"COLORECTAL CARCINOMA"

"INTRODUCTION:

Colorectal cancer (CRC) is a common and lethal disease and can occur anywhere in the colon or rectum. About two thirds of tumors develop in the colon and the remainder in the rectum. Colorectal cancer is the second leading cause of death due to malignancy in the United States [1]

DIAGNOSTIC CRITERIA:

Symptoms or signs depend on tumor location [2].

· Proximal colon: fecal occult blood, anemia.

· Distal colon: change in bowel habits, hematochezia.

· Characteristic findings on barium enema.

· Diagnosis established with colonoscopy.

EPIDEMIOLOGY:

Approximately 148,610 new cases of large bowel cancer are diagnosed each year in the United States, of which 106,680 are colon and the remainder rectal cancers [1]. In 2006, more than 55,000 Americans will die of CRC, accounting for approximately 10 percent of all cancer deaths. In the United States, CRC ranks second to lung cancer as a cause of cancer death, and it is third both in frequency and cause of cancer death among Americans [1]

According to the World Health Organization's April 2003 report on global cancer rates more than 940,000 new cases of colorectal cancer and nearly 500,000 deaths are reported worldwide each year [3].

In many developing countries the incidence is less than 10/100,000. In India the estimated incidence rate of colon cancer is documented at 7/1, 00,000 [4]. In Pakistan it constitutes 25.4% and 20.1% of gastrointestinal malignancies in males and females respectively [61].

Race: Recent data demonstrate a decrease in incidence rates of colorectal carcinoma in whites since the mid 1980s, particularly for the distal colon and rectum. Proximal colon carcinoma rates in blacks are considerably higher than in whites and continue to increase, whereas rates in whites show signs of decline [5].

Sex: The frequency of colon cancer is essentially the same among men and women [5].

Age: Age is a well-known risk factor for colon cancer, and risk begins to rise in people older than 40 and 50, and age-specific incidence rates increase in each succeeding decade thereafter [6]

RISK FACTORS

• Age is a major risk factor for sporadic CRC. It is a rare diagnosis before the age of 40, the incidence begins to increase significantly between the ages of 40 and 50, and age-specific incidence rates increase in each succeeding decade thereafter [6]
• The incidence of colon adenocarcinoma is higher in blacks than in whites. It is unclear whether this is due to genetic or socioeconomic factors (eg, diet or reduced access to screening) [6]
• If patients have familial adenomatous polyposis (FAP) and its variants (Gardner's syndrome, Turcot's syndrome, and attenuated adenomatous polyposis coli) symptoms appear at an average age of approximately 16 years and colonic cancer occurs in 90 percent of untreated individuals by age 45. Accounts for 1% CRC [6]
• If patient has hereditary nonpolyposis colorectal cancer (HNPCC), it is an autosomal dominant syndrome, which is more common than FAP, and accounts for approximately 2 to 6 percent of all colonic adenocarcinomas. The mean age at initial cancer diagnosis is 48 years, with some patients presenting in their 20s [7]
• If patients have a personal history of CRC or adenomatous polyps, are at risk for the development of a future large bowel cancer in 1.5 to 3 percent of patients in the first five years postoperatively [8]
• A personal history of large (>1 cm) adenomatous polyps and polyps with villous or tubulovillous histology also increase the risk of CRC, particularly if multiple. The relative risk ranges from approximately 3.5 to 6.5 in such patients [9]
• There is a well documented association between chronic ulcerative colitis and crohn’s disease and colonic neoplasia, with the extent and duration of disease being the primary determinants. Pan colitis confers a 5- to 15-fold increase in risk compared to the expected incidence in the general population, and left-sided disease is associated with about a threefold relative risk; in comparison, the risk does not appear to be significantly increased with proctitis alone. The cumulative risk approaches 5-10% after 20 years and 20% after 30 years. [10]
• Diabetes mellitus is associated with an elevated risk of colon cancer. Risk of colorectal cancer among diabetics is approximately 30 percent higher than no diabetics [11]
• An association between alcohol consumption and an increased risk of colorectal cancer has been observed in several studies. Risk is increased modestly in those whose alcohol consumption exceeds 45 g/d [12]
• Cigarette smoking, which has been associated both with increased incidence and mortality from colorectal cancer [13]
• Prior pelvic irradiation may be associated with a higher incidence of colorectal malignancy after a 5- to 10-year latency, but further characterization of this risk is required [14].
• A history of radiation therapy for prostate cancer was associated with an increased risk of rectal cancer in a large database study [17]
• Colonic adenomas and gastrointestinal cancer both occur with increased frequency in acromegaly [15]
• Consumption of red meat or processed meats is associated with an increased risk of colorectal cancer, particularly left sided tumors [16].
• A significant increase in the incidence of colorectal neoplasia in HIV-positive patients [18]
• A relationship between cholecystectomy and right-sided colon cancer has been described in some reports. Several meta-analyses have confirmed this association with proximal colon cancers [19, 20], although discordant data have also been reported
• Ureterocolic anastomoses after extensive bladder surgery also are associated with an increased risk of neoplasia in close proximity to the ureteric stoma [21]

CLINICAL FEATURES:

Presentation of CRC depends on the site of cancer whether it is involving right or left sided colon or rectum [22]:

SYMPTOMS

• Right colon cancers: weight loss, anemia, occult bleeding, mass in right iliac fossa, disease more likely to be advanced at presentation.
• Left colon cancers: often colicky pain, rectal bleeding, bowel obstruction, tenesmus, mass in left iliac fossa, early change in bowel habit, less advanced disease at presentation.
• The most common presenting symptoms and signs of cancer or large polyps are rectal bleeding, persisting change in bowel habit and anemia.
• In some patients, symptoms do not become apparent until the cancer is far advanced. Approximately 55% of patients present with advanced colorectal cancer (spread to the lymph nodes, metastasised to other organs, or is so locally invasive that surgery to remove the primary tumour alone is unlikely to be sufficient for cure [23].
• Rarer clinical presentations include: pneumaturia, gastro-colic fistula, ischiorectal or perineal abscesses, deep vein thrombosis
• Rarely patient with CRC may present as fever of unknown origin, intraabdominal, retroperitoneal, or abdominal wall abscesses
• Streptococcus bovis bacteremia and Clostridium septicum sepsis are due to underlying colonic malignancies in 10 to 25 percent of patients [24].

Frequency of various symptoms as presenting complaints of CRC [25]

· Abdominal pain — 44 percent

· Change in bowel habit — 43 percent

· Hematochezia or melena — 40 percent

· Weakness — 20 percent

· Anemia without other gastrointestinal symptoms — 11 percent

· Weight loss — 6 percent

Signs

• All patients with symptoms suspicious of colorectal cancer must have a thorough abdominal and rectal examination [23]
• Jaundice and hepatomegaly indicate advanced disease with extensive liver metastases. Peritoneal metastases with ascites are often also present. 20-25% of patients have clinically detectable liver metastases at the time of the initial diagnosis and a further 40-50% of patients develop liver metastases within three years of primary surgery [24]."