Colorectal cancer: a review

Abstract

Colorectal cancer (CCR) is the third most common cancer worldwide in men and women, the second largest cause of death related to cancer, and the main cause of death in gastrointestinal cancer. The risk of developing this cancer is related to bad alimentary habits, smoking, intestinal inflammatory disease, polyps, genetic factors, and aging. Of the patients that are diagnosed with colorectal cancer 90% are older than 50, with a median age of 64 years; however, the disease is more aggressive in patients that are diagnosed at younger ages. According to the American Cancer Association, it was accounted for more than 49,700 deaths in 2015. The goal is to reduce the mortality rate with early diagnosis and treatment. Currently, the survival rate is used to predict a patient’s prognosis. The patient is considered to have a positive familial history if a first-degree relative has been diagnosed with colorectal cancer or colonic polyps before the age of 60, or also if two or more first-degree relatives have been diagnosed with cancer or polyps at any age. There are several methods for detecting colorectal cancer, such as the guaiac test, immunochemical test of stool, DNA stool test, sigmoidoscopy, colonoscopy, and barium enema. The stage in which the cancer is detected determines the prognosis, survival, and treatment of the patient. Provide a review about generalities, genetic basis, risk factors, protective factors, clinical course, diagnostic methods, therapy and survival in colorectal cancer. Conducted research from different databases such as PubMed, Medline, MedScape, on the definition, genetic factors, classification, risk factors, protective factors, diagnostic methods, epidemiology, survival and treatment of colorectal cancer. Articles from 2000 to 2017 were included using the following keywords.

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International Journal of Research in Medical Sciences | November 2017 | Vol 5 | Issue 11 Page 4667
International Journal of Research in Medical Sciences
Granados-Romero JJ et al. Int J Res Med Sci. 2017 Nov;5(11):4667-4676
www.msjonline.org
pISSN 2320-6071 | eISSN 2320-6012
Review Article
Colorectal cancer: a review
Juan José Granados-Romero1, Alan Isaac Valderrama-Treviño2*,
Ericka Hazzel Contreras-Flores3, Baltazar Barrera-Mera4, Miguel Herrera Enríquez2,
Karen Uriarte-Ruíz3, Jesús Carlos Ceballos-Villalva3, Aranza Guadalupe Estrada-Mata3,
Cristopher Alvarado Rodríguez3, Gerardo Arauz-Peña3
INTRODUCTION
Colorectal cancer is the third most common type of
cancer in oncologic pathology.1 Currently, it is the most
common malignant cancer in the gastrointestinal tract,
representing 13% of all malignant tumors, and it is
considered the second most common cause of death
related to cancer affecting men as women in the same
manner worldwide, developed and undeveloped
1Departamento de Cirugía General, Hospital General de México. Secretaría de Salud (SSa), Ciudad de México, México
2Laboratorio de inmunoterapia experimental e ingeniería de tejidos, Facultad de Medicina, Universidad Nacional
Autónoma de México, Ciudad de México. México
3Programa de Apoyo y Fomento de la Investigación Estudiantil (AFINES), Facultad de Medicina, Universidad
Nacional Autónoma de México, Ciudad de México. México
4Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México
México
Received: 17 August 2017
Accepted: 20 September 2017
*Correspondence:
Dr. Alan Isaac Valderrama-Treviño,
E-mail: alan_valderrama@hotmail.com
Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Colorectal cancer (CCR) is the third most common cancer worldwide in men and women, the second largest cause of
death related to cancer, and the main cause of death in gastrointestinal cancer. The risk of developing this cancer is
related to bad alimentary habits, smoking, intestinal inflammatory disease, polyps, genetic factors, and aging. Of the
patients that are diagnosed with colorectal cancer 90% are older than 50, with a median age of 64 years; however, the
disease is more aggressive in patients that are diagnosed at younger ages. According to the American Cancer
Association, it was accounted for more than 49,700 deaths in 2015. The goal is to reduce the mortality rate with early
diagnosis and treatment. Currently, the survival rate is used to predict a patient’s prognosis. The patient is considered
to have a positive familial history if a first-degree relative has been diagnosed with colorectal cancer or colonic polyps
before the age of 60, or also if two or more first-degree relatives have been diagnosed with cancer or polyps at any
age. There are several methods for detecting colorectal cancer, such as the guaiac test, immunochemical test of stool,
DNA stool test, sigmoidoscopy, colonoscopy, and barium enema. The stage in which the cancer is detected
determines the prognosis, survival, and treatment of the patient. Provide a review about generalities, genetic basis,
risk factors, protective factors, clinical course, diagnostic methods, therapy and survival in colorectal cancer.
