CRC Lecture 2011

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Surgery of Colorectal Cancer

By

Professor Ahmed Hussein

Chairman of Unit of Colon and Rectal SurgeryUniversity of Alexandria

Incidence

In Egypt, colorectal cancer is the fourth most commonly diagnosed cancer in both men

and women.

World Age-adjusted Incidence Rates by GenderMales Females M/F Ratio

World 20.1 14.6 1.2

More Developed Countries 40.0 26.6 1.2Less Developed Countries 10.2 7.7 1.2

Incidence Rates/100,000

The Incidence of CRC in Egypt

EgyptianNew CRC

CasesIncidence/100,000

MedianAge

M/FRatio

Number ofDeaths

Males 2263 6.3 48.0 1.1 1426

Females 2057 5.3 48.8 1.0 1295

Total 4320 5.8 48.4 1.1 2721

Middle East Cancer Consortium (MECC), Egypt

Risk Factors for Colorectal Cancer:

1. Hereditary CRC Syndromesa. Adenomatous polyposis syndromes

i. Familial adenoamtous polyposis (FAP)ii. MYH-associated polyposis (MAP)

b. Nonpolyposis syndrome

i. Hereditary nonpolyposis CRC (HNPCC)c. Hamartomatous polyp syndromes

i. Peutz-Jeghers syndrome (PJS)ii. Juvenile polyposis syndrome (JPS)

iii. Cowden disease (Bannayan-Ruvalcaba-Riley)2. Inflammatory Bowel Disease: Ulcerative Colitis3. Personal History of CRC4. Family History of CRC5. Ethnic background: Ashkenazi Jews6. Age: above 50 years in the western community.

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SurgeryofCRCProfessorAhmedHussein

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a. In Egypt the median age of CRC less than 50 yearsEnvironmental Factors

Increased risk of CRC with a diet high in:

1. Red meat and animal fat

2. Low-fiber diet: low overall intake of fruits and vegetables

Lifestyle choices that are associated with increased risk for CRC:

1. Alcohol and tobacco consumption

2. Obesity

3. Sedentary habits

Factors associated with lower risk include:

1. Folate intake

2. Calcium intake

3. Estrogen replacement therapy

Genetics of Colorectal Cancer

Genetics does not mean inherited, genetics means pathogenesis. Genetically, colorectal

cancer represents a complex disease, and accumulation of genetic alterations is associated

with progression from normal epithelial cells or premalignant lesion (adenoma) to

invasive adenocarcinoma. Colorectal cancers have several gene expression profiles with

different pathogenic (genetic) pathways.

Types of Colorectal Cancer

Type %Sporadic 75%

Family History of CRC 18%HNPCC 5%

FAP 1%

MAP 1%PJS & JP

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Pathway I CIN (Chromosomal Instability)

Acquired (somatic) or inherited (germline) macrogenetic alterations at chromosomal

level either in the form of abnormal number (aneuploidy) or gross changes i.e. loss of

heterozygosity (LOH).

The important genes involved in these chromosome losses are APC (5q), DCC (18q), and

TP53 (17p).

This pathway is seen in Familial Adenomatous Polyposis (FAP) and adenoma-carcinoma

model.

Pathway II Microsatellite Instability (MSI) Mismatch Repair Pathway (MMR)

Germline or somatic microgenetic (intragenic) mutations of DNA damage-repair genes

result in Microsatellite Instability (MSI) i.e. insertion or deletion of nucleotides in one ormore alleles. MSI means alterations in repeating units of DNA that occur normally

throughout the genome.

The important genes involved in this MSI are MMR genes (hMSH2, hMSH6, hMLH1,

hMLH3, hPMS1, hPMS2)

This pathway is seen in 95% of HNPCC and 18% of sporadic colorectal cancer.

Alternative Pathways

1. Flat & depressed adenoma2. De Novo CRC

3. Colitis induced CRC

4. Serrated Pathway

Alternative pathways are involved in up to 30% of CRC, precursors not easily seen with

rapid evolution following genetic instability.

Normal

Epithelium

APC

Early

Adenoma

K-ras

Intermediate

Adenoma

DCC

Late

Adenoma

p53

Cancer

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Colitis induced CRC

This pathway is seen in ulcerative colitis and schistosomiasis Japonicum. Chronic

inflammation results in free O2 radicals cause DNA damage. Dysplasia-carcinoma

model.

Serrated Pathway: CpG I sland Methylator Phenotype (CIMP)

Epigenetic factors are mechanisms outside the gene such as a cells exposure to

carcinogens or hormones, or genetic variations that modify a gene or its protein by

methylation, demethylation, phosphorylation, or dephosphorylation. Genes that must be

expressed in all tissues have unmethylated regions, called CpG islands. On the other

hand, genes that must be turned off in differentiated tissues have these islands

methylated.

