Surgery, after all, is an affair of the spirit it is a fierce test of a mans technical skill, someti

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Surgery, after all, is an affair of the spirit
it is a fierce test of a mans technical skill,
sometimes, but, in a grim or long fight, it is
above all a trial of the spirit and there are
few things that cannot be conquered if a mans
heart is set on victory. Sir Berkeley
Moynihan
3
Colon CancerNew in Diagnosis and Management

• Boris V. Vinogradsky, MDDepartment of
  SurgeryLake West HospitalCleveland, Ohio
• Russian American Medical Association
• The 2nd National Conference
• Boston, MA
• September 11, 2004

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Colorectal carcinoma comprises 13 of all
cancers, and is the 2nd leading cause of cancer
related death in the United States Colorectal
cancer causes 10 of all cancer deaths
5
The lifetime risk of being diagnosed with
colorectal cancer is 6 and the risk of dying
from it is 2.5In 2000, 130 000 cases were
diagnosed and 57 000 people died of the
diseaseBetween 1990 and 1995 the incidence of
colorectal cancer decreased 2 per year
6
History

• 1710 Morgagni Suggested excision of rectal cancer
• 1714 Littre Concept of colostomy
• 1823 Reybard First successful colon resection and
  anastomosis
• 1879 Martini Concept of Hartmanns procedure
• 1885 Kraske Transsacral approach
• 1898 Bevan Performed first APR

Polk HC, Carcinoma of the Colon and Rectum, 1959
7
History
1908 Moynihan En bloc resection1909 Dobson Estab
lished routes of lymphatic spread1923 Fischer Ai
r-contrast Ba enema1926 Dukes Adenoma-to-carcino
ma sequence1932 Dukes Staging1939 Dixon Introd
uced LAR1941 McIntyre Extended study of regional
metastases1943 Wangensteen Pre-op bowel
preparation1954 Astler-Coller Modified Dukes
classification
Polk HC, Carcinoma of the Colon and Rectum, 1959
8
History 1961 Hirschowitz Introduced
fibrogastroscope1967 Turnbull Introduced Stage D
of colon cancer1968 Muir Intraoperative colonic
lavage1973 Wolff Polypectomy through
colonoscope1986 Mullis PCR1990 Laparoscopic
colectomy1991 Groden Identification of the APC
gene
Wu JS, Fazio VW, Dis Colon Rectum, Nov 2000
9
Colon Cancer Distribution
1. 75 2. 18 3. 5 4. 1 5. 1
Cameron JL, Current Surgical Therapy, 7th Ed, 2001
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Board Question 1

• Of the following, the most significant risk
  factor for colorectal cancer is
• A. Low-Ca diet
• B. High-fiber diet
• C. Tobacco
• D. High-fat diet

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Risk factors

• 75 of cases are sporadic
• High-fat diet
• Inflammatory Bowel Disease
• Previous Colon Carcinoma

12
Risk factors

• History of First-Degree Relatives with Bowel
  Cancer
• Average risk of general population is 5
• Family history of colon cancer or advanced
  adenoma increases the risk 2-8 times
• The risk is higher, if more than one relative is
  affected and, if cancer developed earlier than at
  the age of 45
• People with known family history but without
  known genetic syndrome comprise 15-20 of
  patients at high risk

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Polyps

• Approximately 30 of adults in Western countries
  have adenomatous polyps
• Most lesions are less than 1 cm in size
• 60 of people have single adenoma
• 40 have multiple adenoma
• 60 of lesions located distal to splenic flexure
• 24 of patients with adenomatous polyp left
  untreated will develop cancer in this polyp
  within 20 years

15
Polyps

• Non-neoplastic
• Hyperplastic
• Multiple
• Sessile
• Less than 1 cm in diameter
• No cellular atypia
• Patients with distal hyperplastic polyps may have
  proximal adenomas
• Inflammatory
• Regenerating epithelium is seen
• Mucosal

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Polyps

• Juvenile
• Seen in children younger than 10 years of age
• Hamartomatous
• Aquired
• 75 are found in the rectum
• Red and pedunculated
• Mucus filled
• Frequent hematochezia

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Polyps
Wu JS, Fazio VW, Dis Colon Rectum, Nov 2000
18
Genetics of Colon Cancer

• Three major categories of genes
• Oncogenes
• Tumor suppressor genes
• Mismatch repair genes
• Two major pathways
• Inactivation of tumor suppressing APC gene
• Alterations in DNA mismatch repair genes
• Major benefit of genetic studies is the ability
  to do a presymptomatic testing

Wu JS, Fazio VW, Dis Colon Rectum, Nov 2000
19
Polyps
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
20
Polyps

