COLORECTAL CANCER

NURUL FARAHANI BINTI UMAR (K3)

Colorectal Cancer

Colorectal cancer refers to cancer originating in the colon or rectum and can develop in any of the four sections Colorectal cancer begins as a polyp Colorectal cancer develops slowly over a period of years (~10-15 yrs)

Colorectal cancer on the rise..

WHO's Globocan 2008 : 1 in 33 Malaysians are at risk of developing colorectal cancer. Male recorded for 52.3% while female recorded 47.7% for colorectal cancers.

The incidence of this cancer increased exponentially after age of 40

National Cancer Registry Report

Risk Factors
Age Smoking, Heavy alcohol use

Personal history

Risk Factors
Physical inactivity, Obesity Certain types of diets Family history

Risk Factors
Risk Factor
Age History of polyps History of bowel disease

Description
9 out of 10 cases are over 50 years old risk if large size, high frequency, or specific types Ulcerative colitis and Crohns disease (IBDs) risk

Certain hereditary family syndromes

Family history (excluding syndromes) Diet Lack of exercise/ Overweight Smoking

Having a family history of familial adenomatous polyposis or hereditary nonpolyposis colon cancer (Lynch Syndrome) risk
Close relatives with colon cancer risk esp. if before 60 years (degree of relatedness and # of affected relatives is important) High in fat, especially animal fat, red meats and processed meats risk risk - risk of incidence and death -30-40% more likely to die of colorectal cancer

Distribution of Colorectal Cancer

Pathology
Columnar cell carcinoma originating in the colonic epithelium.

Microscopically

4 forms: Annular (obstructive symptoms) Tubular Macrocopically Ulcer bleeding symptom Cauliflower

The spread of carcinoma of the colon

Lymphatic spread

Local spread

Bloodstream spread

Transcoelomic spread

Local Spread
Can spread in longitudinal, tranverse or radial directions Spread round the intestinal wall & usually causes intestinal obstruction before it invades adjacent structures. The ulcerative type more commonly invades locally internal fistula local perforation with an abscess external fecal fistula The progression of invasion submucosa muscularis propia serosa and fat lymphatics and veins in the mesentry alongside the bowel wall

Lymphatic Spread

N1 : nodes in the immediate vicinity of the bowel wall N2 : nodes arranged along the ileocolic, right colic, middle colic, left colic and sigmoid arteries N3 : the apical nodes around the superior and inferior mesenteric vessels where the arise from abdominal aorta.
Involvement of the lymph nodes by the tumor progresses in a gradual manner from those closest to the growth along the course of the lymphatic vessels

Bloodstream spread

Transcoelomic spread

This accounts for a large proportion (30-40%) of late deaths.

Metastases are carried to the liver via the portal system, sometimes at an early stage before clinical or operative evidence detected.
Venous spread Principal sites for blood-borne metastases are liver( 34%) lungs(22%)

Spread by way cells dislodging from the serosa of the bowel/ via the subperitoneal lymphatics other structures within the peritoneal cavity. Peritoneal dissemination. May follow penetration of the peritoneal coat by a high-lying rectal carcinoma.

Clinical Features

Per Rectal Bleed

Tenesmus

Alteration Bowel Habit

Age >55 years old with 6 month of early symptoms that usually not significant to patient

 Earliest to occur and most constant Slight in amount but viable. Usually separate from feces and come in drops of blood Occur at end of defecation Notice usually stain on clothing Sometimes coexist with hemorrhoids

Tenesmus
Sense of incomplete defecation as ineffectual + pain straining on defecation Go to empty rectum several times/day Often faeces that go out in small amount Faeces with bloody slime(mucus) with blood stained.

Get up early morning to defecate with early morning bloody diarhhea Explosive watery diarrhea due to rectum distention + mucus causing distension Commonly patient will have 5 weeks of costipation then one week of these diarrhea But if tumor at rectosigmoid junction=constipation

Bleeding Per Rectum (Hematochezia)

Alteration Bowel Habit

Abdominal Pain

Systemic Symptoms

a) b)

c)

Colicky in nature due to late symptom from intestinal obstruction or from rectosigmoid ostruction Can also cause severe pain when carcinoma ulcer erodes prostate or bladder Sciatic pain (pain at back) when invade sacral plexus 20% from sigmoid cancers will also have diverticulitis with: Pain + fever More to cause obstruction symptoms Also with colovesical or colovaginal fistula

Fever Loss of weight Loss of appetite

Physical Examination
1)

Abdominal Examination

Ascites develop when peritoneum become studded Rectosigmoid cancer most likely to cause abdomial obstructive features

2) Rectal Examination Nodule with indurated base Shallow depression when centres ulcerate Bimanual check for abscess also consistency. When ulcer distal put finger posterior to tumor to search for any raised hard oval swellinglymph node involvement.