In this pathway type C tumor suppressor genes silenced by promoter region CpG

methylation.

This pathway is seen in Juvenile Polyposis, Peutz-Jeghers Syndrome and Serrated

adenomas

Normal

Epithelium

Aneuploidy

p53

IndefiniteDysplasia

p53

Low GradeDysplasia

K-ras

MSI

High GradeDysplasia

DCC

Cancer

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Clinical Picture of Colorectal Cancer

1. Asymptomatic by screening program

2. Primary Lesion

3. Metastases

4. Complications

Screening for Colorectal Cancer

Life-Time Risk of CRC

Group Life Time Risk of CRCGeneral Population 5%Ashkenazi Jews 6-10%

Family History of CRC 10-15%

Personal History of CRC 15-20%IBD 15-40%

PJS 50%

JP 50%HNPCC 70-80%

FAP >95%

High Risk Group

1. 10-100% lifetime risk according to:a. Family history criteria

b. Pathological criteria

c. Pathogenic gene mutation

2. Screening Method: in Genetics Centre for formal counseling & mutation analysis

Moderate Risk Group

1. First degree relative (FDR) with CRC aged

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b. Flexible Sigmoidoscpy / 5 years

c. Colonoscopy / 10 years

Clinical Picture of Primary Colorectal Cancer

The most common presenting symptoms associated with colon cancer are abdominal

pain, followed by change in bowel habits, rectal bleeding, and occult blood in the stool.

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Cancer Right Colon

1. Change in Bowel Habits

a. Diarrhea

2. Pain

a. Vague upper abdominal

3. Iron Deficiency Anemia

4. Weight Loss

5. Mass (advanced )

6. Obstruction Rare

Cancer Left Colon

1. Change in Bowel Habitsa. Increasing Constipation

2. Pain

a. Colicky with distension

3. Weight Loss

4. Mass (advanced or fecal matter)

5. Obstruction common or 1st presentation

6. Bleeding /Rectum

7. Mucous/ Rectum

Cancer Rectum

1. Bleeding /Rectum

2. Mucous/ Rectum

3. Tensmus (Sense of incomplete evacuation)

4. Change in Bowel Habits

a. Spurious morning diarrhea

5. Pain

a. Colicky in rectosigmoid lesions

b. Severe pelvic ( advanced due to infiltration)

6. Weight Loss7. Rare Obstruction in rectosigmoid lesions

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Symptom Rt. Side Lt. Side Rectum

Change in Bowel Habits Diarrhea ConstipationConstipation

spurious morning

diarrhea

Bleeding /Rectum Altered Dark FreshColicky Pain + ++++ upper 1/3

Mass +++ ++ -

Mucous/ Rectum - + ++++Tensmus

Incomplete Evacuation- - +++++

Weight Loss +++ + ++Iron Deficiency Anemia ++++ + +

Spread of Colorectal Cancer

1. Direct spread

a. Intramural

i. Circumferential

ii. Longitudinal

b. Transmural

2. Lymphatic spread

3. Venous spread: Liver & Lung metastases

4. Transperitoneal spread

a. Malignant ascites

b. Krukenbergs tumor

Complications of Colorectal Cancer

1. Intestinal obstruction

2. Penetration (fistula)

3. Bleeding (anemia or hypovolemia)

4. Intussusception: incomplete obstruction

5. Perforation

a. Tumor perforationb. Caecal perforation caused by a left-sided colon cancer

Diagnosis

An individualized approach to the diagnosis considers:

1- The patients symptoms

2- Age

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3- Personal history of inflammatory bowel disease, colon polyps, or colorectal

cancer

4- Family history of colon cancer or predisposing genetic syndromes (e.g., familialadenomatous polyposis or hereditary nonpolyposis colorectal cancer)

Diagnostic Evaluation

1- Colonoscopy: A crucial part of this evaluation is to ensure that the patients entire

colon and rectum have been assessed with colonoscopy for the presence of

synchronous neoplasms. Colonoscopy allows biopsy and histologic confirmation

of the diagnosis. It also allows for identification and endoscopic removal of

synchronous polyps. Pre-operative histology should be done in all rectal tumors.

2- Depending on the patients age and health status, a variety of laboratory,

radiologic, and cardiorespiratory tests may be appropriate to assess the patients

operative risk.

Preoperative Assessment

1- Preoperative, carcinoembryonic antigen level:

Is beneficial for two reasons:

a. Postoperative return to normal of an elevated preoperative CEA is associated with

complete tumor resection, whereas persistently elevated values indicate the

presence of visible or occult residual disease.

b. Elevated preoperative CEA levels have been found to be an independent

prognosticator of poor outcome.