• Neoplastic (adenomatous)
• Benign or malignant
• Nearly all carcinomas of the colon develop in
  previously benign polyps
• Polyps can cause intussusception, bleeding,
  diarrhea and obstruction
• Malignant polyp has invasion through muscularis
  mucosae layer
• Polyps larger than 2 cm harbor cancer 25 of the
  time, although 65 of malignant polyps are less
  than 2 cm in size

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Polyps

• Tubular Adenoma
• 75-87 of all polyps
• Mild cellular atypia
• 20 have severe atypia
• Less than 5 are malignant
• May be pedunculated or sessile
• Complex branching glands on histology

22
Polyps

• Tubulovillous Adenoma
• 8-15 of polyps
• 20-25 of them are malignant
• Intermediate malignant potential
• Both branching and villous (fingerlike) glands on
  histology

23
Polyps

• Villous Adenoma
• 5-10 of all polyps
• Usually located in the rectum
• Usually larger than 2 cm in size
• High malignant potential
• 35-40 are malignant
• May cause mucous diarrhea with hypokalemic
  alkalosis and hypoalbuminemia

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Polyps

• Polyp size and malignant potential
• Adenomas lt1 cm - 1.3
• Adenomas 1-2 cm - 9.5
• Adenomas gt2 cm - 46.0
• Level of dysplasia and malignant potential
• Mild - 5.7 risk of developing a malignancy
• Moderate - 18.0
• Severe - 34.5

M.D.Anderson Surgical Oncology Handbook, 2001
25
Polyps

• Haggits classification of the depth of
  invasion
• Invasion limited to the tip of the polyp (Level
  1)
• Invasion of the neck
• Invasion into the stalk
• Invasion into the submucosa beneath the
• base of the polyp (Level 4)
• Single most important prognostic factor for
  mesenteric lymph node involvement
• Sessile polyps are levels 4 and above

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Polyps
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
27
Polyps Hamartomatous Polyposis
SyndromesIntestinal hamartoma is a focal
malformation, overgrowth of epithelial cells,
usually pedunculated, with the stalk lined with
normal mucosaDoes not cause compression of
adjacent tissueMinimal malignant potentialNo
need for resection
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Polyps

• Hamartomatous Polyposis Syndromes
• Cronkhite-Canada Syndrome
• Cowdens Disease
• Basal Cell Nevus Syndrome
• Neurofibromatosis (Type I Von Recklinghausens
  disease)
• Peutz-Jeghers Syndrome

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Board Question 2

• All the following are true regarding familial
  polyposis (FAP), EXCEPT
• A. It is associated with an increased risk of
  polyps anywhere in the GI tract
• B. Essentially, 100 of untreated colons will
  ultimately manifest invasive cancer
• C. Other than retinal pigmentation,
  extraintestinal manifestations are unusual
• D. Less than 1 of patients have no prior family
  history of polyposis
• E. The colon is carpeted with hundreds of polyps

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Polyps

• Hereditary Polyposis Syndromes
• Familial adenomatous polyposis is the best
  characterized syndrome that carries a 100 risk
  of cancer development unless colon is
  prophylactically resected
• Autosomal-dominant disease
• Accounts for 1 of colorectal cancers
• Affects 1 in 7,000 people
• Germline mutation of the APC gene on chromosome 5
• Aneuploid and more aggressive

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Polyps

• Hereditary Polyposis Syndromes
• All associated with extraintestinal
  manifestations and multiple benign and malignant
  tumors of other organs
• Gardners syndrome
• Turcots syndrome
• Oldfields syndrome

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Effect of COX 2 Inhibitors in Patients with FAP

• 6 months of treatment of patients with FAP with
  Celebrex reduced the number of polyps by 28 and
  the polyp burden was reduced by 31
• Other NSAIDs and Aspirin have been used with the
  similar results

Steinbach G et al, N Engl J Med, June 2000 Janne
PA et al, N Engl J Med, June 2000
33
Polyps

• Hereditary non-polyposis colorectal cancer
  (HNPCC)
• Lynch I and II syndromes
• Accounts for 5 of colorectal cancers
• Diploid
• Amsterdam criteria
• 3 relatives (1 first-degree relative of the
  others) affected
• These 3 people should be in two generations
• One of them should develop colon Ca by the age of
  50

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Polyps

• Hereditary non-polyposis colorectal cancer
  (HNPCC)
• Autosomal-dominant disease
• Germline mutation of the hMLH1, hPMS1, hPMS2 and
  hMSH2 genes on chromosomes 2, 3 and 7
• Lynch I - isolated colonic involvement
• Lynch II - associated with other malignancies -
  endometrial, ovarian, gastric and small bowel
• Both behave as fairly benign cancers
• 70 of lesions are proximal to splenic flexure

