Medbear Colorectal Flashcards
Define massive LBGIT
- Bleeding that requires >3 units of blood over 24 hours
- In patients with hemodynamic instability
What are the important hereditary CRC syndromes to ask in colorectal CA?
- FAP
- Lynch Syndrome
- Peutz-Jeghers Syndrome
- Juvenile polyposis
Others: Cowden syndrome, Cronkhite-Canada
How do we diagnose familial cancer syndromes (HNPCC)?
Diagnosed with AMSTERDAM CRITERIA (a.k.a 3-2-1 RULE)
- At least 3 relatives with histological confirmed colorectal CA
- At least 2 successive generation involved
- At least 1 of the cancer diagnosed before age of 50
Describe about the APC pathway (adenoma-carcinoma sequence) of colorectal CA.
It involves a stepwise accumulation of mutations in a series of oncogenes and tumor suppressor gene:
1. Loss of the APC suppressor gene on 5q21 (Absent in patient with FAP)
2. With the loss of APC, Beta-catenin accumulates and activates the transcriptions of gene (MYC and cyclin D1) which promotes cell proliferation
3. K-RAS (12p12) mutation follows the loss of APC -> activating mutation causing the RAS to keep delivering MITOTIC SIGNALS and PREVENT APOPTOSIS
4. Loss of tumor suppressor gene at 18q21 (SMAD2 and SMAD4) -> leads to UNRESTRAINED CELL GROWTH
5. Loss of p53 (17p13) occurs late in carcinogenesis -> prevents DNA repair/cell apoptosis
Describe the other defect or pathway in colorectal CA
Defects in DNA mismatch repair or microsatellite instability
- Like the APC pathway, there is accumulation of mutations, BUT WITHOUT CLEAR IDENTIFIABLE MORPHOLOGIC CORRELATES (e.g no adenomas)
- Due to mutations in one of the 5 DNA mismatch repair genes - deficiency in the ability to repair mismatched base pairs in the DNA that are accidentally introduced during replication, this gives rise to HNPCC
- MLH1 -> most commonly involved in sporadic colorectal CA
- Loss of DNA mismatch repair genes -> MICROSATELLITE INSTABILITY which affects BAX gene (promote apoptosis) and Type 2 TGF b-receptor (inhibits growth of colonic epithelial cells)
- Accumulated mutation in these growth-regulating genes leads to colorectal CA
Tumors that arise from this pathway have a better prognosis
State the tumor complications in colorectal CA
- Tumor bleeding -> symptomatic anemia
- Tumor obstruction -> IO
- Tumor perforation -> sepsis
- Tumor fistula -> fecaluria, pneumaturia, recurrent UTI
- Tumor invasion -> intractable pain (SACRAL N), LUTS (TRIGONE OF BLADDER)
State some metastatic symptoms for colorectal CA
- Constitutional symptoms - LOW, LOA
- Liver - RHC discomfort, jaundice
- Lungs - SOB
- Malignant ascites
- Bone - bone pain, pathological fractures
- Brain - altered mental status
State the mode of spread of coloreactal CA
- Direct extension
- Lymphatics (Progress from paracolic nodes -> para-aortic nodes)
- Hematogenous (Liver via PORTAL VENOUS SYSTEM, 2nd most common site is the LUNGS)
- Transcoelomic (CARICNOMATOSIS PERITONEI - via subperitoneal lymphatic)
- Define CEA
- State the function of CEA
- State the conditions when there is a false positive raised in CEA values
- What to do if there is a raised CEA level?
