UNIVERSITY OF KHARTOUM

The Graduate College

Medical& Health Studies Board

CLINICOPATHOLOGICAL STUDY OF COLORECTAL CANCERS IN SUDANESE PATIENTS

By Dr. Asma Mukhtar Shammet Ahmed

M.B.B.S. Faculty of Medicine (U of K) 1996

A thesis submitted in partial fulfillment for the requirements

of the degree of clinical MD in Pathology of the University of Khartoum

August 2005

Supervisor

Dr.Mohammed Mohammed Osman, M.B.B.S, MD. Pathology

Assistant Professor of Pathology Department of pathology

Faculty of Medicine University of Khartoum

Π

:قال اهللا تعالى

) رب العالمينقل إن صالتى و نسكي ومحياي و مماتي هللا ( صدق اهللا العظيم

)162( اآلية -سورة األنعام

CONTENTS

Dedication………………………………………………………………..I

Acknowledgment……………………………………………………….II

Abbreviations…………………………………………………………..III

English abstract………………………………………..………………IV

Arabic abstract……………………………………..………………….VI List of tables………………………………………………………….VIII

List of figures………………………………………………………… IX

CHAPTER ONE INTRODUCTION AND LITRATURE REVIEW………………...……1

1.1. Definition…………………………………….…………………….2

1.2. Normal anatomy…………………………………………….……2

1.3. Epidemiology……………………………………………….…….4

1.4. Aetiology and pathogenesis…………………………….………5

1.5. Genetics……………………………………………..…………….8

1.6. Localization………………………………………….…………....9

1.7. Metastasis and mode of spread……………………….………10

1.8. Diagnosis………………………………………………….……..10

1.9. Pathologic diagnosis………………………….………………..15

1.10. Treatment………………………………...……………….……25

1.11. Prognosis…………………………………………...………….27

1.12. Recurrence…………………………………...……………….28

OBJECTIVES……………………………………………………..….29

CHAPTER TWO METHODOLOGY……………………………………………………..30

CHAPTER THREE RESULTS…………………………………………………...…………32

CHAPTER FOUR DISCUSSION…………………………………………..……………..54

CONCLUSION……………………………………...…………………59

RECOMMENDATION……………………………..…………………60

REFERENCES……………………………………...…………….…..61

APPENDIX (questionnaire)

I

DEDICATION

To the soul of my brother,

To my parents & sisters with great love.

II

ACKN0WLEDGEMENT

I would like to express my deep thank to my supervisor Dr.

Mohammed Mohammed Osman for his continuous guidance,

generous advice, encouragement& co-operation throughout this

work.

I am also grateful to my parents & sisters who were always

there whenever I needed them.

Many thanks & best wishes to Dr. Mahdi Moh. Ahmed

Shammad, consultant dermatologist for his valuable advices

throughout the preparation this study.

I wish to thank Dr. Moh. Abd Elhameed, the director of the

laboratories in Ibn Sina Hospital, for making the records at the

histopathology lab available for this analysis.

Thanks also to the technicians at the histopathology lab& to

the staff at the statistic unit in Ibn Sina Hospital for their help to get

the patients’ records& histopathology slides.

I would like to thank Ms. Widad Abd El Magsoud who helped

me to print out this work.

Lastly my thanks to every one who helped me to do this

study.

III

List of Abbreviations

ACS : American Cancer Society.

AGCC : American Joint Committee on Cancer.

APC-gene : Adenomatous Polyposis Coli-gene.

CAP : College of American Pathologists.

CEA : Carcinoembryonic Antigen.

CRC : Colorectal Cancer.

CT : Computed Tomography.

DCBE : Double Contrast Barium Enema.

DCC-gene : Deleted in Colon Cancer-gene.

DNA : Deoxyribonucleic Acid.

FAP : Familial Adenomatous Polyposis.

FOBT : Faecal Occult Blood Test.

5-FU : 5-Fluorouracil.

GCC-B1TM : Guanylyl Cyclase C-B1TM protein.

MSI-H. gene: Microsatellite Instability gene with High frequency.

TEM : Transanal Endoscopic Microsurgery.

TNM system: Tumor Node Metastasis system.

UICC : Union Internationale Center Le Cancer.

WHO : World Health Organization.

IV

ABSTRACT

Colorectal cancer is an important tumor of the GIT arising

from the epithelial lining the inner surface of the colon& rectum&

from the crypts of Liberkϋhn.

This is a retrospective study conducted on Sudanese patients

during the period from January 2001 to December 2004 at Ibn

Sina Hospital, Khartoum, Sudan.

The study aimed to determine the histopathological pattern of

CRC, & to show the correlation between the histopathological type

of the tumor& the age, sex, residency distribution, & clinical

presentation. comprised 100 patients, of which 56 were males&

44 were females with a ratio of 1.1: 1 to each other. The age for all

patients ranges between 14- 85 years.

In this study there was a high proportion of early onset tumor

(33% of cases were < 40 years), & left sided subsite distribution of

CRC (77% of cases were in the rectum, sigmoid colon, & recto-

sigmoid junction).

Rectal bleeding represented the majority (76%) of the

symptoms of CRC. The duration of symptoms varied from one to

twelve months with the majority of patients (61.2%) having

symptoms < 6 months.

V

By reviewing the slides, only five histological types were

identified. There were 74(74%) adenocarcinoma, 13(13%)

mucinous adenocarcinoma, 7(7%) signet ring cell carcinoma,

5(5%) papillary carcinoma, & one (1%) anaplastic carcinoma.

In conclusion, we share many epidemiological features of

developing countries for CRC. These include left subsite

distribution& early-onset CRC. We stress the significance of the

public health education& national screening program regarding

CRC to improve the outcome.

VI

حةملخص االطرو

يعتبرسرطان القولون و المستقيم من اهم االورام التي تصيب الجهاز الهضمي

وهو ينمو من الخاليا المبطنة للغشاء الداخلي للقولون و المستقيم و من جريبات . لالنسان

.ليبرخون

ضي دراسة الي الوراء عن سرطان القولون و المستقيم في المر هده الدراسة

في مستشفي ابن سيناء 2004 وحتي ديسمبر2001 سودانيين في الفترة من ينايرال

هده الدراسة هو بحث التغييرات المرضية في االنسجة في سرطان و الغرض من.بالخرطوم

القولون و المستقيم و ايضا بحث عالقة كل من العمر، الجنس و المسكن مع نوع سرطان

.القولون و المستقيم

و نسبة . من النساء44 من الرجال و 56 مريض منهم 100الدراسة تضمنت

، و متوسط اعمار المرضي يتراوح ما 1.1: 1 نسبة المرض في الرجال مقارنة بالنساء هي

. سنة85 سنة الي 14بين

من % 33( و لقد وجدنا في هده الدراسة بان هدا المرض يحدث مبكرا بين السودانيين

في كل % 77(وثه في الجانب االيسر من القولونو يتركز حد) تحت سن االربعينالمرضي

و قد كان نزف ). من المستقيم، القولون السيني، و منطقة التحام المستقيم مع القولون السيني

تراوحت %). 76(ي مرضي سرطان القولون و المستقيم من االعراض الغالبة علالمستقيم

ية المرضي كانت فترة اعراضهم ي اثني عشر شهرا، بينما غالبفترة االعراض ما بين شهر ال

.عن الستة اشهرتقل

VII

من هدا السرطان، و قد كان بالرجوع الي الشرائح تم التعرف علي خمسة انواع

مرضي بالسرطان الغددي 13، %)74(ا لديه سرطان غددي مريض74 تقسيمها كاالتي

مرضي لديهم السرطان الحليمي 5، %)7( مرضي بالسرطان الخاتمي 7، %)13 (المخاطي

%).1(، و مريض واحد بالسرطان المتحول او االرتدادي%)5(

الخصائص و لقد خلصت هده الدراسة الي ان السودان يشارك الدول النامية في بعض

و تركزه البيئية لسرطان القولون و المستقيم و التي تتمثل في الحدوث المبكر لهدا المرض،

و ايضا تطرقت . في الجانب االيسر من القولون مما يتطلب المزيد من البحث لمعرفة االسباب

الدراسة الي اهمية التثقيف الصحي و برنامج الفحص الطبي الدوري لسرطان القولون و

.ستقيم من اجل الوصول الي نتائج افضلالم

VIII

LIST OF TABLES

Table Page

(1) Sex distribution& male to female incidence rate ratios for

cancer of the colon& rectum among the studied

group……..............................................................................

37

(2) Presenting symptoms of colorectal cancer among the studied

group …………………………………………………………….

38

(3)Grading of colorectal cancer among the studied group……… 39

IX

LIST OF FIGURES

Figure Page

(1) Age distribution of colorectal cancer among the studied

group…………………………………………………………

40

(3) Sex Distribution in colorectal cancer among the studied

group ………………………………….……………………..

41

(3) Age specific incidence rate of colorectal cancer in males

& females among the studied group…………………..

42

(4) Residence distribution of colorectal cancer among the

studied group………………………………………………..

43

(5) Subsite distribution of colorectal cancer among the

studied group……………………………………………...

44

(6) Histological patterns (Diagnosis) of colorectal cancer

among the studied group………………………………….

45

(7) Relationship between the diagnosis& different age

groups among the studied group……………………….

