Colorectal cancer

Helen imseeh

Colon polyps

Generally non-neoplastic

Hyperplastic polyps

Inflammatory pseudopolyps

Hamartomatous polyps

Mucosal polyps

Submucosal polyps

refers to a protuberance into the lumen above the surrounding colonic mucosa . Grossly characterized as flat, sessile, or pedunculated

Malignant potential

Adenomatous polyps

Serrated polyps

Hyperplastic polyp

• Benign

• Normal cellular structure, no dysplasia

• Most common type of polyp

• Common in rectosigmoid colon

• No specific therapy required, but they can be difficult to distinguish from neoplastic polyps and so are commonly removed.

Hamartomatous polyps

● Growths of normal colonic tissue with distorted architecture.● Solitary lesions do not have significant risk of transformation.● Associated with juvenile polyposis & Peutz-Jeghers syndrome.

Juvenile polypBenign tumors (hamartomas) that occur in children (typically in children younger than 10 years)

• Usually in rectosigmoid colon

• Usually pedunculated

•Asymptomatic patients do not require treatment

• Can cause painless rectal bleeding→ require polypectomy

• Often “auto-amputate” Juvenile polyposis syndrome :- Multiple (usually >10) polyps -Increased risk of cancer -Surveillance colonoscopy

Hamartomatous polyps

● Autosomal dominant disorder● Pigmented spots around lips, oral mucosa, face, genitalia, and palmar surfaces.● Single or multiple hamartomas that may be scattered through the entire GI tract: in

small bowel (78%), colon (60%), stomach (30%). ● The polyps are usually benign, but may grow progressively and produce symptoms

or undergo malignant transformation● Slightly increased incidence of various carcinomas (e.g., stomach,small bowel,

colon, pancreas) and nongastrointestinal ovary, breast, cervix, testicle, lung). ● Intussusception or GI bleeding may occur.

Hamartomatous polypsPeutz- jeghers syndrome

Inflammatory pseudopolypsInflammatory pseudopolyps are irregularly shaped islands of residual intact colonic mucosa that are the result of the mucosal ulceration and regeneration that occurs in response to localized or diffuse inflammation (eg, ulcerative colitis or Crohn disease).

Inflammatory pseudopolyps do not require excision unless they cause symptoms (eg, bleeding, obstruction).

Treatment is directed at the underlying cause of inflammation.

Mucosal polyps

Submucosal polyps

Small, usually < 5 mm. Look similar to normal mucosa. Clinically insignificant

Adenomatous polyp

• Dysplastic with malignant potential

• mutation in APC gene

• Several sub-classifications

➔ Shape Sessile //Pedunculated

➔ Histology Tubular //tubulovillous // Villous

Sessile: broad base attached to colonPedunculated: attached via stalk

Malignant potential

Tubular

• Most common subtype (80%+)

• Adenomatous epithelium forming tubules

•smallest risk of malignancy only 5% of cases

• Less common type

• Often sessile

• Long projections extending from surface

• High risk of development into colon

cancer

may harbor cancer in up to 40%

Villous

Tubular Villous

Clinical presentation

• Almost always asymptomatic

• Screening colonoscopy done for detection

• Large polyps may cause bleeding

• Usually not visible in stool (“occult”)

• Basis for screening with fecal occult blood testing

Villous adenoma

• Can lead to excessive mucous secretion --> Rarely cause a secretory diarrhea

• Watery diarrhea Hypokalemia

Most pedunculated polyps are amenable to colonoscopic snare excision.

Removal of sessile polyps is often more challenging. Special colonoscopic techniques, including saline lift, piecemeal snare excision, and endoscopic mucosal resection facilitate successful removal of many sessile polyps.

Management

Serrated polyps

Malignant potential

Characterized by CpG island methylator phenotype

Defect may silence MMR gene (DNA mismatch repair)

expression. Mutations lead to microsatellite instability .

Epidemiology● Colorectal cancer is the third most commonly diagnosed cancer, and the second in terms

of mortality● Most common GI cancer● male-to-female ratio? ≈1:1● Globally, the regional incidence of CRC varies over 10-fold. More common in developed

countries

Risk factors● Age—Aging is the dominant risk factor for colorectal cancer, with incidence rising

steadily after age 50 years. ○ More than 90% of cases diagnosed are in people older than age 50 years.

● Personal or family history of CRCs or adenomatous polyps● Obesity● Red and processed meat● Diabetes● Smoking● Inflammatory bowel disease (IBD)

○ Both ulcerative colitis (UC) and Crohn disease pose an increased risk for CRC, but UC poses a greater risk than Crohn disease.

○ It is hypothesized that chronic inflammation predisposes the mucosa to malignant changes, and there is some evidence that degree of inflammation influences risk.

