Colorectal - Colon Cancer Flashcards
1
Q
What are modifiable risk factors for Colon Cancer?
A
- Diet - Red Meat, Animal Fat, Alcohol
- Lifestyle - Smoking and Obesity
2
Q
What are protective factors against colon cancer?
A
Fruits and Vegetables
High Fibre
Vitamin Supplements
Physical Activity
HRT
Aspirin
NSAIDs
3
Q
What are nonmodifiable factors for colon cancer?
A
- Age > 50
- Chinese Race
- FMH
- Herediary Syndromes
- FAP
- Lynch
- Peutz Jeghers
- Juvenile Polyposis Syndrome - Familial Cancer Syndromes (HNPCC)
- Personal History of IBD, Colorectal Polyps, large (> 1cm) adenomatous polyps, and polyps with tubulovillous or villous histology, particularly if multiple; pelvic RT, acromegaly, endocarditis 2’ strep bovis
4
Q
What is the pathophysiology of FAP-related colon cancer?
A
- Loss of the APC suppressor gene on 5q21 (absent in patients with familial adenomatous polyposis)
- With the loss of APC, Beta-catenin accumulates and activates the transcription of genes (MYC and cyclin D1) which promote cell proliferation (APC is required to break down beta-catenin)
- K-RAS* (12p12) mutation follows the loss of APC – an activating mutation that causes the RAS to keep delivering mitotic signals and prevent apoptosis, more common in larger lesions, suggesting that it develops later in the mutagenesis pathway
- Loss of tumour suppressor gene at 18q21 (SMAD2 and SMAD4) leads to unrestrained cell growth
- Loss of p53 (17p13) (tumour suppressor gene) occurs late in carcinogenesis (frequently mutated in carcinomas, but not adenomas, and is thus thought to mark the devt of invasion) → prevents DNA repair / cell apoptosis
5
Q
For sporadic colorectal carcinomas, what are two underlying etiologies? How do each present?
A
- Chromosomal Instability - left sided predominant; Tubular, tubulovillous, and villous adenomas, Moderately differentiated adenocarcinomas
- Microsatellite Instability; right sided predominant; No precursor lesions, Sessile serrated adenomas, Large hyperplastic polyps, Mucinous carcinomas
6
Q
What is the distribution of presentation of CRC?
A
Most common sites of CRC: sigmoid colon (25%), rectum (21%), cecum (20%), recto-sigmoid junction (20%), transverse colon (15%), and ascending colon (10%). There can be variation in the sites of the CRC. In general, left sided colon cancers are more common than right sided cancer.
7
Q
Symptoms of Colon Cancer?
A
- Abdominal pain
- PR bleed (hematochezia / melena)
- Any symptomatic anemia
- Any changes in bowel habits – in rule out red flags
8
Q
What is the Amsterdam Criteria for HNPCC?
A
a. Atleast 3 relatives with histologically confirmed colorectal cancer*(1ofwhomisafirstdegreerelative
of the other 2) – FAP excluded
b. Atleast2successivegenerationinvolved
c. At least 1 of the cancer diagnosed before age of 50
9
Q
What are the 7 points that would suggest familial heritary syndromes?
A
- Diagnosed under the age of 45
- Adenomas >2cm diagnosed under the age of 40
- Multiple primary cancers – either colonic or extracolonic
- ≥ 10 adenomas present over a lifetime in addition to a family history of colon cancer
- Multiple closely related family members who have been diagnosed with colon cancer
- Colon cancer in more than 1 generation
- Clustering of extracolonic cancers in family members (i.e. gastric, breast, thyroid, uterine)
10
Q
What are complications of the colon cancer?
A
- Tumour Bleeding
- Tumour Obstruction
- Tumour Perforation
- Tumour Fistula
- Tumour Invasion
11
Q
What are symptoms that would suggest metastases?
A
- Constitutional Symptoms – Loss of Weight (must quantify), Loss of Appetite
- Liver – RHC discomfort, jaundice
- Lungs – SOB (pleural effusion most common), decreased effort tolerance
- Malignant Ascites
- Bone – bone pain, pathological fractures
- Brain – altered mental status
12
Q
What are key things on Physical examination in a patient with colon cancer?
A
- Vital Signs – Temperature, Blood Pressure, Pulse Rate, RR, Pain Score
- General Appearance
a. Any signs of altered mental state – alert, orientated to TPP
b. any signs of poor nutritional status – cachexia
c. any signs of anaemia – nailbed pallor, palmar crease pallor, conjunctival pallor
d. any signs of jaundice – scleral icterus, jaundice - Abdominal Examination (remember to check hernia orifice)
a. any previous scars – check for incisional hernia
b. any organomegaly (enlarged liver, irregular surface)
c. any tenderness, any masses, abdominal distension (i.e. malignant ascites)
d. any signs suggestive of IO – abdominal distention, abdominal tenderness, tinkling bowel sounds
e. any supraclavicular LN enlargement (Virchow’s node)
f. any inguinal LN enlargement (very low rectal tumours, near the dentate line, have a risk of spread to inguinal LN) - Digital Rectal Examination
a. Any masses felt
b. Any PR bleeding
c. Is anal tone intact - Lung Examination – any pleural effusion, consolidation
- Cardiac Examination
- Any bony tenderness
13
Q
What are 4 modes of spread of colon cancer?
