CLINICO PATHOLOGICAL STUDY OF COLORECTAL CARCINOMA IN YOUNG ADULT AGE GROUP IN TERTIARY LEVEL HOSPITAL
Overall, colorectal cancer is the second most common malignancy in western countries, with approximately 18,000 patients dying per anum in the UK.1
Distribution of colorectal carcinoma by site- Rectum= 38%, sigmoid colon= 21%, rectosigmoid junction= 7%, desending colon= 4%, splenic flexure= 3%, transrerse colon= 5.5%, hepatic flexure= 2%, ascending colon= 5%, caecum= 12%, appendix= 0.5%, anaus= 2%.1
There is no single cause of colon cancer. Nearly all colon cancers begin as non cancerous (benign) polyps, which slowly develop into cancer. Higher risk for colon cancer are- older than 60 years, eat a diet high in red or processed meats, have cancel elsewhere in the body, colorectal polyps, inflammatory bowel disease (Crohn’s disease or ulceratic colitis). Family history of colon cancer, personal history of breast cancer. Certain genetic syndromes also increase the risk of developing colon cancer. Two of the most common are familial adenomatous polyposis (FAP) hereditary nonpolyposis colorectal cancer (HNPCC) also known as Lynch syndrome, smoking cigarettes and drinking alcohol are other risk factors for colorectal cancer.2
Colorectal cancer incidence was negligible before 1900. The incidence of colorectal cancer has been rising dramatically following economic development and industrialization, currently colorectal cancer is the tired leading cause of cancer deaths in both males and females in the United States.3,4
Adeno carcinomas comprise the vast majority (98%) of colorectal cancers. Other rectal cancer are carcinoid (0.4%), lymphoma (1.3%) and sarcoma (0.3%). Squamous cell carcinoma may develop in the transition area from the rectum to the anal verge and are considered anal carcinoma. Very rare case of squamous cell carcinoma of the rectum have been reported.5
Grossly colorectal carcinomas are described as polypoidal mass projecting into the lumen, like- anular, tubular ulcerative and cauliflower.1
Symptoms in patients with the bowel cancer depend upon the anatomic location of the lesion, its type and extent and upon complication, including perforation, obstruction and hemorrhage. Marked systemic manifestation such as cachexia are indication of advanced disease. The average delay between the onset of symptoms and definitive therapy is 7 to 9 months. Both patients and physicians are responsible. The right colon has a large caliber and a thin and distensible wall and the faecal content is fluid. Carcinoma of the right colon may attain a large size before it is diagnosed. Unexplained anemia should always raise the possibility of carcinoma of the ascending colon. Gross blood may not be visible in the stool, but occult blood may be detected. Patients may complain of vague right abdominal discomfort, which is often postprandial and may be mistakenly attributed to gall bladder or gastroduodenal diseases. Alteration in bowel habit are not characteristic of carcinoma of right colon and obstruction is uncommon. In about 10% of cases, the first evidence of the disease is discovery of a mass by the patients or by physician. The left colon has a smaller lumen and the faeces are semisolid. Tumours of the left colon can gradually occlude the lumen, causing changes in bowel habit with alternating constipation and increased frequency of defecation. Partial of complete obstruction may be the initial picture. Bleeding is common but rarely is massive. The stool may be streaked or mixed with bright red or dark blood and mucus is often passed together with small blood clot. In cancer of the rectum, the most common symptom is the passage of red blood with bowel movements (hematochezia). Bleeding is usually persistent. It may be slight or copious. Blood may or may not be mixed with stool or mucus. Whenever rectal bleeding occurs in an aged or older individual, even in the presence of hemorrhoid, coexisting cancer must be ruled out. There may be tenesmus (painful incomplete evacuation). Physical examination is important to determine the extent of the local disease of other organ systems that may influence treatment. The supraclavicular areas should be carefully palpated for metastatic nodes. Examination of the abdomen may disclose a mass, enlargement of the liver, ascites or engorgement of the abdominal wall veins, if there is portal obstruction. If a mass is palpated, its location and extent of fixation are important.
Treatment of the colon cancer consist wide surgical resection of the lesion and its regional lymphatic drainage after preparation of bowel. Resection of primary tumour may be indicated even it distant metastasis have occurred. Since prevention of obstruction or bleeding may offer palliation for long periods.
For cancer of the rectum, the choice of operation depends on the height of the lesion above the anal verge, the configuration (whether polypoid or infiltrative) the gross extension of the tumor, the degree of differentiation and the patients size, habitus and general condition, pre operative staging by digital rectal examination followed by CT, MRI, endorectal ultrasound or some combination of this tests helps tailor the treatment of patient, preservation of the anal sphincter and avoidance of colostomy are desirable if possible.
