Colon Cancer Update Review An updated information of colon cancer is revealed here! Tue, 08 Nov 2011 11:15:59 +0000 en hourly 1 Overview of Colon Cancer Wed, 23 Feb 2011 15:58:59 +0000 admin It is important to recognize the increased risk for cancer in patients with hereditary cancer syndromes, but by far the most common form of colon cancer is sporadic in nature, without an associated strong family history.

Although the cause and pathogenesis of adenocarcinoma are similar throughout the large bowel, colon cancer, significant differences in the use of diagnostic and therapeutic modalities separate colonic from rectal cancers. This distinction is largely due to the confinement of the rectum by the bony pelvis. The limited mobility of the rectum allows MRI to generate better images and

colon cancer

colon cancer

increases its sensitivity. In addition, the proximity of the rectum to the anus permits easy access of ultrasound probes for more accurate assessment of the extent of penetration of the bowel wall and the involvement of adjacent lymph nodes. The limited accessibility of the rectum, the proximity to the anal sphincter, and the close association with the autonomic nerves supplying the bladder and genitalia require special and unique consideration when planning treatment for cancer of the rectum. Therefore, colon and rectal adenocarcinomas are discussed separately.

The signs and symptoms of colon cancer are varied, nonspecific, and somewhat dependent on the location of the tumor in the colon as well as the extent of constriction of the lumen caused by the cancer. During the past several decades, the incidence of cancer in the right colon has increased in comparison to cancer arising in the left colon and rectum. This is an important consideration, in that at least half of all colon cancers are located proximal to the area that can be visualized by the flexible sigmoidoscope. colon cancers can bleed, causing red blood to appear in the stool (hematochezia). Bleeding from right-sided colon tumors can cause dark, tarry stools (melena). Often, the bleeding is asymptomatic and detected only by anemia discovered by a routine hemoglobin determination. Iron deficiency anemia in any male or nonmenstruating female should lead to a search for a source of bleeding from the gastrointestinal tract. Bleeding is often associated with colon cancer, but in about one third of patients with a proven colon cancer, the hemoglobin is normal and the stool tests negative for occult blood.

Cancers located in the left colon are often constrictive in nature. Patients with left-sided colon cancers may notice a change in bowel habit, most often reported as increasing constipation. Sigmoid cancers can mimic diverticulitis, presenting with pain, fever, and obstructive symptoms. At least 20% of patients with sigmoid cancer also have diverticular disease, making the correct diagnosis difficult at times. Sigmoid cancers can also cause colovesical or colovaginal fistulas. Such fistulas are more commonly caused by diverticulitis, but it is imperative that the correct diagnosis be established because treatment of colon cancer is substantially different than treatment of diverticulitis.

Cancers in the right colon more often present with melena, fatigue associated with anemia, or, if the tumor is advanced, abdominal pain. Although obstructive symptoms are more commonly associated with cancers of the left colon, any advanced colon cancer can cause a change in bowel habits and intestinal obstruction

Colonoscopy is the gold standard for establishing the diagnosis of colon cancer. It permits biopsy of the tumor to verify the diagnosis while allowing inspection of the entire colon to exclude metachronous polyps or cancers (the incidence of a synchronous cancer is about 3%). Colonoscopy is generally performed even after a cancer is detected by barium enema to obtain a biopsy and to detect (and remove) small polyps that may be missed by the contrast study .

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Ulcerative Colitis & Crohn’s Disease with Colon Cancer ? Tue, 22 Feb 2011 10:05:15 +0000 admin Cancer that occurs in patients with ulcerative colitis can arise in any portion of the large bowel, and it carries the same prognosis as colon cancer in general. Although the risk of cancer is relatively low in the first decade after the onset of colitis, it increases to approximately 20% each decade thereafter. In addition to duration of disease, the incidence of colon cancer rises with extent of colonic involvement and severity of disease.Because all currently available screening tests (including repetitive biopsies linking dysplasia and bowel mucosa transformation to cancer) are problematic,most patients with this unusually high risk for colon cancer will probably benefit at some point from prophylactic colectomy. The application of molecular markers (e.g., sucrase isomaltase) may more quantitatively define risk for transformation in an individual patient, allowing a more rational recommendation for preemptive surgery.When ileoproctostomy is performed, preserving the distal rectum and anus, a worrisome incidence of carcinoma has still been observed. Proctocolectomy with a Brooke ileostomy or abdominal colectomy, mucosal proctectomy, and ileoanal reconnection with one of the reservoir procedures can be applied to individual patients, which provides complete freedom from subsequent cancer development and the most appropriate bowel function for the patient’s psychological and functional well-being to be chosen.

