Makindo Medical Notes

Related Subjects: |Colorectal cancer |Colorectal polyps |Ulcerative Colitis |Acute Severe Colitis |Crohn's disease

Suspected colorectal cancer can only be excluded with a barium enema + rigid sigmoidoscopy, CT pneumocolon, or colonoscopy. Serial CEA monitoring can aid in detecting recurrence.

About

• A common cause of cancer in older patients, often due to a series of genetic mutations leading to malignancy.
• Most colorectal cancers (CRCs) arise from colorectal adenomas that accumulate genetic mutations over time.
• Exceptions include hereditary nonpolyposis colorectal cancer (HNPCC) and colorectal cancer associated with ulcerative colitis.

Risk Factors

• Male sex, diets low in fibre, fruits, and vegetables.
• High intake of fat and red meat, history of cholecystectomy (related to bile salts).
• Sporadic cases account for approximately 70%.
• Ulcerative colitis (especially >10 years) and Crohn's colitis over long durations increase risk.

Familial Risk (10-30%)

• Hereditary nonpolyposis colorectal cancer (HNPCC): 2-3% of cases.
• Familial adenomatous polyposis (FAP): <1%.
• Gardner's syndrome and hamartomatous polyposis syndromes: <0.1%.

Aetiology

• Dietary factors: low fibre, high-fat diet.
• Genetic predispositions: e.g., FAP, HNPCC.
• Inflammatory bowel disease increases risk.
• NSAIDs/Aspirin may offer some protective effect.

Genetic Mechanisms

• Activation of oncogenes (e.g., K-ras, c-myc) and loss of tumor suppressor gene function (e.g., p53, APC, MCC, DCC).
• Mismatch repair gene mutations (hMSH2, hMLH1) are common in HNPCC.
• Progression sequence: Normal epithelium → dysplasia → adenoma → adenocarcinoma.
• Right-sided tumours are more common in familial syndromes (FAP, HNPCC).

Pathology Types

• Ulcerating type: Causes bleeding and anaemia.
• Polypoid type.
• Annular type: Can obstruct the bowel.
• Diffuse, infiltrating, and colloid (mucus-secreting) types.

Polyps and Malignancy Risk

• Histology: Villous adenomas have higher malignancy risk than tubular adenomas.
• Size: Larger polyps carry a higher risk of malignancy.
• Degree of epithelial dysplasia increases malignancy risk.

Histological Grades

• Grade I: Well differentiated.
• Grade II/III: Moderately differentiated.
• Grade IV: Anaplastic.

Tumor Location

• Rectum and sigmoid colon: 60%.
• Ascending colon: 20%.
• Transverse and descending colon: 20%.

Spread and Metastasis

• Direct spread within 2 cm of the margin.
• Distant metastasis to the liver, lungs, adrenal glands, kidneys, and bones.
• Lymphatic spread to para-aortic and supraclavicular nodes.
• Krukenberg tumours: Ovarian metastasis.
• Possible spread to surgical wounds, colostomy, and laparoscopic ports.

Clinical Presentation

• Rectal Lesions: Visible blood on stool, tenesmus, altered bowel habit, and palpable mass on PR exam.
• Left-Sided Colonic Lesions: Altered bowel habits, constipation, blood in stool, iron deficiency anaemia, and palpable sigmoid mass.
• Right-Sided Colonic Lesions: Often occult with anaemia, late obstruction symptoms, weight loss, and malaise.
• Possible presentations: Obstruction, perforation, peritonitis, haemorrhage, or fistulas to the bladder or vagina.

Investigations

• Blood Tests: FBC (for anaemia), ferritin, B12, folate, LFTs (especially ALP for liver metastasis).
• Imaging: Abdominal USS, CT, CXR, MRI for staging; endorectal ultrasound for rectal cancer.
• Endoscopy: Colonoscopy with biopsy for direct visualization; barium enema and CT pneumocolon for less invasive options.
• Markers: Elevated CEA (Carcinoembryonic Antigen) is useful for monitoring response to treatment but not for diagnosis.

Management Summary

• Multidisciplinary approach involving surgeons, pathologists, radiologists, and oncologists.

Preventive Management

• Prophylactic colectomy in FAP patients can extend life expectancy significantly.

Definitive Management

• Resection techniques based on tumour location (e.g., right or left hemicolectomy, sigmoid colectomy).
• Anterior resection for high rectal disease; low rectal tumours require abdominoperineal resection and colostomy.
• Single hepatic metastases may be resectable for a curative approach.

Chemotherapy

• 5-Fluorouracil and leucovorin commonly used in Dukes C and some Dukes B cases.
• Additional agents include oxaliplatin, irinotecan, cetuximab (EGFR inhibitor), and bevacizumab (VEGF inhibitor).

Palliative Care

• Surgery may relieve symptoms in advanced metastatic disease (e.g., colostomy for unresectable tumours).
• Radiotherapy is mainly for rectal disease to control pain and bleeding, or pre/post-surgery in high recurrence risk cases.