The clinico pathologic stage of disease is the most important determinant of survival, in general the results of surgical treatment are better for cancer of the colon than for cancer of the rectum and low rectal cancer has a worse prognosis than cancer higher in rectum.
Average crude 5 years survival rates for colorectal cancer using the Dukes system were as follows state A 80%, stage B 60%, stage C 30%, Stage D 5%. Adjuvant therapy particularly with some of the newer agents in addition to improved surgical techniques has lead to 5 years survival rates approaching 80% for stage III (Dukes C).6
1.2 Rationale of the study:
Colorectal carcinoma is third most common malignancy world-wide. It is often regarded as a disease of the elderly with a peak incidence in the 6th and 7th decades. Recently several studies from different countries have reported colorectal carcinoma occurring in patients below 40 years of age. It has been suggested that low survival in this young age group is due to more aggressive histological grades of tumour, low suspicion of malignancy in young people and delay in diagnosis. The objective of this study was to determine the clinicopathological features of colorectal malignancies in Bangladeshi patients aged 40 years or younger.
1.3 Aims & Objectives:
- To identify the clinical features of colorectal carcinoma.
- To identify the pathological features.
1. Site of involvement with incidence.
2. Staging & grading of tumour during diagnosis.
1.4 Literature Review
Relevant previous work:
Prognosis of colorectal carcinoma for patients younger than 40 years of age is poorer than that of the general population. This is probably because colorectal cancer seldom affects young adults (2% to 6%), which leads to a delayed diagnosis. In addition, the biological behavior of the tumor is more aggressive than in adults older than 40 years of age, with a higher incidence of undifferentiated and mucinous tumors and a higher incidence of Dukes C and D patients.
Numerous reports have raised special concerns with respect to the unfavorable prognosis of this disease when it occurs in young adults. It is reported that, because of the rarity of this disease in the young, the diagnosis is often delayed. This, in addition to the more frequent occurrence of poorly differentiated and mucinous tumors in the young population, may contribute to the poor outcome. This study was undertaken to investigate further the pattern of colon cancer in patients under the age of 40 and to identify reasons for the higher mortality in these individuals.
HC Umpleby and RCN Williamson studied carcinoma of the large bowel in the first four decades. This 32 years review article was conducted at University Department of Surgery, Bristol, Royal Infirmary, UK. Where 53% of males and 47% of females. Male female ratio 1.1:1. Site of involvement 13% occurred in the right colon, 16% occurred in transverse colon, 39% occurred in left colon, 32% occurred in rectum, staging 13% were Dukes A, 28% dukes B, 59% Dukes C. On histopathological report, 20% were well differentiated, 49% moderately differentiated, 31% poorly differentiated or anaplastic.7-11
MVC de Silva and D Fernando studied comparisons of some clinical and histological features of colorectal carcinoma occurring in patients below and above 40 years. That prospective study was conducted university department of pathology, Colombo, for the 15 years period commencing from 1982. That male female ratio 1.6:1. Site of involvement, rectum 46.7%, sigmoid colon 12.7%, transverse colon 8.3%, right colon 20%. Symptoms of colorectal malignancy, rectal bleeding 31.6%, altered bowel habits 20%, abdominal mass 6.7%, anorexia 5%, weight loss 3%, pain full defecation 20%. Histopathological shows adeno carcinoma 78.3%, squamous cell carcinoma 0%, others- mucoid carcinoma 13.3%, signet ring 5%, carcinoid 1.5%, melanoma 1.7%.12-17
Abdulrahman M. Aljebreen studied clinico-pathological patterns of colorectal cancer in Saudi Arabia: Younger with an Advanced Stage Presentation that was retrospective study of all patient diagnosed colorectal carcinoma at Kind Khaled University Hospital in Riyad, Saudi Arabia over 10 years period (1995-2005). Total 113 patients were included, where 58% of the patients were males and 42% were females. Male female ratio 1.4:1. Site of involvement were rectum 48%, sigmoid and descending colon in 28%, transverse colon 3.5%, right colon 22%. Common clinical presentation were abdominal 68%, rectal bleeding 62%, weight loss 55%, constipation 50%, melena 14%, fever and anaemia 6%.