Fecal Occult Blood Test

Stool Blood Test (FOBT): Used to find small amounts of blood in the stool. If found further testing should be done.

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Flexible Sigmoidoscopy

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Flexible Sigmoidoscopy: A sigmoidoscope, a slender, lighted tube is placed into lower part of colon through rectum Look at inside of rectum and lower third of colon for cancer or polyps Is uncomfortable but not painful. Preparation consists of an enema to clean out lower colon If small polyp found then will be removed. If adenoma polyp or cancer found, then colonoscopy will be done to look at the entire colon

Barium Enema

Barium enema with air contrast: A chalky substance is used to partially fill and open up the colon Air is then pumped in which causes the colon to expand and allows clear x-rays to be taken If an area looks abnormal then a colonoscopy will be done

Virtual Colonoscopy

Virtual Colonoscopy: Air is pumped into the colon in order for it to expand followed by a CT scan Bowel prep is needed but procedure is completely noninvasive and no sedation is needed Is not recommended by ACS for early detection. More studies need to be done to determine its effectiveness in regard to early detection Is not recommended if pt have a history of colorectal cancer, Chrons disease, or ulcerative colitis

Colonoscopy

Colonoscopy: A colonoscope, a long, flexible, lighted tube is inserted through the rectum up into the colon To see the entire colon Bowel prep of strong laxatives to clean out colon, and the day of the procedure an enema will be given

Procedure lasts ~15-30 minutes and are under mild sedation

Can exclude polyp, diverticulosis or ulcerative http://www.cadth.ca/media/healthupdate/Issue6/hta_update_mr-colonograpy2.jpg colitis

If cant extend full due to obstruction do CT

Guidelines
Screening
Fecal Occult Blood Test (FOBT)
Flexible Sigmoidoscopy (FS)+FOBT * Colonoscopy
(preferred method b/c polyps can be biopsied and removed)

Guidelines
Annually starting at age 50

Advantages
-Cost effective -Noninvasive -Can be done at home
-Cost effective -Can be done w/o sedation -Performed in clinic -Any polyps can be biopsied -Patient sedated -Outpatient screening -Views entire colon and rectum -Polyps can be removed and biopsied -Relatively noninvasive -No sedation needed -Can show 2- or 3-D imagery

Disadvantages
-False-positive/false-negative results -Dietary restrictions -Duration of testing period
-Examines only portion of colon (additional screening may be done) -Discomfort for patient -Bowel cleansing -Bowel cleansing -Sedation may be a problem for some -Cost if uninsured -Risk of perforation -Small polyps may go undetected -Bowel cleansing -Cost -If polyps found, colonoscopy required -Exposure to radiation -Patient discomfort

Every 5 years starting at age 50

Every 10 yrs starting at age 50

Virtual Colonoscopy (a.k.a. computed tomography colonography-CT)

Every 10 yrs starting at age 50

*American Cancer Society

Guidelines
DRE Sigmoidoscopy or colonoscopy + biopsy

Suspected Case

Define staging by endoluminal ultrasound or Established Case MRI or CT scan Do CT liver & chest for metastase

Staging

Staging is a standardized way that describes the spread of cancer in relation to the layers of the wall of the colon or rectum, nearby lymph nodes, and other organs The stage is dependent on the extent of spread through the different tissue layers affected The stage is an important factor in determining treatment options and prognosis One of the major staging systems in use is the AJCC (American Joint Committee on Cancer) staging scheme, which is defined in terms of primary tumor (T), regional lymph nodes(N), and distant metastasis (M)

T Staging-American Joint Committee on

Cancer system (AJCC/TNM)

T Categories: Describes the extent of spread of the primary tumor (T) through the layers of tissue that form the wall of the colon and rectum Tis: Cancer is in its earliest stage, has not grown beyond mucosa. Also known as carcinoma in situ or intramucosal carcinoma T1: Cancer has grown through mucosa and extends into submucosa T2: Cancer extends into thick muscle layer T3: Cancer has spread to subserosa but not to any nearby organs or tissues T4: Cancer has spread completely through wall of the colon or rectum into nearby

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N and M Staging-American Joint Committee

on Cancer system (AJCC/TNM)

N categories: describes the absence or presence of metastasis to nearby lymph nodes (N)

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N0: No lymph node involvement N1: Cancer cells found in 1-3 regional lymph nodes N2: Cancer cells found in 4 or more regional lymph nodes