Wu JS, Fazio VW, Dis Colon Rectum, Nov 2000
35
Polypectomy

• Characteristics of lesions amenable to
  colonoscopic treatment
• Arise in a pedunculated polyp
• Well- or moderately differentiated
• Have no venous or lymphatic invasion
• Haggitts level 1-3
• Have negative resection margin

Cameron JL, Current Surgical Therapy, 7th Ed, 2001
36
Polypectomy

• Level 1-3 polyps can be removed without risk of
  metastases
• Partial snare excision can be done to confirm
  presence of the invasive cancer
• Resection margin is the most important factor of
  treatment outcome 2 mm margin is adequate
• Poor histologic differentiation is an absolute
  indication for colon resection
• Follow-up colostomy should be performed in 3-6
  months

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Surveillance After Polypectomy

• Colonoscopy and/or BE can be used
• The detection of polyps by BE is significantly
  related to the size of the adenomas
• Colonoscopy was more accurate than BE
• Importance of this superiority is unclear since
  only 3 of lesions were larger than 1 cm

Winaver SJ and the National Polyp Study Work
Group, N Engl J Med, 2000
39
Screening

• Screening is a stratification of risk among
  apparently asymptomatic average-risk individuals
• 20 of the general population are at risk of
  developing adenomatous polyps
• Fecal occult blood test and endoscopy are the
  most widely employed screening tools
• Colonoscopy is cost-effective, if a 10-year
  interval is used once the colon is cleared of
  polyps
• CEA has no role in screening for primary lesions

M.D.Anderson Surgical Oncology Handbook, 2001
40
Colonoscopy
Courtesy of Dr. Strobel, Dept of Pathology,
St.Vs Hospital
41
Screening

• Recommendations
• Average-Risk Patients (start at the age of 50)
• Annual fecal occult blood testing (FOBT)
• If () colonoscopy or DCBE/flex sig
• Flexible sigmoidoscopy every 5 years
• If () colonoscopy
• Combined FOBT and flexible sigmoidoscopy
• Double-contrast Ba enema (DCBE) every 5 years
• Colonoscopy every 10 years

M.D.Anderson Surgical Oncology Handbook, 2001
42
Screening

• High-Risk Patients (asymptomatic)
• Same as for average-risk but start at the age of
  40
• High-Risk Patients (family history of FAP)
• Genetic counseling and testing
• Gene carriers flex sig every 12 months starting
  at puberty
• High-Risk Patients (family history of HNPCC)
• Colonoscopy every 1-2 years starting at the age
  of 25, or 5 years before the earliest age of
  onset of any cancer in a family, whichever is
  earlier and every year after 40

M.D.Anderson Surgical Oncology Handbook, 2001
43
Screening

• High-Risk Patients (history of adenomatous
  polyps)
• 1 cm polyp(s) repeat initial exam in 3 years
• 2nd exam NL, or small, single or tubular
  adenoma repeat exam in 5 years
• 2nd exam multiple polyps repeat exam per
  clinical judgment
• High-Risk Patients (history of colon cancer)
• Colonoscopy within 1 year of surgery
• 2nd exam NL - repeat initial exam in 3 years
• 3rd exam NL - repeat initial exam in 5 years

M.D.Anderson Surgical Oncology Handbook, 2001
44
Colonoscopy
Courtesy of Dr. Strobel, Dept of Pathology,
St.Vs Hospital
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Colonoscopy in Screening for Colon Cancer

• Overall shift towards right-sided colon lesions
  was noted recently
• Of the 1,765 patients in patients over 50 years
  of age with no lesions distal to splenic flexure
  48 (2.7) had advanced proximal lesions, 30 of
  those were cancers
• 62 of patients with advanced proximal neoplasms
  had no distal lesions

Lieberman DA et al, N Engl J Med, 2000 Imperiale
TF et al, N Engl J Med, 2000
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Pathology

• More than 90 of colon cancers are
  adenocarcinomas
• The most frequently used grading system is based
  on the degree of formation of glandular
  structures, nuclear polymorphism, and number of
  mitoses
• Morphologic variants
• Ulcerative
• Exophytic
• Annular (scirrhous)
• Submucosal infiltrative (linitis plastica type)

M.D.Anderson Surgical Oncology Handbook, 2001
47
Pathology
Courtesy of Dr. Strobel, Dept of Pathology,
St.Vs Hospital
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Pathology
Courtesy of Dr. Strobel, Dept of Pathology,
St.Vs Hospital
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Natural history

