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1
Ministry of Higher Education
and Scientific Research
University of Missan
College of Medicine
Epidemiological, Clinical
and Descriptive Study of
Colorectal Cancer in
Missan province, Iraq
Graduation Research by
Aya Ali Gumaah Altemimi
stage) thstudent (6Medical
Supervisor
Dr. Hayder Saadoon Qasim Alhilfi
Assistant Professor; F.I.B.M.S; Oncologist; Consultant; Department of Medicine
2016-2017
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DEDICATION
To All
Science and Knowledge
Students
Aya 2017
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ACKNOWLEDGEMENTS
First and foremost, I am very grateful to offer my humble gratitude to
“ALMIGHTY ALLAH” who provide me with an opportunity to achieve one of my
wishes, I have been blessed with the presence of many people who have assisted me
with this research.
Then
I would like to express sincere appreciations and gratitude to my supervisor,
Assistant Professor Dr. Haider Saadoon Qasim Alhilfi for helping and guiding me
during the course of the work. Also I would like to thank the deanery of the Collage
Veterinary Medicine.
I am also thanking to the head and stuff of Alshifaa Oncology Center for helping
in my work.
Great thanks also extend to Dr. Rasha K. Al-Saad, Assistant Lecturer, M. Sc.
Parasitology, Department of Microbiology, Medicine College / Missan University and
Dr. Ahmed S. Al-Shewered, Radiotherapy doctor, Missan Radiotherapy Centre for
facilitating my work.
Aya 2017
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Summary
Colorectal carcinoma is the commonest cancer of GIT. It is the third common cancer in man
worldwide after lung and prostate cancers. Also it is the fourth common cancer in woman after
breast, lung and uterus cancers. Deaths from colorectal cancer is more in compare with other GIT
cancers.
Our study conducted in Missan province, Iraq. The data were collected from patients files from 2013
to 2016 for that whom attended to Al-Shifaa Oncology Center in Missan. Seventy one patients that
found have colorectal cancer. An epidemiological, clinical and descriptive study perform which
included percentage of gender, age, residency, site of cancer, family history, past history, year of
onset, smoking history, alcohol intake, presentation of cancer at time of diagnosis, staging and
histopathology pattern in relation to colorectal cancer.
In this study the most of results were resampling those obtained in another studies worldwide. The
overall prevalence of colorectal carcinoma was 3.75%, which was the commonest GIT cancer. The
most age group affected in this study was 51-60 years, in percentage 30.99% and it was much less in
other aged groups. The gender and residency of patients have no effect on cancer percent. Obesity,
Family history of cancer, Cigarette smoking and alcohol consumption represented risk factors for
colorectal cancer. In present study 42.25% of patients had family history of cancer. Most common
site of colorectal carcinoma in this study was left colon, which present in 61.97%, rather than other
sites such as right colon, sigmoid, rectosigmoid and transverse colon. There was slight increase in
new cases detection of colorectal carcinoma from 2013 to 2016. The viable symptoms and sings in
presentation were found in different proportions in this study. Advanced stages of colorectal cancer
were the most common stages description as stage III A, III B, III C and stage IV in percentages
12.67%, 16.90%, 19.72% and 15.49% respectively. The common histopathological pattern of
colorectal cancer was moderately differentiated adenocarcinoma as 53.52%.
Aims of study:
1- Determine the epidemiological and clinical data of colorectal cancer in Missan province.
2- Descriptive studying of colorectal carcinoma patients attended to Al-Shifaa Oncology center.
3- Explanation of different relationships between colorectal cancer and other risk factors in
population.
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Introduction
Cancer of the colon or rectum is called colorectal cancer, bowel cancer or cancer of the large
intestine. Bowel cancer can affect any part of the colon or rectum. However, it most commonly
develops in the lower part of the descending colon, the sigmoid colon, or rectum. Most cases occur in
people aged over 50. If bowel cancer is diagnosed at an early stage, there is a good chance of a cure.
In general, the more advanced the cancer, the less chance that treatment will be curative. Colorectal
cancer usually develops slowly, over a period of 10 to 20 years.
Bowel cancer usually develops from a small fleshy growth (polyp) which has formed on the lining of
the colon or rectum. The most common kind of polyp is called an adenomatous polyp or adenoma.