46

(8) Relationship between the diagnosis & sex among the

studied group………………….……………………………

47

(9)-(14) Colored slides of some types of colorectal cancer… 48-53

X

1

INTRODUCTION & LITERATURE REVIEW

Colorectal cancer (CRC) is a major health problem

throughout the world, with the highest incidence rates in North

America, Western Europe, Australia and Newsland.(1)It is the fourth

most common internal malignancy and is second to carcinoma of

the lung as a cause of cancer death.(2)

Virtually 90%-98% of all cancers in the large bowel are

adenocarcinoma.(1,3,4,5)The remainder are neoplasms of the

neuroendocrine cells, mainly carcinoid tumors; direct invasion of

the colon and rectum by other visceral malignancies, such as

carcinoma of the prostate, urinary bladder and uterus; metastatic

tumors, such as malignant melanoma;(4)lymphomas and

mesenchymal tumors.(6)

Colorectal cancer usually occurs over the age of 50 years.(4)

In Sudan it was reported to affect younger age group and about

30% of the lesions were of the mucoid & undifferentiated types.(7)

The main precursor lesion for CRC is adenoma, which is

readily detected& treated by endoscopic techniques. While most of

adenomas are polypoid, flat and depressed lesions may be more

prevalent than previously recognized.(8) Non neoplastic polyps

(hyperplastic, juvenile, hamartomatous, and lymphoid polyps) are

2

not considered precancerous unless they occur in polyposis

syndromes (juvenile polyposis and hyperplastic polyposis).(6,9,10,11)

1.1.Definition:

Colorectal cancer (CRC) is a disease in which cells in the

colon or rectum become abnormal & divide without normal control

or order, forming a mass called tumor.(12)It arises from the

epithelium lining the inner surface of the colon &rectum and from

the crypts of Leiberkühn.(13)

1.2.Normal Anatomy:

Normally the large bowel comprises the terminal 1-1.5m of

the gastrointestinal tract and is subdivided into: cecum, ascending

(right) colon, transverse colon, descending (left) colon, sigmoid

colon, and rectum. The hepatic flexure is at the junction of the

ascending and the transverse colon, and the splenic flexure is at

the junction of the transverse and descending colon. The rectum

forms the distal 8-15cm of extraperitoneal large bowel.

Histologically, the large bowel wall is composed of 4 layers which

are (from lumen outwards):(14) mucosa, submucosa, muscularis

externa, and serosa (or, in the rectum, perimuscular tissue).The

mucosa has 3 components: epithelium, lamina propria, and

muscularis mucosa. The mucosal surface is covered by a single

3

layer of low columnar to cuboidal epithelium which is composed of

absorptive cells (with basally located nuclei, mucin negative

acidophilic cytoplasm, and apical striations) and goblet cells

(contain mucin granules). Crypts of Leiberkühn open into the

mucosal surface. They have tubular shape and arranged in parallel

to each other, and their epithelium contains mature absorptive

cells, undifferentiated precursor cells, goblet cells, endocrine cells,

and paneth cells. Both the precursor and the endocrine cells

predominate at the base of crypts. The paneth cells are identified

by their numerous eosinophilic secretory granules, and they are

only present in the cecum and right colon.(14)

The lamina propria consists of connective tissue cells &

fibers. It contains blood vessels, lymphatics, nerves &lymphoid

follicles which extend from the mucosa through the muscularis

mucosa into the submucosa.(14)

The submucosa composed of loose connective tissue contains

cells similar to those in the lamina propria, and also contains the

Meissner’s plexus.(14)

The muscularis externa includes a circular inner layer and a

longitudinal outer layer of muscles, with the myenteric plexus of

Auerbach between them.(14)

4

The serosa is composed of a single layer of flattened to

cuboidal mesothelial cells and the subjacent fibroblastic tissue.

The large bowel is supplied by branches of the superior mesenteric

artery (from the cecum to the splenic flexure) and the inferior

mesenteric artery (distal to the splenic flexure). The lower portion

of the rectum is irrigated by the middle and inferior rectal arteries,

which are branches of the internal iliac artery (14).

The lymphatic drainage of the colon is mainly through the

mesentery into the paracolic lymph group, then to intermediate

nodal group, to central group, and finely to the paraortic chain. The

lymphatic drainage of rectum is toward the inferior mesenteric

artery nodes, the superior haemorroidal chain, the hypogastric and

the common iliac nodes.(14)

1.3. Epidemiology:

Colorectal cancer is an important health problem. There are

one million new cases diagnosed worldwide each year and

approximately half a million death (15), making this cancer the fourth

most common incident cancer and cause of death throughout the

world. The developed countries account for >63% of the total

global incidence. High-risk areas include North America, Europe

and Australia. Central and South America, Africa and Asia are

5

areas with low risk factors.(16)CRC is slightly more common in

males. Sporadic cases of CRC occur over the age of 50 years(4),

with peak incidence at 60-70 years & fewer than 20% occur before

the age of 50 years. When CRC is found in a young person, pre-

existing ulcerative colitis or one of the polyposis syndromes must

be suspected.(3)

1.4. Etiology & Pathogenesis:

CRC either occur on a preexisting adenoma or on a normal

mucosa without evidence of adenomatous precursors.(3) The exact

cause of CRC is unknown, but there are many risk factors which

include:

1- Age and sex: CRC is more common in males above the age of

50 years.(4,17)

2- Inflammatory bowel diseases: as chronic ulcerative colitis (U.C)

is associated with increased risk of CRC. The lesion that occurs

in U.C. tend to be flat and invasive, and is difficult to be detected

endoscopically at an early stage.(4)So patients with U.C. are

commonly screened every one to two years by colonoscopy &

biopsy to look for dysplasia.(18)

3- Family history of CRC or adenomatous polyps: In general, closer

familial relationship to affected relatives, younger age of affected

6

relatives, and larger number of affected relatives all increase the

risk of CRC.(18)About 5%-10% of patients with CRC have an

inherited genetic abnormality that causes the cancer. These

abnormalities are Familial Adenomatous Polyposis (FAP) &

Hereditary Non Polyposis Colorectal Cancer (HNPCC), and they

should be excluded by careful family history.(19)

• Familial Adenomatous Polyposis (FAP): An autosomal

dominant syndrome that result from defect in the

adenomatous polyposis coli (APC) gene.(20)It is characterized

by presence of hundreds of polyps which occur at young age

and develop into CRC by the age of 40 years if preventive

surgery is not done.(21,22)About 1% of all CRC are due to this

syndrome.(19)

• Hereditary Nonpolyposis Colorectal Cancer (HNPCC): Is an

autosomal dominant syndrome that is a result of germline

mutations in mismatch repair genes (genes that code for

proteins responsible for correcting errors during DNA

replication). It is characterized also by presence of few polyps,

but not hundreds, at young age & then developed into

malignancy between the ages of 40 & 50 years.(23)

4- Dietary factors: Research is going on the role of dietary factors

such as red meat especially overcooked or processed, high fat

7

intake, low fiber diet, high refined carbohydrates, decreased

intake of protective micronutrients, obesity, alcohol

consumption, & deficiency of calcium & folate. All these factors

increase the incidence of CRC risk.(16,24,25,26,27,28,29,30,31,32) It is

theorized that reduced fiber content lead to decreased stool

bulk, increased fecal transit time in the bowel, and altered

bacteria flora of the intestine. Potentially toxic byproducts of

carbohydrate degradation are therefore present in higher in the

small stools and are held in contact with the colonic mucosa for

longer period of time. Moreover high cholesterol intake in the

red meat enhances the synthesis of bile acids by the liver,

which, in turn, may be converted into potential carcinogens by

intestinal bacteria. Refined diet also contains less vitamin A, C,

and E, which may act as oxygen scavengers.(3)

5- Other risk factors:

- It has been reported that the use of aspirin,

postmenopausal female hormone therapy, and oral

contraceptive pills are associated with low risk for

CRC.(33,34,35,36,37,38)

- Low physical activity & cigarette smoking are associated

with high tendency to develop CRC.(39,40,41,42,43,44)

8

- Infection with Helicobacter pylori, cytomegalovirus, or

human polyoma virus JCV was reported to be associated

with CRC.(45-47)

- Hyperinsulinaemia is associated with increased risk of

endometrial, colorectal, & breast carcinoma. The insulin

acts as growth factor for tumor formation.(48)

However 75% of all CRC occur in people with no known

predisposing factors for the disease. This makes early detection

and management with different screening modalities is an

important mean for significant reduction in CRC incidence and

mortality.(17)

1.5. Genetics of CRC:

Most CRC occurs sporadically in absence of well-defined

familial syndromes (3), while the remainder of CRC occur in patient

with inherited germline defects.(4) Regardless of the inciting event,

there are two pathogenically distinct pathways for the development

of CRC(49), both of which involve stepwise accumulation of multiple

mutations. However the genes involved and mechanisms by which

the mutations accumulate are different.(3)These pathways are:

(1) Adenoma-carcinoma sequence: characterized by chromosomal

instability that result in accumulation of mutations in a series of

9

oncogenes and tumor suppresser genes. These genes include:

APC gene, K-RAS gene, SMAD2&SMAD4 genes, and

P53gene.(3)

(2) Microsatellite Instability Pathway: characterized by genetic

lesions in DNA mismatch repair genes. It is involved in 10%-

15% of sporadic cases & in the HNPCC syndrome.(3)

1.6. Localization:

Most CRC are located in the sigmoid colon and rectum, but

there is evidence in changing distribution in the recent years, with

increased proportion of more proximal carcinoma.(50) Molecular

pathology has also shown site differences: tumors with high levels

of microsatellite instability (MSI-H) or RAS proto-oncogene

mutations are more frequently located in the cecum, ascending

colon & transverse colon.(51,52,53)

1.7. Metastasis & Mode of spread:

Colorectal cancer arises in the mucosa and tends to

spread to other organs through one of the following routes:(54)

(1) Direct extension of the tumor through all layers of the colon

wall to the adjacent structures or organs.

