colon cancer.
- What are the lifetime risks
- What are the associated screening recommendations
- Risk reduction strategies
Endometrial and ovarian cancers
- both have an increased risk and have an earlier onset in Lynch syndrome
Endometrial cancer
- lifetime risk is 25-70% depending on the mutation
- mean age ~50
- screening:
- women should be counselled for the increased risk and have dynfunctional bleeding promptly investigated
- annual endometrail sampling should begin at the age of 30-35 or 5-10 years earlier than the earliest family member
Ovarian cancer
- lifetime risk is 10-25% depending on the underlying mutation
- mean age ~45
- screening:
- annual TVUS at the age of 30-35 or 5-10 years earlier than the earliest family member
- CA125 every 6-12 months
- all screening has a high rate of false positives and potential harm in ovarian cancer
Risk reduction
- ultimately prophylactic TAH and BSO from age 35-45 is warranted
- it is reasonable to wait until child bearing is complete
- earlier if there is a family history of early onset of cancers
What criteria for family history are used to diagnose Lynch syndrome?
Amsterdam II criteria
- There should be at least three relatives with any Lynch syndrome-associated cancer (colorectal cancer, cancer of the endometrium, small bowel, ureter, or renal pelvis)
- One should be a first-degree relative of the other two
- At least two successive generations should be affected
- At least one should be diagnosed before age 50
- Familial adenomatous polyposis should be excluded in the colorectal cancer case(s), if any
- Tumors should be verified by pathological examination
What guidelines are used to guide testing for MSI
The revised Bethesda guidelines
- Colorectal cancer diagnosed in a patient who is less than 50 years of age.
- Presence of synchronous, metachronous colorectal, or other HNPCC-associated tumors regardless of age.
- Colorectal cancer with the MSI-H-like histology diagnosed in a patient who is less than 60 years of age
- Colorectal cancer diagnosed in a patient with one or more first-degree relatives with an HNPCC-related tumor, with one of the cancers being diagnosed under age 50 years.
- Colorectal cancer diagnosed in a patient with two or more first- or second-degree relatives with HNPCC-related tumors, regardless of age.
What is the lifetime risk of colorectal cancer in Lynch syndrome
This depends on the genetic mutation
- MLH1 and MSH2 are higher risk
- 35-45%
- MSH6 and PMS2 are lower risk
- 15-25%
When should screening colonoscopy in Lynch syndrome begin
At age 25
What anatomic classification may be used for rectovaginal fistulae
- what is the anatomical entry point for each
- what are the common causes of each
Divided into three anatomic classes
- forniceal
- enter high, through the posterior fornix of the vagina
- common causes:
- crohns
- bowel cancer
- diverticular
- radiation to gynaecological cancers
- post operative from bowel anastomosis
- common causes:
- enter high, through the posterior fornix of the vagina
- septal
- pass through the rectovaginal septum (middle third of the vagina) and are suprasphincteric
- common causes:
- rectal cancer
- crohns
- radiation
- cervical cancer
- obstructed labour with pressure necrosis
- common causes:
- pass through the rectovaginal septum (middle third of the vagina) and are suprasphincteric
- perineal
- pass through the sphincter mechanism
- common causes
- crypotoglandular infections
- obstetric tears
- crohns
- surgery
- common causes
- pass through the sphincter mechanism
Familial GI cancer risk:
who is at a mildly increased risk of colorectal cancer
What are the guidelines for colonoscopy
the risk of colorectal cancer is mildly increased in patients with 1 first degree relative with bowel cancer over the age of 55
colonoscopy should begin at age 50
Familial GI cancer risk:
who is at a moderately increased risk of colon cancer
what are the guidelines for colonoscopy
Either
- 1 FDR with colon cancer under the age of 55 or
- 2 FDR with colon cancer at any age
Colonoscopy should begin at 50 or 10 years before the first family member
Familial GI cancer risk
who is at a high risk?
what are the recommendations on colonoscopy
There are multiple risk groups in the NZGG document:
- those with a known genetic mutation
- taylor recommendations to that syndrome
- those with polyps
- 1 FDR or SDR with cancer and multiple polyps
- 1 FDR with multiple polyps
- those with FDR with colon cancer
- 1 FDR plus 2 other FDR or SDR with cancer any age
- 2 FDR and one has any of:
- cancer age <55
- multiple cancers
- extracolonic cancer suggestive of a syndrome
- 1 FDR <50
- esp. if dMMR
What is our local protocol for neoadjuvant treatment of rectal cancer where there is not a need for downstaging?
Our local protocol is for short course radiotherapy only, without chemosensitization.
- 25 in 5
- surgery within 1 week of cessation
What is our local protocol for dneoadjavant treatment in rectal cancer where there is a need for downstaging
Patients receive long course radiotherapy with 5-FU sensitization.
- Post treatment surgery is based on the mercury study
- MRI at 1 month
- if there is progressive or non responsive disease then progression to surgery within the week
- if there is response then surgery is undertaken 6-12 weeks post neoadjuvant therapy
- if there is progressive or non responsive disease then progression to surgery within the week
- MRI at 1 month