Conducted research from different databases such as PubMed, Medline, MedScape, on the definition, genetic factors,
classification, risk factors, protective factors, diagnostic methods, epidemiology, survival and treatment of colorectal
cancer. Articles from 2000 to 2017 were included using the following keywords.
Keywords: Colorectal cancer, Mortality, Epidemiology, Risk factors, Survival, Tumoral markers
DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20174914

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International Journal of Research in Medical Sciences | November 2017 | Vol 5 | Issue 11 Page 4668
countries, and it is expected to overcome the mortality
rate of heart diseases in the coming years.2-4 It is a
prevalent disease in those aged 65-74, with a higher
prevalence in women5. However, this pathology is
diagnosed more frequently in younger patients, due to
risk factors such as obesity, sedentarism, bad nutritional
habits (high in fats and proteins), smoking, and the
progressive aging of the population. In patients with
colorectal cancer, the clinical presentation depends on the
location, size, as well as the presence or absence of
metastases. The clinical presentation includes symptoms
such as abdominal pain, alteration of chronic bowel
habits, changes in bowel movements, involuntary weight
loss, nausea, vomit, malaise, anorexia, and abdominal
distensión.3 Distal cancers cause evident rectal bleeding
in comparison to proximal cancer that can give mixed
blood with stool, so it tends to occulted and in
consequence, anemia may be presented as secondary
sign.3 Among the unusual clinical findings we can find a
peripheral lymphadenopathy especially the Virchow
lymph node in the left supraclavicular space, and
hepatomegaly from hepatic metastases, as well as loss of
the muscular mass by cachexy.6 The carcinogenic models
of the colorectal cancer models on colorectal cancer
carcinogenesis include the suppressor or classic pathway,
and it also include a mutator or alternative pathway. The
first one is known as the pathway of chromosomal
instability following a pattern of progression of adenoma
present in 80% of sporadic colorectal cancer, and the
second is known as the pathway of microsatellite
instability where there are a wide range of mutations of
genes that are present in 20% of sporadic cancer and 80%
of hereditary colorectal cancer mainly by the APC 60%,
p53 70%, DCC 70%, KRAS 40% y BAX 50%.7
Colorectal cancer usually starts as polyp in the intestinal
mucosa, however it can also exist as an initial benign
lesion called adenoma that has the ability to transform
into a malignant lesion depending on its histological
presentation (Table 1), and its size (Table 2), of which
60% of cases are simple adenoma, and 40% are multiple
adenomas. 24% of the patients with untreated polyps will
develop cancer.8 Presently, it is classified under the
Astler-coller-Dukes system or TNM system established
by The American Joint Committee on Cancer.9 Which
represents the stage of the colorectal cancer by categories.
The letter T represents the spread of propagation
extension through the layers of the colonic or rectal wall,
the letter N indicates if there is presence in the lymph
node, and M indicates metastasis in distant organs.
EPIDEMIOLOGY
According to Surveillance, Epidemiology and Final
Results program, in the United States there were an
estimated of 132,700 new cases of colorectal cancer in
2015. This represents 8% of all the new cases of cancer,
and there were an estimated of 49,700 deaths from this
disease, with a mortality rate of 8.1/100.000 habitants.