M Categories: describes the absence or presence of distant metastasis (M) M0: No distant spread M1: Distant spread is present

Staging-American Joint Committee on Cancer system (AJCC/TNM)

Staging is an indicator of survival Stage grouping: From least advanced (stage 0) to most advanced (stage IV) stage of colorectal cancer
TNM Category
Tis, N0, M0 T1, N0, M0 T2, N0, M0 T3, N0, M0 T4, N0, M0 T1-T2, N1, M0 93%

Stage
Stage 0: Stage I:

Survival Rate
The earliest stage. Has not grown beyond inner layer (mucosa) of colon or rectum. Has grown into submucosa (T1) or muscularis propria (T2)

Stage IIA: Stage IIB: Stage IIIA:

85% 72% 83%

IIA: Has spread into subserosa (T3). IIB: Has grown into other nearby tissues or organs (T4). IIIA: Has grown into submucosa (T1) or into muscularis propria (T2) and has spread to 1-3 nearby lymph nodes (N1) IIIB: Has spread into subserosa (T3) or into nearby tissues or organs (T4), and has spread to 1-3 nearby lymph nodes (N1) IIIC: Any stage of T, but has spread to 4 or more nearby lymph nodes (N2). Any T or N, and has spread to distant sites such as liver, lung, peritoneum (membrane lining abdominal cavity), or ovaries (M1).

Stage IIIB:
Stage IIIC: Stage IV:

T3-T4, N1, M0
Any T, N2, M0 Any T, Any N, M1

64%
44% 8%

Histopthological Grading

Most is columnar cell adenocarcinoma More undifferentiated more malignant more bad prognosis
G1 (11%) Low Grade Well differentiated Prognosis good

G2 (64%)

Average Grade Less differentiated High Grade Undifferentiate d

Prognosis Fair

G3 (25%)

Prognosis poor

If invade vascular or perineural very poor prognosis as more infiltative feature rather than pushing

CANCER TREATMENT

PART 2

Amsterdam Criteria

Treatment
Priciples of management of colorectal cancer

Assesment of local and distant tumor spread shoud be performed both preoperatively and intraoperatively to allow planning of surgery

Snycrhonous tumor(5%) should be excluded preoperatively

Operations are planned to remove the primary tumour and its draining locoregional lymph nodes

Histological exmnation of resected tumors contributes to decision making regarding of the need of adjuvant therapy.

Adjuvant therapy Operations

The test of operability

Preoperative preparation

Preoperative preparation

Preoperative staging is required to guide surgery and preoperative adjuvant radiotherapy Compression stockings and heparin are required thromboprophylaxis Pt should be fasted prior to surgery Bowel preparation. Preoperative antibiotic prophylaxis is essential (3rd gen cephalosporin, or gentamicin and ampicillin, and metronidazole)

The test of operability

The liver is palpated for secondary deposits, the presence of which is not necessarily a contraindication to resection because the best palliative treatment for carcinoma of the colon is removal of the tumour. The peritoneum, particularly the pelvic peritoneum, is inspected for signs of small, white, seed-like, neoplastic implantations. Similar changes can occur in the omentum.

The various groups of lymph nodes that drain the involved segment are palpated. Their enlargement does not necessarily mean that they are invaded by metastases, because the enlargement may be inflammatory.

The neoplasm is examined with a view to mobility and operability. Local fixation, however, does not always imply local invasion because some tumours excite a brisk inflammatory response.

Target of Surgery

Removal of primary cancer plus blood supplied involved

Regional Lymphadenoctomy

Restore continuity by anastomoses

Areas for resection at colon

Resectable by right hemicolectomy Ascending colon or end-to-end anastomosis is caecum fashioned between the ileum and the transverse colon
Cecum+ascending the resection must be extended colon+ hepatic correspondingly flexure

Tranverse colon

Do extended right hemicholectomy Cut all ascending colon & transverse colon+ anastomoses terminal ileum with proximal descending colon

 Do left hemicolectomy- from Splenic splenic flexure to rectosigmoid Flexure or junction Descending Sometimes, removal of the colon up to the ileum, with an ileorectal Colon anastomosis

If multiple tumors Do total colectomy- cut all colon from terminal involved all colon or ileum to rectum. Then complete anastomoses rectum obstruction sigmoid cancer with ileum.

Rectal Cancer
o

How close to anal sphincter? Depth penetration into bowel wall?

(using rigid proctosigmoidscope)-resectable

o

By DRE: superficial invasive tumor=mobile but if deep invasive tumor=tethered & fixed
o

Spread to adjacent nodes?

