Part two - colorectal Flashcards
Risk of colorectal cancer
Cumulative risk 6% by 75 years
Slight increase x2 -> no specific surveillance
- one 1st degree relative with CRC > 55 years
Moderate increased risk x2-6 -> 5 yearly scopes from 50 years or 10 years before relative’s dx
- one 1st degree relative with CRC < 55 years
- two 1st degree relatives any age on same side
High risk up to 50x -> refer to genetic service
- family hx of FAP, HNPCC or other familial cancer service
- one 1st degree & 2+ 1st or 2nd degree relatives on same side any age
- one 1st degree < 50 especially if loss of MLH1, MSH2, MSH6, PMS2
- one 1st/2nd degree with CRC and multiple polyps
- two 1st or 2nd degree relatives on same side whom:
- diagnosed < 55, or
- developed multiple bowel cancers, or
- developed extra-colonic tumour(s) suggestive of HNPCC
- endometrial
- ovarian
- stomach
- small bowel
- renal pelvis
- pancreas
- brain
Distribution of colorectal cancer
Right colon - 30% Transverse colon - 10% Left colon - 15% Sigmoid colon - 25% Rectum - 20%
TNM staging colorectal cancer
T1 = invades submucosa T2 = invades muscularis propria T3 = invades through musc prop into subserosa, nonperitoneal peri-colic or -rectal tissues T4 = perforates visceral peritoneum or directly invades other organs or structures
N1 = 1-3 peri-colic or peri-rectal lymph node metastases N2 = 4+ peri-colic or peri-rectal lymph node metastases
M1 = distant metastases
Stage I = T1 and T2 with no nodal disease
Stage II = T3 and T4 with no nodal disease
Stage III = any T with nodal disease
Stage IV = any T, any N with distant metastases
Duke’s classification
Dukes’ A = invasion into but not through bowel wall - 90% five year survival
Dukes’ B = invasion through the bowel wall but not involving nodes - 70%
Dukes’ C = involvement of lymph nodes - 30%
Dukes’ D = distant metastases - <15%
FAP
FAP = familial adenomatous polyposis = cluster of genetic syndromes characterised by development of numerous GIT polyps
Actual FAP is an inherited disorder causing hundreds to thousands of polyps in the colon and rectum of varying size and configuration with associated increased risk of CRC due to mutated APC gene.
CRC approaches 100% by aged 35.
Duodenal & periampullary polyps -> cululative cancer risk 10% by 60 and second most common cause of disease related morbidity.
FAP
FAP = familial adenomatous polyposis = cluster of genetic syndromes characterised by development of numerous GIT polyps
Actual FAP is an inherited disorder causing hundreds to thousands of polyps in the colon and rectum of varying size and configuration with associated increased risk of CRC due to mutated APC gene.
CRC approaches 100% by aged 35.
Duodenal & periampullary polyps -> cumulative cancer risk 10% by 60 and second most common cause of disease related morbidity.
AD inheritance, chromosome 5, >100 mutations
Gardner syndrome
An example of FAP with variations in expression of the extra colonic manifestation:
- polyposis
- desmoid tumours
- osteomas of mandible or skull
- sebaceous cysts
Turcot syndrome
An example of FAP with variations in expression of the extra colonic manifestations:
- polyposis
- childhood cerebellar medulloblastoma
- May also be associated with HNPCC and defects in MMR genes - CRC with gliomas
Amsterdam II criteria
Defines HNPCC by history alone
At least 3 relatives must have a cancer associated with HNPCC - CRC, endometrial, stomach, ovary, ureter, renal pelvis, brain, small bowel, hepatobiliary tract, skin sebaceous tumours:
- One must be a first degree relative of the other two
- At least two successive generations must be affected
- At least one of the relatives must haves received the diagnosis by age 50
Revised Bethesda Criteria for HNPCC
In a new diagnosis of CRC, the presence of any one of the Revised Bethesda Criteria warrants testing for MSI:
- < 50 years
- Synchronous or metachronous HNPCC-related tumour regardless of age
- MSI-H-like histology < 60 years
- 1+ 1st degree relative with HNPCC-related tumour with one in <50 years
- 2+ first- or second-degree relatives with HNPCC-related tumours regardless of age
What is the pathogenesis of colorectal cancer?