- An oncofetal protein lacking both sensitivity and specificity
- Useful prognostic and surveillance tumor marker. It is measured pre-operatively as a baseline level
- False positive raised CEA conditions:
- Smoking
- Adjuvant therapy with 5-FU
- Inflammatory states
- CA (e.g thyroid, breast) - If there is raised CEA
- Determine if patient is a smoker
- OGD/colonoscopy
- Consider CT TAP
- Consider US thyroid
- Mammogram for female patients
Describe how you would investigate a case of colorectal CA
Establish the diagnosis
- Colonoscopy (Diagnostic and therapeutic)
- Histology
Other investigative tools:
- CT colonography
- Double-contrast barium (APPLE CORE SIGN) and air enema
Staging investigation
- CT TAP
Supportive investigation
- FBC -> assess Hb level
- U/E/Cr -> Cr may be elevated (pre-renal failure) -> increase the risk of contrast nephropathy
- LFT -> Albumin level, any liver mets (elevated ALP)
- CEA (Take a baseline before surgery)
- Erect and supine AXR -> Look for IO, colon cut off sign
- Erect CXR -> TRO air under diaphragm
State the layers of GIT
How would you stage colorectal CA based on the TNM staging?
State the residual tumor classification (R0, R1, R2)
List the pre-operative management of colorectal CA
- Multidisciplinary tumor board meeting
- Pre-operative investigation + anesthesia referral
- Mechanical bowel preparation
- +/- Stoma site discussion with stoma care nursing specialist
- Prophylactic IV antibiotics (IV ceftriaxone and metronidazole within 30-60 mins of incision)
- Chest physiotherapy
- DVT prophylaxis
1. Subcut low molecular weight heparin (LMWH)
2. Anti-embolism stocking
3. Early ambulation
State the surgical principle of CRC
Complete mesocolic excision (CME)
- Dissection in the embryological defined mesocolic plane
- Central ligation of the vascular pedicle
- Resection of an adequate length of colon
- Bowel continuity restored with a well-vascularized, tension-free anastomosis
The selection of the appropriate surgical procedure depends on the location of the primary tumor
Describe on the management strategy of stage 4 colon CA (with liver metastases)
- Sandwich therapy: Neoadjuvant chemotherapy, surgical resection followed by adjuvant chemotherapy
- Inclusion of biological agents (such as BEVACIZUMAB or CETUXIMAB)
Surgical goals: adequate resection of all metastases with adequate liver reserve
List the immediate complications of CRC intra-operatively
- Intra-operative complication -> Bleeding, Injury to surrounding organs
- Ureteric injuries (During (1) Take off of IMA (2) Pelvic brim (3) between the lateral ligament)
- During APR, urethral injury can occur
Define rectum + state its anatomy
- Segment of large bowel within the true pelvis
- Part of the large bowel at the 3rd sacral vertebrae represents the top of the rectum
- Measures 12-15cm long
- ANORECTAL JUNCTION is the reference point between anal canal and and the rectum
State the anatomy of anal canal
- Measures 2-4cm long and passes downwards and backwards
- Surrounded by a complex arrangement of sphincter
- DENTATE LINE divides the upper half and lower half of anal canal
State the clinical presentation of rectum CA
- PR bleed (hematochezia/melena)
- Tenesmus
- Diminished stool calibre - PENCIL-THIN STOOL
- Mucoid stool (suggestive polypoid masses)
- Change in the bowel habits
What are the systemic complication of rectal CA based on the following headings:
- Constitutional symptoms
- Liver
- Lungs
- Bone
- Brain
- Constitutional symptoms - LOW, LOA
- Liver - RHC discomfort, jaundice
- Lungs - SOB (pleural effusion), decreased effort tolerance
- Bone - Bone pain, pathological fractures
- Brain - altered mental status
How can we establish the diagnosis of rectal CA during investigation?
FLEXIBLE COLONOSCOPY
- Allow for direct visualization
- Allow for biopsy for histological diagnosis
- Allow for assessment of SYNCHRONOUS LESIONS
- Allow for therapeutic procedures (e.g POLYPECTOMY)
Other investigation tools:
1. Rigid sigmoidoscopy
2. CT colonography
3. Double-contrast enema
Staging of rectal CA can be divided into local and systemic staging
State the investigations you would order to stage the CA
Local staging
- MRI rectum (Superior to EUS as can assess the circumferential resection margin)
- Endorectal US (Superior in delineating depth of tumor invasion and can assess local lymph node status)
Systemic staging
- CT TAP