•Acohol•Cholecystectomy

Aspirin and colon cancer:

➢ COX enzyme is thought to be related to the pathogenesis of colon CA. ➢ Low dose (81mg) causes mild decrease risk of recurrent adenomas but no decrease risk of colon cancer.➢ Full dose aspirin decrease the risk of colon cancer➢ Protective effect of aspirin is related to: 1. dose of ASA. 2. frequency of use. 3. duration of use

Pathogenesis

Two well-defined genetic pathways to colon cancer

• Chromosomal Instability Pathway

• Microsatellite Instability

•CpG Island Methylation Pathway

80% of colorectal carcinomas appear to arise from mutation in this pathway More common in left sided tumors

adenomacarcinoma sequence Loss of Heterozygosity Pathway

Familial Adenomatous Polyposis• Autosomal dominant disorder• Germline mutation of APC gene (chromosome 5q)•The mean age of adenoma development is 16 years•Characterized by hundreds of adenomatous polyps in the colon. The colon is always involved, and the duodenum is involved in 90% of cases. Polyps may also form in the stomach, jejunum, and ileum. • Always (100%) progresses to colon cancer by the third or fourth decade of life.•management : Tracing and screening of relatives is essential, usually after 12 years of age, and affected individuals should be offered a prophylactic colectomy, often before the age of 20

Gardner’s Syndrome

● Polyposis plus multiple extra-colonic manifestations

● Benign bone growths (osteomas) especially mandible

● Skin cysts: Epidermal cysts, fibromas, lipomas,

● Connective tissue growths:● “desmoid tumors”, “fibromatosis” ● dental abnormalities● Hypertrophy of retinal pigment● Risk of CRC is 100% by

approximately age 40.

• Polyposis plus brain tumors

• Mostly medulloblastomas and gliomas

Turcot Syndrome

Microsatellite Instability

• Less common mechanism of colon CA development

•mutations of mismatch repair genes (eg, MLH1)

• Tumors with MSI are more likely to be in the right colon and are associated with a better prognosis than tumors that arise from the LOH pathway

Hereditary Non-Polyposis Colorectal CancerLynch Syndrome

• Inherited mutation of DNA mismatch repair enzyme• Leads to colon cancer via microsatellite instability • About 80% lifetime risk • Arise with out pre-existing adenoma• Usually right-sided tumors • Also increased risk of: - Endometrial cancer (most common non-colon malignancy) -Other cancers (ovary, stomach, others)

The Amsterdam criteria for clinical diagnosis of HNPCC are three affected relatives with histologically verified adenocarcinoma of the large bowel (one must be a first-degree relative of one of the others) in two successive generations of a family with one patient diagnosed before age 50 years. The presence of other HNPCC-related carcinomas should raise the suspicion of this syndrome.

CpG Island Methylation Pathway

This process has been called epigenetic alteration to differentiate it from the more traditional genetic alterations or true mutations.

This pathway has also been called the serrated methylated pathway because of the observation that serrated polyps often harbor aberrant methylation in contrast to adenomatous polyps that are more often associated with mutations in the APC gene (LOH pathway).

Clinical presentation The presence of symptoms is typically a manifestation of relatively advanced disease.

● abdominal pain is the most common presenting symptom. Can be caused by partial obstruction or peritoneal dissemination. Remember that CRC is the most common cause of large bowel obstruction in adults. Colonic perforation can lead to peritonitis and is the most life-threatening Complications

● Symptoms include melena or hematochezia

● unexplained iron deficiency anemia

larger luminal diameter allowing for large tumor growth to go undetected.

Rectal cancer (20% to 30% of all CRCs) Symptoms include hematochezia (most common), tenesmus, rectal mass, and feeling of incomplete evacuation of stool due to mass.

signs of obstruction more common Change in bowel habits more commonalternating constipation/diarrhea; narrowing of stools (“pencil stools”)

Iron deficiency anemia in males (especially > 50 years old) & postmenopausal femaless should raise suspicion of colon cancer

Pattern of spread

● Direct extension—circumferentially and then through the bowel wall to later invade other abdominoperineal organs

● Hematogenous○ Portal circulation to liver- most common site of distant spread ○ Lumbar/vertebral veins to lungs

● Lymphatic—regionally ● Transperitoneal and intraluminal

○ Carcinomatosis (diffuse peritoneal metastases) occurs by peritoneal seeding and has a dismal prognosis

Diagnosis● Colonoscopy is the ‘gold standard’ for investigation and allows biopsy for

histology. Biopsy of the tumour is mandatory, usually at endoscopy.● Double-contrast barium enema can visualize the large bowel but is now

superseded by CT colonography.● Endoanal ultrasound and pelvic MRI are used for staging rectal cancer.● Chest, abdominal and pelvic CT scanning to evaluate tumour size, local spread

and liver and lung metastases – this contributes to the tumour staging.● MR is also useful for evaluating suspicious lesions found on CT or US, especially

in the liver● PET scanning is useful for detecting occult metastases and for evaluation of

suspicious lesions found on CT or MR.● Serum carcinoembryonic antigen (CEA) is of little use for primary diagnosis and

should not be performed as a screening test. It is useful for follow-up; rising levels suggest recurrence.*CEA does have prognostic significance: Patients with preoperative CEA >5 ng/mL have a worse prognosis.