Is by a combination of molecular events that are heterogeneous and include genetic and epigenetic abnormalities.
There are two well described genetic pathways which involve the stepwise accumulation of multiple mutations with differing genes and mechanisms by which the mutations accumulate.
Epigenetic events, most commonly methylation-induced gene silencing, may enhance progression along both pathways.
The adenoma-carcinoma-sequence
Also known as chromosomal instability.
80% of sporadic cancers.
Requires “two” hits to the APC tumour suppressor gene to mutate both alleles - the first may be acquired or sporadic.
Subsequent accumulation of mutations in KRAS, SMAD2, SMAD4 and p53 causes adenomas and then carcinomas.
DNA mismatch repair deficiency
Also known as micro satellite instability.
15% sporadic cancers.
Loss of mismatch repair genes causes mutations to accumulate in microsatellite repeats which may be located in promoting or coding region of genes regulating growth such as type II TGF-beta, BRAF and BAX protein. Dysregulated growth, differentiation and apoptosis predispose to carcinogenesis.
Morphologically this involves sessile serrated adenoma.
Pathologic features associated with microsatellite instability
- L = lymphocytes / lymphoid aggregates
- A = associated extra-colonic cancers - endometrial, small bowel, uroepithelial, ovarian, stomach
- M = mucinous / metachronous tumours / medullary growth pattern
- P = proximal colon tumours
- S = signet ring / synchronous tumours
What is FOLFOX?
FOLinic acid-Fluorouracil-OXaliplatin regimen
Chemotherapy regimen that includes:
- leucovorin calcium (calcium folinate)
- 5-fluorouracil
- oxaliplatin
Used in advanced-stage and metastatic colorectal cancer.
FOLFOX regimens differ in agent dosing and administration schedule and include FOLFOX 4, FOLFOX 6 and FOLFOX 7.
What is a polyp?
Masses of tissue that project into a lumen.
Morphological term only as does not imply histological diagnosis.
Polyposis = multiple polyps
Incidence of colorectal polyps
30% at 50 years
40% at 60 years
50% at 70 years
55% at 80 years
50% have more than one polyp
15% have more than two polyps
HNPCC-related tumours
Colorectal cancer Stomach cancer Ovarian cancer Uterine cancer Small bowel cancer Uroepithelial cancer Pancreas cancer
MSI-H histological features
- Tumour infiltrating lymphocytes
- Crohn-like lymphocytic reaction
- Mucinous/signet ring differentiation
- Medullary growth pattern
Levels of rectum in cm
From anal verge:
- lower 0-6 cm
- middle 7-11 cm
- upper 12-15cm
Peritoneal reflection - 7-9cm and may be as low as 5cm from the anal verge in women
Levels of rectum in cm
From anal verge:
- lower 0-6 cm
- middle 7-11 cm
- upper 12-15cm
When is oncological segmental resection indicated for a malignant colorectal polyp
1) Haggitt level 4 lesions with distal third submucosa invasion
2) Malignant polyp with margin of resection < 2 mm
3) Evidence of vascular or lymphatic invasion
4) Incomplete resection or inability to assess margin (piecemeal technique)
5) Sessile lesion with Sm3 invasion
What is serrated polyposis syndrome
hyperplastic polyposis syndrome
Clinical diagnosis based on 1+ of WHO criteria:
1) More than 20 polyps of any size distributed throughout the colon
2) At least five serrated polyps proximal to the sigmoid colon with 2+ larger than 10mm
3) Any number of serrated polyps proximal to the sigmoid colon in an individual who has a first degree relative with SPS
Define pseudopolyp
Inflammatory pseudopolyps are irregularly shaped islands of residual intact mucosa resultant from ulceration and regeneration in IBD.
What is juvenile polyposis coli (JPC)?
10+ juvenile polyps where a juvenile polyp is a hamartomatous lesion consisting of dilated cystic glands rather than increased epithelial cells.
- Any age though more common in children
- Removed due to high likelihood of bleeding
What is familial juvenile polyposis (FJP)?
10+ juvenile polyps and a first degree relative with the same. This occurs in ~1/3 of JPC cases.