10

(2) Haematogenous: through the blood to the liver

(commonly), lungs, brain, adrenals, kidney, bone and others.

This route is associated with poor prognosis.

(3) Lymphatic: through the submucosal blood vessels to the

regional lymph nodes.

(4) Transcelomic: through the peritoneal cavity (54).

1.8. Diagnosis:

Clinical picture:

The presentation of large bowel malignancy generally falls

into three categories: insidious onset of chronic symptoms, acute

onset of intestinal obstruction, or acute perforation. The most

common is that of the insidious onset of chronic symptoms(2),

which are:

Rectal bleeding, chronic anaemia, change in bowel habits,

abdominal or rectal pain.(54) Less common symptoms include

weight loss, palpable mass, malaise, fever, symptoms of urinary

tract involvement, mucus discharge, obstruction or perforation of

the colon, acute appendicitis (from obstruction of the appendiceal

lumen by a cecal tumor) or signs of distant metastasis to the liver,

lungs or brain.(2,54)Rectal bleeding is visible in lesions of the

sigmoid colon and rectum, and will be the cause of anaemia

11

.Alteration in bowel habits(constipation &diarrhoea)are more

common with left colon or more distal tumors, because of narrow

lumen and more solid stool that traverse the segment containing

the tumor. Abdominal pain is crampy or constant.(54) Left-sided

obstructing lesions may present with cramping abdominal pain

associated with nausea & vomiting.(2) Presence of peritonitis

indicates colonic perforation. Palpable mass, signs of distant

metastasis and weight loss are associated with poor prognosis.(54)

Screening:

Screening means checking for health problem before they

cause symptoms.(12) Because early detection greatly influence

survival in CRC, mass population screening has been

recommended in many high-risk populations. High-risk patients

include patients over 40 years of age, patients with Familial

Adenomatous Polyposis (FAP) and Hereditary Non Polyposis

Colon Cancer (HNPCC), and patients with chronic ulcerative colitis

(U.C).(4)Currently, it is estimated that screening of average risk

people over the age of 50 would reduce the mortality of CRC by

50%.(55)

Screening for sporadic CRC is unsatisfactory. Several

different screening methods have been advocated (4):

12

a) Faecal Occult Blood Testing(FOBT) annually: Fecal Occult

Blood Test is nonspecific test that fail to detect many small

cancers and precancerous lesions.(56)But a positive annual or

biannual FOBT that is followed by complete diagnostic

evaluation of the colon will reduce the number of deaths caused

by CRC.(57),(58)

b) Flexible sigmoidoscopy every five years: Is an examination of

the rectum &lower colon using sigmoidoscope.(12)The

effectiveness of this method as a screening tool depends on its

ability to detect cancers & adenomatous polyps in average risk

asymptomatic patients with negative FOBT.(59) If sigmoidoscopy

detects polyps, it should be followed by colonoscopy.(60) FOBT

annually accompanied by sigmoidoscopy every five years is

recommended by American Cancer Society (ACS)&other

experts.(61)

c) Double Contrast Barium Enema(DCBE)every five to 10 years:

Is series of X-Rays of the entire colon & rectum.(12) The efficacy

of barium enema in preventing CRC has not been

evaluated.(59)Single-column barium enema is less sensitive than

DCBE, so if it is used as a screening tool, it should be combined

with flexible sigmoidoscopy.(18)If lesions are detected by barium

enema the patient require colonoscopy.(59)

13

d) Colonoscopy every 10 years: Colonoscopy is examination of

rectum & entire colon using colonoscope.(12) It allows detection

& removal of premalignant & malignant lesions through out the

entire colon & rectum(12,59), and so reduces deaths from CRC.(62)

e) Genetic testing: Is recommended only for: (1) Those with

familial polyposis syndrome & HNPCC to see whether they

have the inherited genetic defect. (2) Patients with sporadic

CRC who satisfy the Amsterdam Criteria for HNPCC,(4) which

are: a) At least 3 family members with CRC, at least 2 being

first degree relatives. b) At least 2 generations with CRC. c) At

least one CRC patient younger than 50 years old at diagnosis.

Over 70% of families that meet these criteria have genetic

mutations associated with HNPCC.(63)

There are new tests under study for CRC screening:

(1) Virtual Colonoscopy (Computed Tomographic Colonoscopy).

(2) Genetic testing of stool sample.(12)

Diagnostic Studies:

Colonoscopy with biopsies is best; proctosigmoidoscopy

gives limited data due to shorter length of scope, and DCBE is

useful but requires colonoscopy if lesions are seen.(1)Brush

cytology has been described as useful in diagnosis of rectal

14

cancer, but now is not recommended because of high cost & rare

false positive diagnosis.(4)

Lab Studies:

Complete blood count with differential, showing anaemia in

right-sided tumors due to chronic blood loss; chemistry panel

including liver and renal functions.(1)

Preoperative Studies:

Chest X-Ray (CXR); serum Carcinoembryonic Antigen

(CEA) level; metastatic search if suspected; abdominal CT &

radionuclide scanning are costy, so have no role in majority of

patients.(1)

1.9. Pathologic diagnosis:

The diagnosis of CRC is established by histologic

examination of a biopsy specimen which obtained endoscopically

or, rarely, intraoperatively when the endoscopy is impossible

because of tight strictures.(4)

Gross:

CRC may be exophytic/fungating with predominantly

intraluminal growth, endophytic/ulcerative with predominantly

intramural growth, diffusely infilterative/linitis plastica with subtle

endophytic growth, and annular with circumferential involvement of

15

the colorectal wall & constriction of the lumen.(6) Right-sided colon

cancers tend to be polypoid, exophytic masses that project from

the wall into the lumen. Left-sided colon cancers tend to be annular

with mucosal ulceration & thickening of the wall causing luminal

narrowing. Rectal cancers are exophytic or ulcerative.(4) But

overlap among these types is common.(6)

The incidence trends of CRC differ for each subsite (64) as

follows: the cecum & ascending colon, 22%; transverse colon,11%;

descending colon, 6%; rectosigmoid, 55%; &other sites, 6%.(3) In

other words about 50% of CRC occurs in the rectosigmoid

area.(14)

In cross section, grayish white tissue is seen replacing the

bowel wall. Highly mucinous tumors have a gelatinous, glaring

appearance, with mucus separating the layers of the bowel wall.(14)

Histological types:

The internationally accepted histologic classification of CRC

proposed by the World Health Organization (WHO) is

recommended by the College of American Pathologists (CAP) and

is usually used in pathology reports.(65,66) Medullary carcinoma,

which previously classified as an undifferentiated carcinoma, has

been added to the revised WHO classification.(67)

16

* World Health Organization classification of colorectal

carcinoma:(6)

- Adenocarcinoma insitu/severe displasia.

- Adenocarcinoma.

- Mucinous (colloid) adenocarcinoma.

- Signet-ring cell carcinoma.

- Squamous cell (epidermoid) carcinoma.

- Adenosquamous carcinoma.

- Small cell (oat-cell) carcinoma.

- Medullary carcinoma.

- Undifferentiated carcinoma.

- Others (e.g. papillary carcinoma).

Adenocarcinoma:

About 85% of CRC are well and moderately differentiated

Adenocarcinoma. These are composed of irregularly infiltrating

malignant glands. The cells are columnar & have elongated “cigar-

shaped” nuclei. The invasive tumor is surrounded by a

desmoplastic response. There is focal necrosis & variable mitotic

activity.(4)

17

Mucinous adenocarcinoma:

Comprises 10% of CRC and include signet-ring cancers.

The mucinous adenocarcinoma is characterized by extracellular

mucin with the tumor cells floating in it.(68)The definition of

mucinous carcinoma is variable: some say that 50% of the lesion

must be mucinous(66), where as others say that 75% of the lesion

must be mucinous.(69,70)

Signet-ring cell carcinoma:

Defined by the presence of >50% of tumor cells with

prominent intracytoplasmic mucin.(71) It can occurs in the mucin

pools of mucinous adenocarcinoma.(6) Signet-ring carcinoma has a

poor prognosis.

Squamous/Adenosquamous cancers:

Are very rare & are associated with U.C, schistosomiasis,

and pelvic irradiation.(14)To classify a lesion as adenosquamous

carcinoma, occasional foci of squamous differentiation must be

present.(6) Certain criteria must be present to diagnose primary

CRC as squamous or adenosquamous: (1) No other sites of

squamous carcinoma in the body. (2) No involvement of

colacogenic or squamous-lined mucosa.(72)

18

Small cell carcinoma:

Rare and is about <1% of CRC. It is a malignant

neuroendocrine tumor that is similar histologically & biologically to

small cell (oat cell) carcinoma of the lung. As signet-ring

carcinoma, the small cell carcinoma has unfavorable

prognosis.(67,68)

Medullary carcinoma:

Uncommon & about 1% of CRC.(68) It is non-gland forming

carcinoma that previously had been classified as undifferentiated

carcinoma by the WHO system, but now known to be associated

with microsatellite instability and/or HNPCC syndrome.(67)

Histologically medullary carcinoma has pushing borders & is

composed of uniform, rounded cells which have small to medium-

sized nuclei & prominent nucleoli. It exhibits numerous mitosis &

brisk lymphocytic infiltrate.(68,73) Medullary carcinoma has a good

prognosis.(74)

Undifferentiated carcinomas:

These are tumors lack morphological evidence of

differentiation beyond that of epithelial tumor and have variable

histological features.(75)

19

Unusual forms of CRC:

Are very rare &for example:

Papillary carcinoma: the carcinoma forms papillations with

fibrovascular cores & epithelial tufts.(67)

Spindle cell (sarcomatoid or metaplastic) carcinoma.(76)

Clear cell adenocarcinoma: resemble renal cell adenocarcinoma,

but differentiated from it by presence of high level of

Carcinoembryonic Antigen (CEA) in the former.(14),(77)

Basaloid (colacogenic) carcinoma: similar to it is anal

counterpart,& has been reported on a few occasions in the

colorectum.(14)

Carcinoid tumor: of the large bowel is more common in the

rectum.(14) It is composed of small & uniform cells with rounded

nuclei with granular chromatin. The cells arranged in nests or

trabecular pattern.(4)

Adenocarcinoma-carcinoid tumor: are very rare in the colorectum.

