2. Introduction
• Colorectal cancer (CRC) is one of the commonest
cancers and the third leading cause of cancer death.
• More than 1·2 million patients are diagnosed with
colorectal cancer every year, and more than 600 000
die from the disease.
• Incidence is higher in men than women and strongly
increases with age; median age at diagnosis is about 70
years in developed countries.
3. Anatomy-Embryology
• From the anatomical and embryological
standpoints, the proximal and distal colons are
located within the peritoneal cavity, while the
rectum lies within the pelvis, the location of
which is relatively inaccessible.
• Proximal colon embryologically originates from
the midgut, while segments from the splenic
flexure to the upper anal canal containing the
distal colon and rectum arise from the hindgut.
4.
5. • Anatomically, the proximal colon is nourished
by branches of the superior mesenteric artery;
distal colon and rectum are supplied by
branches from the inferior mesenteric artery.
• The innervation to the proximal colon derives
from the vagus nerve, while fibers from S2~S4
innervate distal colon and rectum.
6. Genetic Pathway
• Proximal colon cancer is usually related to the
nucleotide instability pathway, as
microsatellite instability (MSI) as a
consequence of the alteration in mismatch
repair (MMR) genes the hereditary cancer
known as hereditary nonpolyposis colorectal
cancer (HNPCC) occurs.
7. Genetic Pathway
• Distal colon cancer is usually associated with
specific chromosomal instability (CIN) the
progress of which involves both oncogenes
and tumor-suppressor genes.
• K-ras is the most common oncogene following
this pattern. As far as tumor-suppressor genes
are concerned, genes of APC, TP53,
DCC/SMAD4 play important roles in this
sequential adenoma to carcinoma pattern.
8. Genetic Pathway
• FAP and HNPCC, the two major familial forms of CRC,
exhibit a distal location preference and a proximal
location preference, respectively.
• The former has an involvement in the CIN pathway,
while the latter, in contrast, in the MSI pathway.
• It has been reported that 60%~70% of HNPCC
carcinomas are located proximal to the splenic flexure,
compared with 30% among the sporadic cases.
9. Genetic Pathway
• The incidence of CIN is high in rectal cancer.
• Rectal cancer is less K-ras-dependent and the APC
gene-restricting pattern is more common.
• A high level of TP53 expression in rectal cancer
was also revealed.
• In these respects, therefore, rectal cancer might
be viewed as a different entity from colon cancer
to some extent.
10. Etiology and risk factors
1. Dietary factors
• Diet is definitely the most important exogenous
factor identified up to now in the etiology of
colorectal cancer.
• Recently, the World Cancer Research Fund and
the American Institute for Cancer Research in
their extensive report on diet, physical activity
and prevention of cancer have concluded that
colorectal cancer is mostly preventable by
appropriate diet and associated factors.
11. 2. Non-dietary factors
• Smoking.
• NSAIDs, aspirin significantly reduced the
recurrence of sporadic adenomatous polyps.
whereas there was evidence from short-term
trials to support regression, but not elimination
or prevention, of colorectal polyps in familial.
• Inflammatory bowel diseases.
• Previous colo-rectal malignancy.
12. Screening
• The identification of the adenomatous polyp
as a well-determined premalignant lesion,
together with the good survival associated
with early disease, makes colorectal cancer an
ideal candidate for screening.
• Two strategies have been available: faecal
occult blood test (FOBT) and endoscopy.
13. • Colonoscopy should be used for the follow-up
of test-positive cases.
• Screening should be offered to men and
women aged 50 years until ∼74 years.
• The screening interval should be 1–2 years
and the strategies should be implemented
within organized programs.
14. Diagnosis
• Symptoms are non-specific (change in bowel habits,
general abdominal discomfort, weight loss with no
apparent cause, constant tiredness).
• History: personal medical history, the family history of
colorectal cancer, polyps and other cancers should be
obtained.
• Physical examination: hepatomegaly, ascites and
lymphadenopathy. In women, rule out synchronous breast,
ovarian and endometrial cancer.