Which mainly affects developed regions (25.1/100.000
habitants), while the rate is significantly inferior in
undeveloped regions (3.9/100.000 habitants).10 However,
a gradual decline in the incidence has been observed,
which reflects the increase of early detection by
colonoscopy with removal of precancerous lesions in
adults from 50 to 75 years of age.11,12 The use of
colonoscopy increased from 19.1% to 54% in 2013. In
the last report of GLOBOCAN 2012, colorectal cancer
was reported as the third most common in men with
1361,000 cases representing 10% of all cancers, and it is
the second most common type of cancer in women with
614, 000 cases representing 9.2% of all cancers. The
occurrence for both genders oscillate in 1361,000 cases
with a mortality of 694,000 (8.5% of all cancers) which is
inferior with more deaths (52%) in the less developed
regions of the world.13 The INEGI reported 74,685 deaths
from cancer in 2010 (13% of the deaths in Mexico) from
which 5.4% are cause by colorectal cancer. Colorectal
cancer may be caused by sporadic or non-hereditary
related to mutation errors in DNA, transcriptional
silencing of suppressor tumor genes, genes involved in
the control of the cellular cycle, repair, and apoptosis or
genetic in origin related to mutations in suppressor gene
tumors such as APC, DCC, BRAF,PIK3CA, AKT, and
TP53 or the presence oncogenes as K-RAS and
CTNNB1.14 (Table 3) As well as chromosomal
anomalies, gene mutations, epigenetic changes involving
proliferation, differentiation, apoptosis and angiogenesis
are also causes.15 However, it is currently considered
biomarker that predicts the response to therapy through
EGFR17. Sporadic colorectal cancer, by activating the
oncogene K-RAS located on chromosome 12 shows
mutation mainly in codon 12 and 13 (95% of the
mutations) and just 5% of the mutations are in codons
61,146, 154, these mutations are mainly observed in
patients with metastasis. Associations with 12 codon
present mucinous type cancer mutations, while mutations
in codon 13 are related to non-mucinous cancer, however
this type is more aggressive with higher metastatic rate.16-
18 A KRAS mutation can be considered as bad prognosis
mainly in the codon 13, and is also considered to be a
biomarker that predicts the response to therapy through
EGFR.17 The genetic mechanism begins with an inactive
mutation of the tumor suppressor gene APC, which is
responsible for familial adenomatous polyposis, and
approximately 85% of colorectal cancer without
hereditary relationship. Some of the adenocarcinomas
develop after a mutational activation of the B-catenin
(CTNNB1) regulated by APC, or by a second mechanism
initiated by the inactivation of a family of tumor
suppressor genes involved in the repair of the DNA.
These genes are known as MMR genes or Mismatch
including the human homolog mutS (MSH2), the human
homolog 1 Mutl, (MLH1), and the posmeiotic
segregation gene increased type 2 (PMS2) including both
in hereditary affections as well as sporadic colorectal
cancer. Mutations always occur in specific ways, first
those that affect the APC gene followed by those that
affect the RAS gene.19 Changes in TP5, the suppressor
tumor gene is affected in 50% of the cases and it tend to
appear more towards at the end of the sequence.20 In the

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somatic alterations, it can affect the glicoproteic signal
pathway WNT/B-catenin that is associated with cellular
proliferation, tissue homeostasis, and its mutation is
associated to human diseases such as congenital
malformations, cancer, osteoporosis, and is found in 95%
of patients with colorectal cancer.21,22 The rs59336 allele
located in the intron of the TBX3 gen of the WTN/B
catenin pathway has been associated with an increase risk
in developing colorectal cancer.23
However, alterations in genes such as SMAD7 have been
associated with affecting the progression of colorectal
cancer, and there are three known variants of the SMAD7
gene (rs44939827, rs12953717, and rs4464248) in the
8q21 chromosome that increase the risk of colorectal
cancer.24,25 However, these are not the only genetic errors
that can influence the risk of colorectal cancer.26
Currently, metastases protective genes have been
identified, such as KISS1, which connects to the KISS
receptor. This is essential for the suppression of
metastasis, and the survival rate significantly improves to
high levels of KISS1 and KISS1R”.27 Genes that protect
against metastasis have been identified, such as KISS1,
which connects to the KISS receptor. This is essential for
the suppression of metastasis, and the survival rate
significantly improves with high levels of KISS1.
Table 1: Histological variety and malignancy
association.
Table 2: Porcentual relation between size and
malignancy.
Size (cm)
Percentage of cases
<1 cm
1.3%
1-2 cm
19%
>2cm
46%
Table 3: Gen function and mutation.
Gen
Function
Mutation
APC
Codifies a tumor suppressor protein that acts as an antagonist
of Wnt signal pathway. Migration and cellular adhesion
Colorectal Cancer
DCC
Codifies netrin-1 protein, Tumor suppressor
Colorectal cancer, Esophageal cancer
TP53
Tumor suppressor
Colorectal cancer
BRAF
Map/Kinase pathway, related to cellular division and
differentiation and secretion.
Colorectal cancer, Non Hodgking
lymphoma, Malignant melanoma,
Thyroid cancer, Lung carcinoma of
non small cells
PIK3CA
Codifies p110 alpha working as a kinase in cellular pathway,
cellular proliferation division, migration and cellular survival.