Histopathology showed that 56% tumours were moderately differentiated, 24% were well differentiated, 10% were poorly differentiated adeno carcinoma where 9% had only dysplasia (including carcinoma in situ).18-22
Jessica BO Connell et al conducted a study in department of surgery of different medical school of USA shows 51.4% males and 48.6% female are suffering colorectal carcinoma. Male female ratio 1.05:1 and highest incidence fourth decade 63%.23-24
Burt Cagir study was concluded that, male female ratio 1.37:1, modality rates for colororectal carcinoma were also higher in male (25.4 per 100,000) than in female (18 per 100,000) in 1999. Left colon carcinomas were more likely to be observed in males and right colon cancer were more likely to be observed in females.
Approximately 20% of colon cancer developed in caecum, another 20% in the rectum and additional 10% in the recto sigmoid junction. 25% of colon cancer developed in sigmoid colon. Adenocarcinomas comprised the vast majority (98%) of colorectal cancer, other rectal including carcinoid (0.4%), lymphoma (1.3%) and sarcoma (0.3%). Squamous cell carcinoma may develope in the transition area from the rectum to the anal verge and are considered anal carcinoma. Vary rare cases of squamous cell carcinoma of rectum have been reported.
D. Ashely Hill studied, colorectal carcinoma in childhood and adolescent shows male 60%, female 40%. Race white 62%, African American 38%. Site of involvement of tumour right colon 20%, rectum 48%, transverse colon 12%, sigmoid colon 15% and anus 5%. Histopathology showed that adenocarcinoma 62%, non adenocarcinoma 38%. On differentiation poorly differentiated 12%, moderately differentiated 87% and well differentiated 1%.
S Penegar’s study was concluded that, male 59%, female 41%. Age less than 30 years (0.1%), 31-35 years (0.8%) and 36-40 years (2%). Site of involvement colorectal carcinoma were rectum 40% and rest of 60% were involvement in ascending colon, hepatic flexure, splenic flexure, transverse colon, descending colon, sigmoid colon and caecum.
According to J. Domergue study, colorectal carcinoma in patients younger than 40 years of age shows that male female ratio 1.05:1. Age ranged from 18-40 years but most of the patients were in the 30 to 40 years.
There was as higher incidence of rectal tumours 55%, right colon 23%, left colon 19%, transverse colon 2.6%. Most common symptom was blood in the stools (35%), abdominal pain 15%, change in bowel habits were 12%. Histopathologically adenocarcinoma 20% and carcinoid 6%. Well differentiated 51.5% and poorly differentiated 21.5%. There was a high incidence of poorly differentiated and mucinous tumours (41.5%). According to Dukes classification, most patients had stage C (53%) or stage D (27%). Forty-seven patients had lymph node metastasis.
Materials and Methods
MATERIALS AND METHODS
2.1 Place of the study : Department of Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU).
2.2 Sample Size : Fifty (50) cases.
2.3 Case selection : Patients presented with per rectal bleeding, altered bowel habit, weight loss and diagnosed as a case of colorectal carcinoma were selected and allocated in this group.
2.4 Type of study : Cross sectional study.
2.5 Inclusion Criteria : Young adult age group (18-40 years).
2.6 Exclusion Criteria:
· Colorectal carcinoma with-
a. Ischemic heart disease
b. Diabetes mellitus
c. Renal failure
d. Cirrhosis of liver
e. Acute myocardial infraction
· Age more than 40 years and below 18 years.
2.7 Study Procedure:
All the relevant information was collected (age, sex, clinical presentation, routine investigation, histopathological report) and recorded in a pre-designed data sheet for each patient for evaluation (Appendix).
Fifty case of colorectal carcinoma were admitted in surgical unit of Bangabandhu Sheikh Mujib Medical University.
After admission each case evaluated by taking detailed history, complete physical examination and per-rectal examination. Each case were examined thoroughly physically and the findings regarding anaemia, jaundice, dehydration, edema, lymph adenopathy, nutrition, pulse, blood pressure, abdominal signs like ascities, distension, rigidity, mass, hepatosplenomegally etc were recorded. Digital rectal examination was done in each case. Distal rectal cancer can be felt as a flat, hard, oval tumour with rolled edges and central depression. It extent the size of the lumen at the site of the tumour and degree of fixation should be noted. Blood may be found on the examining finger. Vaginal and rectovaginal examination will yield additional information on the extent of the tumour.
Routine investigation like Hb%, TC, DC, ESR, Blood sugar, blood urea, serum creatinine, blood grouping, urine R/M/E were done in all cases. X-ray chest P/A views, plain X-ray abdomen A/P view, Barium enema of large gut or colonoscopy were done, except those with intestinal obstruction. USG of whole abdomen was done for metastatic assessment. Intravenous urography was also done for selected case.