• At diagnosis
• 10 of patients will have in situ disease
• 33 will have local disease
• 33 will have regional disease
• 25 will have metastases
• 50-60 will develop metastases over their
  lifetime
• Overall 5-year survival is about 50

M.D.Anderson Surgical Oncology Handbook, 2001
50
Diagnosis

• Colon Cancer
• Clinical evaluation includes colonoscopy with
  biopsy, BE, CXR, CBC, UA
• CT of the abdomen and pelvis, LFT and CEA are
  controversial
• Only 15 of patients with liver metastases have
  abnormal LFT
• 40 of patients without liver metastases have
  abnormal LFT
• Intraoperative liver US is the most accurate
  method of detection of metastases
• 15-20 of liver metastases are nonpalpable
• 10-15 of liver lesions are missed on pre- and
  intraoperative evaluation

M.D.Anderson Surgical Oncology Handbook, 2001
51
Ultrasound in Colorectal Cancer Diagnosis
Staren ED, Ultrasound for the Surgeon, 1997
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Ultrasound in Rectal Cancer Diagnosis

• Sensitivity and specificity
• Depth of invasion 55-97 and 24-100
• Identification of LN() 57-89 and 64-100
• Indications
• Tumors that satisfy criteria for local excision
• Accessible, no larger than 4 cm
• Demonstrate minimal invasion of the rectal wall
• Not associated with nodal metastases

Staren ED, Ultrasound for the Surgeon, 1997
53
Ultrasound in Rectal Cancer Diagnosis
Cameron JL, Current Surgical Therapy, 7th Ed, 2001
54
CEA in Colorectal Cancer

• CEA testing is recommended for monitoring of
  recurrence at 2-3 months intervals for gt2 years
  after diagnosis of Stage II or III tumors
• CEA first detected resectable recurrences more
  frequently than any other tests and was the most
  cost effective approach for identifying
  potentially resectable disease
• Poorly differentiated tumors may not make CEA

Benson AB, J Clin Oncol, 2000
55
CEA in Colorectal Cancer

• 20-30 of patients with recurrent disease have
  normal CEA level
• 60-90 of asymptomatic patients with elevated CEA
  will have recurrent disease
• 12-60 of them will have resectable disease at
  the time of laparotomy
• 30-40 of these patients will survive 5 years
  following resection of the recurrence

M.D.Anderson Surgical Oncology Handbook, 2001
56
Immunoscanning (radioimmunodetection)

• First suggested by Goldenberg in 1974
• Accomplished by obtaining whole body or spot
  planar gamma scans on patient who has been
  injected intravenously with an antibody that has
  been labeled or conjugated with a gamma-emitting
  radionuclide. Antibodies were engineered for two
  antigens TAG-72 and CEA.
• HAMA is the most serious limitation
• Can only be used once
• Initial enthusiasm faded

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Immunoscanning
Indium-111 (OncoScint) or Technetium-99
(CEA-Scan) can be used
58
RIGS

• In patients with rising CEA levels and negative
  metastatic work-up an exploratory laparotomy
  should be performed
• I-125 labeled antibodies to CEA injected 6 weeks
  before the second-look surgery and detected
  intraoperatively by a hand-held gamma probe
• Detection is accurate in 81 of patients
• To date, no study has demonstrated a survival
  advantage with this technique
• Radioimmunoguided Surgery

M.D.Anderson Surgical Oncology Handbook, 2001
59
Virtual Colonoscopy

• Novel technique where overlapping transaxial
  helical CT images reconstructed following a
  standard bowel preparation and air insufflation
• 2-D multiplanar reformations and 3-D endoluminal
  images are viewed
• Sensitivity for detection of lesions gt10 mm in
  size was 75-91
• Successful in 90 of patients with occlusive
  colon cancer

Brink JA et al,Contemporary Surgery, May 2000
60
Virtual Colonoscopy
Brink JA et al,Contemporary Surgery, May 2000
61
PET scanning

• New controversial imaging technology currently in
  use only as a research tool
• Relies on the increased uptake of glucose (FDG)
  in tumors compared with normal tissues
• Expensive and has not yet been approved for
  general use

M.D.Anderson Surgical Oncology Handbook, 2001
62
Board Question 3

• Regarding colon cancer staging
• A. Cancer in the head of a polyp, invading into
  the submucosa is Stage 0
• B. Primary tumor invading the muscularis propria
  but not through is Stage I
• C. Less than 3 lymph nodes involved is Stage II
• D. Perforation of a tumor constitutes Stage III
• E. Stage IV (AJCC) is equivalent to Dukes Stage
  D