Colorectal cancer, Ovary cancer,
Breast cancer, Stomach cancer, Lung
cancer, Brain cancer
P53
Tumor suppressor, stopping the cellular cycle, apoptosis and
DNA repair.
Hereditary cancer
KISS1
Metastasis suppressor by joining KISS1R
Colorectal cancer
AKT1
Signal pathway, oncogenesis, cellular proliferation, cellular
survival apoptosis and angiogenesesis. Codifies serine and
treonin kinase PKB
Colorectal cancer
SMAD4
Pathway of growing beta transforming factor (TGF-β),
controls the adhesion of DNA for particular genes and
suppressor genes.
Polyposis syndroms, Colon cancer,
Pancreas cancer
K-RAS
Oncogen Codifies KRAS, a GTPASE involve in the cellular
division differentiation and apoptosis.
Colorectal cancer
CTNNB1
Cellular adhesion necessary for creation and maintenance of
epithelial layers for regulation of cellular growth.
Colorectal cancer, Meduloblastoma
Ovary cancer
RISK FACTORS
Among the risk factors related to developing colorectal
cancer, which is estimated that 35% can be explained by
hereditary factors. Nevertheless, family history has great
relevance for risk of colorectal cancer, as well as colon or
rectal cancer, hereditary diseases such as familial
adenomatous polyposis, hereditary colon cancer without
polyposis which is known as Lynch syndrome.28 It is
associated with gene mutations implicated in the pathway
Histological
Type
Percentage of
Colorectal
Cancer cases
Percentage of
malignancy
Tubular
60-80%
< 5%
Tubulovillous
10-25%
20-25%
Villous
5-10%
35-45%

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of repair of bad DNA coupling/ mating (MMR, mismatch
repair) specifically MLH1, MSHS2, MSH6, and PMS2.
The mutations in MLH1 and MLH2 are majority about
90% of the mutations found in families of hereditary
colon cancer with or without polyposis. However APC
germinal online mutations, repair MTHYU, SMAD4,
BMPR (Alq3), STK11, represent less than 5% of all
cases of colorectal cancer.29 It is estimated that these
genetic syndromes represent about 10% of all cases of
colorectal cancer; however about 25% of cases the
familial history contributes to an increased risk of
developing colorectal cancer in the absence of these
genetic syndromes 30. Factors such as history of ulcerous
colitis, Chron’s disease, personal history of polyposis,
colon, rectal, ovarian, endometrium, breast cancer, and
diabetes mellitus are related to a 30-50% greater risk of
developing colorectal cancer, and about 75% of the
malignant tumors of the colon and rectum are presented
without related any of these risk factors; The relationship
between hyperplastic polyposis and cancer is
controversial. Adenomatous polyps are common in adults
which are over 50 years old, but most polyps will not turn
malignant. Its histology and size determine its clinical
relevance. Risk factors for malignancy in hyperplastic
polyps include polyp size equal to or above 10mm, or
dysplasia, right colon localization. A focus of an
adenoma within the polyp (mixed polyp hyperplastic-
adenomatous); in which the presence of more than 20
hyperplastic polyps in the colon, and familial history of
colon cancer. In a period of a clear evolution between 10-
15 years with define stages, iniciating as a minor
dysplasia that progresses depending on the genetic
modifications to moderate or severe. The dissemination
pathways is determined by either hematic or lymphatic,
which defines the speed of growth and the time of
evolution of the disease, however there have been
reported cases of implantation by surgical manipulation
after a laparoscopic colectomy.3 The adenomatous polyps
are common in adults over 50, but most of the polyps will
not turn malignant. The histology and size will determine
its clinical relevance. The risk factors for a hyperplastic
polyp to turn malignant includes size equal to or above to
10mm, dysplasia, location in the right colon, a focus of
adenoma inside another polyp (mixed hyperplastic-
adenomatous polyp), presence of more than 20
hyperplastic polyps in the colon, and familial history. It
develops with a clear evolution between 10-15 years
starting as mild dysplasia that progresses depending on
the genetic modifications to moderate or severe. The
dissemination pathways are either hematic or lymphatic,
and defines the growing rate and the time of progression
of the disease; however cases have been reported of
surgical implantation following a laparoscopic
colectomy. The adenomatous polyps are common in
adults over 50, but most of the polyps will not turn
malignant. The histology and size will determine its
clinical relevance. The risk factors for a hyperplastic
polyp to turn malignant includes size equal to or above to
10mm, dysplasia, location in the right colon, a focus of