A
- Direct extension: Longitudinally, transversely and radially; Radial spread – may involve ureter, duodenum, muscles of posterior abdominal wall, small intestine, stomach, pelvic organs or anterior abdominal wall; Rectal tumours may involve the pelvic organs or side wall
- Lymphatic – paracolic nodes (along main colonic vessels) eventually reaching the para-aortic nodes. In contrast to rectal disease, it is rare for colonic cancer that has not breached the muscle wall to exhibit LN Mets (~
15% of cases confined to bowel wall will be found to have LN Mets) - Hematogenous
– Liver via the portal venous system. 1⁄3 have liver mets at the time of dx, 50% will develop liver mets eventually.
– 2nd most common site – lungs
– Other sites include ovary, adrenal, bone, brain and kidney - Transcoelomic
- Carcinomatosis Peritonei – via subperitoneal lymphatic or viable tumour cells shed from serosal surface
- Malignant ascites (rare)
14
Q
What is the song for investigations for colon cancer?
A
Once the diagnosis is suspected based on history, physical examination, I will perform a colonoscopy to establish the diagnosis via biopsy and to localize the lesion.
Also, colonoscopy can help to rule out synchronous cancer (3% to 5%) and synchronous polyp (30%). In addition to establishing the histology,
I will look for the level of differentiation on the histology report.
Following which, I will proceed to stage the tumour with local as well as systemic staging investigations.
Depending on the circumstances, I would perform supportive investigations to assess for complications.
If the patient is suitable for curative surgery, I would proceed to perform pre-operative investigations.
15
Q
What modalities are used to stage colon cancer?
A
- CT Thorax – Lung
- CT AP
– invasion into bladder, ureter, uterus, duodenum (esp. for right-sided colonic tumours)
– Regional lymph node Mets
– Peritoneal seeding, omental kinking, malignant ascites,
hydroureter, hydronephrosis, IO (i.e. carcinomatosis peritonei)
– Hepatic Mets – most common site of Mets in CRC - PET CT
- Recommended when surgical resection of metastases is being considered to exclude occult disease
16
Q
What are supporting investigations for colon cancer?
A
- FBC
- Kidney Function Tests
- LFTs
- CEA
- Supine and Erect AXR
- Erect CXR
17
Q
What are pre-op investigations to be done?
A
- GXM
- PT/PTT
- ECG, 2D Echo, Trops, Myocardial Perfusion Scan KIV Cardiology Referral
18
Q
What is the use of CEA?
A
CEA is a useful prognostic and surveillance tumour marker in colorectal cancer (in patients with established disease absolute level
of serum CEA correlates with disease burden)
19
Q
Apart from Colon Cancer, what are other causes of raised CEA?
A
False positive raised CEA: smoking, adjuvant therapy with 5-FU, inflammatory states (i.e. pancreatitis, diverticulitis, cholecystitis
etc.) and cancers (i.e. thyroid, stomach, lung, breast, pancreas, cervix, bladder, kidney etc.)
20
Q
Tell me about the staging for Colon cancer?
A
21
Q
What is the pre-operative management for colorectal cancer?
A
- Multidisciplinary tumour board meeting – involves medical oncologist, pathologist, radiologist and surgeon (Curative/Palliative –> Chemo/RT –> Open/MIS –> Specimen Removal –> lateralisation –>
- Pre-operative investigations (see above) & Anaesthesia referral +/- subspeciality referral (i.e. cardiology)
- Mechanical Bowel Preparation (MBP) with PEG (Modification of diet – 3 days low residue diet (reduce frequency and volume of stools – low fibre, reduce food that increases bowel activity), and one day clear feeds, NBM from 12mn (day of operation))
– contraindicated in IO, perforation - Stoma site discussion with stoma care nursing specialist
- Prophylactic intravenous antibiotics (IV ceftriaxone and metronidazole within 30-60 mins of skin incision)
- Chest Physiotherapy – incentive spirometry
- DVT Prophylaxis
▪ Subcut Low Molecular Weight Heparin (LMWH) – 40mg OD start on POD 1-2
▪ Anti-embolism (TED) stockings are fitted
▪ Early Ambulation
22
Q
What are the surgical principles for colorectal cancer?
