Colorectal Cancer

Colorectal Cancer

Presentation

·        Change in shape of stools significant (e.g. pencil shaped)

·        Rectal bleeding/mucus

·        Persistent changes in bowel habit

·        Tenesmus: constant feeling of need to defacate, even after passing stool

·        Weight loss

·        Anaemia

·        Abdominal or rectal mass in late presentation

·        Hepatomegaly (from secondaries)

·        By 75 years, 1 in 20 males and 1 in 25 females (Victoria)

Risk Factors

·        Environmental factors: diet, lifestyle, smoking

·        Family history

·        Premalignant lesions

Family History and Colorectal Cancer

·        Average risk = up to two 1^st or 2^nd degree relatives with bowel cancer at 55 or older (as long as on different sides of family). 98% of population 

·        Moderate risk = either one 1^st degree relative diagnosed before 55 years, or two 1^st or 2^nd degree relatives on one side of family diagnosed at any age. 1% population. Refer for colonoscopy every 5 years from age 50 or 10 years younger than earliest diagnosis in family 

·        High risk = more than above, including FAP or identified high-risk mutation in near relative. <1% of population. Suggest genetic testing. Referral to plan appropriate surveillance

·        Incidence has been declining since 1950‟s (5.8% decrease in men, 12.9% decrease in women)

·        People may not know family history: can they get death certificates of relatives

Polyps

·        = Any lesion which protrudes above the level of the surrounding mucosa

·        Hyperplastic polyps

o   90% of all polyps, measure < 0.5 cm, mainly in rectosigmoid

o   Benign, no premalignant potential

o   “Dew drop” appearance, on top of mucosal fold

o   Sessile (no stalk), often multiple, very common

o   Microscopically: elongated crypts, goblet and absorptive cells, excess mucin

·        Adenomatous polyps

o   10% of polyps 

o   Neoplasms: precursors of most colonic carcinomas. Normally removed as don‟t know which will become invasive 

o   Malignancy related to size: <1.5 cm only 1% contains a carcinoma, > 1.5 cm 10% will contain a carcinoma-in-situ. As long as it‟s confined to the mucosa, there is no metastatic potential. If submucosal invasion then segmental resection 

o   Macroscopically: stalk (ie pedunculated)

o   Microscopically: neoplastic glands, hyperchromatic, etc 

o   Tubular adenomas: Most common (75%), usually pedunculated, most common in left colon, M > F, 50% are solitary, continued colonoscopic follow-up necessary. Head has closely packed tubules/glands lined by non-differentiated neoplastic columnar cells. Stalk has normal colonic mucosa 

o   Villous adenomas: Papillary projections, larger, more likely to harbour carcinoma, sessile, 10 – 15% of adenomatous polyps, mainly rectosigmoid

o   Tubulovillous adenomas: contain 25 – 75% of villous component.  May secrete lots of mucous

·        Juvenile polyps:

o   Left side of large bowel of kids

o   Cause rectal bleeding

o   Grossly look similar to adenomas 

o   Microscopically not neoplastic. Cystically dilated mucous glands, inflammation of lamina propria, maybe ulceration

·        Peutz-Jeghers Syndrome: Polyp containing mucin filled cysts and smooth muscle in the lamina propria. No malignant potential. Maybe pigmentation in the mouth

·        Polyposis syndromes:

o   Familial Adenomatous Polyposis (FAP): 0.5% of all colorectal cancers.  Autosomal dominant, 

o   antioncogene mutation of APC gene. APC gene: 1 in 10,000 have mutation ® 100s of adenomatous polyps appearing in 2^nd or 3^rd decade. Will develop carcinoma Þ prophylactic colectomy. APC gene also mutated in sporadic cancer 

o   Hereditary Non-polyposis Colon Cancer (HNPCC): Aka Lynch Syndrome. 5% of non-FAP colorectal cancers. Patients often young with multiple tumours. 1 – 5 % of all CR cancer. Autosomal dominant – defect of DNA mismatch repair genes – MMR gene (mismatch repair) - 1 in 1,000 have mutation

·        Gardener‟s Syndrome: colonic polyposis, epidermoid cysts (skin), osteoid osteomas (benign bone tumours). High risk of carcinoma