63
Staging
M.D.Anderson Surgical Oncology Handbook, 2001
64
Staging

• Extent of Resection (R) in TNM classification
• RX - Presence of residual tumor cannot be
  assessed
• R0 - No residual tumor
• R1 - Microscopic residual tumor
• R2 - Macroscopic residual tumor
• Level of evidence IV
• Grade of recommendation B

Journal of NCI, Vol.93, No.8, April 18, 2001
65
Staging
TNM classification for the Staging of Colorectal
Cancer 0 Tis N0 M0 I T1 (submucosa) N0 M0
T2 (muscularis) N0 M0 II T3
(serosa) N0 M0 T4 (adjacent
organ) N0 M0 III Any T N1 (1-3
nodes) M0 IV Any T Any N M1 N2 (gt4
nodes) N3 (LN on vascular trunk)
Cameron JL, Current Surgical Therapy, 7th Ed, 2001
66
Staging

• Radial Margin
• T4 lesions represent a complex group and should
  be considered separately
• Patients who do not have histologic assessment of
  radial tumor margin or had an R1 or R2 resections
  are considered to have an incomplete resection
  for cure
• Incomplete resection does not change the TNM
  stage, but it does affect curability
• Level of evidence III
• Grade of recommendation B

Journal of NCI, Vol.93, No.8, April 18, 2001
67
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Management of Colon Cancer

• Surgical Options
• 90-92 of patients with colon cancer and 84 of
  patients with rectal cancer are treated
  surgically
• In most cases surgery is performed with curative
  intent
• Surgery is the only treatment modality that has a
  potential for cure
• Standard resection is the only therapy required
  for early-stage cancer
• Adjuvant Therapy
• 5-FU is the single most effective agent for colon
  cancer

M.D.Anderson Surgical Oncology Handbook, 2001
69
Management of Colon Cancer

• Anatomic Definitions Colon vs. Rectum
• Colon - greater than 12 cm from anal verge by
  rigid proctoscopy
• Rectum - 12 cm or less from anal verge
• It is important from a stand point of local
  recurrence rates 9.6 vs. 30.7
• Level of evidence IV-V
• Grade of recommendation B

Journal of NCI, Vol.93, No.8, April 18, 2001
70
Management of Colon Cancer

• Surgical Aspects
• Abdominal Exploration
• Should be performed in every patient and must be
  thorough
• Includes inspection and bimanual palpation of the
  liver, peritoneal surface, omentum,
  retroperitoneum and ovaries, if present
• The primary tumor should be checked for local
  adherence
• Palpation of periaortic, celiac and portohepatic
  lymph nodes is important
• Level of evidence V
• Grade of recommendation D

Journal of NCI, Vol.93, No.8, April 18, 2001
71
Management of Colon Cancer
Wu JS, Fazio VW, Dis Colon Rectum, Nov 2000
72
Management of Colon Cancer

• Surgical Options
• Right hemicolectomy
• Extended right hemicolectomy
• Transverse colectomy
• Left hemicolectomy
• Low anterior resection
• Subtotal colectomy
• Abdominal perineal resection

Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
73
Management of Rectal Cancer

• Surgical Options
• Transanal excision
• Transanal endoscopic microsurgery
• Low anterior resection
• Abdominal perineal resection
• Non-surgical Options
• Endocavitary radiation
• Laser ablation

M.D.Anderson Surgical Oncology Handbook, 2001
74
Management of Colon Cancer

• Surgical Options
• Ideal Bowel Resection and Margins
• The ideal extent of a bowel resections is defined
  by removing the blood supply and lymphatics at
  the level of the origin of the primary feeding
  blood vessel
• IMA resection at its origin is not mandated by
  available evidence
• Ileal resection should be minimal
• Level of evidence IV
• Grade of recommendation D

Journal of NCI, Vol.93, No.8, April 18, 2001
75
Abdominal Perineal Resection
Wilmore DW, Scientific American Surgery, 1998
76
Management of Colon Cancer

• Surgical Aspects
• No-Touch Technique
• Controversial issue
• Turnbull et al (Ann Surg, 1967) demonstrated a
  difference in 5-year survival but the study had
  serious design flaws
• Wiggers et al (Brit J Surg, 1988) in the
  prospective randomized trial demonstrated no
  statistically significant difference (56 vs.
  59)
• Level of evidence II
• Grade of recommendation B