• Laboratory data: Blood count, CEA and liver chemistry.
15. • Endoscopy is the main tool for diagnosis and it can be performed to varying
lengths using either a sigmoidoscope or a colonoscope.
• Virtual colonoscopy or CT colonography (not yet standard, they could also help to
detect other synchronous colonic lesions or polyps if colonoscopy could not
explore the whole colon due to obstructive tumor).
• Endorectal U/S and Endorectal MRI (for rectal cancer)
• Barium enema.
• Double contrast barium enema.
• Positron emission tomography CT with the glucose analogue 18-fluoro-2-deoxy-D-
glucose (FDG-PET/CT) can be useful to detect recurrent colorectal cancer
differentiating scar and tumour tissue after surgery and/or radiotherapy. its
routine use is not recommended. PET should be considered also in metastatic
disease, chiefly in the liver, suitable for salvage surgery in order to exclude other
metastatic sites.
• Carcinoembryonic antigen (CEA) mainly for follow-up.
16. • Preoperative chest radiograph and liver
ultrasonography could be adequate even though
CT scan (chest and abdomen) is more
appropriate.
• Nuclear magnetic resonance tomography (MRI)
might be useful for locally advanced cases, but its
use is generally restricted to rectal cancer.
• Intraoperative ultrasound is a more accurate
assessment for liver metastases: occult liver
metastases can be found in 15% of patients.
17.
18. Staging
• The American Joint Committee on Cancer (AJCC)
and a National Cancer Institute–sponsored panel
recommended that at least 12 lymph nodes be
examined in patients with colon and rectal cancer
to confirm the absence of nodal involvement by
tumor.
• The number of lymph nodes examined is a
reflection of the aggressiveness of
lymphovascular mesenteric dissection at the time
of surgical resection.
20. Stage I
T1, N0, M0 (Dukes
A,MAC A)
T2, N0, M0 (Dukes
A, MAC B1)
T1 = Tumor invades
submucosa.
T2 = Tumor invades
muscularis propria.
21. Stage II
IIA=T3, N0, M0 (Dukes B,
MAC B2)
IIB= T4a, N0, M0 (Dukes B,
MAC B2)
IIC= T4b, N0, M0 (Dukes B,
MAC B3)
T3 = Tumor invades through
the muscularis propria into
pericolorectal tissues.
T4a = Tumor penetrates to
the surface of the visceral
peritoneum.
T4b = Tumor directly invades
or is adherent to other organs
or structures.
22. Stage IIIA
T1–T2, N1/N1c, M0 (Dukes
C, MAC C1)
T1, N2a, M0 (Dukes C,
MAC C1)
N1 = Metastases in 1–3
regional lymph nodes.
N1c = Tumor deposit(s) in
the subserosa, mesentery,
or nonperitonealized
pericolic or perirectal
tissues without regional
nodal metastasis.
N2a = Metastases in 4–6
regional lymph nodes.
23. Stage IIIB
T3–T4a, N1/N1c, M0 (Dukes C,
MAC C2).
T2–T3, N2a, M0 (Dukes C, MAC
C1/C2).
T1–T2, N2b, M0 (Dukes C, MAC
C1).
N2b = Metastases in ≥7 regional
lymph nodes.
24. Stage IIIC
T4a, N2a, M0 (Dukes
C, MAC C2).
T3–T4a, N2b, M0
(Dukes C, MAC C2).
T4b, N1–N2, M0
(Dukes C, MAC C3).
25. Stage IV
Any T, Any N, M1a
Any T, Any N, M1b
M1a = Metastasis
confined to 1 organ or
site (e.g., liver, lung,
ovary, nonregional
node).
M1b = Metastases in
>1 organ/site or the
peritoneum.
26. Strategy of treatment
Treatment of malignant polyps
• Complete endoscopic polypectomy should be
performed whenever the morphological
structure of the polyp permits.
• The presence of invasive carcinoma in a polyp
requires a thorough review with the
pathologist for histological features that are
associated with an adverse outcome.