Crohn’s disease has also been found to predispose to large bowel cancer. Excess risk is probably age dependent. Overall, the probability of the development of colon cancer may be low, but in patients who are found to have symptomatic Crohn’s disease early in life, the excess risk of colon cancer may be anywhere from 3- to 20-fold that of the non-Crohn’s disease cohort.

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Colon Cancer and Polyposis FAP – HNPPC ? Mon, 21 Feb 2011 08:57:27 +0000 admin Certain groups of patients have a predisposition to the development of cancer of the large bowel. These identifiable high-risk cohorts also have a greater possibility for early intervention and cancer prevention and include patients with inherited conditions such as familial adenomatous polyposis (FAP), hereditary nonpolyposis colon cancer (HNPCC), and ulcerative colitis. Patients with FAP (frequency estimated at 1:7,000 to 10,000 live births) have a lifetime risk of the development of colon cancer that approaches 100%. The disease is inherited as an autosomal dominant trait, and affected individuals will transmit this predisposition, with each of their offspring having nearly a 50% chance of developing polyposis coli. The gene that causes FAP (adenomatous polyposis coli [APC] gene) resides on chromosome 5 and has been cloned and sequenced.

Occasionally, patients with polyposis are found to have no affected family members. Presumably, this represents a new mutation.Numerous molecular, biologic, and biochemical screening tests have attempted to define better predictors of mucosal transformation in such patients.However, without a proven screening test, the offspring of affected patients should have annual or biannual colonoscopy or air-contrast barium enema studies starting at age 15 years. Screening should continue until about 30 years of age. The median age at which colon cancer is diagnosed in polyposis patients is approximately 40 years, which is approximately 2 decades earlier than its occurrence in the general population. Because stage-specific survival of colon cancer appears to be the same for polyposis patients as for those who have sporadic bowel cancer, total colectomy at the time polyposis is diagnosed remains the treatment of choice, particularly because recent technical modifications have allowed the surgeon to remove all of the large bowel mucosa without sacrificing continence.

Other polyposis variants have been recorded, including Turçot’s syndrome (polyposis and malignant central nervous system tumors) and Gardner’s syndrome, which feature not only multiple polyposis associated with osteomas of the jaw and other bones, cutaneous fibromas, and occasionally desmoids of the abdomen after surgery but also carcinoma of the ampulla of Vater and the thyroid gland. All of these syndromes, in which true polyps of the bowel proliferate, predispose to colon cancer.

Patients with hamartomatous polyps of the intestine, as in the dominantly inherited Peutz-Jeghers syndrome and juvenile polyposis coli,[25][65] do not have a particularly high risk of colon or rectal adenocarcinoma. Aggressive screening and surgical management for these inherited polyposis diseases are not necessary.

HNPCC, a familial disorder characterized by a high incidence of colon cancer without the excessive polyps identified in FAP, may account for up to 6% of colon cancers.HNPCC encompasses two syndromes: Lynch I (colonic tumors only) and Lynch II (colonic and extra colonic [endometrial, ovarian, gastric, breast, and hepatobiliary] adenocarcinomas). Diagnostic criteria for identifying individuals with HNPCC have been established . The molecular genetic marker reflective of HNPCC is microsatellite instability, which is a consequence of mutations in DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2). Patients with HNPCC develop colon cancer at an early age with a propensity for right-sided lesions. In retrospective reviews, survival for this cohort is reportedly better than that for patients with sporadic colon cancer, but this may reflect inherent bias with this type of analysis

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Nature of Colon Cancer – Natural History Sun, 20 Feb 2011 09:00:45 +0000 admin Most colon cancers were reported to arise in the distal bowel. The rubric that rectal examination plus rigid proctosigmoidoscopy finds 75% of all colon cancers is no longer valid . Approximately 25% of all polyps can be reached by the rigid proctoscope and 60% can be reached with the 60-cm flexible sigmoidoscope. Although no satisfactory explanation for the change in the segmental distribution of colon and rectal carcinoma is conclusive, there are numerous possibilities. First, because the more proximal colon is more accessible through the wider application of endoscopic techniques and because there is greater use of double-contrast barium studies, more right-sided or proximal bowel lesions may be diagnosed that were always there but were less frequently diagnosed. Second, there may actually be multiple environmental and genetic risk factors that determine right-sided or proximal bowel lesions that are distinct from the causes of left-sided or distal bowel tumors. Numerous formalized treatment protocols of bowel cancer demonstrate that the natural history of right-sided lesions differs from that of left-sided lesions. The natural history of sigmoid cancers differs from that of more proximal colonic tumor. The natural history of rectal cancer is different from that of colon cancer. These differences are reflected in patterns of recurrence and include responsiveness to multimodality adjuvant therapy.