By Endorectal ultrasound or MRI

Problem occurred when involved Distal 3rd rectum as to preserve anal sphincter + can damage prostate,urethra,vagina,servix & bladder. So do preoperative downstaging by chemo or radiotherapy then do resection.

Rectal Resection Technique

Proximal 3rd Middle 3rd Distal 3rd

Anterior resection or Hartmann

Low anterior resection or Anterior resection

Low anterior resection or Abdominal perineal resection

Local Excision
o

Indicate if not penetrate muscularis propria (T1) , N0 as cant clear node, size <4cm, <40% circumferential & located within 6cm from anal. Transanal approach by excise full thickness rectal wall with underlying tumor Can for T2 but must + adjuvant therapy as recurrence rate=20%

Anterior Resection

Low Anterior Resection

Resection through abdominal incision Do when involved proximal 3rd rectum which above peritoneal reflection Resect proximal rectum & rectosigmoid junction (proctosigmoidectomy ) Then do colorectal

Whenever involved below peritoneal reflection Always remove also sigmoid colon as cant establish anastomoses sigmoid with rectum as blood supply from IMA being cut Also must do mesorectal excision- cut rectum + intact mesorectum to reduce metastases by lymphatic channel Increase 5 years survival rate 50 to 75%, decrease recurrence 30 to 5% and reduce bladder dysfunction 85 to 15%

Low Anterior Resection

Do anastomoses between descending colon with distal residual rectum or anus by connect outside or using stapler Check anastomoses fully healed or not through anal proctoscope Risk of increase small bowel movement that can resolved by J pouch

Abdominal Perineal Resection

Complete resection rectum & anus through abdominal & perineum incision + suture closure perineuem + permanent colostomy When tumor involve anal sphincter or anus and cant be preserved anymore Abdominal incision: remove rectum & sigmoid colon + pelvic dissection to level levator ani muscles Perineal incision: excise anus + anal sphincter + distal rectum

Radiotherapy

Adjuvant preoperative radiotherapy has an important place in the management of rectal cancer shown to reduce local recurrence rates Short-course : 5-day regimen of 45Gy daily Long-course regimen of 52Gy given weekly over 3months

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Adjuvant Chemotherapy
Drug Fluorouracil -(5FU) Description
-most common drug, usually given with other drugs, such as leucovorin, to help increase effectiveness -along with radiation therapy, 5-FU is given as a continuous infusion intravenously to increase radiation effectiveness -The de Gramont regimen: -5-FU is given continuously over 2 days with a rapid injection/day -leucovorin given each day over 2 hours -regiment given every other week -With colorectal metastases to liver, a hepatic artery infusion is given involving: 5-FU or floxuridine (FUDR) given directly into the artery which supplies blood to the liver -treatment is called FOLFIRI: adds irinotecan to de Gramont 5-FU/leucovorin regimen -studies have shown a chance for excessive side effects when all three are combined

Ironetican

Oxaliplatin Capecitabine

-treatment is called FOLFOX: it may be used in place of irinotecan in the de Gramont regimen -drug is given orally -is changed to 5-FU once it reaches the tumor site -can be given instead of intravenous 5-FU -acts as if 5-FU being administered continuously

Immunotherapy
May kill cancer cells, slow their growth, or activate patients immune system 2 new monoclonal antibodies :

Bevacizumab Cetuximab

STOMAS

Colostomy

A colostomy is an artificial opening made in the large bowel to divert faeces and flatus to the exterior, where it can be collected in an external appliance. Depending on the purpose for which the diversion has been necessary, a colostomy may be temporary or permanent

Temporary colostomy
A transverse loop colostomy
has in the past been most commonly used to defunction an anastomosis after an anterior resection. It is now less commonly employed as it is fraught with complications and is difficult to manage; a loop ileostomy is preferred.

A loop left iliac fossa colostomy

is still sometimes used to prevent faecal peritonitis developing following traumatic injury to the rectum, to facilitate the operative treatment of a high fistulai-n-ano and incontinence.

Bringing a loop of colon to the surface, where it is held in place by a plastic bridge passed through the mesentery

Abdomen closed, then colostomy is opened, and the edges of the colonic incision are sutured to the adjacent skin margin .

When firm adhesion of the colostomy to the abdominal wall has taken place, the bridge can be removed after 7 days.

Following the surgical cure or healing of the distal lesion for which the temporary stoma was constructed, the colostomy can be closed.

It is usual to perform a contrast examination to check that there is no distal obstruction or continuing problem at the site of previous surgery.