About 1 in 4 people over the age of 50 develop at least one bowel polyp. Polyps are non-cancerous
(benign) and usually cause no problems. About two thirds of all colorectal tumours develop in the
colon and the remainder in the rectum. Most tumours are adenocarcinomas. Colorectal cancer is
locally invasive but metastatic spread may be evident before local growth produces symptoms. The
most common site for metastatic spread is the liver. Other sites (eg, the lungs, brain and bone) are
unusual in the absence of liver metastases. Early diagnosis is essential for effective treatment to
provide the greatest chance of survival.
Review of Literatures
Etiology
The exact reason why a cell becomes cancerous is unclear. It is thought that something damages or
alters certain genes in the cell. These make the cell abnormal and multiply out of control.
Inherited gene mutations that increase the risk of colon cancer can be passed through families,but the
se inherited genes are linked to only a small percentage of colon cancers. Studies of large groups of p
eople have shown an association between a typical Western dietand an increased risk of colon cancer
. A typical Western diet is high in fat and low in fiber.When people move from areas where the typic
al diet is low in fat and high in fiber to areaswhere the typical Western diet is most common, the risk
of colon cancer in these people increases significantly.
Risk Factors
1- Older age. The great majority of people diagnosed with colon cancer are older than 50.
2- AfricanAmerican race.
3- History of colorectal cancer or polyps.
4- Inflammatory intestinal conditions. Chronic inflammatory diseases of the colon, such as
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ulcerative colitis and Crohn's disease.
5- Inherited syndromes that increase colon cancer risk. These syndromes include
familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer,
which is also known as Lynch syndrome. Gardner's syndrome, Turcot's syndrome, attenuated
adenomatous polyposis coli, flat adenoma syndrome, hamartomatous polyposis syndromes (Peutz-
Jeghers syndrome, juvenile polyposis syndrome, Cowden's syndrome).
6- Family history of colon cancer.
7- Low fiber, high fat diet.
8- A sedentary lifestyle.
9- Diabetes.
10- Obesity.
11- Smoking.
12- Alcohol.
13- Radiation therapy for cancer.
Epidemiology
Globally more than 1 million people get colorectal cancer every year resulting in about 715,000
deaths as of 2010 up from 490,000 in 1990. As of 2012, it is the second most common cause of
cancer in women (9.2% of diagnoses) and the third most common in men (10.0%) with it being the
fourth most common cause of cancer death after lung, stomach, and liver cancer. It is more common
in developed than developing countries. Globally incidences vary 10-fold with highest rates in
Australia, New Zealand, Europe and the US and lowest rates in Africa and South-Central Asia.
Colorectal cancer is the third most common cancer in the UK after breast and lung cancer, with
approximately 40,000 new cases registered each year. Colorectal cancer is the second most common
cause of cancer death in the UK. Occurrence is strongly related to age, with almost three quarters of
cases of colorectal cancer occurring in people aged 65 or over. In the United States and European
Union, only about 2-8% of cases occur in individuals under 40 years of age , whereas Egypt, Saudi
Arabia, the Philippines, and Iran show rates of 38%, 21%, 17%, and 15-35%, respectively for this
same age group.
Presentation
1- Right colon cancers: weight loss, anaemia, occult bleeding, mass in right iliac fossa, disease
more likely to be advanced at presentation.
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2- Left colon cancers: often colicky pain, rectal bleeding, bowel obstruction, tenesmus, mass in
left iliac fossa, early change in bowel habit, less advanced disease at presentation.
3- The most common presenting symptoms and signs of cancer or large polyps are rectal
bleeding, persisting change in bowel habit, constipation, intestinal obstruction and anaemia.
4- In some patients, symptoms do not become apparent until the cancer is far advanced.
Jaundice and hepatomegaly indicate advanced disease with extensive liver metastases.
Peritoneal metastases with ascites are often also present.
5- Rarer clinical signs include: pneumaturia, gastrocolic fistula, ischiorectal or perineal
abscesses, deep vein thrombosis.
Diagnosis
When patient is suspected to having colorectal cancer careful physical and examination should be
performed with careful attention paid to past and family history. Colonoscopy should be offered to
patients without major comorbidity to confirm the diagnosis of colorectal cancer.
1. FBC and LFTs.
2. Proctoscopy with or without sigmoidoscopy.
3. Flexible sigmoidoscope.
4. Colonoscopy is the gold standard for diagnosis of colorectal cancer.
5. Barium enema.
6. Histopathology: macroscopic and microscopic.
7. Immunhistitochemistry.
8. CT scan.
9. Liver ultrasound and CT scan.
10. MRI is more specific than CT in showing liver metastases.
11. Positron emission tomography (PET).
12. Elevated pre-treatment serum levels of carcinoembryonic antigen (CEA).
Differential diagnosis
1. Diverticular disease.
2. Irritable bowel syndrome.
3. Inflammatory bowel disease.
4. Local rectal pathology - eg, haemorrhoids.
5. Anal cancer.
6. Ischaemic colitis.
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Staging
The Dukes' staging classification is now gradually being replaced by the tumour/node/metastases
(TNM) classification:
TX: primary cannot be assessed.
