Colorectal Cancer

Henry Yao

HMO1, Royal Melbourne Hospital

Colorectal Cancer

• Epidemiology– Most common internal cancer in Western Societies– Second most common cancer death after lung cancer– Lifetime risk

• 1 in 10 for men• 1 in 14 for women

– Generally affect patients > 50 years (>90% of cases)

Colorectal Cancer

• Forms

– Hereditary

• Family history, younger age of onset, specific gene defects

• E.g. Familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome)

– Sporadic

• Absence of family history, older population, isolated lesion

– Familial

• Family history, higher risk of index case is young (<50years) and the relative is close (1st degree)

• Histopathology

– Generally adenocarcinoma

Risk Stratification

• Risk factors– Past history of colorectal cancer, pre-existing adenoma,

ulcerative colitis, radiation– Family history – 1st degree relative < 55 yo and relatives

with identified genetic predisposition (e.g. FAP, HNPCC, Peutz-Jegher’s syndrome) = more risk

– Diet – carcinogenic foods• Risk category (for asymptomatic pts)

– Category 1 (2x risk) – 1o or 2o relative with colorectal cancer >55 yo

– Category 2 (3~6x) – 1o relative < 55yo or 2 of 1o or 2o relative at any age

– Category 3 (1 in 2) – HNPCC, FAP, other mutations identified

Screening

Group Screening Evidence

General Population FOBT every 2 years from age 50 to 75 1A

Category 1 FOBT yearly +/- 5 yearly sigmoidoscopy from age 50

Category 2 FOBT yearly + colonoscopy 5 yearly from age 50 or 10 years younger than index case

IIIB

Category 3 Variable Consult Oncology, e.g.- FAP – colonoscopy every 12 months from 12-15 yo until age 35 then 3 yearly- HNPCC – 1~2yearly colonoscopy from age 50 or 5 years younger than index case

IIIB

Clinical Presentation

• Depends on location of cancer• Locations

– ⅔ in descending colon and rectum– ½ in sigmoid colon and rectum (i.e. within reach of

flexible sigmoidoscope)• Caecal and right sided cancer

– Iron deficiency anaemia (most common)– Distal ileum obstruction (late)– Palpable mass (late)

Clinical Presentation

• Left sided and sigmoid carcinoma– Change of bowel habit

• Alternating constipation + diarrhoea• Tenesmus• Thin stool

– PR bleeding, mucus• Rectal carcinoma

– PR bleeding, mucus– Change of bowel habits– Anal, perineal, sacral pain

• Constitutional symptoms– LOA, LOW, malaise

• Bowel obstruction

Clinical Presentation

• Local invasion– Bladder symptoms– Female genital tract symptoms

• Metastasis– Liver (hepatic pain, jaundice)– Lung (cough)– Bone (leucoerythroblastic anaemia)– Regional lymph nodes– Peritoneum (Sister Marie Joseph nodule)– Others

Examination

• Signs of primary cancer– Abdominal tenderness and distension – large bowel

obstruction– Intra-abdominal mass– Digital rectal examination – most are in the lowest 12cm

and reached by examining finger– Rigid sigmoidoscope

• Signs of metastasis and complications– Signs of anaemia– Hepatomegaly (mets)– Monophonic wheeze– Bone pain

Investigations

• Faecal occult blood– Guaiac test (Hemoccult) – based on pseudoperoxidase

activity of haematin• Sensitivity of 40-80%; Specificity of 98%• Dietary restrictions – avoid red meat, melons, horse-

radish, vitamin C and NSAIDs for 3 days before test– Immunochemical test (HemeSelect, Hemolex) – based on

antibodies to human haemoglobins– Used for screening and NOT diagnosis

Investigations

• Colonoscopy– Can visualize lesions < 5mm– Small polyps can be removed or at a later stage by

endoscopic mucosal resection– Performed under sedation– Consent: bleeding, infection, perforation (1 in 3000), missed

diagnosis, failed procedure, anaesthetic/medical risks– Warn: bowel prep, abdominal bloating/discomfort

afterwards, no driving for 24 hours

Bowel Prep

Investigations

• Double contrast barium enema– Does not require sedation– Avoids risk of perforation– More limited in detecting small lesions– All lesions need to be confirmed by colonoscopy and biopsy– Performed with sigmoidoscopy– Second line in patients who failed / cannot undergo

colonoscopy

Other Imaging

• CT colonoscopy• Endorectal ultrasound

– Determine: depth, mesorectal lymph node involvements– No bowel prep or sedation required– Help choose between abdominoperineal resection or ultra-

low anterior resection• CT and MRI – staging prior to treatment• Blood tests

– FBE – anaemia– Coagulation studies – for surgery– UECr - ?take contrast, ?NAC required– Tumour marker CEA