What is a serrated polyp?
Heterogenous group of polyps with variable malignant potential including:
- Hyperplastic polyps
- Traditional serrated adenomas
- Sessile serrated adenomas/polyps
Define adenoma
Neoplasm of glandular epithelial tissues
Define advanced adenoma
An adenoma with:
1) High grade dysplasia
2) > 10mm
3) A villous component
Define synchronous adenoma
An adenoma diagnosed at the same time as a pathologically more advanced colorectal neoplasm
Define metachronous adenoma
An adenoma diagnosed after six months after the diagnosis of a previous adenoma
When does the sigmoid become the rectum?
Cessation of mesocolon Cessation of colonic hausfrau Blending of lateral and anti- mesenteric taeniae Approximately S3 6cm distal to sacral promontory
Origin right colic artery
Absent - 50%
Off middle colic artery - 30%
Off SMA - 20%
Most variable colic artery
Ileocolic least variable
When does sigmoid become rectum?
Cessation of sigmoid mesocolon Cessation of colonic hausfrau Blending of lateral and antimesenteric taeniae Usually at about S3 6cm distal to sacral promontory
What is the arc of Riolan?
An early branch from the left colic artery in the base of the mesocolon which joins the middle colic artery in 10%
What are the peritoneal white lines?
White line evident at the lateral margins of the ascending and descending colon which when divided mobilises the colon.
Formed by infolding of the peritoneum as it leaves the colonic wall fusing the former colonic mesentery with parietal peritoneum
How do lap and open colectomies compare for oncologic resections?
Comparable for:
- extent of resection
- recurrence
- survival
Lap better for:
- earlier return of bowel function
- reduced postop pain
- early discharge
- reduced wound complications
Lap worse for:
- longer operating times (no longer if expert)
- learning curve is about 50 cases
Principles of Hartmann Procedure
Access Control of contamination Mobilisation left colon Isolation and resection of diseased segment Drainage Maturation of end colostomy
Pathogenesis of clostridium difficle diarrhoea
Antibiotic therapy Disruption of colonic microflora C. difficile exposure and colonisation Release of toxins A (enterotoxin) and B (cytotoxin) Mucosal injury and inflammation
Antibiotics most commonly associated with Clostridium difficile colitis
Fluoroquinolones
Clindamycin
Penicillins (broad spectrum)
Cephalosporins (broad spectrum)
Describe C diff
Clostridium difficile is an anaerobic gram-positive, spore-forming, toxin-producing bacillus
Treatment principles for C diff infection
Stop precipitating antibiotics if possible
Confirm diagnosis
Treat with oral metronidazole (400mg tds) or vanc (125mg tds) for two weeks or one week after ceasing other ABs
Supportive cares - electrolytes
Isolate patient and contact precautions - soap and water
Watch for fulminant colitis and toxic megacolon
Up & coming:
- faecal transplant
- probiotics
Differential for large bowel obstruction
Tumour - malignant or benign
Volvulus
Stricture - inflammatory, diverticular, iatrogenic
Faecal impaction
Intussusception (usually secondary to other)
Functional - toxic megacolon, pseudo-obstruction
Hernia
Adhesive
How does neostigmine work?
Inhibits destruction of acetylcholine by acetylcholinesterases
Give 1-2mg IV/SC (repeat in three hours if required) with HDU monitoring for bradycardia, especially in patients with cardiac history
Investigations for rectal prolapse
Colonoscopy (BaE) to exclude precipitant DPG Anorectal physiology - EAS for sphincter assessment - manometry to assess tone, function and length - EMG to assess pudendal nerve
Procedures for rectal prolapse
Transabdominal rectopexy +/- sigmoid resection
- recurrence up to 10%
- morbidity up to 20%
Perineal proctosigmoidectomy (Altemeier procedure)
- recurrence up to 60%
- low morbidity
Rectal mucosectomy and plication of muscle (Delormes)
- recurrence up to 40%
- low morbidity
How is rectal prolapse classified?
Occult = intussusception of fullthickness rectum which does not protrude through the anal canal
Mucosal = protrusion of rectal muscoa through the anal canal, may be circumferential
Complete = full thickness rectal protrusion through the anal orifice
Types of anal cancer?