Colostomy closure is most easily and safely accomplished if the stoma is mature, i.e. after the colostomy has been established for 2-3 months.

Permanent colostomy

This is usually formed after excision of the rectum for a carcinoma by the abdominoperineal technique. It is formed by bringing the distal end (endcolostomy) of the divided colon to the surface in the left iliac fossawhere it is sutured in place, joining the colonic margin to the surrounding skin.

The point at which the colon is brought to the surface must be carefully selected to allow a colostomy bag to be applied without impinging on the bony prominence of the anterosuperior iliac spine. The best site is usually through the lateral edge of the rectus sheath, 6 cm above and medial to the bony prominence. This is completed by mucous fistula or

Colostomy bags and appliances

Faeces from a permanent colostomy are collected in disposable adhesive bags. A wide range of such bags is currently available.

Complications of colostomies
Prolapse

Colostomy Diarrhoea

Retraction

Bleeding

Complications

Necrosis Distal End

Colostomy Hernia Stenosis Of The Orifice

Fistula Formation

Loop ileostomy

An ileostomy is now often used as an alternative to colostomy, particularly for defunctioning a low rectal anastomosis. The advantages of a loop ileostomy over a loop colostomy are the ease with which the bowel can be brought to the surface and the absence of odour. Care is needed, when the ileostomy is closed, that suture line obstruction does not occur.

Prognosis
Stage
Stage I Stage IIa Stage IIb Stage III Stage IV

Level
T1 or T2 T3 T4 Any Node involve Metastases

5 year survival rate

90% 75% 75% 50% <5%

#CASE 1

History: A 65-year-old white female, was in good health until about 6 weeks ago, when she noted occasional cramps in the left lower quadrant of the abdomen associated with constipation. The episodes of cramping last about 30 minutes each and are most severe in the hour following her meals. She has taken laxatives which have partially relieved her symptoms, but she has had a decreased appetite and 5kg weight loss over the past four weeks. In addition, she has become increasingly fatigued over this period. When questioned about her bowel habits, she reported bright red blood in her stools and a smaller caliber of stool over the past two weeks.

Physical Examination: She appeared fatigued and distressed. Head and neck exams were normal, as was her thorax. Palpation of the abdomen revealed tenderness in the left lower quadrant. Percussion over this area revealed a hollow, tympanic sound. Hepatomegaly was noted, and a hard and slightly tender liver edge was felt in the right upper quadrant. Bowel sounds were noticeably reduced. A stool sample was tested with Guaiac paper and was positive for blood.

What is your differential diagnosis? What should you do next? What are the risk factor for colorectal cancer? What are the treatment option? 5-year survival rate for this patient?

Stage?

THANK YOU!!

BOWEL PREPARATION FOR COLONOSCOPY

ONE WEEK BEFORE

If you are taking iron tablets or constipating medications such as loperamide (Imodium) or codeine phosphate, these should be stopped at least 5 days before the test. Continue with all other medications until your appointment.

TWO DAYS BEFORE

Foods from the following list are acceptable: boiled or steamed white fish, boiled chicken, potato (no skin), egg, cheese, white bread, butter (or margarine), seedless jam, Marmite, honey, rich tea biscuits, chocolate, yoghurt, jelly (any colour except red) and ice-cream.

From two days before the test you may eat only low residue foods.

Do not eat red meat, fruit, vegetables, nuts, pulses or cereals in any form.

You should aim to drink plenty of fluid during the day.

THE DAY BEFORE

You are now ready to begin taking the bowel clearing medicine No solid food but drink as much clear fluid as possible. Clear fluids include fruit juices (without pulp), fizzy drinks or tea and coffee (without milk). The more you drink, the better your bowel preparation will be.

PICOLAX PREP

three sachets of Picolax These must be taken on the day before the test according to the following instructions.

At 10 oclock in the morning empty one sachet of Picolax into a glass and mix with 4 dessert spoonfuls of water. Then fill the glass with cold water, making it up to about 150ml (1/4 pint) of liquid. Drink the solution.

At 2 oclock in the afternoon dissolve the second sachet of Picolax as described above and drink. During the afternoon aim to drink a further 2 pints of clear fluid.

At 6 oclock in the evening dissolve the final sachet of Picolax as described above and drink. During the evening aim to drink a further 2 pints of clear fluid.

ON THE DAY OF THE TEST

Take no solid food. Take your regular medication with a small amount of water You should continue to drink clear fluid (preferably water) until two hours before the appointment time for your colonoscopy. You must not eat or drink for 2 hours before the test. You will usually be allowed to eat and drink again one hour after the test.