CEA has never been useful as a screening tool as it is elevated in a variety of

conditions, including colorectal cancer, proximal gastrointestinal cancers, lung and

breast cancers, benign inflammatory conditions of the gastrointestinal tract, and

smoking.

2- Preoperative CT scanning

CT scans can be used to evaluate local extension of the tumor and regionallymphadenopathy, as well as for the presence of hepatic metastases.

3- Preoperative chest x-rays or chest CT scanning: to evaluate the lungs for evidence of

metastatic disease.

4- PET CT scan is not routinely indicated.

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TNM Staging

T

Tx: Incomplete informationTis: It involves only the mucosa

T1: Extends into the submucosa

T2: Extends into the muscularis propria

T3: Extends into subserosa

T4a: Penetrates visceral peritoneum

T4b: Tumor invades other organs or structures

NNx: Incomplete information

N0: No LN involvement

N1: In 1- 3 regional LNs.

N1a: in 1 regional LNs

N1b: in 2- 3 regional LNsN1c: Tumor Deposits in subserosa, mesentry, nonperitonealized pericolic or

perirectal tissues without regional LNs metastasis

N2: In 4 or more regional LNsN2a: in 4-6 regional LNs

N2b: in 7 or more regional LNs

MM0: No distant Metastasis

M1: Distant MetastasisM1a: Metastasis confined to one organ or site (Liver, lung, ovary, non-regional LNs)

M1b: Metastasis in more than one organ/site or peritonium

5-years Survival

Stage I 92%

Stage II 73%IIA 85%

IIB 72%

Stage III 56%IIIA 83%

IIIB 64%

IIIC 44%

Stage IV 8%

TNM Dukes

Stage 0 Tis N0 M0 -

Stage I T1 N0 M0 AT2 N0 M0 A

Stage IIA T3 N0 M0 BIIB T4a N0 M0 BIIC T4b N0 M0 B

Stage IIIA T1-2 N1/N1c M0 CT1 N2a M0 C

IIIB T3-4 N1/N1c M0 C

T2-T3 N2a M0 CT1-T2 N2b M0 C

IIIC T4a N2a M0 CT3-T4a N2b M0 C

T4b N1-N2 M0 C

Stage IVA Any T Any N M1a -IVB Any T Any N M1b -

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Preparation for Operation

A. Informed Consent

All patients who are to undergo surgery for colon cancer need to be clearly informed of

the reasons for and the extent of the proposed resection, the likely outcome of the

surgery, the pertinent complications and their likelihood of occurring, expected length of

hospitalization and recovery, alternatives to the proposed surgery, and prognosis.

B. Mechanical Bowel Preparation

Mechanical bowel preparation is nearly universally used in elective surgery. Despite its

nearly universal use, the literature does not support a defined benefit for preoperative

mechanical preparation of the bowel. The persistence in using a preoperative bowel

preparation may be justified simply on the basis of the advantages it affords in ease of

handling the prepared colon, the proven safety of the methods used for bowel cleansing,

and the relatively low cost. Outpatient bowel preparation (the day before surgery) is

generally safe and cost effective.

C. Prophylactic Antibiotics

Prophylactic antibiotics have proven effectiveness in decreasing the rate of infection,

mortality, and cost of hospitalization after colonic resection. There are a wide variety of

antibiotic regimens that are effective. Regardless which parenteral antibiotic regimen is

selected, it is agreed that it must be given before the start of the operation to be effective.

D. Blood Cross Match and Transfusion

Blood transfusion should be based on physiologic need. The need for transfusion is

primarily based on the starting hemoglobin, the patients physiologic status, and extent of

intraoperative blood loss.

The immunosuppressive effect of transfusion is well established. Patients who receive

perioperative blood transfusions have a greater incidence of infection. However, recently

it was found that the immunosuppressive effect of transfusion does not increase the rate

of cancer recurrence. Other factors (extent of resection required, location of tumor, and

experience of surgeon) in patients requiring transfusion may actually be the cause for the

increased recurrence rate.

E. Thromboembolism Prophylaxis

All patients undergoing surgery for colon cancer should receive prophylaxis against

thromboembolic disease. Patients undergoing colon resection for cancer have a high

incidence of venous thromboembolism, including deep venous thrombosis and

pulmonary embolism.

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Operative Issues

A. Operative Technique

The extent of resection of the colon should correspond to the lymphovascular drainage of

the site of the colon cancer. The determinant of adequate bowel resection for colon

cancer is removal of the primary feeding arterial vessel and its corresponding lymphatics.