Composed of approximately equal amounts of adenocarcinoma &

well differentiated carcinoid tumor.(4)

Choriocarcinomatous differentiation: rare cases of

adenocarcinoma with areas of choriocarcinoma have been

reported.(68)

20

Lymphomas: are less frequent than in the small intestine &

stomach.(14)

Staging:

Pathologic staging is an expression of the degree of invasion

& metastatic spread of the tumor.(4) It is based on the size of the

primary lesion, its extent of spread to regional lymph nodes, and

the presence or absence of distant metastasis.(3)

Three different systems for staging CRC have been developed

over years(4):

(1) Duke’s System(78)*: is the simplest & is widely used in

Europe.(4)

• Duke’s Classification of carcinoma of the colon & rectum:

Stage A: cancer restricted to colorectal wall.

Stage B: the cancer invades outside the muscularis externa.

Stage C: cancer with positive nodes.

Stage D: distant metastasis.

(2) Astler-Coller System (79)**: Modified Duke’s System. It is used in

the United States in addition to the Duke’s System. It provides

better distinction between minimally invasive tumors in term of

their nodal status.(4)

21

** Astler-Coller Classification of carcinoma of the colon and

rectum:

Stage A: lesion limited to the mucosa.

Stage B1: lesion involves muscularis propria, but does not

penetrate through it; uninvolved nodes.

Stage B2: lesion penetrates through the muscularis propria,

uninvolved nodes.

Stage C1: extending into the muscularis propria, but not

penetrating through it; involved nodes.

Stage C2: penetrating through the muscularis propria;

Involved nodes.

Stage D: distant metastatic spread

(3)TNM (Tumor, Node, Metastasis) System(80)***: This system

had been advocated by American Joint Committee on Cancer

(AJCC) and Union Internationale Contre Le Cancer

(UINCC),and is recommended by the College of American

Pathologists (CAP).(65,81)It is more accurate, but too

cumbersome for general use.(4) Currently the TNM system is

widely used, & is internationally accepted.(67)

22

*** TNM Classification of carcinoma of the colon & rectum:

T: primary tumor.

TX: primary tumor can not be assessed.

Tis: carcinoma insitu (intraepithelial) or intramucosal

(lamina propria invasion).

T1: tumor invades submucosa.

T2: extending into the muscularis propria, but not penetrating

through it.

T3: penetrating through the muscularis propria into the serosa

into non-peritonealized paracolic or perirectal tissues.

T4: tumor directly invades other organs or structures and/or

perforates visceral peritoneum.

N: regional lymph nodes.

NX: regional lymph nodes can not be assessed.

N0: no regional lymph node metastasis.

N1: metastasis in 1 or 3 lymph nodes.

N2: metastasis in 4 or more lymph nodes.

M: distance metastasis.

MX: distant metastasis can not be assessed.

M0: no distant metastasis.

M1: distant metastasis.

23

Stage grouping:

Stage 0 Tis N0 M0

Stage I T1 N0 M0

T2 N0 M0

Stage ІΙ T3 N0 M0

T4 N0 M0

Stage ΙΙΙ any T N1 M0

any T N2 M0

Stage ΙV any T any N M1

Tumor Grading:

Grading of a tumor is an expression of the aggressiveness

of the neoplasm. It is based on the degree of differentiation of the

tumor cells&the number of the mitosis within the tumor.(3)

The histological grading of CRC is evaluated subjectively.

Although a number of grading systems have been suggested in

the literature, there is no single accepted standard for grading. The

number of grades & the criteria in each differ among the various

grading schemes. In some systems, grades are defined on the

basis of a single microscopic feature, such as the degree of gland

formation, &in others the grades based on a number of features.(67)

However, most systems stratify tumors into three or four grades as

follows:

24

GRADE 1: well differentiated. The glandular structure is

> 95% of the tumor,(6) & is composed of simple tubule

with easily discerned nuclear polarity.(68)

GRADE 2: moderately differentiated. The glands are 50% - 95%

of the tumor,(6) & are irregular with barely discernable

or lost nuclear polarity.(68)

GRADE 3: poorly differentiated. The glandular structure is

5%-50%(6) or absent with loss of the nuclear polarity.(68)

GRADE 4: undifferentiated,(67) & the glandular structure is <5% of

the tumor.(6)

Mucinous adenocarcinoma & signet ring cell carcinomas are

considered poorly differentiated (grade 3). Medullary carcinoma

with MSI-H appears undifferentiated.(6)

In general a two-typed grading system based solely on

proportion of gland formation (> or < 50% glands formation) would

be expected to reduce interobservor variability. This system is as

follows:

LOW GRADE: include the well differentiated& moderately

differentiated tumors.(58)

HIGH GRADE: include poorly differentiated & undifferentiated

tumors.(82)

25

So the use of a two-typed grading system for CRC is

advisable, & such system has been recommended by colorectal

working group of a 1999 Consensus Conference sponsored by the

College of American Pathologists (CAP).(83)

1.10.Treatment:

The three main types of treatment for CRC are surgery,

radiation therapy, and chemotherapy.(19) Surgery includes

segmental resection of the tumor with adequate margins along with

potentially involved lymph nodes.(4)

Newer targeted therapies called monoclonal antibodies are

now beginning to be used as well. Depending on the stage of the

cancer, two or more types of treatment may be used at the same

time, or one after the other.(19)

♦ Early stage colon cancer:

Surgery is initial therapy for choice for localized, potentially

curable cases.(1) It is either open surgery (colectomy with

colostomy) or laproscopic resection.(4,84)

Postoperative radiation and adjuvant chemotherapy with

5-Fluorouracil (5-FU) reduce the risk of recurrence.(85,86)

26

• Early stage rectal cancer: Also surgery is the main treatment. Transanal endoscopic

microsurgery (TEM) is now preferred form of local treatment for

rectal polyps & stage І rectal cancer that are small & near the

anus.(4,84) A low anterior resection is for cancers near the upper

part of the rectum.(19) For cancers in the lower part of the rectum,

abdominoperitoneal resection with colostomy is done.(4,19) The

surgery should be followed by chemoradiation which improve

survival and local control of the tumor.(87)

Most studies regimens consist of surgery and postoperative

chemotherapy with 5-FU & mitomycin within 6 weeks, followed by

radiation plus concurrent chemotherapy.(88)

• Metastatic cancer:

Is treated by surgery (after preoperative evaluation),

postoperative radiation (for palliative treatment of symptoms), and

systemic chemotherapy with various 5-FU based regimens.(1)

• New developments in treatment of CRC:

- Drugs being developed to enhance the tumor-killing ability of

radiation therapy & chemotherapy, and stop the angiogenesis.

- Gene therapy.

- Immunotherapy: enhances the body’s immune system to kill

tumor cells.

27

- Monoclonal antibodies to identify tumor cells for destruction or

prevent their division.

- Vaccines: cause the body to produce more antibodies to kill

cancer cells.(89)

1.11. Prognosis:

The 5-year crude survival rate after curative resection for

CRC ranges between 40%-60%. Local recurrence and/or regional

lymph node metastasis occur in over 90% of the failure cases.(14)

The prognosis of CRC is affected by a number of clinical

variables, pathological features, oncogenetic, molecular, &

immunological variables. The pathologic stage & the factors

affecting it remain the most prognostic factors.(90) The 5-year

survival rate are ~90% for Duke’s A, 5o-65% for Duke’s B, and

15-25% for Duke’s C.(14,90)

Poor prognostic factors include: elevated CEA level, which is

the only consistently predictive clinical feature; mucinous & signet

ring pattern on histology; bowel wall/ regional lymph node/

perineural invasion; evidence of bowel obstruction or

perforation;(1)DNA ploidy; DCC gene deletion; P53 & Ki-ras

mutation;(91) mucin associated antigens;(92) growth factors &

receptors expression.(93)

28

1.12. Recurrence:

Is manifested by occurrence of symptoms after

treatment,(94)& can be:

(1) Locoregional: the recurrence is in or around the anastomotic

site. It results from positive surgical margins.(4)

(2) Peritoneal metastasis: result from seeding of the peritoneal

cavity by the tumor prior to surgery.(4)

(3) Distant metastasis: may manifest in lymph nodes more

proximal to those in the field of initial surgery&elsewhere in

the body due to haematogenous spread.(4)

Recurrence is best detected by: serial serum assays for

CEA, CT scans, radionuclide liver scans, & regular colonoscopy in

the first year after surgery.(4,14)

Recently, a new blood test for detection of recurrence has

been announced. This test is called GCC-B1TM.It tests for the

presence of the protein guanylyl cyclase C in the blood, which is

normally only found in the intestine. This test has the ability to

detect 90%-100% of CRC metastasis.(95)

29

OBJECTIVES

General objectives:

To study the pattern of patients with CRC in Khartoum State,

Sudan; from January 2001 through to December 2004 with view to

determine various epidemiological & clinicopathological features of

this malignancy.

