Colorectal Carcinoma- An Overview

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Colorectal Carcinoma- An Overview

• Dr C. L Chaw
• ST4, Clinical Oncology
• Tayside

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Colorectal Cancer (CRC)

• 3rd most common form of cancer and the 3rd
  leading cause of death in the Western World.
• Annual incidence in UK -54/100 000, and 35000 new
  cases per year,gt16000 deaths per year, making it
  the 2nd most common cause of cancer death in UK
• Peak incidence ages 60-70 yrs old
• ?? ratio for colonic and rectal cancer is 23
  and 21
• Colonic cancer ( 60) is more commongt than rectal
  cancer (40)

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Risk Factors Aetioloy

• Environmental Factors
• Genetic
• The aetiology is complex, involving interplay of
  environmental and genetic factors. These factors
  conspire to change the normal mucosa to a
  premalignant adenomatous polyp to a frank
  colorectal cancer over the course of many years

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Environmental Factors

• Diet
• Total calories obesity and ? BMI (25-30kg/m2
  )?risk of CRC
• ? consumption of Meat (red meat) /Fat (saturated)
  /Protein - ? risk of CRC
• High Fiber - ? risk of CRC
• Vegetables/ Fruits Protective effects due to
  presence of antioxidants
• Lifestyles
• Physical inactivity -? risk of CRC
• Cigarette smoking -? risk of CRC
• ? alcohol consumption -? risk of CRC

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Genetics/Inherited predisposition

• ve family history of CRC, esp in 1st degree
  relative 40 yrs old --? risk of CRC
• 15 of CRC are familial in origins
• FAP (Familial Adenomatous Polyposis)
• HNPCC (Hereditary Nonpolyposis Colorectal Cancer)
  /Lynch Syndrome

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FAP

• Autosomal Dominant, mutation of APC gene (5q21)
• 1 of all CRC
• Development of hundred to thousands of polyps in
  patients in their teen-30s, almost 100 progress
  to CRC if not surgically resected
• Extracolonic features benign or malignant
• Benignmandibular osteoma, epidermal cyst
• Gardners syndrome- desmoid tumour, osteoma and
  adematous polyps
• Malignant thyroid CA, brain tumours (Turcots
  Syndrome), duodenal and ampullary CA.

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HNPCC

• Autosomal Dominant, mutation of mismatch repair
  genes hMLH1,hMLH2, hMSH6, hPMS1
• 3 of all CRC
• Presence of up 100 colonic polyps ( hence
  nonpolyposis), preferentially in right or
  proximal colon
• Type I and Type II (distinguished by extracolonic
  tumours originating in stomach, small bowel, bile
  duct. Pelvis, ureter, uterus, bladder, ovary,
  skin)
• Mean age of developing Ca 40 yrs old
• Lifetime risk of Ca in HNPCC is 80 for CRC, 40
  for endometrial Ca.

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HNPCC (Amsterdam Criteria)

• Criteria 1
• 3 family members with CRC, one of whom is 1st
  degree of the other 2
• 2 successive affected generations
• 1 or more cancer diagnosed lt 50 years old
• FAP excluded
• Criteria 2
• 3 family members with HNPCC related cancer, one
  of whom is the 1st degree of the other 2
• 2 successive affected generation
• 1 or more cancer diagnosed lt 50yrs old
• FAP excluded
• Lab testing of MSH 12 and PMS 12

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Pathogenesis

• Vogelstein model
• Multistep to carcinoma formation
• Mutation of APC gene polyposis
• K-RAS (40-50), P53, SMAD mutation
• DCC gene helps to initiate metastatic potential
• Other pathway through MSI (DNA microsatellite
  instability) - HNPCC

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Features of tumour
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Spread

• Adjacent organs small/ large bowel, bladder,
  uterus
• Transcoelomic spread- peritoneal disease
• Regional lymph node involvement ( 40-70) at
  presentation usually follows the supplying
  blood vessels pararectal, hypogastric,
  pre-sacral)
• Haematogenous liver lung bone and brain
• 25-30 patients at presentations, the tumour will
  have spread either locally or distant sites, and
  will be unsuitable for radical treatment

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Assessment Management

• History
• Presenting complaints
• Family history
• Systemic enquiries
• Physical examination (PR examination)
• Investigations
• Treatments

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Signs Symptoms

• Symptoms
• Lower GI bleeding
• Altered bowel habits
• Abdominal pain
• Weight loss
• Loss of appetite
• Obstructive symptoms vomiting, unable to pass
  wind, severe abdo pain

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Signs

• Inspection Jaundice, pallor , (freckles around
  the lip, buccal mucosal Peutze Jeghers)
• Palpable abdominal / rectal massdont forget
  about the liver hepatomegaly distant mets
• PR bleeding fresh red ( left-sided colon/
  rectum), malena (right-sided colon)
• Alarming signs Abdominal distension, peritonism,
  rebound tenderness, tingling bowel sound bowel
  obstruction, perforation.
• Pulmonary signs and neurological signs can
  sometime present if the disease is advanced.