27. • Unfavourable histological findings include:
1. Lymphatic or venous invasion.
2. Grade 3 differentiation.
3. Level 4 invasion (invades the submucosa of
the bowel wall below the polyp) or involved
margins of excision.
4. Invasive carcinoma in a sessile polyp usually
should be interpreted as having level 4
invasion. Consequently, standard surgical
resection is recommended.
28. Localized disease
• A wide resection of the involved segment of
bowel together with removal of its lymphatic
drainage.
• The extent of the colonic resection is determined
by the blood supply and distribution of regional
lymph nodes.
• The resection should include a segment of colon
of at least 5 cm on either side of the tumor.
29.
30. Laparoscopic Colectomy
• Laparoscopic colectomy can be safely performed for colon
cancer, particularly for left-sided cancer.
• For right-sided colonic cancers, the benefit is less obvious
since anastomosis must be hand sewn which requires a
laparotomy.
• The long-term oncological results of laparoscopic colectomy
are similar to those of the conventional approach.
• Advantages of laparoscopy over the conventional approach
are reduced pain, reduced length of hospital stay and
reduced duration of ileus.
31. Treatment by stage
• Stage 0 (Tis N0 M0, T1 N0 M0).
(i) local excision or simple polypectomy.
(ii) Segmental resection for larger lesions not amenable to local
excision.
• Stage I (T2 N0 M0) (old staging: Dukes’ A or MAC A and B1).
Wide surgical resection and anastomosis.
• Stage II (T3 N0 M0, T4 N0 M0) (old staging: Dukes’ B or MAC B2 and
B3).
(i) wide surgical resection and anastomosis;
(ii) Following surgery adjuvant therapy could be considered (if high
risk).
32. • stage III (any T, N1 M0, any T, N2 M0) (old staging: Dukes’ C or
MAC C1–C3).
(i) Wide surgical resection and anastomosis.
(ii) Following surgery the standard treatment is a doublet
schedule with oxaliplatin and 5FU/folinic acid (LV) (FOLFOX4 or
FLOX).
33. Adjuvant treatment
• Adjuvant treatment is recommended for stage III and
‘high-risk’ stage II patients.
• In general, stages I and IIA can be considered low-risk
while stages IIB and III are widely felt to deserve
adjuvant treatment.
• Patients with stage II are at high risk if they present at
least one of the following characteristics: lymph nodes
sampling <12; poorly differentiated tumor; vascular or
lymphatic or perineural invasion; tumour presentation
with obstruction or tumour perforation and pT4 stage.
34. • Local failure rates in the range of 4% to 8% following
rectal resection with appropriate mesorectal excision
(total mesorectal excision [TME] for low/middle rectal
tumors and mesorectal excision at least 5 cm below the
tumor for high rectal tumors) have been reported.
• This has led some investigators to question the routine
use of adjuvant radiation therapy in rectal cancer.
• Because of an increased tendency for first failure in
locoregional sites only, the impact of perioperative
radiation therapy is greater in rectal cancer than in
colon cancer.
35. Preoperative Chemoradiation Therapy
• Preoperative chemoradiation therapy has become the
standard of care for patients with clinically staged T3–T4 or
node-positive disease rectal cancer.
• German Rectal Cancer Study Group improved the toxicity
profile of chemoradiation and enhanced the possibility of
sphincter-sparing surgery.
• National Surgical Adjuvant Breast and Bowel Project
(NSABP) significant improvement in 5-year DFS. Similar
to the German Rectal Study,
• Both studies No significant difference seen in OS
between pre- and post-operative Chemoradiation.
36. When to consider Preoperative
Chemoradiation Therapy in rectal cancer?
1. T3 large (more than 5 mm
extrarectal spread) or less
than 1 mm from the
mesorectal fascia
2. Extensive extra mural
vascular invasion
3. N2: four or more regional
LN
4. Nodes out side
mesorectum (obturator-
internal iliac or presacral).
37.
38. Surgical management of rectal carcinoma
• Surgery is the most important part in the
treatment of rectal cancer.
• Local excision with the new surgical rectoscope,
transanal endoscopic microsurgery (TEM), it is
possible to perform a locally curative operation in
patients with a tumor in stage T1 and T2.