Specific objectives:

1- To determine the histopathological patterns of CRC.

2- To determine the residency distribution, clinical presentation &

relation of CRC with age & sex.

30

METHODOLOGY

2.1. Study design:

A descriptive retrospective study.

2.2. Study field:

Ibn Sina Hospital at Khartoum, Sudan. It is specified for

renal & gastrointestinal diseases. It receives patients from different

regions of Sudan for diagnosis & management.

2.3. Study Population:

All cases of colorectal cancer presented to Ibn Sina Hospital

between January 2001 through to December 2004.

2.4. Inclusion Criteria:

Colorectal cancer patients who under-went endoscopic and

histopathological studies for diagnosis, with or without laboratory

and radiological studies.

2.5. Exclusion Criteria:

Colorectal cancer patients who had no histopathological

slides in the histopathology lab of the hospital.

2.6. Tools of data collection:

Data were collected from the patients’ request forms into a

predesigned questionnaire with detailed history and investigations.

The patients in this study had been diagnosed by histological

31

examination of surgical or endoscopic biopsies which had been

processed to provide slides for microscopic examination. The

processing include fixation (in 10% formalin), dehydration (by

different concentrations of alcohol), clearing (using xylene), &

impregnation (with paraffin wax). Then the tissues were blocked by

transferring them from the final wax bath into a mold filled with

molten wax. The block was then quickly cooled. The tissue was cut

by microtome, & the cut sections were flooded on a mounting bath.

Then the sections were mounted on an ordinary slides, put in a hot

oven or hot plate to remove the wax & finally stained by routine H

& E method. The slides of the histopathological diagnosis for

patients were collected& reviewed to: confirm the CRC diagnosis;

determine the histopathological type of the tumor using the WHO

classification of CRC; and grade the tumor using the well

differentiated, moderately differentiated, poorly differentiated,

&undifferentiated Grading System.

2.7. Statistics:

The data were analyzed using computer S.P.S.S program,

version 10.

32

RESULTS

There were 123 patients with CRC during the 4 years study.

When the slides reviewed, 23 patients had no available slides & so

were excluded from this study. The remainders (100 cases) were

analyzed.

3.1. Characteristics of the studied patients:

3.1.1. Age distribution: The ages ranged from 14-85 years with a mean of 49.89±

16.86.Thirty-three (33%) patients were below 40 years of age. The

youngest patient was 14 years old. The peak age of incidence was

> 60 years (Figure 1).

3.1.2.Sex distribution:

Fifty-six (56%) patients were males compared to 44 (44%)

females (Figure 2). The colon cancer cases were 45 cases, while

those of the rectum were 55 cases. The 45 colon cancer cases

distributed almost equally between males & females (23 males &

22 females), where as rectal cancers (55 cases) encountered more

among males (33 cases) compared to females (22 cases). As a

result of these findings, the male to female incidence rate ratio

(R.R) for colon cancer was 1:1 and for rectal cancer was 1.5:1. For

all CRC it was 1.1:1 (Table 1).

33

The incidence rate for males increases slowly with age until

reaching peak at the age of 60 & over, while females had two

peaks, one at the age group 20-<40, & the other at the age group

60 & over (Figure 3).

3.1.3.Residency distribution in CRC:

As regard to residency, seventy-four (74%) patients were

from the middle of Sudan (more than two thirds of them were

from Khartoum), thirteen (13%) patients were from the North,

eleven (11%) patients were from the West, two (2%) patients were

from the East, and no one was from the South (Figure 4).

3.2. Distribution of the clinical symptoms in the

studied patients:

Table 2 shows the various presentations of CRC in the

studied patients. Rectal bleeding represented the majority (76%) of

the symptoms. About 90% of patients with rectal cancer presented

with frank rectal bleeding on presentation. The duration of the

symptoms varied from one to twelve months in the majority of

patients. Among the total, 61.2% of patients had symptoms ≤6

months duration, while 38.7% of patients had symptoms of >6

months.

34

3.3. Subsite distribution of CRC in the studied

patients:

The majority of the tumors arising from the rectum, sigmoid

colon & rectosigmoid junction (77%), the transverse colon was the

least involved site (2%) (Figure 5).

3.4 . Histopathological characteristics of CRC in the

studied patients:

3.4.1.Histological patterns:

The diagnosis of CRC in this study is based on

histopathological examination of endoscopic biopsies, combined

with U.S. examination. The serum level of CEA had been reported

in only 3 patients.

Adenocarcinoma was the most common tumor seen in 74%

of cases. 13 (13%) were Mucinous adenocarcinoma, 7 (7%) Signet

ring cell carcinoma, 5 (5%) Papillary carcinoma, & 1 (1%)

anaplastic carcinoma. (Figure 6).

3.4.2.Grading:

The moderately differentiated adenocarcinoma represented

the majority of CRC cases (38.3%), followed by the poorly

differentiated adenocarcinoma, & then the well-differentiated

adenocarcinoma became the least (Table 3).

35

3.5. Relationship between the histological patterns of

CRC & the age groups in the studied patients:

The adenocarcinoma was predominant (43.2%) among

those ≥ 60 years of age compared to the other age groups. The

mucinous type was highest (40%) and equally distributed between

the age groups 20-<40 & ≥ 60 years. The signet ring carcinoma

was more common (71%) among the age group 20-<40 years.

Finally the anaplastic type was found to be confined to the age

group ≥ 60 years (Figure 7).

3.6. Relationship between the histological patterns &

the sex in the studied patients:

All the histological types of CRC were found to be more in

males than females. No female was reported with the anaplastic

type (Figure 8).

In the present study 3 patients were reported as cases of

recurrence of CRC, one patient with signet ring cell carcinoma &

the other two with well-differentiated adenocarcinoma.

Metastasis was reported in one patient.

Histology of tissue biopsies was shown in (Figures 9, 10,

11, 12, 13& 14 ) as well differentiated adenocarcinoma,

36

moderately differentiated adenocarcinoma, poorly differentiated

adenocarcinoma, mucinous adenocarcinoma, signet ring cell

carcinoma & papillary carcinoma, respectively.

37

Table (1): Sex distribution and male to female incidence rate

ratios for cancer of the colon & rectum among the

studied group.

Male Female

Site Frequency Percent Frequency Percent

Incidence

Rate Ratio

Rectum 33 60% 22 40% 1.5:1

Colon 23 51.1% 22 48.9% 1:1

38

Table (2): Presenting symptoms of colorectal cancer among

the studied group.

Symptoms Frequency Percent

Rectal bleeding 76 76%

Abdominal pain 19 19%

Altered bowel habit 12 12%

Constipation 5 5%

Diarrhoea 23 23%

Weight loss 13 13%

Vomiting 1 1%

Fatigability 4 4%

Painful defecation 9 9%

Abdominal mass 11 11%

Others 23 23%

39

Table (3): Grading of colorectal cancer among the studied

group.

Tumor differentiation Frequency Percent

Well differentiated 26 27.37%

Moderately differentiated 36 37.89%

Poorly differentiated 32 33.68%

Undifferentiated 1 1.05%

Total 95 100%

40

40%

27%31%

2%

0%

5%

10%

15%

20%

25%

30%

35%

40%

Perc

enta

ge

60&over 40-<60 20-<40 <20

Age (years)

Figure(1): Age distribution of colorectal cancer among the studied group. (N=100)

41

Figure(2): Sex distribution of colorectal cancer among the studied group. (N=100)

Female44%

Male56%

42

Figure(3): Age specific incidence rate of colorectal cancer in males & females among the studied group.

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

>20 20-<40 40-<60 60 & over

Age (years)

Perc

enta

ge

Female

Male

43

74%

2%

11%13%

0%

10%

20%

30%

40%

50%

60%

70%

80%P

erce

ntag

e

Centre East West North

Residence

Figure(4): Residence distribution of colorectal cancer among the studied group. (N=100)

44

Figure(5): Subsite distribution of colorectal cancer among the studied group. (N=100)

8%7%2%3%3%6%

16%

55%

Non specified Cecum Transverse colon Ascending colon

Descending colon Rectosigmoid Sigmoid colon Rectum

45

Figure (6): Histological patterns (Diagnosis) of colorectal cancer among the studied group. (N=100)

1%5%7%13%

74%

Anaplastic carcinoma Papillary carcinomaSignet ring carcinoma Mucinous adenocarcinomaAdenocarcinoma

46

0% 0% 0%

100.00%

0%

20.00%

40%40%

29%

71.00%

0% 0%

0%

38.50%

23.10%

38.50%

0.00%

27.00%

29.70%

43.20%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Perc

enta

ge

Anapla

sticc

arcino

ma

Papilla

ry ca

rcino

ma

Signet

ring c

arcinom

a

Mucinou

s ade

noca

rcino

ma

Adeno

carci

noma

Diagnosis

Figyre (7): Relationship between the diagnosis & age groups among the studied group.

<2020-<4040-<6060 & over

47

100.00%

0%

80.00%

20.00%

57.10%

42.90%

69.20%

30.80%

51.40% 48.60%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Perc

enta

ge

Anaplas

tic ca

rcinoma

Papilla

ry ca

rcinoma

Signet rin

g carci

noma

Mucinous a

denoca

rcinoma

Adenoca

rcinoma

Diagnosis

Figure(8): Relationship between the diagnosis & sex among the studied group.