• Useful for monitoring progress but not specific for diagnosis

Management

• Pre-operative– Bowel prep – picolax, go lytely, fleet

• Normally 1 day prior• Partial obstruction – 2~3 days prior• Complete obstruction – intra-operative lavage

– Antibiotics prophylaxis (up to 24 hours post-op)• Ampicillin• Metronidazole• Gentamicin

– DVT/PE prophylaxis

Arterial supply

Resection

Management

• Caecum or ascending colon– Right hemicolectomy– Vessels divided – ileocaecal and right colic– Anastamosis between terminal ileum and transverse colon

• Transverse colon– Close to hepatic flexure right hemicolectomy– Mid-transverse extended right hemicolectomy (up to

descending) + omentum removed en-bloc with tumour– Splenic flexure subtotal colectomy (up to sigmoid)

• Descending colon– Left hemicolectomy– Vessels divided – inferior mesenteric, left colic, sigmoid

Management

• Sigmoid colon

– High anterior resection

– Vessels ligated – inferior mesenteric, left colic and sigmoid

– Anastomoses of mid-descending colon to upper rectum

• Obstructing colon carcinoma

– Right and transverse colon – resection and primary anastomosis

– Left sided obstruction

• Hartmann’s procedure – proximal end colostomy (LIF) + oversewing distal bowel + reversal in 4-6 months

• Primary anastamosis – subtotal colectomy (ileosigmoid or ileorectal anastomosis)

• Intraoperative bowel prep with primary anastomosis (5% bowel leak)

• Proximal diverting stoma then resection 2 weeks later

• Palliative stent

Rectal Cancer

• Options– Low anterior resection– Transanal local excision– Abdomino-perineal resection– Palliative procedure

• Factors influencing choice– Level of lesion – distance from dentate line, <5cm requires

abdomino-perineal resection to obtain adequate margin• Note: only 3% of tumours spread beyond 2cm

– Grade – poorly differentiated larger margin– Patient factors – incotinence– Mesorectal node status – resect if LN mets

Rectal Cancer

• Anterior resection

– Upper and mid rectum cacinoma

– Sigmoid and rectum resected

– Vessels divided – inferior mesenteric and left colic

– Mesorectum resected

– Coloanal anastomosis

– High – intraperitoneal anastamosis (upper 1/3 of rectum)

– Low – extra-peritoneal anastomosis

– Post-op recovery

• Increased stool frequency

• 12-18 month to acquire normal bowel function

• 1~4% anastamotic leak

Rectal Cancer

• Abdominoperineal resection

– Larger T2 and T3 or poorly differentiated tumour

– Rectum mobilised to pelvic floor through abdominal incision

– Sigmoid end colostomy

– Separate perianal elliptical incision to mobilise and deliver anus and distal rectum

– Vessels ligated – inferior mesenteric

Rectal Cancer

• Hartmann’s procedure– Acute obstruction– Palliative

• Transanal local exision– Early stage– Too low to allow restorative surgery

• En block resection – for locally advanced colorectal carcinoma (remove adherent viscera and abdominal wall)

• Palliative procedures– Diverting stoma– Radiotherapy– Chemotherapy– Local therapy – laser, electrocoagulation, cryosurgery– Nerve block

Staging

• TNM Staging

– Stage 0 – Tis N0 M0 – i.e. small tumour within the lining of the colon or rectum

– Stage 1 – T1 N0 M0 or T2 N0 M0 – i.e. tumour has invaded layers of the colon without spread beyond wall

– Stage 2 – T3 N0 M0 or T4 N0 M0 – i.e. tumour has spread beyond wall and into nearby tissue but no LNs

– Stage 3 – Any T with any N but M0 – i.e. spread to nearby LNs but not to other organs

– Stage 4 – Any T with any N and M1 – i.e. spread to other organs (e.g. liver and lungs)

• Duke’s staging

– Duke A – tumour confined to bowel wall

– Duke B – tumour invading through serosa

– Duke C – lymph node involvement

– Distant metastasis

Colon Cancer Summary

• Wholistic care

– Education and counselling (about risk in family members as well)

– Lifestyle management – diet changes

– Support from cancer council

• Surgical (hemicolectomy, stents for palliation)

– Stage 0 and 1 – surgical resection only with NO adjuvant chemo (NNT to high and SE of chemo too high)

– Stage 2,3,4 – surgery, chemotherapy, radiotherapy, targeted therapy

– Prepare patient for surgery – explain diagnosis, surg under GA, hospital for 7d, bowel prep, proph antibiotics, primary anastomosis, may require colostomy or ileostomy to facilitate healing but temp and only for 12wk, risk is infection, bleeding, anastomotic leak, mortality