Journal of NCI, Vol.93, No.8, April 18, 2001
77
Management of Colon Cancer

• Laparoscopic Colectomy
• Benefits
• Decreased length of stay
• Decreased pain and narcotic usage
• Improved cosmetic results
• Lower cost
• Difficulties
• Mobile and bulky specimen
• Inability to palpate the tumor
• Long learning curve

Stocchi L, Nelson H, Journal of Surgical
Oncology, 1998
78
Management of Colon Cancer

• Laparoscopic Colectomy
• Complications
• Bleeding
• Major blood vessel injury
• Ureteral injury
• Bowel injury
• Malrotation of anastomosis
• Tumor not in the specimen
• Inadequate margins and lymph node clearance
• Trocar site recurrence

Stocchi L, Nelson H, Journal of Surgical
Oncology, 1998
79
Management of Colon Cancer

• Surgical Options
• Obstructing Colorectal Cancers
• Up to 30 patients with primary colon cancer
  present with large-bowel obstruction
• One or two-stage operations can be performed
• Stent placement could be considered for
  preoperative decompression and for palliation of
  cancerous obstruction
• Successful stent placement , with resolution of
  obstruction within 96 hours was achieved in 93
  of patients

Baron TH, N Engl J Med, Vol. 344, No. 22, May 2001
80
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Stenting of Colon Cancer

• Problems
• Inability to pass a
• guide wire through
• the mass (up to 40)
• Perforation (5-15)
• Stent occlusion
• Stent migration
• Tenesmus

Tamim WZ, Archives of Surgery, April 2000
82
Management of Colon Cancer

• Surgical Aspects
• Bowel Washout
• Performed when creation of primary anastomosis is
  planned
• More common in emergency situations
• Takes about 45-60 minutes
• Does not decrease local recurrence or anastomotic
  implantation rates

Wu JS, Fazio VW, Dis Colon Rectum, Nov 2000
83
Management of Colon Cancer

• Surgical Aspects
• Inadvertent Perforation
• Has been reported in 8-26 of cases
• Increases local recurrence rate and decreases
  survival
• Lesion should be considered T4, and Stage III, if
  it occurs during resection
• Resection should be considered complete (R0) if
  margins and resected lymph nodes are negative
• Inadvertent perforation must be carefully
  documented
• Level of evidence III
• Grade of recommendation B

Journal of NCI, Vol.93, No.8, April 18, 2001
84
Management of Colon Cancer

• Surgical Options
• Lymphadenectomy
• In all cases for cure, the lymph node resection
  should be radical, nodes should be removed en
  bloc
• Nodes should be excised to the level of a primary
  feeding vessel
• Nodes suspected of being positive outside of the
  field of resection should have a biopsy
• Extended radical lymphadenectomy is not indicated
• A minimum of 12 negative nodes have to be
  examined to confirm that disease does not involve
  the nodes
• Level of evidence III-IV
• Grade of recommendation C

Journal of NCI, Vol.93, No.8, April 18, 2001
85
Management of Colon Cancer

• Surgical Aspects
• Oophorectomy
• Ovarian metastases occur in up to 7 of patients
• Grossly abnormal ovaries or ovaries with direct
  extension of the tumor should be removed
• May be an option in patients who receive
  preoperative XRT or who are postmenopausal
• Routine prophylactic oophorectomy is not
  indicated
• Level of evidence IV
• Grade of recommendation D

Journal of NCI, Vol.93, No.8, April 18, 2001
86
Sentinel Lymph Node Biopsy in Colon Cancer

• SLN identification was successful in 98,8 of
  patients and 34 of them were positive for cancer
• In 52 of positive cases SLN was the only
  positive node
• False-negative rate in this study was 9
• SLN identification upstaged 8 of patients from
  Stage I-II to Stage III. These patients received
  adjuvant therapy

Saha S et al, Ann Surg Oncol, 2000
87
Treatment of Locally Advanced Colon Cancer

• Surgical Aspects
• En bloc Resection of Adherent Tumors
• Adherence to adjacent intraabdominal structures
  encountered in 15 of patients, up to 84 of
  adhesions are malignant
• Urinary bladder is the most commonly involved
  organ
• Lesions that are treated as T4 by en bloc
  resection but that contain only inflammatory
  adhesions are not considered to be T4 lesions
• Local recurrence rate is 36 (with) vs. 77
  (without EBR)
• 5-year survival is 61 vs. 23
• Level of evidence III
• Grade of recommendation B

Journal of NCI, Vol.93, No.8, April 18, 2001
88
Management of Rectal Cancer

• Surgical Aspects
• Mesorectal Excision
• Mesorectum - lymphovascular, fatty and neural
  tissue that is circumferentially adherent to the
  rectum, starting at the level of sacral
  promontory
• Resection should be done under direct vision
• 4-cm fresh distal mesorectal margin should be
  obtained
• Circumferential margin involvement indicates
  advanced disease, not inadequate surgery
• Level of evidence III
• Grade of recommendation C