• In cases with T1-tumors data do support that a
local excision is as good as a bowel resection in
terms of long term survival.
39. Abdomino-perineal resection
(APR)
• First described by Miles in 1908.
• Refinements in technique continued through the first half
of the 20th century.
• Lloyd–Davies' synchronous approach to the abdomen
and perineum with the patient in the lithotomy position
eliminated the cumbersome and sometimes dangerous
need to reposition the patient while under anesthesia.
• Recent advances have included total mesorectal excision
in patients undergoing APR
45. Indications for APR in rectal cancer
Inter-sphincteric APR
• Patients unsuitable for bowel reconstruction
e.g. Preoperative history of incontinence.
• Adenomas, T1 cancer.
47. Ischio-anal APR
• Locally advanced cancer infiltrating
Levator muscles
Ischio-anal fat
Perianal skin
• Perforated cancer with
abscess or fistula
in ischio-anal fossa
48. Sphincter-Sparing Resection for Rectal Cancer
• Although there is still a place for APR in the
treatment of rectal cancer, the state of the art is
sphincter-preserving resection.
• Even for the lowest of rectal cancers, using a
combination of neoadjuvant chemo/radiation,
total mesorectal excision, and intersphincteric
proctectomy and colonic J-pouch to anal
anastomosis, sphincter preservation can be
achieved for most patients.
49. • Unless the rectal tumor involves the external
sphincter muscle, there is no oncologic need
to remove it, and following resection of the
tumor, gastrointestinal tract continuity can be
restored.
50. • Advances in stapling instruments have been very
important as aids in reconstruction
,revolutionized low pelvic surgery and improved
the surgeon's ability to properly resect and then
reconstruct at the lowest levels of the pelvis.
• Narrow, low-profile staplers allow the surgeon to
place a staple line across the rectum at the level
of the anorectal ring or below.
• This, combined with the circular stapler, allows
the surgeon to construct a quick and reliable
“double-stapled” anastomosis even at the level of
the anal canal.
52. Options for low rectal cancer
• Tumor 1-2 cm from the
upper extent of the
sphincter
• APR vs ultra-low LAR
• Abdominal approach
(technically challenging in
obese or large prostate) vs
transanal approach ( easier)
1- Ultra-low LAR
53. 2- Total proctectomy & colo-anal anastomoses
Patient Selection Criteria:
• Patients with cancers 3 to 7 cm from the anal verge (by
rigid scope).
• Exophytic or sessile lesions invading muscularis propria but
thought not to be transmural (T2).
• The cancer should be a minimum of ( 2 cm ) above the
anorectal ring to be considered for a proctectomy and colo-
anal reconstruction.
54. Exclusion of:
• Patients with anaplastic or poorly differentiated histology.
• Patients with baseline poor anal function.
• Patients with severe diverticulosis.
55. All patients must accept:
1. A temporary stoma.
2. Abdomino-perineal resection may be required if colo-anal
reconstruction is not feasible at the time of laparotomy for
oncologic ( T3,4 or low tumor) or technical reasons (obesity
or narrow pelvis or large prostate).
3. Considerable urgency and frequency of bowel activity for
the first 3 to 6 months after closure of the temporary
stoma.
4. Small risk of fecal spillage.
56. 3- Intersphincteric resection
Considered in:
• Selected patients with
ultra-low rectal cancer
2.5-5.5 cm from the anal
verge.
Contraindicated in:
• External sphincter or
levator ani invasion.
• Poorly differentiated or
mucinous tumor.
57. Total Mesorectal Excision
“What is TME?”
• The best description of the TME is still Heald's
Presidential address to the Royal Society of
Medicine, Surgery Section, in 1987: The “Holy
Plane” paper.
• He describes the rectum and the mesorectum
as one distinct lymphovascular entity that
should be removed as one intact unit.
58. “How do you do a TME?” three basic principles:
First:
The rectum and its mesentery, encased by the
fascia propria of the mesorectum are separate
from those structures outside of this fascial
envelope.
