Colon Cancer

 Introduction and Epidemiology

Colon cancer is one of the commonest cancers world wide and also one of the most curable, particularly, if caught early.

Epidemiology

Cancers of the colon are common in Kenya, constituting 40-50% of all cancers of the large bowel.

The mean age of diagnosis is around 50 years. It is highly curable when localized in the bowel.

Known risk factors include personal history of colon or other cancer, tobacco, inflammatory bowel diseases, family history of ovarian, endometrial, breast cancer, familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer. 

Fecal occult blood test (FOBT) is recommended for screening at risk population; this reduces mortality from colorectal cancer by up to 25% when used correctly.

Colonoscopy is advised after a positive FOBT. The screening interval should be every 3 years. CT colonography (virtual colonoscopy) may be used to screen high risk patients with polyps.

Diagnosis

Early clinical features are not specific (discomfort, weight loss, change in bowel habits, tiredness).

Symptomatic disease is diagnosed using history, physical examination, double contrast barium enema, and colonoscopy.

Biopsy for histopathology is taken during endoscopy. 

Staging And Risk assessment

TNM classification is used in staging the disease. Radiological investigations should include Chest Xray, CT scans of chest, abdomen and pelvis. Malignant polyps should be classified according to the Haggit system. 

Diagnosis

Early clinical features are not specific (discomfort, weight loss, change in bowel habits, tiredness).

Symptomatic disease is diagnosed using history, physical examination, double contrast barium enema, and colonoscopy.

Biopsy for histopathology is taken during  endoscopy. 

3. Diagnosis

Early clinical features are not specific (discomfort, weight loss, change in bowel habits, tiredness).

Symptomatic disease is diagnosed using history, physical examination, double contrast barium enema, and colonoscopy.

Biopsy for histopathology is taken during endoscopy. 

Staging and risk management

TNM classification is used in staging the disease. Radiological investigations should include Chest Xray, CT scans of chest, abdomen and pelvis.

Malignant polyps should be classified according to the Haggit system. 

TNM classification of Colon Cancer
Distant Metastases (M)
TX  primary tumor cannot be assessed
T0  no evidence of primary tumor
Tis  Carcinoma in situ: intraepithelial or invasion of lamina propria.
T1  tumor invades submucosa
T2  tumor invades muscularis propria
T3  tumor invades through muscularis propria into subserosa or into 
 nonperitonealized pericolic or perirectal tissues
T4  tumor directly invades other organs or structures and/or perforates 
 visceral peritoneum
Regional Lymph Nodes (N)
NX regional lymph nodes cannot be assessed
N0  no regional lymph node metastasis
N1 metastasis in one to three regional lymph nodes
N2 metastasis in four or more regional lymph nodes
Distant Metastases (M)
MX distant metastasis cannot be assessed
M0  no distant metastasis
M1  distant metastasis

 

Stage Grouping for Colon Cancer

AJCC Classification Dukes
Stages       Stages
Stage 0  Tis  N0  M0  
Stage I  T1  N0  M0  A
  T2  N0  M0 B1
Stage II T3  N0  M0 B2
  T4  N0  M0  B2
Stage III  T1, T2  N1 or N2 M0 M0
  T3, T4  N1 or N2 M0  C2
Stage IV  Any T  Any N  M1 D
Stage V        

 

Duke’s Staging System for Colorectal Cancer
Stage A:  Limited to mucosa
Stage B1: Extending into muscuaris propria but not penetrating through it; 
 nodes not involved
Stage B2 Penetrating through muscularis propria; nodes not involved.
Stage C1 Extending into muscularis propria but not penetrating through 
 it. Nodes involved
Stage C2: Penetrating through muscularis propria. Nodes involved.
Stage D: Distant metastatic spread.

Duke’s  staging gives valuable information for the prognosis and management of the particular cancer.

Haggit system for polyps with invasive cancer
Level 0 Carcinoma in situ, not invading muscularis mucosa
Level 1 Invasion into submucosa, limited to head of polyp
Level 2 Cancer invades neck of polyp
Level 3 Cancer invades stalk of polyp
Level 4 Cancer invades submucosa of bowel wall = T1

All sessile polyps with invasive cancer are level 4 by Haggitt’s criteria.

Level 1-3 are limited to polyp wall and do not involve normal bowel wall.

For proper nodal staging at least 12 nodes should be submitted. 

Prognostication

Clinico-pathologic factors related to prognosis which should be considered during  patient evaluation include (i) disease stage (ii) grading (iii) lymphatic or venous 
or perineural invasion (iv) lymphoid inflammatory response (v) involvement of resection margins (vi) bowel obstruction and perforation (vii) pre-treatment 
elevated levels of CEA.

 Management

The mainstay of treatment of colon cancer is surgery which removes the lesion with wide margins and loco-regional nodes.

Operations include open or laparoscopic  segmental resections, hemicolectomies, and anterior resections as appropriate. 

Adjuvant treatment is given to for stage III and high risk stage II patients [A].