A
- Complete Mesocolic Excision (CME)
▪ Dissection in the embryological defined mesocolic plane – includes all mesentery and potentially involved LNs
▪ Central ligation of the vascular pedicle (Minimum number of 12 lymph nodes in resected specimen)
▪ Resection of an adequate length of colon on either side of the tumour (in general 5cm margins)
▪ Bowel continuity restored with a well-vascularized, tension free anastomosis
23
Q
What procedures are there for colon cancer, and what are the indications? what does each procedure entail?
A
The selection of the appropriate surgical procedure depends on the location of the primary tumour
- Right Hemicolectomy
▪ For cancer involving the caecum, ascending colon, hepatic flexure
▪ Involves resection of the ileocolic artery, the right colic artery (if present) & right branch of the middle colic artery
▪ Terminal Ileum is transected 10-15cm from IC valve and anastomosis with proximal transverse colon - Extended Right Hemicolectomy
▪ For cancer involving the mid-transverse colon
▪ Involves resection of the ileocolic artery, the right colic artery (if present) & middle colic artery
▪ Terminal Ileum is transected 10-15cm from IC valve and anastomosis with distal transverse colon - Left Hemicolectomy
▪ For cancer involving the distal transverse colon, splenic flexure, descending colon, proximal sigmoid colon
▪ Involves resection of the inferior mesenteric artery (IMA)
▪ Requires mobilization of the splenic flexure to ensure tension free anastomosis - Sigmoid Colectomy
▪ For cancer involving the sigmoid colon
▪ Involves resection of the inferior mesenteric artery (IMA) - Other Surgical Resections
▪ Subtotal Colectomy: terminal Ileum is transected and is anastomosis with sigmoid colon
▪ Total Abdominal Colectomy: terminal ileum is transected and anastomosis is with rectum (ileorectal anastomosis)
- Hartmann’s Procedure
▪ Hartmann’s Procedure: surgical resection of the (i.e. recto-sigmoid colon) with closure of the rectal stump and formation of a temporary end colostomy (it is used when immediate anastomosis is not possible) – usually in
emergency settings
▪ Can be performed for benign (i.e. perforated diverticulitis) or malignant conditions (i.e. perforated / obstructed
sigmoid tumour or upper rectal tumour)
24
Q
When should adjuvant therapy for colon cancer be initiated? what medications in this?
A
Stage III (node positive) → aim to initiate chemotherapy within 6-8 weeks of surgery, i.e. chemotherapy regimen: 6-month
course of oxaliplatin-based regimen – FOLFOX114 (oxaliplatin + leucovorin (LV) and short-term infusion 5-FU)
25
What is the surgical management strategy for stage 4 colon cancer with hepatic mets
- Sandwich Therapy: neoadjuvant chemotherapy, surgical resection followed by adjuvant chemotherapy
- Inclusion of biological agents (i.e. bevacizumab or cetuximab) depending on the RAS and BRAF status
- Surgical Goals – adequate resection of all metastases (margins negative*) with adequate hepatic reserve (at least 2
contiguous hepatic segments, preservation of vascular inflow / outflow and biliary drainage, preserve adequate future liver
remnant (>20% in a healthy liver))115
- Synchronous liver metastases – no difference in mortality and morbidity for staged vs. simultaneous colectomy and
hepatectomy
26
What are complications to look out for post op?
27
What are the risk factors for recurrence?
High Risk Factors for Recurrence (Stage II)
- Poorly differentiated on histology
- Presence of lymphovascular invasion (LVI), perineural invasion (PNI)
- Close / Indeterminate or positive margins
- Tumour complications (i.e. bowel obstruction, tumour perforation)
- Less than 12 lymph nodes examined
28
Tell me about the follow up plans for resected colorectal cancer?
Follow-up
- The goal for close follow-up is to detect resectable recurrence and to improve survival – most recurrences occur within 2 years
of original diagnosis
- Follow-up visits (history and physical exam) with CEA at each visit
- Colonoscopy to identify metachronous CRC → see schedule below
- CT TAP to detect radiological recurrence → see schedule below
- For patients who presented with obstructed tumour (did not have complete colonoscopy pre-operatively), ensure completion colonoscopy performed
29
What constitutes for an emergency colorectal cancer surgery? What surgery is performed?
Obstruction --> Bleeding --> Perforation
For obstructed right sided cancer
▪ Consider emergency right hemicolectomy +/- stoma vs primary anastomosis - For obstructed left sided cancer
▪ Emergency Surgery vs. Colonic Stenting
▪ Colonic stenting can be used as a “bridge to surgery”, to allow for optimization of medical status prior to surgery, surgery
will be converted from emergency to elective. Lower rates of stoma creation but evidence for long-term oncological
outcome is suboptimal
▪ If endoscopic stenting fails, will require surgical intervention
30
What are the Surgical Consideration prior to Surgery for Liver Metastases.
While we're at it, what is the general principle for surgical treatment of mets?