Journal of NCI, Vol.93, No.8, April 18, 2001
89
Management of Rectal Cancer

• Surgical Aspects
• Distal and Proximal Bowel Margins
• Distal intramural spread beyond 1 cm was reported
  in only 4-10 of rectal cancers
• Distal spread beyond 1 cm is associated with
  advanced and aggressive disease
• Associated poor prognosis is not improved by a
  wider margin
• 2-cm margin of resection is adequate
• Level of evidence III-IV
• Grade of recommendation B

Journal of NCI, Vol.93, No.8, April 18, 2001
90
Board Question 4

• A 55-year old female with rectal cancer, 6 cm
  from the anal verge, less than a 30 of rectal
  circumference, non-fixed and uT2 depth on
  endorectal ultrasound. Biopsy showed a
  well-differentiated lesion with lymphatic
  invasion
• The patient should undergo an APR.
• TRUE OR FALSE?

91
Management of Rectal Cancer

• Surgical Aspects
• Ileo- or coloanal anastomosis with J-pouch
• Can be done after sphincter-preserving operation
  to improve continence
• Preservation of ileocolic artery is mandatory
• Proximal diversion is indicated, if
• anastomosis is less than 5 cm above the anal
  verge
• patient has received preoperative XRT
• patient is on steroids
• integrity of the anastomosis is in question
• any episode of hemodynamic instability occurred
  intraoperatively

M.D.Anderson Surgical Oncology Handbook, 2001
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Recurrent and Metastatic Disease

• 95 of recurrences occur within 5 years of
  surgery
• After surgery, 80 of failures have a component
  of metastatic disease
• Liver is the site of first recurrence in 35 of
  patients, lungs - in 20 of patients
• Local failure occurs as a first site in 15 of
  patients with Stage II or III disease
• The high risk of distant disease mandates
  systemic adjuvant therapy
• Tumors at high risk for local recurrence may
  benefit from radiotherapy

Cameron JL, Current Surgical Therapy, 7th Ed, 2001
93
Recurrent and Metastatic Disease

• Adjuvant Therapy
• Still evolving and controversial subject,
  especially for patients with Stage II lesions
  (may be indicated for high-risk patient with
  Stage II (B2) lesions)
• 5-FU is the most effective single agent for colon
  carcinoma
• Adjuvant therapy trials using 5-FU in combination
  with vinblastine and/or semustine produced
  conflicting results

M.D.Anderson Surgical Oncology Handbook, 2001
94
Adjuvant Therapy

• 5-FU/Levamisole
• PRS of 12 month course of 5-FU/Lev compared with
  surgery alone in patients with Stage II and III
  tumors showed 41 decrease in recurrence and 33
  decrease in mortality for Stage III disease
• 5-FU/Leucovorin
• A 6 months course of 5-FU/Leu showed results
  similar to 5-FU/Lev regimen. PRS of this
  combination have not yet been completed
• Prospective randomized study

M.D.Anderson Surgical Oncology Handbook, 2001
95
Adjuvant Therapy
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
96
Adjuvant Therapy

• Postoperative Radiation (Colon)
• The role is not yet defined
• Patients at high risk for local recurrence (T4No
  T3-4N1-3) may benefit from abdominal radiation
• Administration of XRT remains at the discretion
  of treating physician and patient
• Postoperative Radiation (Rectum)
• There was only one trial that showed decrease in
  local recurrence from 25 to 16 in the
  postoperative XRT arm
• Despite the performance of several large PRS,
  survival, local pelvic control, and extrapelvic
  recurrence rates have not been improved
  consistently by radiation

M.D.Anderson Surgical Oncology Handbook, 2001
97
Adjuvant Therapy

• IORT
• Increases local control rate (77)
• Allows shielding of sensitive
• structures
• Lowers the dose of radiation
• (20 vs. 45-50 Gy)
• Allows accurate treatment of
• focal areas at risk

M.D.Anderson Surgical Oncology Handbook, 2001
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Management of Colorectal Cancer

• Complications of Surgical and Adjuvant Therapy
• Nonspecific (bleeding, infection, adjacent organ
  injury)
• Anastomotic leak occurs in 5-10 of cases
• Anastomotic strictures
• Sexual and urinary dysfunction in 15-25
• Mortality rate from surgery varies from 2 to 6
• Radiation enteritis and dermatitis, 5-FU
  stomatitis
• Hematologic toxicity
• Wound and stoma complications