Male

Female

48

Fig (9): Well-differentiated adenocarcinoma. Invasive simple malignant glands surrounded by desmoplasia (H&E. X10).

49

Fig (10): Moderately differentiated adenocarci-noma. Complex infiltrating malignant glands with

areas of solid pattern.(H&E. X10).

50

Fig. (11): Poorly differentiated adenocarcinoma. Solid pattern without significant gland formation (H&E. X20).

51

Fig (12): Mucinous adenocarcinoma. Consisting of malignant glandular elements in extracellular

mucin lakes.(H&E. X10).

52

Fig (13): Signet ring carcinoma. Consisting of signet ring cells containing intracellular

mucin.(H&E. X20).

53

Fig (14): Papillary carcinoma Consists of papillations with fibrovascular cores

and epithelial tufts.(H&E. X20).

54

DISCUSSION

This is a descriptive retrospective study about CRC in

Sudanese patients. It was carried in the period from January 2001

to December 2004 & includes analysis of 100 cases.

The epidemiology of CRC has generated more interest

recently due to new developments in genetics and molecular

biology of this disease. The epidemiological pattern of the disease

varies markedly between different population groups.(96)

The incidence of CRC has been of great interest to many

workers particularly in African countries, were it has been reported

to be relatively lower than in affluent societies.(7) The World Health

Organization(WHO) forsees the overall global situation in respect

to CRC will be worsen.(97) During the latter years in Sudan, there

has been a significant increase not in the total number of cancers

but also in the cancers of the large bowel. The socioeconomic

changes & urbanization, which take place in Sudanese society,

entails characterization of this cancer, which is usually linked with

economic development.

In Sudan as in most developing countries, there is at

present no reliable statistical information on absolute cancer rates.

55

As our study was limited to registered data, many difficulties were

faced in the interpretation of the results due to undetailed history,

histopathological diagnosis & staging of the neoplasia. As a result

of this, our study indicated that 74% were adenocarcinoma, in

contrast to what accepted globally that, up to 98% of CRC are

adenocarcinoma.(16) But in general the adenocarcinoma

represented the majority (74%) of histopathological patterns of

CRC in this study. Other histological types seen were signet ring

carcinoma (7%), mucinous carcinoma (13%), papillary carcinoma

(5%) & anaplastic carcinoma (1%). No cases of anaplastic or

papillary carcinoma were reported in reviewed local studies.

In this study, our results are in accordance with the literature

regarding the occurrence of high number of cases among

males.(16,17) It was reported that CRC has a different sex

distribution with nearly similar incidence between the males &

females for colon cancer and a male preponderance for rectal

cancer.(16) This is almost the same trend encountered with males

to females incidence rate ratio for colon & for rectal cancer in this

study. The high incidence of rectal cancer in males can also be

explained by the fact that Sudanese females are very shy & very

reluctant to specific examination as proctoscopy & sigmoidoscopy.

56

Another important features highlighted by the study is the

resemblance of our data with those from developing countries

regarding the early age of onset of CRC & left side subsite

preponderance,(98,99,100,101,102) compared to late age at diagnosis &

right side cancer (proximal shift) in the developed countries.(103)

Early age of incidence is a characteristic in developing countries.

Under age of 40, there are more than one-third of cases in

Egypt,(99) 21.4% in Saudi Arabia,(104) & 17% in Philippine,(102)

compared to 3.6% in USA,(105) & 7.6% in Canada,(106) In our study

only four patients were reported to have history of U.C. & all the

four were young patients. This in addition to another young patient

with positive family history of CRC. But these can not fully explain

the early incidence of CRC.

In the present study, left side preponderance is clear as 77%

of cases in the rectum, rectosigmoid junction, & sigmoid colon. In

addition to 2% of cases in the descending colon. The proximal shift

in developed countries is not clearly discussed in the literature,

although some relate it to possibly more effective screening in the

right side, or to real reduction In rectal cancer incidence.(103)

In this study the incidence rate for males increases with age,

at first rapidly till the age group 20-<40 years, then slowly until

reaching a peak at the age group 60 years & over. While females

57

had two peaks, one at the age group 20-<40 years & the other at

the age group 60 years & over. Both of the females’ peaks were

higher than those of males. This compared to a study done in

Yemen in which both sexes showed their peak incidence at the

age group 55-<65 years, but the peak for males was higher than

that for females.(107)

Regarding the residency, most of the patients (74%) were

from the central region of Sudan, of them about two thirds were

from Khartoum. No one was found to be from the South. These

may be due to the following factors:

(1) Most of the Sudanese are clustered in the big towns.

(2) There is discrepancy between the number of doctors,

particularly specialists, & the populations they serve.

(3) Because of difficulty in the transportation, many patients,

especially from the rural regions, are unlikely to reach

hospitals.

(4) Finally, the shortage in medical services & the war situations in

Southern Sudan prevented southern patients from reaching

hospital.

The racial history of the patients was not found in the

records, so was not analyzed.

58

The majority of patients present with symptoms of bleeding

per rectum (76%), diarrhoea (23%), abdominal pain (19%), weight

loss (13%) & altered bowel habits (12%) in various combinations.

While acute obstruction & perforation were not features, as this

hospital deals with elective operations only. The duration of

symptoms varies from one month to one year in the majority of

patients, with a median of 6 month of the total duration. In fact

>50% of patients had symptoms < 6-month duration & this can be

explained by the fact that: most of the patients in this study

presented with rectal bleeding, which is the symptom that make

patient to seek medical advice.

The majority of patients in this study present with tumors at

early stages of differentiation (moderately & well differentiated),

while few number present with poorly & undifferentiated tumors.

This may be due to increase awareness of cancer & improved

facilities for diagnosis.

In this study anaplastic carcinoma show the highest

incidence in males, while in females adenocarcinoma show the

highest incidence. Signet ring carcinoma was predominant in the

younger age group compared to other age groups, while

anaplastic carcinoma & adenocarcinoma were predominant in the

age group 60 years & over.

59

CONCLUSION

• Only 5 histological variants were identified in this study i.e.

adenocarcinoma, mucinous carcinoma, signet ring carcinoma,

papillary carcinoma, & anaplastic carcinoma.

• CRC is not an uncommon disease in this part of the world as

used to be considered previously.

• Despite limitation in the background history, detailed

histopathological diagnosis & staging, the study indicated that

developing countries characteristics as the presence of relatively

high proportion of early onset tumor & left-sided preponderance

are clear.

60

RECOMMENDATIONS

• Further in-depth studies should be carried out to address the

possible community-related risk factors of this cancer & to know

the causes of early-onset CRC.

• Education of the public about the nature of the disease & about

the warning signs of CRC. And to achieve this; efficient use of

press & audiovisual media is necessary. • Execution of screening programs for early detection & better

outcome. • Detailed histopathological diagnosis & staging, & improvement

of cancer reporting & registering activities. • The request form should be designed to contain detailed history

about the patient. • Construction of a bowel clinic for the lower gastrointestinal

problems.

61

REFERENCES

1. www.oncolink.upenn.edu. Colorectal cancers general

information. December 2001.

2. Norton JA, Bollinger RR, Chang AE, Lowry SF, Mulvihill SJ,

Pass HI. Colorectal polyps and cancer. Surgery: Basic science

and clinical evidence. New York: Springer-verlag; 2001. P. 701-

707.

3. Kumar V, Abbas Ab.K, Fausto N. Colorectal carcinoma.

Robbins & Cotran, Pathologic Basis of Diseases. 7th edi.

California: Elseiver Saunders Company; 2005. P. 864-867.

4. Chandrasoma P, Dalton P. Colorectal adenocarcinoma.

Gastrointestinal Pathology. Los Angles: Asimon & Schuster

Company; 1999. P. 339-359.

5. www.nci.gov. Genetics of colorectal cancer. National Cancer

Institute. May 2005.

6. Hamilton AS, Aaltonen AL. Tumors of the colon & rectum.

World Health Organization classification of tumors, Pathology

and genetics of tumors of the digestive system. France, Lyon:

International Agency for Research on Cancer (IARC); 2000. P.

103-119.

62

7. Elmasri SH, Boulos PB. Carcinoma of the large bowel in

Sudan. Br J Surg 1975; 62: 284-286.

8. Zauber AG, O’Brien MJ, Winawer SJ. On finding flat

adenomas: is the search worth the gain? Gastroenterology

2002; 122 (3): 839-840.

9. Howe JR, Mitros FA, Summers RW. The risk of gastrointestinal

carcinoma in familial juvenile polyposis. Ann Surg Oncol 1998;

5 (8): 751-756.

10. Jeevaratnam P, Cottier DS, Browett PJ. Familial giant

hyperplastic polyposis predisposing to colorectal cancer: a new

hereditary bowel cancer syndrome. J Pathol 1996; 179 (1): 20-

25.

11. Rashid A, Houlihan PS, Booker S. Phenotypic and molecular

characteristics of hyperplastic polyposis. Gastroenterology

2000; 119 (2): 323-332.

12. www.cancer.gov/ publications. Colorectal cancer screening.

Cancer facts by National Cancer Institute. 2004 September.

13. Fraser J. Malignant disease of the large intestine. Br J Surg

1973; 25: 647-668.

14. Rosi J. Normal anatomy of the large bowel. Ackerman’s

Surgical Pathology. 8th edi. New York: Mobsy company; 1996.

P. 729-730.

63

15. Poyle P, Leon ME. Epidemiology of colorectal cancer. Br Med

Bull 2002; 64: 1-23.