• Medical

– Adjuvant chemo – FOLFOX (folinic acid, 5-FU, oxaliplatin) – increase 5yr survival, be wary of oxaliplatin causing peripheral neuropathy

– Biological therapy – anti-VEGF (bevacizumab), EGFR inhibitor (cetuximab)

– Radiotherapy – for palliation or liver mets

• Follow-up

– Aim to detect local recurrence, metastasis or new primary

– CEA only useful if high b4 surg and low after surg

– FOBT, repeat CT, colonoscopy – according to hospital protocol

Rectal Cancer Summary

• Wholistic care, conservative, (same colon cancer)

• Medical and Surgical

– Neoadjuvant chemo-radiotherapy to reduce size and sterilize area b4 surgery to reduce risk of recurrence

– Abdominal perineal resection (APR) → require permanent colostomy as anus is removed

– Low anterior resection (LAR) – sphincter sparing surgery, upper ⅓ of rectum remove only and no stoma as anus is functional

– Local excision for superficial cancers

• Follow-up

– Same as colon cancer

Complications

• Liver metastasis – resection, embolisation, chemotherapy, RFA, cryotherapy

• Local invasion → perineal and pelvic pain

• Bowel obstruction

– Palliated surgically (colectomy, stoma, stent placed endoscopically) or else syringe driver (mix of analgesic, anti-emetic, anti-spasmotic)

• Fistula to skin or bladder

• Rectal discharge and bleeding

• Hypoproteinaemia (from poor appetite and absorption → peripheral oedema)

• Poor appetite (steroids can help)

Prognosis

• 5 yr survivals– T1 = >90%, T2 = >80%. T3 = >50%– LN involvement = 30~40%– Distant mets = <5%

Hereditary Colorectal Cancer

• Familial adenomatous polyposis– FAP account for <1% of all colorectal cancers– Due to mutation of the adenomatosis polyposis coli (APC) gene– Numerous adenomas appear as early as childhood and virtually

100% have colorectal cancer by age 50 if untreated

 • Hereditary non-polyposis colorectal cancer / Lynch syndrome

– More common than FAP and account for ~1-5% of all colonic adenocarcinomas

– Due to a mutation in one of the mismatch repair genes– Earlier age onset of colorectal cancer and predominantly involve the

right colon– HNPCC also increases the risk of

• Endometrial, ovarian, breast ca• Stomach, small bowel, hepatobiliary ca

– Renal pelvis or ureter ca

References

• Fry et al., Chapter 50 – Colon and Rectum, Sabiston Textbook of Surgery 18th Edition

• Tjandra et al., Chapter 24 – Colorectal cancer and adenoma, Textbook of Surgery 3rd Edition

• http://www.cancer.org.au//aboutcancer/cancertypes/colorectalcancer.htm

• Google images

Thanks You and Questions

© Copyright The University of Melbourne 2011

Case Scenario

• 70 year old male

• Presented to clinic

• “Doc, I have noticed some blood in my stool.”

What are your differential diagnoses?

What do you want to ask on history?

Differential diagnosis

• Common causes

– Haemorrhoids

– Colorectal cancer

– Diverticular disease

• Anorectal pathology

– Haemorrhoids, anal fissure, anorectal cancer, anal prolapse

• Colonic pathology

– Colorectal polyp/cancer, diverticular disease, angiodysplasia

– Colitis (IBD, infective, pseudomembranous colitis, ischaemic, radiation)

– Post-surgery (e.g. polypectomy)

• Small intestine and stomach pathology

– Massive upper GI bleed haematochezia

– Meckel’s diverticulum, small bowel angiodysplasia

History

• Seven characteristics of HOPC• Key questions to sort out

– Age of onset– Quality

• Insidious onset, mixed in with stool VS• Intermittent, only with hard stools, blood on paper and

bowl and dabs of blood on top of stool– Colour

• Black and tarry, associated with offensive smell• Maroon red• Bright red• Torrential

– Past history of haemorrhoids, bowel cancer– Family history of bowel cancer, breast cancer

Other history and examination

• Other things to ask:

– Risk factors for haemorrhoids – constipation, heavy lifting, chronic cough, pregnancy

– Other features of colorectal cancer

– Other features of colitis – pus and mucus in stool, fever, chills, sweats

– Past medical history

• Abdominal Examination

– Tenderness

– Masses

• PR Examination

– Anorectal pathology

– Colour of blood on finger

– Polyps in rectum

Case Scenario

• Doc, I’ve been noticing blood in my stool for 6 months now.

• The blood seems to be mixed in the stool.

• I’ve also noticed some constipation recently. This is unusual for me. I usually go every day.