Tumors located in border zones should be resected with the neighboring lymphatic

regions to encompass both possible directions of spread. The length of bowel resected is

usually governed by the blood supply to that segment. Ligation of the origin of the

primary feeding vessel ensures the inclusion of the apical nodes, which may convey

prognostic significance for the patient. There is much concern regarding intraoperative

manipulation of the tumor with shedding of cancer cells into the portal circulation.

However, the value of the no touch technique has not been proven, although there is a

theoretic basis for its use.

Arterial Supply of the Colon and Rectum

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Site of the Lesion Operation Vessels Excised Parts

AppendixCecum

Ascending Colon

Right Hemicolectomywith ileotransverse

anastomosis

IleocolicRight Colic

Rt. branch of middle

colic

Cecum, appendix,ascending colon and

the right third of the

transverse colon

Hepatic Flexure Extended Right

Hemicolectomy

with ileotransverse

anastomosis

Ileocolic

Right Colic

Middle Colic

Cecum, appendix,

ascending colon and

the right two thirds of

the transverse colon

Transverse Colon Transverse colectomy

with anastomosis

between the ascending

and descending colons

Middle Colic Transverse colon

including both hepatic

and splenic flexures

greater omentum in

T4 lesionsSplenic Flexure Extended Left

Hemicolectomy with

anastomosis between

transverse and sigmoid

colons

Inferior Mesenteric

Left branch of the

middle colic

Descending Colon

and Left half of the

transverse colon

Descending Colon Left Hemicolectomy

with anastomosis

between transverse

and sigmoid colons or

(Rectum)

Inferior Mesenteric Descending Colon

and Left third of the

transverse colon

sigmoid colon

Sigmoid Colon Sigmoidectomy

With anastomosisbetween left colon and

upper rectum

Inferior Mesenteric Sigmoid Colon

Upper Third Rectum Tumor Specific

Mesorectal Excision

With anastomosis

between descending

colon and middle third

rectum

If the anastomosis

above the peritoneal

reflection = Anterior

ResectionIf the anastomosis

below the peritoneal

reflection = Low

Anterior Resection

Inferior Mesenteric Sigmoid Colon and

upper third Rectum

with distal safety

margin of 5 cm

Middle and lower

Third Rectum down

to > 2 cm from the

dentate line

Total Mesorectal

Excision

With anastomosis

between descending

colon and anal canal

(coloanal anastomosis)

Inferior Mesenteric

Middle Rectal

Sigmoid Colon and

total proctectomy with

distal safety margin at

least 2 cm

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= Ultra-Low Anterior

Resection

< 2 cm from the

dentate line or lesioninfiltrating the anal

sphincter or the pelvic

floor muscles

Total Mesorectal

Excision withAbdominoperineal

Excision of the

Rectum (APER) with

permanent colostomy

Inferior Mesenteric

Middle RectalInferior Rectal

Sigmoid Colon, total

proctectomy, analcanal, anal sphincters

and pelvic floor

muscles

Right Hemicolectomy

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Left Hemicolectomy

Total Colectomy & Ileorectal Anastomosis

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Sigmoid Colectomy

Sigmoid Colectomy with End colostomy and Hartmanns pouch

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Laparoscopic resection of colon cancer is feasible but requires specific surgical expertise.

Adherence to oncologic principles is possible and adequate lymphadenectomy with

disease-free margins can be achieved comparable to open surgery.

Operative IssuesEmergency

A. Obstructing Colon Cancer

a.Patients with an obstructing right or transverse colon cancer should undergo a right

or extended right colectomy. A primary ileocolic anastomosis can be performed in

the appropriate clinical setting.

b.Patient with a left-sided colonic obstruction, the procedure selected should be

individualized from a variety of appropriate operative approaches.

i.Resection with end colostomy and Hartmanns pouchii.Resection with on-table colonic lavage and primary anastomosis

iii.Subtotal colectomy with ileorectal anastomosis.

iv.Insertion of colonic Stent to relieve the acute obstruction thereby permitting

an elective colonic oral lavage, colonoscopy, and subsequent resection with

primary anastomosis.

The three-stage approach of performing proximal diversion, then resection, then

colostomy closure is generally thought to be less advantageous because of its high

mortality and morbidity rates.

B. Colonic Perforation

The site of a colonic perforation caused by colon cancer should be resected, if at all

possible.

a. Right-sided colon perforation from a right colon cancer should be resected. If

there is a free perforation with peritonitis, an anastomosis may be unwise and the

patient is probably best left with an end ileostomy. The distal end may be brought

out as a mucous fistula or stapled off as a Hartmanns pouch. Alternatively, if

there is limited fecal spillage, the surgeon may choose to reanastomose the bowel

with or without fecal diversion.

b. When a left colon cancer perforates resulting in peritonitis, a Hartmanns

resection is the indicated operation in most settings. In cases in which there is

massive proximal colonic distention and/or ischemia, a subtotal colectomy may

be the best choice. If there is a limited degree of peritoneal contamination, the

surgeon may choose to perform an ileorectal or ileosigmoid anastomosis with a

diverting loop ileostomy.

c. In the case of a right colon perforation caused by a left-sided colon cancer, most

experts advocate a subtotal colectomy. Whether an anastomosis or a loop

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ileostomy to protect the anastomosis are performed is dependent on the surgeons

judgment about the degree of contamination and the patients clinical status.