SCC
Basaloid = SCC variant arising from TZ
Adenocarcinoma - treat like a rectal cancer
Perianal skin cancers - stage as skin cancers
- Bowen’s
- Melanoma
- Paget disease of the anus
Chemotherapy for anal cancer
5-FU and mitomycin
Extra-intestinal manifestations of Crohn disease
ABCs…PQR
Arthritis - at least 20%
* Most common extra intestinal manifestation
* Large joints without synovial destruction
* Sacroilitis
* Ankylosing spondylolitis
Bone loss and osteoporosis
Cobalamin deficiency (B12)
Dermatologic
* Erythema nodosum - panniculitis
* Pyoderma gangrenosum - painful ulceration
Eye involvement
* Uveitis
* Iritis
* Episcleritis
Primary sclerosing cholangitis
Quirky thinks like secondary amyloidosis
Respiratory involvement
* Bronchiectasis
* Chronic bronchitis
* Interstitial lung disease
* Bronchiolitis obliterates with organising pneumonia
* Sarcoidosis
* Necrobiotic lung nodules
* Pulmanry infiltrates with eosinophilia (PIE) syndrome
* Serositis
Stones
* Renal
* Gallstones
Thromboembolic
* PE
* Arterial
Microscopic features of Crohn disease
Crypt abscesses Neutrophil infiltrate Paneth cell metaplasia Pseupdopyloric metaplasia Non-caseating granulomas Distortion of mucosal architecture Transmural inflammation
Macroscopic features of Crohn disease
Aphthous ulcers Skip lesions Transmural inflammation Ileocolic/TI/caecum commonly affected Creeping fat Strictures Fissures Cobblestone appearance
Siting of stoma
Within triangle formed by ASIS, umbo and PS with stoma coma through rectus abdomens fibres.
Avoid bony areas, creases and previous scars.
Site above a panus
Components of Crohn’s disease activity index
Number of liquid stools Abdominal pain Subjective assessment of well being Complications - arthritis, eyes, skin, perianal, fistula, fever Taking antidiarrhoeals Abdominal mass Low haematocrit Percentage deviation from standard weight
Treatment principles in Crohn disease
Step-up vs step-down approaches
- indure more remission with step-down
- step-up uses less potent and more understood drugs
- varies depending on location of disease
Aminosalicylate (5-ASA) Antibiotics - metronidazole & ciprofloxacin Steroids Immunosuppressants --Azithioprine -> metabolised to mercaptopurine --> test for thiopurine methyltransferase TPMT as if low need to start low dose else toxicity and agranulocytosis -- Methotrexate Biological = anti-TNF therapies --Infliximab --Adalimumab = Humira Hospitalise
Symptom control - loperamide, cholestyramine, probiotics, lactose avoidance
What is Crohn disease
Chronic condition resulting from inappropriate mucosal immune activation characterised by transmural inflammation, non-caseating granulomata and skip lesions
Pathogenesis of Crohn disease
Combination of:
Genetic susceptibility - NOD2, ATG16L1, IRGM
Epithelial dysfunction - tight junctions, transport
Aberrant mucosal immune responses - complex
Microbiota - the characteristics of intestinal population
Distribution of Crohn
Small bowel 40%
Colon 30%
Both 30%
Stricture formation in Crohn disease
SHIT Submucosa fibrosis Hypertrophy muscularis propria Inflammation Transmural oedema
Sequelae of steatorrhoea
SHOCK Severemalnutrition Hypocalcaemia - tetany Osteomalacia Clotting abnormalities vit K deficiency
Sites of fistula in Crohn disease
BREAST Bladder Retroperitoneal Enteric Anus Skin Twat
Treatment of condyloma acuminata
Prevent - Gardasil (6, 11, 16, 18), safe sex
Medical - podophyllin, dichloroacetic acid, imiquimod
Surgical - cautery, cryo, laser, scissor best with imiquimod
Wear VIRUS mask so you don’t become infected
Truelove & WItt criteria for ulcerative colitis
Bowel motions per day (>6) Blood in stool (+++) Fever (high) Heart rate (>90) ESR (>30) Hb (low / transfusion)