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Signs
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Investigations

• FBC ( Iron deficiency anaemia )
• UE
• LFT ( metastatic disease )
• CEA (carcinoembryonic antigen), is raised in 85
  of patients with CRC, higher value associated
  with worse prognosis

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Investigations

• AXR ( if suspicious of SBO/ BO)
• Double contrast barium enema
• Colonoscopy with biopsy, Flexi/ rigid
  sigmodoscopy
• CT scan Thorax, abdo
• USS liver - liver metastasis
• Pelvic MRI particularly for rectal Ca To asses
  CRM (Circumferential resection margin)
• Endo-anal USS to asses nodal involvement in
  rectal Ca

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Investigations
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Investigations
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Investigations
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Screening

• 50-75 years old
• FOB higher false positive rate
• Colonoscopy more specific and better at picking
  proximal lesion.

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Staging (TMN Dukes )
DukesStage Description Stage (AJCC) TNM
A In situ Cancer confined to submucosa or muscularis propria but not through it 0 I Tis N0M0 T1N0M0 T2N0M0
B(1) Into but not beyond muscularis propriano LN spread II T3N0M0 T4N0M0
B(2) Through the muscularis propria with no nodes involved
C(1) Nodes positive but not apical node III Any T, N1-2, M0
C(2) Apical node positive
D Metastatic IV Any T, Any N, M1
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Prognosis ( 5-yr survival)

• Stage I (Dukes A) 95
• Stage II (Dukes B1/2) 70-80
• Stage III (Dukes C1/2) 40
• Stage IV (Dukes D) 5

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Management

• Radical/Curative
• Non-metastatic disease
• Multimodality approaches
• Surgery, chemotherapy, radiotherapy
• Palliative
• Metastatic disease, inoperable disease
• Surgery, chemotherapy, radiotherapy
• Symptoms control

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Management (Surgery- Curative)

• Depending on site of lesions
• Caecum, ascending colon, hepatic flexure right
  hemicolectomy
• Transverse colon extended hemicolectomy
• Splenic flexure, descending colon left
  hemicolectomy
• Sigmoid colon high anterior resection
• Upper rectum- anterior resection
• Defunctioning loop ileostomy is anastomosis lt12cm
  from anal margin
• Lower rectum- Abdominal perineal resection
• Total mesorectal resection- high rectum

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Management (Chemothrapy)

• Adjuvant Chemotherapy
• T3 disease or node positive tumours (Dukes C
  disease, selective in Dukes B) 4-13 survival
  benefits
• Serosal involvement, perforated tumours,
  extramural vascular invasion or involvement of
  circumferential margin
• 5- Flourouracil based chemo, platinum based chemo
  
• Side effects nausea, myelosuppression,
  diarrhoea, neuropathy

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Management ( Radiotherapy )

• Rectal cancer reduce rate of local recurrence,
  downstaging of inoperable disease
• Pre-operatively or post-operatively
• 25Gy in 5, 45Gy in 25
• Side effects erythema (local skin reaction),
  cystitis, diarrhoea, sterility, urge incotinence,
  bowel dysfunction

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Management ( Palliative )

• Inoperable disease, medically unfit patients
• Defunctiong Colostomy, Surgical/ endoscopic
  stenting for obstructing lesions, aiming to
  improve quality of life
• Resection for isolated liver and pulmonary
  metastasis if patients are fit.
• Radiotherapy palliation of local symtoms, bony
  pain, rectal bleeding

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Management ( palliative )

• Chemotherapy
• Patients selection- performance status 1-2
• Aiming to improve quality of life and control of
  disease
• Improves survival by 3-6 months
• 5-FU based chemo, platinum based.

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References

• SIGN Guidelines no 67
• Practical Clinical Oncology Louise Hanna
• Cancer, Principle Practice of Oncology
  DeVita, Hellman et al