Pre-operative biopsy and histopathology were done. Histopathological examiantion done for each case (Tissue taken from lesion and from lymph node were feasible).
2.8 Data Collection:
Findings of observation were recorded on prescribed data collection from (attached herewith).
2.9 Data Analysis:
After collection, data editing and clearing was done manually and prepared for data entry and calculated by computer based software.
2.10 Ethical Implication:
Permission was taken from director. All documents were preserved confidentially. Written informed consent was taken from the patient.
A total of 50 colorectal carcinoma cases were selected to their different age group, both sex (male, female), anatomical distribution, histopathological type, blood grouping, clinical presentation and outcome of different surgical procedures. This findings derived from data analysis are presented below.
Table- I: Age distribution of the patients (n= 50)
|Age (years)||Frequency||Percentage (%)|
Table- I shows 56% of the patients were between 36-40 years of age group. 16% between 31-35 years, 12% between 26-30 and 21-25 years and 4% in below 20 years of age. The median age was 34.3 years and the lowest and highest ages are 18 and 40 years respectively.
Figure- 1: Sex distribution of the patients (n= 50).
Figure shows that 34 (68%) cases of colorectal carcinoma were male and the rest of 16 (32%) cases were female. Male female ratio is 2.1:1.
Table- II: Distribution of patients by site of lesion (n= 50)
|Site of lesion||Frequency||Percentage (%)|
Table shows that, 54% cases of colorectal carcinoma had their lesion in rectum followed by right colon 18%, sigmoid colon 14%, transverse colon 10% and anus 04%.
Table- III: Distribution of patients by clinical presentation (n= 50)
|Clinical presentation||Frequency||Percentage (%)|
|Altered bowel habit||47||94|
|Per rectal bleeding||48||96|
Table shows that 94% patients presented with altered bowel habit and 96% patients presented with per rectal bleeding, 36% weight loss, 30% abdominal pain, abdominal lump 16% and severe anorexia 8%.
Table- IV: Distribution of patients by examination findings (n= 50).
|Examination findings||Frequency||Percentage (%)|
|Poor body build||04||08|
|Positive per rectal finding||45||90|
Total will not correspond to 100% because multiple response.
Table shows that 90% patients presented with positive per-rectal finding, 16% abdominal lump, 08% poor body build and 06% presented with lymphadenopathy.
Figure- 2: Histopathological diagnosis
Figure shows the histopathological diagnosis of the 50 patients, 47 (94%) were diagnosed as adenocarcinoma and 3 (6%) diagnosed as squamous cell carcinoma.
Table- V: Distribution of patients by blood group (n= 50).
|Blood group||Frequency||Percentage (%)|
Above table shows that, 20 (40%) patients were associated with blood group B, 20 (40%) with group O, 05 (10%) with group AB and rest 05 (10%) associate with group A.
This study of colorectal carcinoma included 50 cases treated in Bangabandhu Sheikh Mujib Medical University during the period of October 2010 to September 2011. All these were finally diagnosed after being confirmed by histopathological examination.
Fifty six percent were between 36-40 years of age, 12% between 21-25 years of age, 18% were 26-30 years of age and 4% below 20 years of age.
A study conducted by Jessica B.O Connell et al in department of surgery of different medical school of USA shows that the highest incidence also was in fourth decade, the percentage being 63%, whereas in present study it was 56% and lowest incidence was 4%.
Regarding sex distribution percentage of male patients was 34 (68%) and that of female was 16 (32%). Male female ratio being approximately 2:1.
A study conducted by Jessica BO Connell et al. showed that, 51.4% were males and 48.6% were females showing minimum difference in sex distribution. But in this study shows male female approximately 2:1.
A study conducted by MVC de Silva, MS Fernando and De Fernando at university department of pathology, Colombo for the 15 years period commencing from 1982 showing male female ratio 1.6:1. In this study shows male female ratio approximately 2:1.
A study conducted by S Penegar et al. showing 59% were male patients and 41% were female. Male female ratio 1.44:1. Burt Cagir MD studied that, the incidence of colorectal malignancy in slightly higher in males than in females. The male female ratio was 1.37:1.26 In this study shows male female ratio approximately 2:1.
Regarding site of lesion highest incidence was colorectal carcinoma found in rectum 54% followed by in order by right colon 18%, sigmoid colon 14%, transvers colon 10% and anal canal 4%.
De Silva MVC shows that site of involvement of rectum more common (46.7%), sigmoid colon 12.7%, transvers colon 8.3% and right colon 20%.