C. Massive Colonic Bleeding

Acutely bleeding colon cancers that require emergent resection should be removed

following the same principles as in elective resection. Because of the cathartic effect of

the bleeding, the bowel has been effectively cleansed of the bulk of fecal matter and a

primary anastomosis can be considered. Whether to proceed with an anastomosis or elect

to perform an end stoma and mucous fistula (or Hartmanns pouch) is based on the

surgeons judgment about the current clinical condition of the patient.

In cases in which the site of the bleeding cannot be identified, a subtotal colectomy is the

preferred procedure.

POSTOPERATIVE STAGING OF COLON CANCER

a. Colon cancers should be staged using the TNM staging system.

b. It is important that accurate pathologic evaluation of the radial margin of resection

be performed. Each operation is given a resection code to denote completeness of

resection:

R0: Complete tumor resection with all margins negative

R1: Incomplete tumor resection with microscopic involvement of the margin

R2: Incomplete tumor resection with gross residual tumor that was not resected.

c. Other factors that have an impact on the patients risk of recurrence and survival.

i. Microscopic venous or lymphatic invasion within the specimen worsen the

prognosis for every stage.

ii. Histologic grade and histologic type

iii. Serum CEA

Lymph node numbers:

To be properly evaluated, one should strive to have a minimum of 15 lymph nodes

examined microscopically.

The accuracy of colon cancer staging improves with increasing the number of lymph

nodes evaluated microscopically. Ten or more lymph nodes can be found in 98 percent of

colon specimens and 13 or more lymph nodes can be found in 91 percent of specimens

without using fat-clearing techniques.

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Adjuvant Therapy

A. Chemotherapy

Postoperative adjuvant systemic chemotherapy has a proven benefit in Stage III colon

cancer and may be beneficial in certain high risk Stage II patients.

Patients with Stage III colon cancer are recognized to be at high risk for recurrence, and

administration of 5-fluorouracil (5-FU)/leucovorin for six months postoperatively has

proven benefit in decreasing recurrence and improving survival.

Patients with Stage II colon cancer who are considered at higher risk for recurrence

include those with one or more of the following characteristics: tumor perforation,

adherence, or invasion of adjacent organs; nondiploidy by flow cytometry; poorlydifferentiated tumor; or venous, lymphatic, and perineural invasion. It may be

advantageous for these patients to receive adjuvant chemotherapy.

The oral chemotherapy agent, capecitabine:

Capecitabine is an oral fluoropyrimidine carbamate preferentially converted to 5-FU in

tumor cells.

B. Immunotherapy

The value of immunotherapy for colon cancer is undetermined. Its use is recommendedwithin the setting of a clinical trial.

C. Intraperitoneal/Intraportal Chemotherapy

Intraperitoneal and intraportal infusions of chemotherapy are recommended only in the

confines of a clinical trial.

D. Radiation Therapy

The role for radiation therapy in colon cancer is limited.

Radiation is rarely used in the treatment of colon cancer. Radiations potential for injuryto the abdominal viscera limits its usefulness.

Surveillance

1. History & Physical Examination: Every 3-6 m for 2 y then every 6 m for a total of 5 yrs

2. Serum CEA: Every 3-6 m for 2 y then every 6 m for a total of 5 yrs

3. CT scan of abdomen & pelvis: Annually for 3 years

4. Colonoscopy: At 1 year then as clinically indicated

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Rectal Cancer

Any cancer whose distal margin is 15 cm or less from the anal verge using a rigid

sigmoidoscope should be classified as rectal.

Rectal cancer comprises approximately 25 percent of the malignancies arising in the large

bowel. Anatomically, the rectum is the distal 15-cm of the large bowel leading to the anal

canal. Cancers of the intraperitoneal rectum behave like colon cancers with regard to

recurrence patterns and prognosis. By contrast, the extraperitoneal rectum resides within

the confines of the bony pelvis; it is this distal 10 to 12 cm that constitutes the rectum

from the oncologic standpoint.