T0: no evidence of primary carcinoma in situ (Tis) - intraepithelial or lamina propria only.
T1: invades submucosa.
T2: invades muscularis propria.
T3: invades subserosa or non-peritonealised pericolic tissues.
T4: directly invades other tissues and/or penetrates visceral peritoneum.
NX: regional nodes cannot be assessed.
N0: no regional nodes involved.
N1: 1-3 regional nodes involved.
N2: 4 or more regional nodes involved.
MX: distant metastasis cannot be assessed.
M0: no distant metastasis.
M1: distant metastasis present (may be transcoelomic spread).
Management
Surgery remains the definitive treatment for apparently localised colorectal cancer. Both
radiotherapy and chemotherapy can improve survival rates after potentially curative surgery. If
colonic stents are considered for patients presenting with acute large bowel obstruction, CT of the
chest, abdomen and pelvis should be offered to confirm the diagnosis of mechanical obstruction, and
to determine whether the patient has metastatic disease or colonic perforation.
Surgery
Total mesorectal excision.
Right hemicolectomy.
Left hemicolectomy.
Sigmoid colectomy.
Anterior resection and anastomosis.
Abdomino-perineal (AP) resection.
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Laparoscopic surgery.
Chemotherapy
It used in addition to surgery in certain cases. This is depends on the stage of the disease.
Chemotherapy drugs include capecitabine, fluorouracil, irinotecan, oxaliplatin and UFT.
Regimens used for treatment are FOLFOX, FOLFOXIRI, and FOLFIRI.
In Stage I, no chemotherapy, and surgery is the definitive treatment.
The Stage II chemotherapy is debatable, and is usually not offered unless risk factors such as
T4 tumor or inadequate lymph node sampling is identified.
For stage III and Stage IV, chemotherapy is an integral part of treatment.
Targeted drug therapy
Drugs that target specific defects that allow cancer cells to grow are available to people with
advanced colon cancer.Targeted drugs can be given along with chemotherapy or alone. Targeted dru
gs are typically reserved for people with advanced colon cancer, including:
1. Bevacizumab (Avastin)
2. Cetuximab (Erbitux)
3. Panitumumab (Vectibix)
4. Ramucirumab (Cyramza)
5. Regorafenib (Stivarga)
6. Zivaflibercept (Zaltrap)
Radiotherapy
While a combination of radiation and chemotherapy may be useful for rectal cancer, its use in colon
cancer is not routine due to the sensitivity of the bowels to radiation. Just as
for chemotherapy, radiotherapy can be used in the neoadjuvant and adjuvant setting for some stages
of rectal cancer.
Palliative (supportive) care
Palliative care is recommended for any person who has advanced colon cancer or has
significant symptoms.
Resection of metastatic disease (hepatic or pulmonary metastases) can lead to five-year
survival rates of 35-58%.
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Patients with solitary, multiple, and bilobar disease who have had radical treatment of the
primary colorectal cancer, are candidates for liver resection.
For patients with metastatic colorectal cancer, chemotherapy aims to improve survival and
quality of life.
Follow-up
1. A medical history and physical examination are recommended every 3 to 6 months for 2
years, then every 6 months for 5 years.
2. CEA Carcinoembryonic antigen blood level.
3. A CT-scan of the chest, abdomen and pelvis.
4. Colonoscopy can be done after 1 year.
Prognosis
In Europe the five-year survival rate for colorectal cancer is less than 60%. In the developed
world about a third of people who get the disease die from it. According to American Cancer Society
statistics in 2006, over 20% of people with colorectal cancer come to medical attention when the
disease is already advanced (stage IV), and up to 25% of this group will have isolated liver
metastasis that is potentially resectable.
Screening
As more than 80% of colorectal cancers arise from adenomatous polyps, screening for this cancer is
effective not only for early detection but also for prevention. Any polyps that are detected can be
removed, usually by colonoscopy or sigmoidoscopy, and thus prevented from turning cancerous.
Screening has the potential to reduce colorectal cancer deaths by 60%. The three main screening tests
are fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy.
Prevention
Increasing surveillance.
Engaging in physical activity.
Consuming a diet high in fiber.
