Colorectal cancer- part 1. diagnosis and staging

What is the epidemiology of colorectal cancer?

Colorectal cancer is 2nd most common cause of cancer deaths. It is influenced by both enviromental and genetic factors There appears to be a 10 fold variation in incidence between developing and developed countries due to diet and genetic susceptibility. Accounts for 13% of new cancer diagnosis.

Risk factors?

1. Age is a major risk factor for sporadic CRC. It is a rare diagnosis before the age of 40, the incidence begins to increase significantly between the ages of 40 and 50, and age-specific incidence rates increase in each succeeding decade thereafter. The lifetime incidence of CRC in patients at average risk is about 5 percent, with 90 percent of cases occurring after age 50.
2. Genetics - Familial adenomatous polyposis (FAP) (accounts for less than 1% of cancers), Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome, which is more common than FAP, and accounts for approximately 1 to 5 percent of all colonic adenocarcinomas.
3. Previous cancers-Patients with a personal history of CRC or adenomatous polyps are at risk for the development of a future large bowel cancer.
4. Inflammatory bowel disease — There is a well documented association between chronic ulcerative colitis and colonic neoplasia, with the extent and duration of disease being the primary determinants. Also Chrohn's disease, ureteric diversion to sigmoid colon.
5. Diabetes mellitus and insulin resistance — Increasing evidence suggests that diabetes mellitus is associated with an elevated risk of colon cancer. A meta-analysis of 15 studies (six case-control and nine cohort) including a total of 2,593,935 participants estimated that the risk of colorectal cancer among diabetics was approximately 30 percent higher than nondiabetics
6. Cholecystectomy
7. Alcohol
8. Obesity - 1.5 fold increase in getting cancer and increase risk of dying

Protective factors: diet high in fruits and vegetables, regular physical activity, the regular use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), and hormone replacement therapy in postmenopausal women.

What is the clinical presentation of colorectal cancer?

Local and distant presentation

Local

• Rectum - tenesmus, PR bleeds, pain in the bottom.
• Descending colon - bowel obstruction, abdominal pain, changes in bowel habit (night diarrhoea is pathogenic)
  
• Ascending colon - IDA, abdominal pain.
  

Abdominal pain — 44 percent
Change in bowel habit(alternating between diarrhoea and constipation) — 43 percent
Hematochezia or melena — 40 percent
Weakness — 20 percent
Anemia without other gastrointestinal symptoms — 11 percent
Weight loss — 6 percent

Others: tenesmus, neuropathic pain syndrom(if sciatic or obturator nerve is affected), palpable abdominal mass, acute bowel obstruction. Diarrhoea in large bowel tends to be more watery than small bowel.

Approximately 20 percent of patients have distant metastatic disease at the time of presentation [1]. CRCs can spread by lymphatic and hematogenous dissemination, as well as by contiguous and transperitoneal routes. The most common metastatic sites are the regional lymph nodes, liver, lungs, and peritoneum, and patients may present with signs or symptoms referable to any of these areas.

What tests to order for diagnosis and managment?

Physical examination- remember to do PR exam. Abdo exam looking for palpable masses and looking for hepatamegaly.

• colonoscopy which can localise the lesion throughout the large bowel, collect a biopsy and even remove it. Consider air-contrast barium enema which flexible sigmoidoscopy but diagnostic yield is less than colonocscopy. In the 5 percent of people who we are unable to reach by colonoscopy(e.g. torturous intestines, blocked intestines)
• CT of the abdo, pelvis, chest. CT-demonstrate regional tumor extension, regional lymphatic and distant metastases, and tumor-related complications (eg, obstruction, perforation, fistula formation)
• PET scan for metabolically active cancers particulary nodal, peritoneal, liver involvment. When lesion is benign or malignant. To determine if localised metastic disease is resectable.
  
• General evaluation - FBC for microcytic anemia, Serum iron studies, liver function test-raised ALP has the most value ( in case of liver mets)
• liver ultrasound
• Tumor markers - carcinoembryonic antigen(CEA), carbohydrate antigen 19-9 are associated with colorectal cancer but they tend to have a lot of overlap with other beningn conditions like diverticultis, COPD, and other acute inflammatory states. Hence they are not recommended as a screening tool. However, they offer prognostic value. Raised levels are bad prognostic indicators. Failure of CEA to fall after the resection imply ongoing disease and a need for continual assessment.
• Genetic testing if family history

Rectal cancer: (additional)

• MRI- able to pick up more hepatic mets and good for rectal cancers as it can pick up characteristics other than size. Pre-op look for rectal cacner on nodal status and mesorectum involvment. If mesorectum is invaded and nodal involvment, recurrence rate is increased. Do pre-op radiotherapy and/or chemotherapy to reduce local recurrence but not metastatic disease.
• transrectal or endorectal ultrasound (EUS)-depth of transmural invasion and the presence of perirectal nodal involvement for rectal cancers. EUS-guided fine needle aspiration (FNA) biopsy improves the accuracy of N staging.

DDX of colonic mass?
Malignant lesions: Adenocarcinoma, Lymphoma, Carcinoid tumor, Kaposi's sarcoma, Prostate cancer
Benign lesions: Crohn's colitis, Diverticulitis, Endometriosis, Solitary rectal ulcer, Lipoma, Tuberculosis, Amebiasis, Cytomegalovirus, Fungal infection, Extrinsic lesion

Staging?

Once diagnosis of CRC is established, the local and distant extent of disease spread should be determined in order to provide a framework for discussing therapy and prognosis. Importantly to decide whether cancer is resectable, even consider whether metastatic cancer(liver/ lungs) is potentially amenable to surgery. Two types of staging exist for colorectal cancer

1.The Duke's classfication

A- beneath the muscularis mucosae B- through the muscularis mucosae

C- involves regional lymph nodes D- distant mets

2. TMN staging of the AJCC

Tumor and Nodal are determined on pathology of resected colon. Metastatic involvment is determined by CT scan.

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PROGNOSIS?

1. TMN staging - most important
   
2. histologic grade - well-differentiated (stage 1 or 2) have a better 5 year survival than with poorly differentiated (grade 3 or 4)
3. The anatomic location - rectal >transverse/descending>ascending
4. Clinical presentation - bowel obstruction or perforated bowel.
5. Genetics - chromosome loss of 18q.