▪ Is it oncologically appropriate - ability to perform a R0 resection
▪ Is the resection margin adequate - 1mm margin sufficient
▪ Is there sufficient future liver remnant (FLR) & quality of liver parenchyma - perform ICG retention test (see below)
▪ Is it technically feasible (open vs. lap)
Resection of symptomatic tumour; resection of asymptomatic tumour is controversial
Where there is metastases noted on staging scans, i will consider first sandwich therapy (neoadjuvant, surgery, adjuvant) and inclusion of biological agents depending on RAS and BRAF status; surgical resection is dependent on a) the ability to perform a R0 resection, achieve adequate margins (to my knowledge 1mm margin is sufficient for mets), c) sufficiemt future liver remnant (& quality of liver parenchyma (assessed using ICG test), and d) technical feasability. Where these conditions are met, surgical resection of mets are possible
I know that in liver metastases we can increase resectability are 1) Portal Vein Embolization and 2) Portal Vein Ligation. Other methods to be considered are locoregional a) radiofrequency ablation and b) TACE. These should be discussed at a MDT, taking into account factors like..
31
In colon cancer with liver mets, how can we increase resectability?
(1) portal vein embolization and staged hepatectomy (to achieve compensatory hypertrophy of remnant liver),
(2) portal vein ligation and staged hepatectomy and
(3) Association of Liver Partition with Portal vein ligation for staged hepatectomy (ALPSS)
32
in patients with liver mets, what are other options?
Other alternatives:
▪ Ablation: radiofrequency ablation, microwave ablation
▪ Regional: Treatment: transarterial chemoembolization (TACE), Y-90
33
Tell me about the ICG Retention
ICG retention at 15 mins (Makuuchi decisional algorithm)
- < 10% for trisectionectomy or bisectorectomy
- 10 - 19% for hemihepatectomy, right sided sectorectomy
- 20 - 29% for segmentectomy
- 30-39% for limited resection (i.e. wedge resection)
- > 40% for enucleation
34
What surgery is performed for patients with peritoneal mets from GI or gynae cancers? What does it involve?
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC
▪ CRS: Removal of all macroscopic peritoneal disease.
▪ HIPEC: Targets microscopic disease (lesions <3mm), administered for 60min. A higher dose of chemotherapy can be
delivered with less systemic effects due to the peritoneal-plasma barrier. The higher temperature also synergistically
increases drug penetration.
Pressurized intraperitoneal aerosol chemotherapy (PIPAC)
35
From any histological/imaging CRC workup, how should treatment be divided? (Locally Infiltrative)
For locally infiltrative (Stage 2 and above, no mets), do a surgical resection.
Stratify low, moderate or high risk
36
From any histological/imaging CRC workup, how should treatment be divided? (Locally Infiltrative Stage 3)
37
From any histological/imaging CRC workup, how should treatment be divided? (Stage 1)
Stage 1 usually are found in polyps.
For a pedunculated polyp with a pT1 carcinoma confined to the head, neck and stalk (Haggitt 1-3) endoscopic resection with proper follow-up is enough even with the presence of submucosal invasion, provided that no other unfavourable factors are present
However, the presence of any unfavourable factor in a sessile or flat polyp (Paris classification) with a pT1 carcinoma mandates surgical resection in patients with average operative risk.
38
From any histological/imaging CRC workup, how should treatment be divided? (mCRC)
MDT to decide if it is potential convertable to resectable or not:
- Palliative Intent: possible stent to prevent IO
If resectable mCRC: With very favourable prognostic criteria and good technical resectability, periop systemic treatment may not be necessary. But where unfavourable criteria or unclear prognostic situation, use of FOLFOX 3 months pre and post op is a standard of care.
If initially unresectable but potential to be: conversion therapy (ie Anti-EGFR mAbs in left sided RAS-wt patients; right sided and RAS-mutant, FOLFOXIRI bevacizumab
Where first line treatment to convert is not working, intra-arterial ChT.
If only peritoneal mets, consider CRS HIPEC
39
In metastatic CRC, discussion with MDT is essential to determine whether it is resectable, able to be converted to resectable, or unresectable.
Where resectable then surgical intervention should proceed, and adjuvant therapy considered when there is poor criteria (to my knowledge this includes FOLFOX 3 months); where able to be converted, therapy should be started (to my knowledge: Anti-EGFR mAbs in left sided RAS-wt patients; right sided and RAS-mutant, FOLFOXIRI bevacizumab)
Where only peritoneal mets: CRS-HIPEC may be considered
Where unresectable: consider palliative intent with colonic stenting to prevent IO. Other therapies like ChT or targeted therapies or Local Therapies like Radiofrequency Ablation, SBRT, TACE should be discussed in great detail at the MDT, weighing up disease severity, prognosis, and patient factors like functional status, fraility and preferences