The definition of high risk in stage II disease include (i) lymph nodes sampling <12 (ii)  poorly differentiated tumour (iii) vascular or lymphatic or perineural invasion (iv) 
tumour presentation with obstruction or (v) tumour perforation and (vi) pT4 stage

STAGE  TREATMENT  COMMENT
Malignant 
polyp, no risk 
of invasion
Polypectomy Assess for invasiveness; this 
suffices for pedunculated polyp 
with invasion to head. 
Malignant 
polyp, 
with risk of 
invasion
Resection and lymph 
node excision
High risk features: lymphatic 
or venous invasion, grade 3 
differentiation, level 4 invasion 
(invades the submucosa of the 
bowel wall below the polyp) or 
involved margins of excision; 
sessile polyp with invasion
Stage 0 (Tis 
N0 M0, T1 N0 
M0).
Stage I (T2 
N0 M0) 
(old staging: 
Dukes’ A, and 
B1)
(i) local excision OR
ii) segmental resection
Wide colectomy
High risk features: lymphatic 
or venous invasion, grade 3 
differentiation, level 4 invasion 
(invades the submucosa of the 
bowel wall below the polyp) or 
involved margins of excision; 
sessile polyp with invasion
Stage II (T3 
N0 M0, T4 
N0 M0) 
(old staging: 
Dukes’ B and 
B2)
Wide surgical resection In high-risk patients adjuvant 
therapy could be considered in 
clinical practice.
Stage III (any 
T, N1 M0, any 
T, N2 M0) 
(old staging: 
Dukes’ C)
Colectomy Adjuvant therapy with: 
Oxaliplatin and 5FU/folinic 
acid (LV) (FOLFOX4 or FLOX) [I, 
A] OR FU/LV infusion OR oral 
fluoropyrimidines (capecitabine)
Metastatic 
disease
Resection of liver and 
lung secondary 
Downsize unresectable 
ones and assess 
Palliative chemo (1st line, 
2nd line, MDT 
Perioperative FOLFOX improves 
survival
Combination of 2 drugs with 
cetuximab & bevacizumab 
increases resection rate in kras 
pts
Obstructive 
colorectal 
cancers
(i) Colostomy first followed by colonic resection, or 
(ii) Hartmann’s procedure first followed by colostomy closure 
     and anastomosis OR 
(iii) one-stage procedure with either subtotal colectomy and 
     ileorectal anastomosis or in selected cases, segmental 
      resection after intraoperative colonic lavage OR Endoscopic 
     stenting to relieve obstruction and allow subsequent one-
     step resection. 


Follow-up

The primary goal of follow up is to detect relapse and improve survival. The follow up recommendations for colon cancer include (i) history and physical examination and CEA 
determination every 3–6 months for 3 years and every 6–12 months at years 4 and 5 after surgery (ii) colonoscopy at year 1 and thereafter every 3–5 years and (iii) CT scan of 
chest and abdomen every 6–12 months for the first 3 years [II, B].

CEA is restricted to patients who would be candidates for resection of lungs and liver. 

Its routine use outside this is not recommended. 

Prevention

  • Prevention practices for colon cancer include:
  •  Maintaining healthy weight (obesity is a risk)
  •  Periodic sigmoidoscopy for those at risk (family history) at least annually initially.
  •  Avoidance of tobacco and alcohol 
  •  Use of aspirin for high risk populatio

 Pharmacological management

5-fluorouracil, folinic acid, capecitabine, oxaliplatin, irinotecan, bevacizumab, cetuximab, panitumumab. 

In resource limited settings, 5-fluorouracil, without or with folinic acid, can be used. 

Where possible, oxalipatin should be added to 5-fluorouracil/folinic acid.

 Prognosis

Early colonic cancer is curable with appropriate treatment. Advanced disease is generally incurable though patients with limited metastasis, particularly in the liver, can be cured. 

In our setting, most patients present at the late stage.

 References

1. Ferlay, J., F. Bray, P. Pisani, and D. M. Parkin. 2001. GLOBOCAN 2000:  Cancer Incidence, Mortality, and Prevalence Worldwide, Version 1.0, IARC 
    CancerBase No. 5. Lyon, France: International Agency for Research on  Cancer and World Health Organization, IARC Press.

2. Colorectal cancer collaborative group. Adjuvant radiotherapy for rectal  cancer: a systemati overview of 8507 patients from 22 randomised trials. 
    Lancet 2001; 345: 638-646

3. Glimelius B, Oliveira J & ESMO guidelines Working Group. Rectal  Cancer: ESMO clinical recommednations for diagnosis, treatment and follow up Annals of Oncology 2009; 20 (supl 4): iv54-iv56

4. MacFarlane JK, Ryall JK, Heald RJ. Msorecta excision for rectal cancer.  Lancet 1993; 341: 457-460

5. Saidi HS, D. Karuri and E.O. Nyaim Correlation of clinical data, anatomical site and disease stage in colorectal cancer, East African Medical
     Journal 2008; , 85 (6): 259-262

6. Saidi H, Abdihakin M, Njihia B, Jumba G, Kiarie G, Githaiga J, Abinya  NO. Clinical outcomes of Colorectal Cancer in Kenya. Annals of African 
      Surgery, 2011; 7:42-49

7. Saidi H, Nyaim EO, Githaiga J, Karuri D. CRC Surgery trends in Kenya, 1993-2005. World J Surg 2008;

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