The plane of dissection is just outside the fascia
propria (the visceral endopelvic fascia) and just
inside the parietal endopelvic fascia. This is the
“holy plane.”
59. Second:
The dissection must be performed sharply (no
ripping or tearing or blunt dissection) with
either scissors, or with the electrocautery, under
direct vision, with good illumination.
Third:
Gentle opening of the plane by continuous
traction and counter traction, but not so much
that the tissue tears or rips.
60. “Why TME?”
(1) A dramatically reduced lateral margin
positivity, leading to astonishingly low local failure
rates.
(2) The need for performing a very low number of
abdomino-perineal resections.
(3) A significant reduction in the incidence of
bladder and sexual dysfunction after surgery—
dissection in the proper planes helped avoid injury
to the sympathetic and parasympathetic nerves in
the pelvis.
61. • Careful lifting of the
vascular pedicle of the
rectum in the avascular
plane
• Entering the avascular
plane between the
fascia propria of the
rectum and the
presacral facia
incision
mesorectal
fascia
hypogastric nerve
CIA
62. • During TME the
Hypogastric Nerve
remains attached to
pelvic wall
• Sometimes a step in
level of dissection is
necessary
63. Colorectal Liver Metastases
Over half of patients with colorectal cancer will
develop metastatic disease, with a quarter
having distant metastatic lesions at diagnosis.
64. What are the options for patients with
colorectal liver metastasis?
• Do nothing
median survival of 6 to 9 months.
• Chemotherapy
14.5-month median survival
• RFA
40% 3-year survival rate
• Resection
5-year survival rate of 45% to 60%
65. Conclusion:
RFA can not be recommended as an alternative to HR. However RFA
may contribute to local control of small CLM in patients who are not
candid for liver resection.
66.
67. Hepatic Resection for colo-rectal cancer
Indications
• The patient has no extrahepatic disease.
• The intrahepatic disease is safely resectable.
• The patient must also be in a good medical
condition.
68. Contraindications
• Non-treatable primary tumor.
• Widespread pulmonary disease.
• Peritoneal disease.
• Extensive nodal disease, such as retroperitoneal
or mediastinal nodes.
• Bone or CNS metastases.
69. Clinical Risk Score
• Nodal status of the primary disease
• Free interval from the discovery of the primary to the
discovery of the liver metastases of <12 months
• Number of tumors >1
• Preoperative CEA level of >200 ng/mL
• Size of the largest tumors >5 cm
Each positive criterion is assigned one point.
5-year survival is 60% with score of 0 points, and falls to
14% in patients with 5 points.
70. What is a Resectable Tumor?
• In 1986, Ekberg et al defined resectability as less than
four metastases (even if bilobar), absence of
extrahepatic disease, and a resection margin of at least
1 cm.
• Today, resections are based on the remnant liver. A
sufficient future remnant liver volume (>20% of the
total estimated liver volume) is a prerequisite.
• If R0 with negative surgical margins (≥1mm) is possible
and sufficient liver parenchyma remains to maintain
liver function, resection should be considered .
71. How to increase RESECTABILITY?
• Portal Vein Occlusion.
• Two-Stage Hepatectomy.
• Tailored hepatectomy.
• Down-staging chemotherapy.
• Local Ablation Techniques.
73. Synchronous tumors: What are the possible
options?
• Colon first: Staged approach
• Colon and liver: Simultaneous approach
• “Reverse Strategy”
74. Factors determine the decision:
• The presence of symptoms.
• Location of primary tumor and liver metastases.
• Extent of tumor (both primary and metastatic).
• Patient performance status, and underlying
comorbidities.
75. Rational for staged approach
• “Test of time”: Scheele et al suggested a “test of
time” approach of waiting up to 6 months to
observe the tumor biology and evolution of
metastases as a means of natural selection for
operable disease.
• “Tumor doubling time”: Mean tumor doubling
time has been assessed using serial computed
tomography to be 155 ± 34 days for overt
metastases and 86 ± 12days for occult lesions not
evident at laparotomy.