Rectal Cancer is a challenging disease because:

1. Common malignancy

2. Difficult dissection

3. Treatment not infrequently entails a permanent stoma

4. Sexual and urinary morbidity

5. Local recurrence

PREOPERATIVE ASSESSMENT

An individualized approach to the diagnosis considers:

1- The patients symptoms2- Age

3- Personal history of inflammatory bowel disease, colon polyps, or colorectal

cancer

4- Family history of colon cancer or predisposing genetic syndromes (e.g., familial

adenomatous polyposis or hereditary nonpolyposis colorectal cancer)

I. DIAGNOSTIC EVALUATION

1- Colonoscopy: A crucial part of this evaluation is to ensure that the patients entire

colon and rectum have been assessed with colonoscopy for the presence ofsynchronous neoplasms. Colonoscopy allows biopsy and histologic confirmation of

the diagnosis. It also allows for identification and endoscopic removal of synchronous

polyps.

2- Depending on the patients age and health status, a variety of laboratory, radiologic,

and cardiorespiratory tests may be appropriate to assess the patients operative risk.

3- When an ostomy is a consideration, preoperative counseling with an enterostomal

therapist should be offered when available.

4- Digital rectal examination and rigid proctosigmoidoscopy

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a. Digital rectal examination enables detection and assessment of the size

and degree of fixation of mid and low rectal tumors.

b. Rigid proctosigmoidoscopy and digital rectal examination allow the mostprecise assessment of tumor location and the distance of the lesions from

the anal verge. These issues are critical in optimizing preoperative

planning.

5- Abdominal and pelvic CT scans often used to evaluate local extension of the tumor

and regional lymphadenopathy, as well as for the presence of hepatic metastases.

However, its role in local staging is limited.

6- Transrectal ultrasound (TRUS) is the diagnostic modality of choice for preoperative

local staging of mid and distal rectal cancers. TRUS may be more accurate in

defining earlier-stage lesions (T1, T2).

7- Pelvic Magnetic Resonance Imaging: MRI is more accurate in assessing T3 and T4lesions. MRI has the added advantage of a multiplanar and larger field of view of the

mesorectal fascia and more accurately predicts the likelihood of obtaining a tumor-

free circumferential resection margin.

8- Preoperative routine chest radiographs or chest CT scanning: Rectal cancer is more

likely than colon cancer to be associated with lung metastases without liver

metastases.

9- Carcinoembryonic antigen (CEA) level is most useful when found to be elevated

preoperatively and then normalizes after resection of the tumor. Subsequent

elevations suggest recurrence or metastatic disease. Because of a lack of sensitivity

and specificity, it is not used as a screening test.

10-PET CT scan is not routinely indicated

TREATMENT CONSIDERATIONS

Informed opinion of the (MDT) Multidisciplinary Team (Radiologist, Pathologist,

Medical Oncologist and Colorectal Surgeon). The patient and family should have the

opportunity to ask questions and to have important information repeated. The patient

should have an access to treatment within 31 days of discussion with MDT.

Surgery is the mainstay of treatment for rectal cancer. The risk of recurrence is dependenton the TNM stage. Early stage cancer can be treated by surgical resection alone. More

advanced lesions require adjuvant therapy to increase the probability of cure.

The surgeon is a critical variable with respect to morbidity, sphincter preservation rate,

and local recurrence.

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SURGICAL THERAPY

Resection Margin

The proximal resection margin is determined by blood supply considerations. For upper

third rectal cancers both the rectum and mesorectum are divided not less than 5 cm below

the lower margin of the tumor. A 2-cm distal margin is adequate for most low rectal

cancers. In smaller cancers of the low rectum without adverse histologic features, a 1-cm

distal margin is acceptable.

Site of the Lesion Operation Vessels Excised Parts

Upper Third Rectum Tumor Specific

Mesorectal Excision

With anastomosis

between descendingcolon and middle third

rectum

If the anastomosis

above the peritoneal

reflection = Anterior

Resection

If the anastomosis

below the peritoneal

reflection = Low

Anterior Resection

Inferior Mesenteric Sigmoid Colon and

upper third Rectum

with distal safety

margin of 5 cm

Middle and lower

Third Rectum downto > 2 cm from the

dentate line

Total Mesorectal

ExcisionWith anastomosis

between descending

colon and anal canal

(coloanal anastomosis)

= Ultra-Low Anterior

Resection

Inferior Mesenteric

Middle Rectal

Sigmoid Colon and

total proctectomy withdistal safety margin at

least 2 cm

< 2 cm from the

dentate line or lesion

infiltrating the anal

sphincter or the pelvic

floor muscles

Total Mesorectal

Excision with

Abdominoperineal

Excision of the

Rectum (APER) with

permanent colostomy

Inferior Mesenteric

Middle Rectal

Inferior Rectal

Sigmoid Colon, total

proctectomy, anal

canal, anal sphincters

and pelvic floor

muscles

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Tu

Total Me

or Specifi

T

25

orectal E

Mesorect

ME with

cision (T

l Excision

PER

Prof

E)