Staging

Colorectal cancer staging is based on tumor depth and the presence or absence of nodal or distant metastases.

Older staging systems, such as the Dukes’ Classification, have been replaced by the tumor node-metastasis (TNM) staging system

⸎surgical resection:➢ 1st option. ➢ Surgeries could be curative or palliative ➢ recurrence happens due to micrometastases. ➢ Hepatic resection increase survival with sold liver metastasis

⸎Adjuvant chemotherapy: 5-FU stage III / VI or locally advanced stage II

⸎RTX (prior to syrgery) is helpful for rectal lesion only.

⸎ stage IV disease, when cannot be cured surgically, the focus of treatment should be palliation.

Management

Surgical ManagementThe objective in treatment of carcinoma of the colon is to remove the primary tumor along with its lymphovascular supply. Because the lymphatics of the colon accompany the main arterial supply, the length of bowel resected depends on which vessels are supplying the segment involved with the cancer. Any adjacent organ or tissue, such as the omentum, that has been invaded should be resected en bloc with the tumor.

➢ resected material: terminal ileum + cecum + ascending colon +proximal transverse colon➢ Plus, resection of right colic artery + iliocecal artery +- middle colic artery➢ Plus, removal of fat and lymph node ➢ indications: right colon cancer / cecum cancer

➢ resected material: same as right hemicolectomy + reminder of transverse colon and splenic flexure

resection of right colic artery, iliocecal artery and middle colic artery

➢ indications: hepatic flexure cancer / transverse colon cancer (proximal mid)

Right hemicolectomy Extended right hemicolectomy:

➢ Resected material: transverse colon + middle colic artery➢ indication: transverse colon cancer

➢ Resected material: descending colon + left colic artery

➢ indications: splenic flexure cancer / left colon cancer

Transverse colectomy: left hemicolectomy

➢ Resected material: sigmoid colon + sigmoid artery. ➢ indications: sigmoid / rectosigmoid cancer.

⸎ removal of the entire colon without the rectum

⸎Proctocolectomy: removal of the entire colon and rectum

⸎Subtotal colectomy: removal of part of colon / all of the colon without complete resection of the rectum

Sigmoid colectomy: Total colectomy:

Management

➢ resection of low rectal tumors through an anterior approach.➢ Indications: proximal rectum cancer ➢ criteria: 1. Tumors >4 cm from anal verge ( with distal intramural spread <2 cm ) 2. must be able to get 2 cm margin➢ If a rectal tumor doesn’t meet these criteria, in some cases, we may give neoadjuvant chemotherapy to down stage the tumor, then we do LAR

Low anterior resection(LAR): Abdominal perineal resection (APR) :

➢ Removal of the rectum and sigmoid colon through abdominal and perineal incisions (patient is left with a colostomy).➢ indications: distal rectum cancer / anal cancer➢ done in tumors not fitting criteria for LAR➢ the anus is closed ➢ permanent colostomy (due to removal of the anus)

Follow up

Follow-up is important, and varies among physicians

● Stool guaiac test

● Annual CT scan of abdomen/pelvis and CXR for up to 5 years

● Colonoscopy at 1 year and then every 3 years

● CEA levels are checked periodically (every 3 to 6 months) A subsequent

increase in CEA is a sensitive marker of recurrence Often, second-look

operations are based on high CEA levels postresection Very high

elevations of CEA suggest liver involvement

About 90% of recurrences occur within 3 years after surgery

OTHER NEOPLASMS

Carcinoid Tumors

● Neuroendocrine tumors ● Neuroendocrine cells = nerve and endocrine

features ● Found in many organs: GI tract, lungs, pancreas ● Most commonly in small bowel ● up to 25% of these tumors are found in the rectum.● proximal colon are less common

• Secrete serotonin• Responsible for majority of clinical effects• Diarrhea (serotonin stimulates GI motility)• ↑fibroblast growth and fibrogenesis valvular lesions• Flushing (other mediators also)• Liver and lung metabolize (inactivate) serotonin• No carcinoid syndrome unless metastatic to liver

Lymphoma

Lymphoma involving the colon and rectum is rare but accounts for about 10% of all gastrointestinal lymphomas.

The cecum is most often involved, probably as a result of spread from the terminal ileum.

Symptoms include bleeding and obstruction, and these tumors may be clinically indistinguishable from adenocarcinomas.

Bowel resection is the treatment of choice for isolated colorectal lymphoma.

Adjuvant therapy may be given based on the stage of disease

Resources

Books:

-schwartzs principles of surgery tenth edition

-kumar and clark

- step up

- first aid

Slides:

- GI surgery ( university of Jordan)

- board and beyond

Articles:

- Up-to-date

Videos:

- osmosis