Colorectal Cancer & Polyps PDF

Colorectal cancer CRC CRC  Colorectal adenocarcinoma is an invasive cancer arising almost always from a mucosal precursor lesion - adenomatous polyp. Recently, serrated polyps have been recognized as precursors to colorectal adenocarcinoma.  Epidemiology CRC is t...

Colorectal cancer CRC CRC  Colorectal adenocarcinoma is an invasive cancer arising almost always from a mucosal precursor lesion - adenomatous polyp. Recently, serrated polyps have been recognized as precursors to colorectal adenocarcinoma.  Epidemiology CRC is the third most common cause of cancer incidence and cancer mortality in the United States and WEurope among both men and women. Estimated incidence of CRC in 2020: 142 820 (men: 73 680; women: 69 140). Estimated mortality from CRC in 2020: 50 830 (men: 26 300; women: 24 530).  Etiology The etiology of sporadic CRC is not known, but likely to be a combination of environmental + genetic factors. Familial cancer Patients with familial adenomatous polyposis (FAP) have an extremely high risk for developing CRC because they inherit a mutated APC gene. Patients with Lynch syndrome also have an extremely high risk for developing CRC (DNA mismatch repair genes).  Pathology/pathogenesis Three predominant molecular pathways have been elucidated: Chromosomal instability (CIN):the classic pathway, accounting for approx. 70% of all colon cancers Microsatellite instability (MSI): this pathway is seen in approximately 15% of sporadic CRC and in 100% CRC arising in patients with Lynch syndrome. CpG island methylator phenotype (CIMP): at least 15% of CRC Risk factors  Sandhu et al. from University of Cambridge and, London UK, published the first meta-analysis of prospective cohort studies on meat consumption and CRC risk in 2001 They included 13 studies to this analysis. Conclusion :daily increase of 100 g (one portion) of all meat or red meat is associated with a significant 12-17% increased risk of CRC (average RR is 1.17 with 95% CI of 1.05-1.31 for the random-effects model). A significant 49% increased risk was also found for a daily increase of 25 g of processed meat (about one slice).  According to guidelines today , the recommended amount of red meat for healthy people is 500 g/week or 70 g/day. They recommend also limiting intake of processed meat. White meat (fish and poultry) is not associated with CRC risk and is recommended safely. To diminish carcinogenic effects of HCAs, diet should be high in dietary fibre sources such as wheat bran and vegetables. Formation of HCAs can be reduced by avoidance of exposure of meat surfaces to flames, usage of aluminum foil to wrap meat before oven roasting and microwave cooking  Clinical diagnosis History should include details about signs and symptoms: change in bowel habit blood in stool abdominal pain, weight loss  Medical history Family history of colon cancer, colonic polyps, and other cancers (especially gynecologic). If considering FAP, ask about history of extraintestinal manifestations: desmoid tumors, soft tissue tumors, gastroduodenal polyps, dental or jaw abnormalities, brain tumors in the family ?? Dietary history should ask about red meat, fruits/vegetables, fiber. ?? Medications such as aspirin and NSAIDs, while they can protect against CRC, can also cause occult GI bleeding which might confound the diagnosis.  Patient examination - abdominal mass - signs of anaemia - Hepatomegaly - Digital rectal examination !!!  List of diagnostic tests Colonoscopy with biopsy (preferred). Sigmoidoscopy with biopsy (if colonoscopy is not available). CT scan of abdomen/pelvis (to rule out metastatic spread). CT colonography (if colonoscopy is not available; does not offer tissue diagnosis). MRI of abdomen/pelvis (if CT not available or to avoid radiation exposure). Serum CEA test - Serum carcinoembryonic antigen (CEA) level(useful mainly for follow-up after treatment, not as a screen). CBC, LFTs (to assess for anemia, liver involvement). How does colon cancer looks like ? Diferential dg  Treatment surgery is typically the cornerstone of treatment. For Stage I and II cancer, surgery alone is often the only treatment necessary , ESD For Stage III cancer, adjuvant chemotherapy is given. For Stage IV cancer, advanced disease chemotherapy regimens are used. In the case of rectal cancers, pre-operative (neoadjuvant) chemo / Rx followed by postoperative chemotherapy is the main approach. If a focus of invasive adenocarcinoma is detected in a colonic adenoma, polypectomy alone (without the need for surgery) is curative.  Distant metastases Liver Lung , brain , bone Follow - up.. Survival rate COLONIC POLYPS and Polyposis Syndromes  Definition GI polyp is a discrete mass of tissue that protrudes into the lumen of the bowel. A polyp may be characterized by : -appearance and overall size, -whether or not it has a stalk, -multiple /single Optical diagnosis Specific definition rests on histologic characteristics.  The greatest concern with polyps is their silent potential to become malignant Serrated polips  Adenomatous polyps Adenomas can be classified further as: 1. tubular (70%-85%) 2. villous (predict lesion types Hyperplastic Tubular Tubulovillous Villous Serrated Type Carcinoma lesion adenoma adenoma adenoma adenoma Advanced Pathology Hyperplastic Neoplastic (with varying dysplasia, risk of invasion of submucosa) neoplasia None/ In-situ: ESD Treatment Resection via polypectomy, EMR, ESD otherwise surgery Resection* Progression from adenoma to carcinoma can take 5 years of longer Progression from adenoma to carcinoma can take 5 years of longer  Heritable Syndromes Cases of hereditary colorectal cancer account for approximately 15% of all large-bowel malignancies Several well-defined syndromes have been recognized Patients with gene mutations are also at increased risk for target organ cancers outside the colorectum  Familial Adenomatous Polyposis (FAP) Cause : genetic mutation that interferes with the normal function of APC The gene mutation is most often inherited from a parent, but 30 % of FAP patients develop the mutation during conception and do not have a parent with FAP. Each child of a parent with FAP has a 50 % chance of inheriting the gene  Familial Adenomatous Polyposis (FAP) colon polyps in FAP always become cancerous Colon polyps can become cancerous in the teenage years, but this happens more commonly in the 20s and 30s. By age 40, all untreated patients will have developed colon cancer.  Familial Adenomatous Polyposis (FAP) FAP detection : genetic blood test : mutations in the APC gene COLONOSCOPY  Familial Adenomatous Polyposis (FAP) Treatment : total procto-colectomy FAP develops polyps in the stomach and duodenum EGD starting at age 20 and continuing every few years.  Lynch syndrome Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is a type of inherited cancer syndrome associated with a genetic predisposition to different cancer types. This means people with Lynch syndrome have a higher risk of certain types of cancer.  Bethesda criteria Developing colorectal or endometrial cancer younger than age 50 Developing colorectal cancer, endometrial cancer, or other type of cancer* with mismatch repair deficiency (MMR-D) or high-level microsatellite instability (MSI-H) found on testing of the tumor specimen Colorectal cancer in 1 or more first-degree relatives who also has or has had another Lynch syndrome-related cancer*, with 1 of these cancers developing before age 50. The phrase “first-degree relatives” include parents, siblings, and children. Colorectal cancer in 2 or more first- or second-degree relatives with another Lynch syndrome-related cancer*. “Second-degree relatives” include aunts, uncles, grandparents, grandchildren, nephews, and nieces.  Diagnosis mismatch repair deficiency (MMR-D) or high-level microsatellite instability (MSI-H)