·        Turcot‟s Syndrome: colon polyps + brain tumours

Adenocarcinomas of the Colon

·        Epidemiology:

o  In US, 2^nd only to lung cancer in cancer deaths. Much lower in third world (Þ environmental factors)

o  Peak incidence in 7^th decade (ie old), except APC and UC

o  70% in recto-sigmoid colon, rest all the way back to caecum

o  M:F is 2:1 for rectal, equal for right sided

·        Aetiology:

o  Adenomatous polyps (esp villous)

o  Ulcerative colitis

o  Familial multiple polyposis

o  Family History 

o  Environmental factors: High incidence in Europe/North America, low in Asia/Africa. Urban > rural 

o  Diet: High fat and low fibre (slower transit ® ?­exposure to carcinogens)

·        Pathogenesis: increasing loss of heterozygosity in genes involved in DNA repair, tumour suppression and oncogene activation. Either through ­turnover due to mucosal damage ® ­risk of gene match failure or directly genotoxic mechanism

·        Presentation:

o  Left sided: annular encircling ® napkin ring or apple core constriction. Signs of obstruction. Poorer prognosis despite earlier detection due to ­invasion 

o   Right sided: large fungating or sessile masses, necrotic areas, occult bleeding, anaemia, weight loss 

o  May produce mucin, ulceration ® blood loss

o  Doubling time of about 2 years

·        Macroscopic description: Early: may still appear to be a polyp or sessile. Later: obliterate precursor adenoma

·        Microscopic appearance: Most are moderately differentiated, irregular glands with pleomorphic cells, usually lack mucin production. Mucinous carcinomas (10 – 15%) have pools of mucin, cleaves through tissue aiding spread (worse prognosis)

·        Variants: Adenosquamous carcinoma, small cell undifferentiated (rare), Ulcerative colitis ® poorly differentiated colitis

Other large bowel tumours (Gastro-intestinal stromal tumours: GIST)

·        Carcinoid tumours: most common in appendix and stomach.

·        Lymphomas: Non-Hodgkin's.  Eg MALT

·        Mesenchymal tumours (eg leiomyomas): much less common

Diagnosis

·        Rectal exam

·        FOBT: sensitivity 50% and low specificity

·        Sigmoidoscopy picks up 40% (& take biopsy).

·        Colonoscopy: expensive, miss rate for cancer 2-3%

·        Double contrast barium enema: cheaper, miss rate for cancer 10 – 15%

·        Check for dissemination: LFT, Abdominal CT, CXR (25% have metastatic disease at presentation)

Differential

·        Diverticular disease, Inflammatory Bowel Disease, Irritable Bowel Syndrome, Rectal ulcer

Treatment of Colorectal Cancer

·        No role for radiotherapy in colon

·        Adjuvant chemotherapy:

o   Improves 5 year survival over surgery alone from 50 to 60/65% (but can‟t predict who will benefit) 

o  ­Quality of life (side effects of cancer are pretty severe, chemo reduces these)

o  Given after surgery

o  Six months of 5FU

o   Currently given to:

§  Dukes C: All patients (C1 = Muscularis propria + lymph node, C2 = serosa + lymph node) 

§  Dukes B2 (serosa): High risk groups, perforation, invasion of adjacent organs, diploid tumours

·        Rectal cancer:

o   No serosa around rectum – cancer infiltrates straight into fat – harder to get clear resection margins 

o   Radiation in rectal cancer good: but ® impaired function and may irradiate small bowel ® fibrosis. Try and predict who needs irradiation and do it pre-operatively 

·        Palliation: hospice + chemotherapy better quality of life than hospice alone

Prognosis of Colorectal Cancer

·        Invade into serosal fat, metastasise to regional lymph nodes then to liver and lungs. Rarely intraperitoneal spread

·        Complications: Obstruction, perforation, haemorrhage, fistulas

·        Prognosis mainly related to stage (how far it‟s spread), to a lesser extent the grade and location

·        Pre-operative staging: ultrasound of liver, Xray of lungs

·        Duke‟s Post-operative staging:

·        Wgtn Hospital uses APC staging (Australasian Pathologists): minor differences to Dukes

·        5 year survival = cured – unlikely to relapse after that

Follow-up

·        Colonoscopy (e.g. initially rest of colon for 2^nd primary, then every 3 years)

·        Monitor tumour marker CEA (colonic embryonic antigen). Also raised in a variety of other tumours & benign cancers. Not sensitive for early cancers (4% of Duke‟s A). Neither sensitive nor specific