adenoma inside another polyp (mixed hyperplastic-
adenomatous polyp), presence of more than 20
hyperplastic polyps in the colon, and familial history. It
develops with a clear evolution between 10-15 years
starting as mild dysplasia that progresses depending on
the genetic modifications to moderate or severe. The
dissemination pathways are either hematic or lymphatic,
and defines the growing rate and the time of progression
of the disease; however cases have been reported of
surgical implantation following a laparoscopic
colectomy.3
PROTECTING FACTORS
The ingestion of non-steroidal anti-inflammatory drugs
reduce the risk of colorectal cancer, however the
molecular basis have demonstrated, which regulates the
overexpression of the receptor of the epidermal growth
Factor (EGFR), which is overexpressed in the 80% of the
cases colorectal cancer, as an early event in colorectal
tumorigenesis. The overexpression of the cyclooxygenase
2 (COX-2) triggers the activation of the transcription
factor of the c-Jun dependent protein activator 1 (AP-1)
that binds to the promoter of EGFR; therefore selective
COX-2 inhibitors can be used as quimiopreventive
activity against colorectal cancer.31 However, it has been
demonstrated that dietary high fiber ingestion is a factor
of prevention against colorectal cancer and other tumors,
as well as high consumption of fruits and vegetables,
however, no association has been found for colorectal
cancer, or association for separate ingestion of fruits and
vegetables.32 The variety in consumption was not
associated with a decrease in the risk of colon cancer, but
if there is an increased with a high in the variety in fruit
consumption reflected in a 41% of higher risk for those
who ingest more than 8 different fruits every two
weeks.33
DIAGNOSTIC METHODS
Current screening methods targeting moderate risk
populations (Table 4) aged 50 or more include the fecal
occult blood test (TSOH) with the high sensibility based
on the Guaiac or immunologic test (TSOHi) with an
annual periodicity; sigmoidoscopy every 5 years with
TSOH every 3 years, or colonoscopy every 10 years.34
Diagnostic methods are largely related to the overlife of a
patient with colorectal cancer, however some methods
such as fecal occult blood can present in false positive
results that coincide in high consumption of red meat,
vegetables, and fruits that may contain peroxidase versus
persons with no bleeding condition that ingest vitamin C
may result in a false positive test.3 Despite this,
technology has enable the development of techniques
such as PCR, which allows to identify biological genetic
markers by doing its specific test, and its purpose is to
identify mutations in specific gene related to colorectal
cancer. Currently for the identification of colon and
colorectal cancer concentrations of the homebox
duodenal pancreatic transcription factor (PDX-1) in the
development and proliferation of pancreas whose levels

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International Journal of Research in Medical Sciences | November 2017 | Vol 5 | Issue 11 Page 4671
increase mainly in malignant cancer that of the pancreas,
breast, colon, prostate, renal and metastasis versus low
levels in primary tumors or null levels in healthy colon
tissue, therefore it is considered biomarker in colorectal
cancer.35-37
The hypoalbuminemia would constitute a simple and
significant marker of bad prognosis, other tests such as
sigmoidoscopy which present improvements day by day
where 65-75% of adenomatous polyps, and 40%-65% of
the colorectal cancers are within reach of sigmoidoscopy;
however about 50% of the advance adenomas (>1cm) and
proximal colon cancer were undetectable in this method.3
Although it is the only technique that is of scrutiny,
diagnosis and therapeutic management of the colon is a
procedure that implies a higher cost, risk and discomfort
for the patient compared to other tests.38 Notwithstanding,
the overexpression of proteins and genetic factors, they
can currently be considered as markers of patient bad
prognosis factors such as high levels of mRNA and
paxiline in colorectal cancer related to the histological
tumor grade, tumor sizes, clinical TNM stage and remote
metastases where it is shown that the prognosis of the
patients with high level of paxiline was unfavorable
versus low expressions of paxilline as well as shows a
Pre-treatment hypoalbulinemia (<3,5 g/dl ) that is related
independently with a lower survival after resection. Both
globally and in colorectal cancer stage II plus
hypoalbunemia, so to confirm these results the
hypoalbuminemia would constitute a simple and
significant marker of bad prognosis, available from the
time of diagnosis.39,40
SURVIVAL TO 5 YEARS