World J Surg 1995;19:59-71; Br J Surg 1988;75:641-4
76. Criteria for synchronous approach
• Age <70 years
• Good surgical fitness.
• An adequate tumor-free margin.
• Lesions that are not advanced (T4),
• Less than 4 colorectal lymph node metastases
• Histology that is not poorly differentiated or
mucinous adenocarcinoma.
• 3 or fewer liver metastases.
• A minor liver resection (less than 3 segments) is
planned.
77. Advantages of simultaneous resection
• The performance of only a single surgical procedure.
• Reduced length of hospital stay.
• The removal of all neoplastic foci and interruption of
the “metastatic cascade”.
• The avoidance of immuno-depression after isolated
primary tumor resection
• No delay in initiating systemic treatment.
78. Disadvantages of simultaneous resections
• The combination of a “clean” and a
“contaminated” surgical procedure and thus
the higher risk of septic complications, which
could cause or worsen a liver dysfunction
• The increased risk of anastomotic leak due to
splanchnic congestion if prolonged pedicle
clamping is needed.
• The inadequate surgical exposure through a
single incision.
80. “Reverse Strategy”
• Brouquet et al.,2010 and the group from M.D.
Anderson Cancer Center.
• Preoperative chemotherapy is followed by
resection of the hepatic metastases and then
by resection of the colorectal primary at a
second operation.
J Am Coll Surg 2010;210:934-41.
81. The rationale for Reverse Strategy
• Complications related to the primary colorectal
tumor are rare and treatment of metastatic
disease is not delayed by local therapy for the
primary tumor or complications associated with
treatment of the primary tumor.
• It can be considered as an alternative option in
patients with advanced hepatic metastases and
an asymptomatic primary.
82. Peritoneal carcinomatosis and role of HIPEC
• At the time of diagnosis of colon malignancies, PC
affects approximately 10% of the patients
• Recurrence with carcinomatosis occurs in 25% of
patients and seems to be the only site of disease
in 25-35% of these.
• Sugarbaker has suggested that peritoneal
carcinomatosis is a locoregional cancer spread as
a result of a molecular crosstalk between cancer
cells and host elements.
83. • Studies reported 5-year survival rates from 20%
to 30%.
• Improved survival of patients affected by
peritoneal carcinomatosis from colorectal
malignancies (22.3 months versus 12.6 months).
• In all the series, an optimal cytoreduction is the
most important prognostic factor for these
patients.
84. • Recently several studies are addressing the
use of HIPEC as adjuvant therapy in Colonic
cancer with trans-serosal invasion (T4a) which
have an increased risk for the development of
peritoneal carcinomatosis (PC).
86. Rationale for CRS + HIPEC
• High local concentration
• Reduced systemic toxicity
• Portal circulation (detoxifying)
• Hyperthermia 42-43 °C :
Direct cytotoxic effect
increase drug penetration
Increase chemosensitivity
Thermal enhancement of cytotoxicity
87. Steps of Peritonectomy
remove all visible tumor implants.
(One or more of following steps)
• Right upper quadrant peritonectomy and glissonian capsule resection.
• Left upper quadrant peritonectomy, left parietal peritonectomy ±
splenectomy.
• Greater omentectomy, right parietal peritonectomy, ± right colon
resection.
• Lesser omentectomy, and dissection of the duodenal-hepatic ligament ±
antrectomy ± cholecystectomy.
• Pelvic peritonectomy ± sigmoid colon resection ± hysterectomy and
bilateral salpingo-oophorectomy.
• Other intestinal resection and/or abdominal mass resection.
115. Drugs used during HIPEC
– Large molecular weight.
– Water-soluble.
– Rapid clearance from systemic circulation.
– Enhanced by hyperthermia.
– Non cell-cycle specific.
116. • Commonly used agents in GI or gynaecological
oncology such as platinum derivatives, 5-FU,
taxanes, irinotecan, adriamycin or mitomycin
C.
• Generally, the highest thermal enhancement
ratios have been observed for alkylating
agents such as melphalan, cyclophosphamide
and ifosfamide.