16. The World Cancer Research Fund, The American Institute for

Cancer Research. Food, Nutrition and the Prevention of

Cancer: a global perspective. The World Cancer Research

Fund and the American Institute for Cancer Research.

Washington (DC): Banta Book Group; 1997.

17. Agency for Health Care Policy and Research (AHCPR).

Colorectal cancer screening: Executive Summary. Silver Spring:

AHCPR Publication Clearinghouse: Publication No. 97-0302:

2002.

18. Winawer SJ, Fletcher RH, Miller L, Godlee F, Stolar MH,

Mulrow CD. Colorectal cancer screening: clinical guideline and

rationale. Gastroenterology 1998; 114: 625.

19. www.cancer.org. What are the risk factors for colorectal cancer

& how colorectal cancer treated? Cancer reference information

by American Cancer Society. 2005 January.

20. Leppert M, Dobbs M, Scambler P, O’Connell, Nakamura Y,

Stauffer D. The gene for familial polyposis coli maps to the long

arm of chromosome 5. Science 1987; 238: 1411-1413.

64

21. Arvanitis ML, Jagelman DG, Fazio VW, Lavery IC, McGannon

E. Mortality in patients with familial adenomatous polyposis. Dis

Colon Rectum 1990; 33: 639-642.

22. Vasen HF, Griffioen G, Offerhaus GJ, Den Hartog Jager FC.

The value of screening and central registration of familial

adenomatous polyposis. A study on families in the Netherlands.

Dis Colon Rectum 1990; 33: 227-230.

23. Burke W, Petersen G, Lynch P, Botkin J, Daly M, Garber J.

Recommendations for follow-up care in individuals with an

inherited predisposition to cancer. I. Hereditary nonpolyposis

colon cancer. JAMA 1997; 277: 915-919.

24. Givannucci E, Willett WC. Dietary factors and risk of colon

cancer. Ann Med 1994; 26: 443.

25. Newcomb PA, Storer BE, Marcus PM. Cancer of the large

bowel in women in relation to alcohol consumption: a case

control study in Wisconsin (United States). Cancer Causes

Control 1993; 4 (5): 405-411.

26. Meyer F, White E. Alcohol and nutrients in relation to colon

cancer in middle-aged adults. Am J Epidemiol 1993; 138 (4):

225-236.

65

27. Potter JD, McMichael AJ. Diet and cancer of the colon and

rectum: a case control study. J Natl Cancer Inst 1986; 76 (4):

557-569.

28. Zheng W, Anderson KE, Kushi LH. A prospective cohort study

of intake of calcium, vitamin D and other micronutrients in

relation to incidence of rectal cancer among post menopausal

women. Cancer Epidemiol Biomarkers Prev 1998; 7 (3): 221-

225.

29. Givannucci E, Stampfer MJ, Colditz GA. Multivitamin use,

folate, and colon cancer in women in the Nurses’ Health Study.

Ann Intern Med 1998; 129 (7): 517-524.

30. Michels KB, Givannucci E, Joshipura KJ. Prospective study of

fruit and vegetable consumption and incidence of colon and

rectal cancers. J Natl Cancer Institute 2000; 92 (21): 1740-

1752.

31. Terry P, Giovannucci E, Michels KB. Fruit, vegetables, dietary

fiber, and risk of colorectal cancer. J Natl Cancer Institute 2001;

93 (7): 525-533.

32. Alberts DS, MartÃnez ME, Roe DJ. Lack of effect of a high-

fiber cereal supplement on the recurrence of colorectal

adenomas. Phoenix Colon Cancer Prevention Physicians’

Network. N Engl J Med 2000; 342 (16): 1156-1162.

66

33. Martin C, Connely A, Keku TO, Mountcasite SB, Galanko J,

Woosley JT. Nonsteroidal anti-inflammatory drugs, apoptosis

and colorectal adenomas. Gastroenterology 2002; 323: 140-

145.

34. Dilleo A, Messa C, Carallini A, Linsalala M. Estrogen and

colorectal cancer. Curr Drug Target Immune Endocr Metabol

Disord 2001; 1: 1-12.

35. Fernadez E, La Vecchia C, Franceschi S, Braga C, Talamini R,

Negri E. Oral contraceptive use and risk of colorectal cancer.

Epidemiology 1998 May; 9 (3): 295-300.

36. Stürmer T, Glynn RJ, Lee IM. Aspirin use and colorectal

cancer: post-trial follow-up data from the Physicians’ Health

Study. Ann Intern Med 1998; 128 (9): 713-720.

37. Grodstein F, Newcomb PA, Stampfer MJ. Postmenopausal

hormone therapy and the risk of colorectal cancer: a review and

meta-analysis. Am J Med 1999; 106 (5): 574-582.

38. Terry MB, Neugut AI, Bostick RM. Risk factors for advanced

colorectal adenomas: a pooled analysis. Cancer Epidemiol

Biomarkers Prev 2002; 11 (7): 622-629.

39. Fridenreich CM, Orenstein MR. Physical activity and cancer

prevention: etiological evidence and biological mechanisms. J

Nutr 2002; 132 (suppl): 3456-3464.

67

40. Kuper A, Boffetta P, Adami HO. Tobacco use and cancer

causation: Association by tumor type. J Intern Med 2002; 252:

206-224.

41. Chao A, Thun MJ, Jacobs EJ. Cigarette smoking and

colorectal cancer mortality in the cancer prevention study II. J

Natl Cancer Inst 2000; 92 (23): 1888-1896.

42. Terry P, Ekbom A, Lichtenstein P. Long-term tobacco smoking

and colorectal cancer in a prospective cohort study. Int J

Cancer 2001; 91 (4): 585-587.

43. White E, Jacob EJ, Daling JR. Physical activity in relation to

colon cancer in middle-aged men and women. Am J Epidemiol

1996; 144 (1): 42-50.

44. Fridenreich CM. Physical activity and cancer prevention: from

observational to intervention research. Cancer Epidemiol

Biomarkers Prev 2001; 10 (4): 287-301.

45. Harkins L, Volk AL, Samanta M, Mikolaenko, Britt WJ, Bland

KI. Specific localization of human cytomegalovirus nucleic acid

and protein in human colorectal cancer. Lancet 2002; 360:

1557-1563.

68

46. Enam S, Del Valle L, Lara C, Gan DD, Ortiz-Hidalgo C,

Palazzo JP. Association of human papilloma virus JCV with

colon cancer: evidence for interaction of viral t- antigen and

beta catenine. Cancer Res 2002; 62: 7093-7101.

47. Hartwich A, Konturek SJ, Pierzchalski P, Zuchowicz M, Labza

H, Konturek PC. Helicobacter pylori infection, gastrin,

cyclooxygenase-2 and apoptosis in colorectal cancer. nIt J

Colorectal Dis 2001; 16: 202-210.

48. Gupta K, Krishnaswamy G, Karnad A, Peiris AN. Insulin: a

novel factor in carcinogenesis. Am J Med Sci 2002; 323: 140-

145.

49. Jass JR. Pathogenesis of colorectal cancer. Surgery Cli N Am

2002; 82: 891.

50. Thomas RM, Sobin LH. Gastrointestinal cancer. Cancer 1995;

75: 154-170.

51. Jass JR, Do KA, Simms LA, Lino H, Wynter C, Pillay SP, et al.

Morphology of sporadic colorectal cancer with DNA replication

errors. Gut 1998; 42: 673-679.

52. Rashid A, Zahurak M, Goodman SN, Hamilton SR. Genetic

epidemiology of mutated K-ras proto-oncogene, altered

suppressor genes, and microsatellite instability in colorectal

adenoma. Gut 1999; 44: 823-826.

69

53. Tang WY, Elantan J, Lee YS, Goh HS, Smith DR. C-Ki_ ras

mutations in colorectal adenocarcinoma from a country with a

rapidly changing colorectal cancer incidnce. Br J Cancer 1999;

81: 237-241.

54. Hardy DJ, Kora SJ, Pass I Harvey. Carcinoma of the colon

and rectum. Hardy’s, Textbook of Surgery. 2cond eddition.

Philadelphia. J.B. Lippincott company. 1988: 609-616.

55. Trowbridge B, Burt RW. Colorectal cancer screening. Surg Clin

North Am 2002; 82: 932-943.

56. Rockey DC, Koch J, Cello JP, Sanders LL, McQuaid K.

Relative frequency of upper gastrointestinal lesions in patients

with positive fecal occult-blood tests. N Engl J Med 1998; 339:

153-159.

57. Hardcastle JD, Chamberlain JO, Robinson MH, Amar SS,

Balfour. Randomized co trial of fecal- occult-blood screening for

colorectal cancer. Lancet 1996; 348: 1472-1477.

58. Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM,

Schuman LM. Reducing mortality from colorectal cancer by

screening for fecal occult blood. Minnesota Colon Cancer

Control Study. N Engl J Med 1993; 328: 1365-1371.

70

59. Read TE, Kodner IJ. Colorectal Cancer: Risk Factors and

Recommendations for Early Detection. Am Fam Phy 1999; 59

(11): cover article.

60. Read TE, Read JD, Butterly LF,. Importance of adenoma 5mm

or less in diameter that is detected by sigmoidoscopy. N Engl J

Med 1997; 336: 8-12.

61. Byers T, Levin B, Rothenberger D, Dodd GD, Smith RA.

American Cancer Society guidelines for screening and

surveillance for early detection for colorectal polyps and cancer:

update 1997. CA Cancer J Clin 1997; 47: 154-160.

62. Winawer SJ, Zauber AG, Ho MN, O’Brien MJ, Gottlieb LS,

Sternberg SS. Prevention of colorectal cancer by colonoscopic

polypectomy. N Engl J Med 1993; 329: 1977-1981.