Survival or survivorship is a value that predicts a
patient’s prognosis; to 5 years refers to the percentage in
which a patient lives at least five years after the diagnosis
of cancer; taking in to account the type and stage of the
cancer, as well as particular factors in the treatment
administrated (the genomic modifications of the cancer
cells as well as the individual and their biological
variability). The 5-year and 10-year relative survival rates
for persons with colorectal cancer are 65% and 58%,
respectively.41 It is to say those patients who survive
more than 5 years, after the diagnosis of colorectal cancer
without taking into account age, histological type, or
stage of the disease. In a study conducted by Wulaningsih
et al. in patients diagnosed with cancer, it shows an
inversely proportional relation to the levels of LDH
(enzyme lactate dehydrogenase) and the survival is to say
they were compared with the pre-diagnostic LDH levels,
increasing the risk of death from prostate, lung,
gastroesophagal, gynecologic and colorectal cancers,
while high intervals near the diagnostic period are related
with the overall and specific mortality of the cancer.42
The survival of patients diagnosed with colon, rectal and
colorectal cancer is variable according to the type and
stage. Patients which got stage IIIA or IIIB cancer have a
better survival than those patients whose got stage II B
cancer, patients so much so that survival in rectal cancer
was better for some patients with stage III cancers than
for some in stage II cancers. However in the study of
Dobras et al; It shows a worse survival for patients in
stage III with mutation in KRAS that in those patients
with KRAS type wild IE without mutation in the
oncogene, another of the genes related to survival is the
expression of the gene KISS1 and KISSR which shows a
direct proportional correlation with the survival of
colorectal to greater expression of the same survivability
increases 44.3 and 39.3 to 45.8 and 42.2% respectively.
with the Gene expression the survival rate increases from
44.3 and 39.3% to a 73.7 and 67.9% respectively.
Patients with low levels of KISS 1 showed in patients a
remote metastasis; statistically significant., therefore
KISS 1 could be a promising prognostic and therapeutic
marker in colorectal cancer.43 As a leading cause of death
in these patients approximately 50-60% of the patients
diagnosed will develop metastasis.44 In general the five-
years lifespan varies from 65% in the United States, 55%
in other developed countries, 14% in Africa, and 39% in
developing countries.31 Survival ranges are significantly
different by stage, 90% for localized disease, 68% for
regional disease with lymphatic affection, and 10% for
disseminated disease related to the early detection unlike
other types of cancer in which the size of the tumor does
not affect the prognosis of the disease; however the
increase in the mortality rate is justified in the increase of
the life expectancy in the population, in the relation of the
increase of genetic alterations due to greater
susceptibility to carcinogenic, immunosuppression and
comorbidity of the patients which explains the greatest
risk of developing colorectal cancer.33 Mortality rates are
variable in terms of gender, with a very slight prevalence
of female sex, in colon cancer (51 vs 49%), and male sex
in colorectal cancer (53 vs 46), mainly by liver
metastases as a leading cause of death in these patients.2
Approximately 50-60% of the patients diagnosed will
develop metastasis.44 Survivors may also suffer from
bladder dys-function, sexual dysfunction, and negative
body image.45,46
DIAGNOSIS BY LOCATION
Most tumors are localized in the rectum (37%), and
sigmoidal (31%), being less frequent in ascending colon
(9%), cecum (8%), descending colon (5%), transverse
colon (4%), hepatic angle (4%), and splenic angle (2%).43
About 65% of colon cancers are distal to the splenic
angle and highly detectable by sigmoidoscopy versus
35% of colon cancers that are proximal to sigmoidal and
not detectable by flex sigmoidocopy.3
The recurrence of the disease is associated with the
elevation of serum values of carcinoembryonic antigen
(ACE) in the 60-70% of the cases, and is considered
value increased the concentration of ACE highet 5mg/l
related to an unfavorable prognosis to the patient;
however its value maintains significance mainly in
stadium TNM II.27

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Table 4: Comparison between diagnostic methods.
Method
Mechanism
Sensibility
Specificity
Observation
Occult blood in
feces
(Guaiac Test)
Detects the peroxidae of the
group Heme in blood that are
present in the feces
30 - 52%
Can
increase to
90% if
used 1-2
years.