Reducing smoking and alcohol consumption.
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Methods and Patients
Area of study: The area of study includes Missan province, Iraq.
Duration of study: The information were collected from 2013 to 2016 from Al-Shifaa Oncology
Center in Missan. All data taken form patients files off center.
Populations: Seventy one over 1894 patients that found had colorectal cancer that attended to center
for chemotherapy treatment and follow up.
Design of study: Epidemiological, clinical and descriptive study included percentage of gender, age,
residency, site of cancer, family history, past history, year of onset, smoking history, staging and
histopathology in relation to colorectal cancer.
Statistical analysis: Determine the statistical significances among different tests variables version
14, was used. Chi-Square test and P value were used to compares between the epidemiological
results.
Results
We obtained two types of results in this study, those were significant and no significant.
Significant result
The relationship of colorectal cancer among overall prevalence, family history of cancer, site of
cancer, year of management and staging were significant differences (P <0.05 and P <0.01), showed
in tables 1, 7, 8, 9 and 11. There were strongly significant differences in colorectal cancer among age
groups and histopathological patterns of cancer (P < 0.001), as showed in tables 2 and 12.
Un-significant results
Other results were recorded no significant differences in percentages of colorectal cancer among
gender of patients, residency, tobacco habits, alcohol consumption and presentation of cancer (P
>0.05 and P >0.01) as in tables 3, 4, 5, 6 and 10.
Table-1 The overall prevalence of colorectal cancer among all cancerous patients.
Patients No %
Other cancerous patients 1823 96.25
Colorectal cancer 71 03.75
Total 1894 100
P <0.05
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Table-2 The percentage of colorectal cancer in relation with age groups.
Age group (years) No %
10-20 1 01.41
21-30 4 05.63
31-40 7 09.86
41-50 17 23.94
51-60 22 30.99
61-70 9 12.68
71-80 9 12.68
81-90 2 02.81
91-100 0 00.00
Total 71 100
P <0.001
Table-3 The percentage of colorectal cancer among gender of patients.
Sex No %
Male 31 43.67
Female 40 56.33
Total 71 100
P >0.05
Table-4 The percentage of colorectal cancer among address.
Residency No %
Rural 36 50.70
Urban 35 49.30
Total 71 100
P=NS
Table-5 The percentage of colorectal cancer among cigarettes smoking.
Tobacco habit No %
Smoking 14 19.72
Non smoking 57 80.28
Total 71 100
P >0.05
Table-6 The percentage of colorectal cancer among alcohol consumption.
Alcohol intake No %
Positive 2 02.82
Negative 69 97.18
Total 71 100
P >0.01
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Table-7 The percentage of colorectal cancer among family history of cancer.
Family history No %
Positive 30 42.25
Negative 24 33.80
Unknown 17 23.95
Total 71 100
P <0.01
Table-8 The percentage of colorectal cancer among site of cancer.
Site No %
Right 24 33.80
Left 44 61.97
Sigmoid 3 04.23
Total 71 100
P <0.05
Table-9 The percentage of colorectal cancer among year of started management.
Year of management No %
2013 12 16.90
2014 16 22.53
2015 19 26.77
2016 24 33.80
Total 71 100
P <0.01
Table-10 The percentage of colorectal cancer among symptoms and signs of presentation of cancer.
Presentation No %
Abdominal pain 19 26.77
Constipating 11 15.49
Repeated vomiting 7 09.86
Bloody diarrhea 3 04.22
Refractory anemia 2 02.82
Bleeding per rectum 12 16.90
Abdominal distention 3 04.22
Systemic (jaundice,…) 14 19.72
Total 71 100
P =NS
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Table-11 Colorectal cancer percentages and it's stages.
Staging No %
0 2 02.82
I 8 11.27
II A 8 11.27
II B 7 09.86
III A 9 12.67
III B 12 16.90
III C 14 19.72
IV 11 15.49
Total 71 100
P <0.01
Table-12 Colorectal cancer percentages and histopathological patterns.