(TSME)

Surger

ssorAhmedyofCRCHussein

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Level of Proximal Vascular Ligation

Proximal lymphovascular ligation at the origin of the superior rectal artery is adequate for

most rectal cancers. There is no demonstrable survival advantage for a high ligation of

the inferior mesenteric artery at its origin. In patients with lymph nodes thought to be

involved clinically, removal of all suspicious nodal disease up to the origin of inferior

mesenteric artery is recommended. High ligation of the inferior mesenteric vessels may

be helpful to provide additional mobility of the left colon, as often is required for a low

colorectal anastomosis.

Circumferential Resection Margin

For distal rectal cancers, total mesorectal excision (TME) is recommended. For upper

rectal cancers, a tumor-specific mesorectal resection is adequate.

The mesorectum is the fatty tissue that encompasses the rectum. It contains

lymphovascular and neural elements. Surgical excision of the mesorectum is

accomplished by sharp dissection in the plane between the fascia propria of the rectum

and the presacral fascia. Radial clearance of mesorectal tissue enables the en bloc

removal of the primary rectal cancer with any associated lymphatic, vascular, or

perineural tumor deposits. Total mesorectal excision is associated with the lowest

reported local recurrence rates.

Pathologic assessment of rectal cancer specimens suggests that distal mesorectal spread

may occur up to 4 cm away from the primary tumor. Thus, a cancer in the distal rectum

should be treated with a total mesorectal excision in most cases. Upper rectal cancers

may be treated with a tumor-specific mesorectal resection with distal safety margin of 5

cm.

Circumferential margin involvement in the presence of an intact mesorectal specimen is a

strong predictor for local recurrence. A margin of 2 mm between tumor and the

mesorectal fascia was considered positive and was associated with a higher local

recurrence rate. Furthermore, patients who had a margin 1 mm had an increased risk of

distant metastases

En Bloc Resection of Adherent (T4) Tumors

Rectal cancers with adjacent organ involvement should be treated by en bloc resection.

Tumors may be adherent to adjacent organs by malignant invasion or inflammatory

adhesions. Locally invasive rectal cancer (T4) is removed by an en bloc resection to

include any adherent tissues. If a tumor is transected at the site of local adherence,

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resection is deemed incomplete, because it is associated with a higher incidence of local

recurrence.

Inadvertent Perforation

Inadvertent perforation of the rectum worsens oncologic outcome and should be

documented. This should be considered in postoperative adjuvant treatment decisions and

outcome measurements.

Other Operative Considerations

1. Role of Oophorectomy

Bilateral oophorectomy is advised when one or both ovaries are grossly abnormal or

involved with contiguous extension of the colon cancer. However, prophylactic

oophorectomy is not recommended..

2. Laparoscopic-assisted resection of rectal cancer is feasible but requires specific

surgical expertise.

3. Emergency intervention:

Hemorrhage, obstruction, and bowel perforation are the most common indications for

emergency intervention for rectal cancer. Appropriate management must be

individualized with options, including resection with anastomosis and proximal

diversion, or diversion alone followed by radiation. Self-expandable metallic stents can

be used to relieve obstruction by a proximal rectal cancer.

Preoperative Clinical Staging

1. T1-2,N0

2. T3, N0 OR T any, N1-2

3. T4 and/or locally unresectable primary

4. T any, N any, M1 resectable metastases

5. T any, N any, M1 unresectable metastases or medically in operable

Treatment of T1-2, N0, M0

Transanal Resection

1. Conventional resection or Transanal Microsurgery

2. Full thickness excision through the bowel wall into the perirectal fat

3. T1N0

4. Small (

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6. within 8 cm of AV

7. < 30% of rectal circumference

8. Negative (> 3 mm) deep & mucosal margins9. No Tumor fragmentation

According to histopathology of the resected specimen, either Surveillance would be

sufficient or further radical surgery might be indicated

Transabdominal Radical Resection is indicated if Unfavorable histological features:

1. LVI + PNI+

2. Grade 3-4

3. Positive Margins

4. T2

Transabdominal Radical Resection:

1. Mid to upper rectum

a. TSME (LAR) 5 cm below distal edge of Tumor + colorectal anastomosis.