M.D.Anderson Surgical Oncology Handbook, 2001
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The best trio in colorectal cancer management
first three members of R-AMA
100
Board Question 5

• All of the following will be considered relative
  contraindications to hepatic metastasectomy in
  colon cancer EXCEPT
• A. More than 4 metastases in one lobe
• B. Concomitant lung mets
• C. 6 cm solitary metastasis in right lobe
• D. Disease-free interval of 3 months
• E. Primary tumor stage III

101
Colorectal Cancer Metastatic to the Liver

• Resection
• Curative hepatic resection requires a
  circumferential tumor-free margin of 1 cm
• Resection is contraindicated in the presence of
  celiac/portal nodal metastases, extrahepatic
  disease and/or more than 5 liver metastases (now
  relative)
• Disease-free interval less than 1 year is a poor
  prognostic indicator
• Resection should be considered only in patients
  who have responded to preoperative systemic
  therapy

Cameron JL, Current Surgical Therapy, 7th Ed, 2001
102
Colorectal Cancer Metastatic to the Liver

• Intraarterial Therapy (HAIC)
• 95 of blood supply of metastases comes from
  hepatic artery
• Floxuridine is the principal agent
• Internal or external pumps can be used
• Chemotherapy-related complications occur in up to
  25 of patients
• There is no improvement in survival after HAIC
• Hepatic Arterial Infusion Chemotherapy

Cameron JL, Current Surgical Therapy, 7th Ed, 2001
103
Metastatic Colorectal Cancer

• Prognostic Factors
• Vessel count in the specimen tissue and
  corresponding expression of VEGF (Vascular
  Endothelial Growth Factor) correlated with time
  of recurrence
• The mean tumor vessel count for patients who
  remained disease-free (20) was significantly
  (plt0.05) fewer than for those who suffered a
  recurrence (33)

Takahashi Y et al, Archives of Surgery, Vol 132,
No 5, May 1997
104
Metastatic Colorectal Cancer

• Patients with sequentially detected hepatic and
  pulmonary metastases are good candidates for
  aggressive metastasectomy
• Simultaneous detection of these metastases does
  not warrant resection

Nagakura S et al, J Am Coll Surg, August 2001
105
Survival After Resection of Colorectal Metastases

• Disease recurrence in 3 years after resection
  occurs in up to 85 of patients
• Operative mortality is 2-5
• 5-year survival is 23-27
• 10-year survival is 20
• Disease-free patient survival beyond 5 years
  represents patient cure in up to 80 of cases

Jamison RL et al, Archives of Surgery, May 1997
106
Nonresective Destructive Techniques

• Cryosurgical ablation (CSA) therapy
• Radiofrequency ablation (RFA) therapy
• Advantages and disadvantages of each technique
  have not yet been statistically determined
• Laparoscopy and intraoperative US are essential
  in staging patients with liver metastases
• These techniques allow treatment of multiple
  lesions and perivascular lesions
• RFA combined with CSA reduces the morbidity of
  multiple freezes
• Lesion size is limited to 8 cm and a 1-cm
  vascular margin is mandatory

Bilchik AJ et al, Archives of Surgery, June 2000
107
Cryosurgical Ablation (CSA)
Cameron JL, Current Surgical Therapy, 7th Ed, 2001
108
Cryosurgical Ablation (CSA)
Bilchik AJ et al, Archives of Surgery, June 2000
109
Survival

• Overall 5-year survival is about 50
• Nodal involvement is the primary determinant of
  5-year survival
• Stratified survival
• 90 for T1-T2 and 80 for T3 LN (-) local disease
• 27-69 for LN () disease (1 vs. 6 nodes)
• 5 for distant disease

M.D.Anderson Surgical Oncology Handbook, 2001
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Survival
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
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Factors Affecting Survival

• Perforation
• Obstruction
• Poor tumor differentiation
• Mucinous or signet ring histology
• Venous invasion
• Perineural invasion
• DNA non-diploid tumor
• Allelic loss

Wu JS, Fazio VW, Dis Colon Rectum, Nov 2000
112
Microsatellite Instability

• High frequency of microsatellite instability was
  found in 17 of specimens and it was associated
  with a significant survival advantage
  independently of all standard prognostic factors,
  including tumor stage

Gryfe R et al, N Engl J Med, 2000
113
Survival
Overall and tumor-free survival of the series (A)
and after palliative and curative resections (B)
60 vs. 38 (Dukes B) and 57 vs. 29 (Dukes C
lesions)
Allison D et al, J Surg Oncol, 1996
114
Follow-up
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
115
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