Histopathological type No %
Undifferentiated adenocarcinoma 5 07.04
Moderately differentiated adenocarcinoma 38 53.52
Poorly differentiated adenocarcinoma 8 11.27
Well differentiated adenocarcinoma 6 08.45
Poorly differentiated mucinous adenocarcinoma 6 08.45
Moderately differentiated mucinous adenocarcinoma 4 05.63
Polyp with early neoplastic change 2 02.82
Squamous cell carcinoma 1 01.41
Stromal tumor moderately differentiated 1 01.41
Total 71 100
P <0.001
Discussion
Because off low socioeconomic status, insufficient screening methods, doubtful early detection
and low educational level of patients, errors in diagnosis and unavailability of diagnostic tools, the
overall prevalence of colorectal carcinoma was 3.75% which more less than expected in comparison
with other reports in other countries in world according to each WHO, NIC, NICE and CRUK. The
percentages of cancer were higher in developed countries as US, UK, Australia, Germany, France,
Italy, Spain, Canada, Japan and Turkey, due to increasing of risky factors such as sedentary lifestyle,
alcohol consumption, cigarette smoking, obesity and meaty food. In developing and poor cities the
ratios of cancer relatively different. The studies showed high prevalence in Jordan, Iran, Egypt and
Saudi Arabia but the percent were low in African countries.
The most age groups affected in this study were 40-60 years, as 41-50 and 51-60, in percentage
23.94% and 30.99% respectively. This was recorded in the most studies conducted worldwide.
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Regarding to the gender and residency of colorectal cancer patients, there were no significant
relationship between them and cancer due to the nature of cancer not related to sex or living areas.
Cigarette smoking and alcohol consumption play as risky roles in causing colorectal carcinoma, but
in this study, there were no significant differences presented according the results obtained. While in
many studies in other countries showed a strong relation between cancer and tobacco habit and
alcohol intake.
According to most studies in America, Europa and Asia, the family history of colorectal cancer, past
history of colorectal cancer, family history of other types of cancer and past history of other types of
cancer if present, it increase the incidence and percentage to effect humanbeing by colorectal cancer
in addition to other risk factors. In present study 42.25% of patients had family history of cancer.
Most common site of colorectal carcinoma in this study was left colon, which present in 61.97% and
this due this site is tend to be circumferential, and can obstruct the bowel lumen. The most common
site of colorectal cancer is the sigmoid colon (25%) followed by the rectum (21%) followed by
cecum (20%) followed by rectosigmoid junction (20%) followed by transverse colon (15%) followed
by ascending colon (10%) according to Schottenfeld D and Fraumeni JF, (2006). This can explain by
many reasons such as inaccuracy of investigation methods or neglected accurate results of
colonoscopy.
Because off increase awareness among national people with increased of buildup of oncology centers
in our countries, we obtained slight increase in new cases detection of colorectal carcinoma from
2013 to 2016.
The viable symptoms and sings in presentation were found in different proportions in this study
which of no significant differences.
Regarding staging of detection of colorectal cancer, the most common stages were advanced stages
as stage III A, III B, III C and stage IV in percentages 12.67%, 16.90%, 19.72% and 15.49%
respectively. These results were similar to other studies conducted in Asia, Europa and South
America. These were due to late diagnosis, un availability of screening tools and decreased
awareness about cancer. Another studies in developed countries as US, UK, Australia, Canada, New
Zealand, Japan, South Korea and China determined cancer in early stages due to increase screening
facilities, increase awareness about it and available of methods of early detection.
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The most common histopathological pattern of colorectal carcinoma was adenocarcinoma (well,
poor, moderate and undifferentiated). The common one was moderately differentiated
adenocarcinoma as 53.52%, which was exactly similar in concluded in all studies conducted about
colorectal cancer over the world.
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Conclusions
The data of present study concluded many results, which are:
1- Colorectal carcinoma is most common gastrointestinal tract (GIT) cancer in Missan
population.
2- Middle aged groups are common age for colorectal cancer.
3- Sex and address of patients have no role in epidemic of cancer.
4- Cigarette smoking and alcohol consumption are risky factors.
5- Family history of cancer is duplicate the occurance of colorectal cancer.
6- Detection ways for diagnosing the new cases of colorectal cancer is increase by time.
7- Different presentation of colorectal carcinoma.
8- Late in diagnosis and management of colorectal cancer causing detection of cancer in
advanced stages rather than detection in early stage.
9- Advanced stages of colorectal cancer are poor prognosis.
10- Early diagnosis of colorectal carcinoma result in better management, prognosis and survival.
11- Adenocarcinoma is the commonest histopathological types of cancer.
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Recommendations
1. Increase awareness about colorectal cancer.
2. Surveillance studies made for more detection of early diagnosis of cancer.
3. Widening preventive measures for protection from colorectal carcinoma.
4. Modified methods of diagnosis.
5. Increase screening tests availability.
6. Treatment of diabetes, obesity and inflammatory bowel diseases.
7. Genetic counseling diagnosis for people who have family history of cancer.
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