Henry Yao HMO1, Royal Melbourne Hospital 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

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 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)

5 yr survivals Prognosis 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

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