2. Low rectal lesions

a. Tumor Within 2 cm above the dentate line

i. APER

ii. ISRR If T1 & T2

b. Tumor Above 2 cm from the dentate line

i. TME with coloanal anastomosis

ii. Spare autonomic nerves

Adjuvant Chemotherapy

If the pathology review after transabdominal resection revealed

1. T3N0

2. T1-3 N1-2

Regimens over 6 months

1. 5-FU +/- LV or FOLFOX or Capecitabine ( 1 Cycle)

2. Concurrent 5-FU/RT or capecitabine/RT

3. 5-FU +/-LV or FOLFOX or capecitabine (2 Cycles)

T3, N0 / T any, N1-2, M0

Preoperative (NeoAdjuvant) Therapy is a MUST

1. Continuous 5-FU/RT

2. Alternatives : bolus 5-FU/LV/RT or Capecitabine/RT

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Operative

Transabdominal approach only, performed 5-10 weeks after completion of neoadjuvant

therapy

Postoperative Adjuvant Therapy

1. 5-FU +/- LV

2. Alternatives : FOLFOX or Capecitabine

All patients receiving preoperative (Neoadjuvant) therapy should receive postoperative

adjuvant therapy for 6 months

T4 and/or locally unresectable primary

Resectable case = anticipated negative (R0) microscopic circumferential resection margin

Preoperative (NeoAdjuvant) Therapy

1. Continuous 5-FU/RT

2. Alternatives : bolus 5-FU/LV/RT or Capecitabine/RT

Operative

More Radical (multi-organ) approach, complete removal of tumor and involved viscera

with R0 margins.

Postoperative Adjuvant Therapy

1. 5-FU +/- LV

2. Alternatives : FOLFOX or Capecitabine

3. All patients receiving preoperative (Neoadjuvant) therapy should receive

postoperative adjuvant therapy for 6 months

T any, N any, M1 resectable metastases

1. Combination chemotherapy:a. FOLFOX/FOLFIRI/capeOX +/- Bevacizumab

b. FOLFIRI/FOLFOX +/- cetuximab (KRAS wild-type gene only)

2. Staged or synchronous resection of metastases and rectal lesion

3. Adjuvant Therapy:

a. Continuous IV 5FU/ RT

b. Bolus 5FU+leucovorin/ RT

c. Capecitabine/RT

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T any, N any, M1 unresectable metastases or medically inoperable

1. Role of palliative surgery

a. Only If Obstruction, Perforation or Bleeding

2. Symptomatic Treatment

a. Chemotherapy alone

b. Combind modality

i. 5FU/RT or Capecitabine /RT.

c. Resection of involved rectal segment + CT

d. Intraluminal Stent + CT

e. Diverting colostomy + CT

Pathologic Evaluation of Rectal Cancer

1. Gross: Tumor & Specimen

2. Grade

3. LVI & PNI

4. T Stage

5. Number of regional LNs evaluated

6. N Stage: Number of +ve LNs

7. M Stage

a. Other organs

b. Peritoneum

c. Nonregional lymph nodes

8. Proximal, distal, & CRM

9. p = pathologic staging

10.yp = pathologic staging following neoadjuvant therapy

Surveillance

1. History & Physical Examination

a. Every 3-6 months for 2 years

b. Then every 6 months for a total of 5 years

2. CT scan of abdomen & pelvis Annually for 3 years3. Colonoscopy At 1 yearthen as clinically indicated

ADJ UVANT THERAPY

Neoadjuvant Therapy (Preoperative chemoradiation) should be offered to patients with

Stage II and III rectal cancers.

1- It is given as long course (45-50 Gy in 25-28 fractions)

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2- 5-FU based chemotherapy should delivered concurrently with radiation

3- All patients receiving preoperative (Neoadjuvant) therapy should receive

postoperative adjuvant therapy for 6 months

Rationale for Neoadjuvant Therapy

1. Avoids irradiation of neorectum & small bowel

2. Systemic Therapy early

a. Less burden of disease

b. Better drug perfusion

i. Nonsurgically manipulated tumor

ii. Well vascularized oxygenated tissue

3. As Radiosensitizers

a. Enhanced rates of downstaging & pathologic complete response (ypCR)

Site AtDL 2cmDL MidRectum UpperRectum

PedunculatedPolyp

LVI,G12

Polypectomy&Observe

SessilePolyporLVI+,

G34

RadicalSurgery

T1,LVI,G12 SCRT

+APR

APR/

CRT+ISRR

Local

Excision

Local

Excision/TME

TSME

T1,LVI+,G34,orT2 SCRT+

APR

APR/

CRT+ISRR

TME TME TSME

GoodT3 CRT+

APR

CRT+APR TME TME TSME

BadT3 CRT+APR CRT+APR CRT+TME CRT+TME CRT+TSME

T4a CRT+APR CRT+APR CRT+TME CRT+TME CRT+TSME

T4b

CRT+APR

CRT+APR CRT+TME CRT+TME CRT+TSME

Documents

CRC Lecture 2011