Pathogenesis
Colorectal cancer is a disease originating from the epithelial cells lining the gastrointestinal tract. Hereditary or somatic mutations in specific DNA sequences, among which are included DNA replication or DNA repair genes and also the APC, K-Ras, NOD2 and p53 genes, lead to unrestricted cell division. The exact reason why (and whether) a diet high in fiber might prevent colorectal cancer remains uncertain. Chronic inflammation, as in inflammatory bowel disease, may predispose patients to malignancy.
Treatment
The treatment depends on the staging of the cancer. When colorectal cancer is caught at early stages (with little spread) it can be curable. However when it is detected at later stages (when distant metastases are present) it is less likely to be curable.
Surgery remains the primary treatment while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors.
Surgery
Surgeries can be categorised into curative, palliative, bypass, fecal diversion, or open-and-close.
Curative Surgical treatment can be offered if the tumor is localized.
- Very early cancer that develops within a polyp can often be cured by removing the polyp (i.e., polypectomy) at the time of colonoscopy.
- In colon cancer, a more advanced tumor typically requires surgical removal of the section of colon containing the tumor with sufficient margins, and radical en-bloc resection of mesentery and lymph nodes to reduce local recurrence (i.e., colectomy). If possible, the remaining parts of colon are anastomosed together to create a functioning colon. In cases when anastomosis is not possible, a stoma (artificial orifice) is created.
- Curative surgery on rectal cancer includes total mesorectal excision (lower anterior resection) or abdominoperineal excision.
In case of multiple metastases, palliative (non curative) resection of the primary tumor is still offered in order to reduce further morbidity caused by tumor bleeding, invasion, and its catabolic effect. Surgical removal of isolated liver metastases is, however, common and may be curative in selected patients; improved chemotherapy has increased the number of patients who are offered surgical removal of isolated liver metastases.
If the tumor invaded into adjacent vital structures which makes excision technically difficult, the surgeons may prefer to bypass the tumor (ileotransverse bypass) or to do a proximal fecal diversion through a stoma.
The worst case would be an open-and-close surgery, when surgeons find the tumor unresectable and the small bowel involved; any more procedures would do more harm than good to the patient. This is uncommon with the advent of laparoscopy and better radiological imaging. Most of these cases formerly subjected to "open and close" procedures are now diagnosed in advance and surgery avoided.
Laparoscopic-assisted colectomy is a minimally-invasive technique that can reduce the size of the incision and may reduce post-operative pain.
As with any surgical procedure, colorectal surgery may result in complications including
- wound infection, Dehiscence (bursting of wound) or hernia
- anastomosis breakdown, leading to abscess or fistula formation, and/or peritonitis
- bleeding with or without hematoma formation
- adhesions resulting in bowel obstruction (especially small bowel)
- adjacent organ injury; most commonly to the small intestine, ureters, spleen, or bladder
- Cardiorespiratory complications such as myocardial infarction, pneumonia, arrythmia, pulmonary embolism etc
Chemotherapy is used to reduce the likelihood of metastasis developing, shrink tumor size, or slow tumor growth. Chemotherapy is often applied after surgery (adjuvant), before surgery (neo-adjuvant), or as the primary therapy (palliative). The treatments listed here have been shown in clinical trials to improve survival and/or reduce mortality rate and have been approved for use by the US Food and Drug Administration. In colon cancer, chemotherapy after surgery is usually only given if the cancer has spread to the lymph nodes (Stage III). At the 2008 annual meeting of the American Society of Clinical Oncology, researchers announced that colorectal cancer patients that have a mutation in the KRAS gene do not respond to certain therapies, those that inhibit the epidermal growth factor receptor (EGFR)--namely Erbitux (cetuximab) and Vectibix (panitumumab). Following recommendations by ASCO, patients should now be tested for the KRAS gene mutation before being offered these EGFR-inhibiting drugs.
- Adjuvant (after surgery) chemotherapy. One regimen involves the combination of infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)
- 5-fluorouracil (5-FU) or Capecitabine (Xeloda)
- Leucovorin (LV, Folinic Acid)
- Oxaliplatin (Eloxatin)
- Chemotherapy for metastatic disease. Commonly used first line chemotherapy regimens involve the combination of infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) with bevacizumab or infusional 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with bevacizumab.
- 5-fluorouracil (5-FU) or Capecitabine
- UFT or Tegafur-uracil
- Leucovorin (LV, Folinic Acid)
- Irinotecan (Camptosar)
- Oxaliplatin (Eloxatin)
- Bevacizumab (Avastin)
- Cetuximab (Erbitux)
- Panitumumab (Vectibix)
- In clinical trials for treated/untreated metastatic disease
- Bortezomib (Velcade)
- Oblimersen (Genasense, G3139)
- Gefitinib and Erlotinib (Tarceva) Topotecan (Hycamtin)
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