Abdul Rahman M. Aljebreen shows that rectum involvement was 48%, sigmoid and descending colon was 28%, transverse colon 3.5% and right colon 22%. In this study rectum was more common site of involvement which was 54% followed in order right colon involvement 18%, sigmoid colon 14%, transverse colon 10% and anal canal involvement was 4%, which are nearer to the other study.
Regarding clinical presentation shows that, 96% patients were presented with per rectal bleeding and 94% of these patients presented with altered bowel habit. 36% of these patients had weight loss. 30% patients complained abdominal pain, 16% patients presented with abdominal lump. Others were 8% presented withsevere anorexia and 4% were painful defecation.
Above reflects that, the presentation pattern of colorectal carcinoma varies widely. Majority of lesion on right colon presented with abdominal pain, anaemia, weight loss with general weakness and abdominal lump. But bleeding per rectum, altered bowel habits were commonly associated with rectum and left colon lesion. Highest percentage abdominal lump in lesion of right colon is likely due to the fact that liquid bowel contents in right colon can easily pass through the lesion, allowing the mass to grow slowly keeping the patient ignorant of it. Until the big mass enough to palpable lump.
Boyle P shows that highest presenting symptoms was bleeding per rectum (68%), 62% patients presented with altered bowel habit, 55% were presented with weight loss and 35% patient presented with abdominal pain, 10% patient presented with abdominal lump.
Mells SE shows that, most common clinical presentation was per rectal bleeding 77%, followed by alter bowel habit 72%, weight loss 30%, abdominal pain 27%, anorexia 17% and abdominal mass 11%.
Regarding histopathological diagnosis shows that, most of the colorectal carcinoma were adenocarcinoma 94% and rest of then squamous cell carcinoma only 6%.
Burt RW2 shows that, adenocarcinoma comprise the vast majority 98% of colorectal cancers. Other rectal cancers including carcinoid (0.4%), lymphoma (1.3%) and sarcoma (0.3%), squamous cell carcinoma may develop in the transitional area from the rectum to the anal verge and are consider anal carcinomas. Vary rare cases of squamous cell carcinoma of the rectum have been reported.
Regarding blood group B and O shared the highest number 40% of cases followed by 10% of cases AB and A blood group. This corresponds with usual population distribution of blood group in our country. But there is no data associated with colorectal carcinoma and blood group.
A total of 50 patients below the 40 years of age were diagnosed as having colorectal carcinoma over the period October 2010 to September 2011 in Department of Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka. Highest incidence (56%) of colorectal carcinoma was 36-40 years age, 18% incidence were 31-35 years of age. 12% incidence were 26-30 years, 21-25 of each ages groups lowest incidence (4%) were below the 20 years ages.
68% patients were males and 32% were females.
The most common clinical presentation was bleeding per rectum (96%) followed by Altered bowel habit (94%), weight loss (36%), abodominal pain (30%), abdominal lump (16%), severe anorexia (8%) and painful defecation (4%).
The tumour was located in the rectum in 27 patients (54%), in the right sided colon (18%), in the sigmoid colon (14%), in the transverse colon (10%) and 4% had anal lesions.
90% patients were found in positive per rectal finding, 16% were abdominal lump, 8% were poor body build and 6% were lymph adenopathy.
Histopathology showed 94% of the tumours were adenocarcinomas whereas 6% had only squamous cell carcinoma.
Blood group B and O shared the highest number 40% of cases followed by 10% of cases AB and A blood group. This corresponds with usual population distribution of blood group in our country.
This study conducted that colorectal carcinoma occur more in male patient at the age of 31-40 years and more frequent clinical presentation are per-rectal bleeding and alteration of bowel habit, lesion in the rectum and histopathologically adeno carcinoma.
The symptoms of rectal bleeding, blood and mucous in the stools and alteration of bowel habits should lead to a suspicion of bowel habits should lead to a suspicion of colorectal malignancy and appropriate investigation even if the patient is young.
4.4 LIMITATIONS OF THE STUDY
The present study had number of limitations. The present study was conducted in a single hospital which may not representative for the whole country. The study was conducted with a small sample size. More representative findings can be obtained from the study with large sample size and in different tertiary level hospital of the country and a long time follow up in necessary.
Colorectal carcinoma is generally though of as a disease of older persons; however a significant proportion of patients less than 40 years present with this disease. Moreover, the disease in younger appears to be more aggressive, present in later stage and have poor pathological findings. However, if detected early young patients with Duke A&B have better overall 5 years survival rates. These findings emphasizes the need for health care provide to have a awareness when caring for this young population.
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