63. Burt RW. Familial risk and colorectal cancer. Gastroenterology

Clin North Am 1996; 25: 793-803.

64. Cancer Epidemiology Services. Colorectal cancer in New

Jersey: colorectal cancer subsites. Cancer surveillance

program. New Jersey, 2001 March.

71

65. Compton CC. Updated protocol for examination of specimen

removed from patients with carcinomas of the colon & rectum,

excluding carcinoid tumors, lymphomas, sarcomas and tumors

of the veriform appendix: a basis for check lists. Arch Path Lab

Med 2000; 124: 1016-1025.

66. Jass JR, Sobin LH. Histological typing of intestinal tumors.

World Health Organization International Histological

Classification of Tumors, 2nd ed. New York: Springer-Verlag;

1989.

67. Willett CG, Compton CC. Pathology and staging. Cancer of the

lower gastrointestinal tract. Hamilton: B.C.Decker Inc; 2001.

P. 53-81.

68. Sternberg SS. Carcinoma of the Large intestine & Rectum.

Diagnostic Surgical Pathology, 3rd ed. Philadelphia: A wolters

Kluwer Company; 1999. P. 1436-1442.

69. Sacki O, Atkin WS, Jass JR. Mucinous carcinoma of the

rectum. Histopathology 1987; 11: 295-272.

70. Symonds DA, Vickery AL. Mucinous carcinoma of the colon

and rectum. Cancer 1976; 37: 1891-1900.

72

71. Sasaki S, Masaki T, Umetani N, Futakawa N, Ando H, Muto T.

Characteristics in primary signet-ring cell carcinoma of the

colorectum, from clinicopathological observations. Jap J Clin

Oncol 1998; 28: 202-206.

72. Comer TP, Beahrs OH, Dockerty MD. Primary squamous cell

carcinoma and adenocarcinoma of the colon. Cancer 1971; 28

(11): 1111-1117.

73. Jass JR, In: Fletcher CDM. Diagnostic histopathology of

tumors. New York: Churchill Livingstone; 1995. P. 243-274.

74. Jesserun J, Romero-Guadarrama M, Manivel JC. Medullary

adenocarcinoma of the colon: clinicopathologic study of11

cases. Hum Pathol 1999; 30: 843-848.

75. Tortola S, Marcuello E, Gonzalez I, Reyes G, Arriba R, Aiza G,

et al. P53 & K-ras gene mutations correlate with tumor

aggressiveness, but are not of routine prognostic value in

colorectal cancer. J Clin Oncol 1999; 17: 1375-1381.

76. Isimbaldi G, Sironi M, Assi A. Sarcomatoid carcinoma of the

colon. Report of the second case with immunohistochemical

study. Pathol Rest Pract 1996; 192: 483-487.

77. Rubio CA. Clear cell adenocarcinoma of the colon. J Clin

Pathol 1995; 48: 1142-1144.

73

78. Dukes CE. The classification of the rectum. J Pathol Bacteriol

1932; 35:322-332.

79. Astler VA, Coller FA. The prognostic significance of direct

extension of carcinoma of the colon & rectum. Ann Surg 1954;

139: 846-852.

80. Beahrs OH, Henson DE, Hulter RV. Colon and rectum: AJCC

Manual for staging of cancer, 4th ed. Philadelphia: JB Lippincott;

1992. P. 75-82.

81. Fleming ID, Cooper JS, Henson DE. AJCC manual for staging

of cancer, 5th ed. Philadelphia: PA Lippincott Raven; 1997.

82. Blenkinsopp WK, Stewart-Brown S, Blesovsky L.

Histopathology reporting in large bowel cancer. J Clin Pathol

1981; 34: 509-513.

83. Compton CC, Fieling LP, Burgart LJ. Prognostic factors in

colorectal cancer. College of American Pathologists consensus

statement. Arch Pathol Lab Med 2000; 124: 979-994.

84. Franklin ME JR, Rosenthal D, Norem RF. Prospective

evaluation of laproscopic colon resection for adenocarcinoma. A

multicenter study. Surg Endosc 1995; 9: 811-816

74

85. Iwamoto RJ. Emerging strategies in radiation therapy for

colorectal cancer: intraoperative and stereotactic radiation

therapy. Colorectal Cancer. Meniscus Educational Institute,

1998; 14-23.

86. Peters M, Haller D. Therapy for early-stage colorectal cancer.

Oncology 1999; 13: 307-315.

87. Ohno S, Tomoda M, Tomiaski S. Improved surgical results

after combining preoperative hyperthermia with chemotherapy

and radiotherapy for patients with carcinoma of the rectum. Dis

Colon Rectum 1997; 40: 401-406.

88. Pazdur RL, Coia L, Wagman L. Cancer Management: A

Multidisciplinary Approach. Colorectal and anal cancer. New

York: 1999. P. 149-175.

89. www.radiologyinfo. Colorectal cancer therapy. Radiology

informations. Radiologic society of North America (RSNA).

2005.

90. www.sgpgi.ac.in/path/seminar/ccaprog.html. Pathology seminars,

SGPGIMS: Prognostic factors in colorectal cancer. India, 1999.

91. Burt R. Update on genetic advances in colorectal cancer. Pract

Gastroenterol- 1997; 21: 9-15.

75

92. Nakamori S, Kameyama M, Imaoka S. Increased expression of

sialyl lewisx antigen correlates with poor survival in patients with

colorectal carcinomas. Clinicopathological & immunohistoch-

emical study. Cancer Res 1993; 53: 3632.

93. Steele RJ, Kelly P, Ellul B, Eremin O. Epidermal growth factor

receptor expression in colorectal cancer. Br J Surg 1990; 77:

1352.

94. Peethambaram P, Weiss M, Loprinzi CL. An evaluation of

preoperative follow-up tests in colon cancer patients treated for

cure. Oncology 1997; 54: 287-292.

95. http://www.patient.cancerConsultants.com. New Colorectal

Cancer Screening Method Approved for Human Testing. Colon

Cancer News. 2003.

96. Schottenfld D. The epidemiology of cancer: an overview.

Cancer 1981; 47: 1095-1108.

97. World Health Organization. The World Health Report 1998. Life

in the 21st century. A vision for all. Geneva: WHO; 1998.

98. Abdel-Rahman SZ, Soliman AS, Bondy ML, Omar S, El-

Badwey SA. Inheritance of the 194 Trp and the 399 Gln

variants alleles of the DNA repair gene XRCCI are associated

with increased risk of early-onset colorectal cancer in Egypt.

Cancer Lett 2000; 159: 79-86.

76

99. Abu-Zaid AA, Khfagy W, Maizoul OM, Alaa A, Mostafa I.

Colorectal cancer in Egypt. Dis Colon Rectum 2002; 45: 1255-

1260.

100. Kim DW, Bang YJ, Hro DS, Kim NK. Colorectal cancer in

Korea: characteristics and trends. Tumori 2002; 88: 262-265.

101. Ayyub MI, Al-Radi AO, Khazeindar AM, Nagi AH, Massiyar IA.

Clinicopathological trends in colorectal cancer in tertiary care

hospitals. Saudi Med J 2002; 23: 160-163.

102. Kaw LL, Puzalan CK, Crisostomo AC, Bowyer MW, Wharry

DC. Surgical patlology of colorectal cancer in Filipinos:

implications for clinical practice. J Am Coll Surg 2002; 195: 188-

195.

103. Takada H, Ohsawa T, Iwamoto S, Yoshida R, Nakaro M,

Imadokuomo. Changing site distribution in Japan. Dis Colon

Rectum 2002; 45: 1244-1254.

104. Mansour I, Zahrani IH, Abdul-aziz S. Colorectal cancer in

Saudi Arabia. Saudi Med J 2002; 23: 322-327.

105. Keswani SG, Boyle MJ, Maramll JP, Mains L, Wilk SM, Hunt

JP. Colorectal cancer in patients younger than 40 years of age.

Am Surg 2002; 68: 871-876.

77

106. Holowaty EJ, Marrett CD, Parkes R, Fehringer G. Colorectal

cancer in Ontario 1971-1996: subsites and morphology.

Surveillance unit, division of preventive oncology, Ontario

(Canada): Cancer Care Ontario; 1998.

107. Basaleem HO, Al-Sakkaf KA. Colorectal cancer among Yemeni

patients: characteristics and trends. Saudi Med J 2004; 25(8):

1002-1005.

78

بسم اهللا الرحمن الرحيم

University of Khartoum The Graduate College

Medical & Health Studies Board Questionnaire

Colorectal cancer

• Lab. No.:.................... 1- Name:........................................................ 2- Age (in years):........................................................ 3- Sex: 1- Male 2- Female

4- Tribe: ..……………………………………..…..........

5- Residence: ………………………………………..

6- Clinical remarks: 1- Rectal bleeding. 2- Diarrhoea. 3- Constipation

4- Fatigability 5- Abdominal pain 6- Weight loss

7- Others: ……………………………………………….

7- Diagnosed by: a. Endoscopy and biopsy: 1- Yes 2- No

Type: ……………………… ………………………….

a. Surgical: 1- Yes 2- No

Type: ……………………… ……………………….

9- Histopathology: Gross: ……………………………………………..

Microscopy: …………………………………………

Diagnosis: ……………………………………………

Stage and grade: ……………………………………

10. Other investigations: - C.B.C: ………………………………….…………………

- Barium enema: ……………………………………………

- U/S: ………………………………………………..………

- C. T scan: …………………………………………………