95.2%
Not specific for human hemoglobin
and can provide false positive result
with food that present peroxidase
activity such as uncooked vegetables,
red meat, therefore the
recommendation is to withdraw 3
days before the sample is taken, as
well as NSAIDS 7 days before.
Feces Inmuno-
histochemical
Monoclonal antibody reaction
or specific polyclonal
antibodies against human
hemoglobin, albumin, or other
components of the blood feces.
76.5%
95.3%
More specific than the Guaiac test
since it is reactive to the human heme
group. Ideal for population screening
A pharmacological or dietary
restriction is not necessary.
DNA
Analyhsis in
fecal resiuds
PCR Identification of
mutations: Kras, ACP, p53 and
high levels of PDX1
52%
94.4%
Rectal
Examination
Just as initial evaluation of the
symptomatic patient
4.9%
97.1%
It is not consider a screening test. It
allows the detection of masses.
Flexible
Sigmoidoscopy
It is performed with a
endoscopy that allows the
examination of the mucus layer
until 60 cm of the anal margin
(rectum, colon sigmoid and
descendent colon)
58-75% in
small
lesions
72-86% in
advanced
lesions
94%
Important reduction of the mortality
in colorectal cancer
Must be performed every 5 years
Colonoscopy
Detection of polyps or
abnormalities Screening
method for colorectal cancer
91%
94%
Associated with a risk of perforation
of 2% Hemorrhage risk of 0.5 % by
performing the polypectomy
Risk of respiratory distress,
arrhythmias and arterial hypotension
Endoscopic
capsule
Ingested video camara for
intestinal pathology
77%
59%
Barium enema
With double contrast barium,
consist in the administration of
barium and pressurize air into
the colon
61% -
100%
100%
patients that
cant
performed a
colonoscopy
Risk: Perforation 1/25,000
Mortality 1/55,000 cases
Limited efficiency, it is used when
colonoscopy is contraindicated or
when no other diagnostic method is
available.
CT scan
Image in ultrathin tissue
sections (0.5, 0.625 o 0.75 mm)
It allows the evaluation of cancer´s dissemination, complications,
recurrence and treatment response.
Virtual
colonoscopy
Variant of Computed
Tomography, where using
contrast media improves
differentiation with fecal
residues
Alternative of barium enema in patients with contraindication
colonoscopy such as anticoagulants, pulmonary fibrosis or allergy
to sedatives
Magnetic
resonance
Distinguishes the
characteristics of the tumor
associated with metastasis
75-90%
96%
Absence of ionizing radiation, less
invasive, with better resolution in soft
tissues so it can be evaluated local
and remote invasion
Endorectal
ultrasound
Using a transducer of 7.5-10
MHz requires a balloon with
saline to produce 360° image,
allows the visualization of
several layers.
69-97%
Main method for rectal cancer mainly stratification.
Local recurrence who presented local resections in
superficial lesions.
PET scan
It allows the staging of the tumor, lymph node, mainly extra hepatic metastasis stage in a single
image session.

Granados-Romero JJ et al. Int J Res Med Sci. 2017 Nov;5(11):4667-4676
International Journal of Research in Medical Sciences | November 2017 | Vol 5 | Issue 11 Page 4673
Likewise, the SEPT9 protein has been implicated as a
biomarker for more than 10 years, it has been shown as a
precise, reliable, fast, and convenient method for
colorectal cancer.47
TREATMENT
Stage 0 cancer can be treated by removing cancer cells by
colonoscopy. For stage I, II and III Cancer, it is necessary
to perform surgery using radical colectomy of the
segment involved with margins > 5 cm.,
lymphadenectomy to the root of the nutrient vessel
(minimum 12N), suspicious ganglion biopsy outside the
resection field. It has been demostrated that the
laparoscpic approach is as safe as the traditional open
approach for colorectal cancer.48 In patients with
metastases in distal organs the addition of irinotecan to
Fluorouracil and Leucovorin was demostrated prolongs
survival in patients and was considered the new first-line
standard therapy for this disease in patients with stage III
cancer receive complementary chemotherapy after
surgery for 6 to 8 months, improving symptoms and
prolonging survival in people with stage IV cancer
primarily.49 The 5-Fluoracil continues to be the cytostatic
mostly used in the treatment of colon cancer, those who
make use of it or at least approach the fulfillment of the
therapeutic standard, achieve better percentages of
survival. Currently, the role of an antibody variant called
Bevacizumab (Avastin) approved by the US Food and
Drug Administration (FDA) has been studied by lowering
