Colorectal - Colon Cancer

Question 1

What are modifiable risk factors for Colon Cancer?

Answer 1

1. Diet - Red Meat, Animal Fat, Alcohol
2. Lifestyle - Smoking and Obesity

Question 2

What are protective factors against colon cancer?

Answer 2

Fruits and Vegetables
High Fibre
Vitamin Supplements

Physical Activity

HRT
Aspirin
NSAIDs

Question 3

What are nonmodifiable factors for colon cancer?

Answer 3

1. Age > 50
2. Chinese Race
3. FMH
4. Herediary Syndromes
   - FAP
   - Lynch
   - Peutz Jeghers
   - Juvenile Polyposis Syndrome
5. Familial Cancer Syndromes (HNPCC)
6. 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

Question 4

What is the pathophysiology of FAP-related colon cancer?

Answer 4

1. Loss of the APC suppressor gene on 5q21 (absent in patients with familial adenomatous polyposis)
2. 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)
3. 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
4. Loss of tumour suppressor gene at 18q21 (SMAD2 and SMAD4) leads to unrestrained cell growth
5. 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

Question 5

For sporadic colorectal carcinomas, what are two underlying etiologies? How do each present?

Answer 5

1. Chromosomal Instability - left sided predominant; Tubular, tubulovillous, and villous adenomas, Moderately differentiated adenocarcinomas
2. Microsatellite Instability; right sided predominant; No precursor lesions, Sessile serrated adenomas, Large hyperplastic polyps, Mucinous carcinomas

Question 6

What is the distribution of presentation of CRC?

Answer 6

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.

Question 7

Symptoms of Colon Cancer?

Answer 7

1. Abdominal pain
2. PR bleed (hematochezia / melena)
3. Any symptomatic anemia
4. Any changes in bowel habits – in rule out red flags

Question 8

What is the Amsterdam Criteria for HNPCC?

Answer 8

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

Question 9

What are the 7 points that would suggest familial heritary syndromes?

Answer 9

• 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)

Question 10

What are complications of the colon cancer?

Answer 10

1. Tumour Bleeding
2. Tumour Obstruction
3. Tumour Perforation
4. Tumour Fistula
5. Tumour Invasion

Question 11

What are symptoms that would suggest metastases?

Answer 11

• 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

Question 12

What are key things on Physical examination in a patient with colon cancer?

Answer 12

1. Vital Signs – Temperature, Blood Pressure, Pulse Rate, RR, Pain Score
2. 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
3. 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)
4. Digital Rectal Examination
   a. Any masses felt
   b. Any PR bleeding
   c. Is anal tone intact
5. Lung Examination – any pleural effusion, consolidation
6. Cardiac Examination
7. Any bony tenderness

Question 13

What are 4 modes of spread of colon cancer?

Answer 13

1. 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
2. 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)
3. 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
4. Transcoelomic
   - Carcinomatosis Peritonei – via subperitoneal lymphatic or viable tumour cells shed from serosal surface
   - Malignant ascites (rare)

Question 14

What is the song for investigations for colon cancer?

Answer 14

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.

Question 15

What modalities are used to stage colon cancer?

Answer 15

1. CT Thorax – Lung
2. 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
3. PET CT
   - Recommended when surgical resection of metastases is being considered to exclude occult disease

Question 16

What are supporting investigations for colon cancer?

Answer 16

1. FBC
2. Kidney Function Tests
3. LFTs
4. CEA
5. Supine and Erect AXR
6. Erect CXR

Question 17

What are pre-op investigations to be done?

Answer 17

1. GXM
2. PT/PTT
3. ECG, 2D Echo, Trops, Myocardial Perfusion Scan KIV Cardiology Referral

Question 18

What is the use of CEA?

Answer 18

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)

Question 19

Apart from Colon Cancer, what are other causes of raised CEA?

Answer 19

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.)

Question 20

Tell me about the staging for Colon cancer?

Answer 20

Question 21

What is the pre-operative management for colorectal cancer?

Answer 21

• 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

Question 22

What are the surgical principles for colorectal cancer?

Answer 22

• 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

Question 23

What procedures are there for colon cancer, and what are the indications? what does each procedure entail?

Answer 23

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)

Question 24

When should adjuvant therapy for colon cancer be initiated? what medications in this?

Answer 24

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)

Question 25

What is the surgical management strategy for stage 4 colon cancer with hepatic mets

Answer 25

• 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

Question 26

What are complications to look out for post op?

Answer 26

Question 27

What are the risk factors for recurrence?

Answer 27

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

Question 28

Tell me about the follow up plans for resected colorectal cancer?

Answer 28

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

Question 29

What constitutes for an emergency colorectal cancer surgery? What surgery is performed?

Answer 29

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

Question 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?

Answer 30

▪ 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..

Question 31

In colon cancer with liver mets, how can we increase resectability?

Answer 31

(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)

Question 32

in patients with liver mets, what are other options?

Answer 32

Other alternatives:
▪ Ablation: radiofrequency ablation, microwave ablation
▪ Regional: Treatment: transarterial chemoembolization (TACE), Y-90

Question 33

Tell me about the ICG Retention

Answer 33

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

Question 34

What surgery is performed for patients with peritoneal mets from GI or gynae cancers? What does it involve?

Answer 34

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)

Question 35

From any histological/imaging CRC workup, how should treatment be divided? (Locally Infiltrative)

Answer 35

For locally infiltrative (Stage 2 and above, no mets), do a surgical resection.
Stratify low, moderate or high risk

Question 36

From any histological/imaging CRC workup, how should treatment be divided? (Locally Infiltrative Stage 3)

Answer 36

Question 37

From any histological/imaging CRC workup, how should treatment be divided? (Stage 1)

Answer 37

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.

Question 38

From any histological/imaging CRC workup, how should treatment be divided? (mCRC)

Answer 38

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

Answer 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