vascular endothelial growth factor (VEGF), the main
angiogenesis regulator, produced by normal and
neoplastic cells 50 Preclinical trials have shown that a
human monoclonal antibody against VEGF can inhibit
the the growth of xenografts of human tumors.50,51
In addition, to its direct antiangiogenic direct effects
becacizumab can improve direct antioantiangiogenic and
may also improve the delivety of chemotherapy by
alterating the tumor vasculature and lowering elevated
interstitial pressure in the tumors.52 The addition to
bevacizumab to IFL improved the global survival;
compared to only IFL the IFL regime plus bevacizumab
increases progression-free survival from a median of 6.2
months to 10.6 months, the overall response rate of 34.8
to 44.8% and the average response duration of 7.1
months to 10.4 months by means of the primary
(becacizumab)) mechanism of tumor growth inhibition
rather than citoreduction.53 However the use of IFL with
or without bavacizumab increase in the incidence of
thrombosis, hemorrhage, proteinuria, and
hypertension.54,55 Radiotherapy is usually used in
combination with chemotherapy for stage III rectal cancer
patients, indicated in those cases where the margin of
surgical resection is compromised, as in the case of
adherence or infiltration to neighboring organs or the
retroperitoneal space. However patients with stage IV
colorectal cancer that has disseminated to the liver, it
should be taken into account, the various therapeutic
approaches targeted specifically to the affected organs
including ablation, chemotherapy or radiotherapy,
cryotherapy or surgery. Patients with metastases present
active the KRAS oncogene showing resistance to
treatment with anti-EGFR antibodies, so you will have to
perform an evaluation of the KRAS (mutated or normal)
for anti-EGFR therapy: approximately 30-050% of
patients with colorectal cancer are known with mutated
KRAS, which could indicate that > 50% of patients
would respond to anti-EGFR therapy, however, only 40-
60% of these patients will respond, patients with mutated
KRAS denote a decrease in survival compared to patients
with wild type KRAS without activation of the
oncogene.56,57
HEPATIC METASTASIS FROM COLORECTAL
CANCER
The most common site of metastases in patients with
colorectal cancer is the liver, due to its anatomical
location with respect to its portal circulation. The liver is
the most common site of metastasis in patients with
colorectal cancer because of its anatomical location with
respect to its portal circulation. Approximately 14-18% of
patients with colorectal cancer have been detected with
this type of cancer from the first medical consultation and
10-25% at the time of primary colorectal cancer
resection.58 The poor prognostic factors remain the
presence of metastases, recurrent disease and the
advancement of local tumors. Despite advances in
chemotherapy, surgery remains the treatment of choice,
overcoming other treatments such as cryosurgery or
radiofrequency ablation. Surgical treatment of isolated
metastasis is a well-established treatment for selected
patients and achieves a 5-year survival of between 39 and
58%. It has been reported that the 5-year survival rate
following the surgical procedure for liver metastasis is
25-44%, with an intraoperative mortality of 0-6.6%.
Modern surgical techniques performed at major
hepatobilliary centers have shown that 70% of
hepatectomy can be achieved with a mortality of less than
5%. With the help of Liver resections, the 5-year survival
rate, even in those with a positive margin of less than 1
mm, could be increased to 25%. In cases where there are
sufficient surgical margins (< 1 mm), 5-year survival
rates could be up to 40%. It is vital to know the
predisposing factors, the mechanisms, the diagnostic
methods, the treatment of liver metastases, due to their
anatomical situation in the abdominal cavity. The
adoption of more and better programs in the health
system is extremely important, with objectives focused
on prevention, early diagnosis and adequate treatment
that help the survival and prognosis of patients.59-61
Funding: No funding sources
Conflict of interest: None declared
Ethical approval: Not required

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International Journal of Research in Medical Sciences | November 2017 | Vol 5 | Issue 11 Page 4674
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Cite this article as: Granados-Romero JJ,
Valderrama-Treviño AI, Contreras-Flores EH,
Barrera-Mera B, Enríquez MH, Uriarte-Ruíz K, et al.
Colorectal cancer: a review. Int J Res Med Sci
2017;5:4667-76.