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Clinical diagnosis – Amsterdam criteria,Besthesda guideline Sat, 19 Feb 2011 17:00:01 +0000 admin
Clinical Diagnostic Criteria for Hereditary Nonpolyposis Colon Cancer

Amsterdam Criteria (1991)
1. Three of more relatives, of whom two are first-degree relative of the third, with documented colorectal cancer
2. Cancer occurring across two or more generations
3. One or more cancers diagnosed before age 50
4. Familial adenomatous polyposis excluded
Bethesda Guidelines (1997)
1. Individuals who meet the Amsterdam criteria
2. Individual with two HNPCC-related cancers (synchronous/metachronous colorectal cancers or extracolonic cancers)
3. Individuals with colorectal cancer and a first-degree relative with
a. Colorectal cancer diagnosed before age 45 or
b. HNPCC-related extracolonic cancer diagnosed before age 45 or
c. Colorectal adenoma diagnosed before age 40
4. Individuals with colorectal cancer or endometrial cancer diagnosed before age 45 or
5. Individuals with proximal colon cancer of undifferentiated type or histopathology diagnosed before age 45
6. Individuals with signet ring cell colorectal cancer diagnosed before age 45
7. Individuals with colorectal adenomas diagnosed before age 40
HNPCC = hereditary nonpolyposis colorectal cancer.
From Rodriguez-Bigas, M.A., Boland, C.R., Hamilton, S.R., et al.: A National Cancer Institute Workshop on hereditary nonpolyposis colorectal cancer syndrome: Meeting highlights and Bethesda guidelines. J. Natl. Cancer. Inst., 89: 1758, 1997
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Diet Leads to Colon Cancer? Fri, 18 Feb 2011 18:00:21 +0000 admin Few occupations have been linked to the development of colon cancer. With the exception of occupational exposure to asbestos, in which an increased risk of colon cancer has been reported to be in the range of twofold to threefold, only slight increases in colon cancer rates have been reported in a smattering of studies of occupational or work hazards.

The association between dietary factors and the development of colon cancer is extraordinarily complex. A positive association has been reported among high meat intake, high saturated fat and cholesterol diets, high caloric intake, dietary fiber, alcohol consumption,increased bowel anaerobic microflora, diets that increase deconjugated fecal bile acid excretion, vitamin D, and calcium content.Undoubtedly, the complexity of the environmental factors, including diet, that are related to colon and rectal cancer is a function of the multiple factors that lead to the development of sporadic polyps: the genetics of at least a two-step process between bowel mucosa initiation and promotion before the polyps occur, the ability of the host to defend itself once polyps occur (because so few of them become malignant), and simple methodologic problems such as the difficulty of designing dietary questionnaires that reliably establish specific dietary intake histories that can be related to polyp and colon cancer rates.

Despite numerous empiric dietary recommendations, at the present, common sense provides as good a set of rules as anything else. High fat intake and high meat intake are probably not good. Although high intake of dietary fiber had been thought to reduce the risk of colon adenoma and cancer, the Nurses Health Study did not demonstrate a protective effect of dietary fiber against colon neoplasia in women.The eventual ability to define precise risks in first-degree relatives of patients with sporadic carcinoma may allow relatively limited populations to specifically avoid specific foodstuffs or supplement their diets. However, the likelihood is much greater that before precise dietary manipulations will be found to prevent colon and rectal cancer, population groups at risk, defined genetically or biochemically, will undergo routine screening of the colon mucosa to diagnose and remove premalignant polyps.

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TUMOR MARKERS in Colon Cancer Tue, 15 Feb 2011 17:57:39 +0000 admin CEA remains the prototypical solid tumor marker of colon cancer. Despite its lack of specificity, if used correctly, CEA determination is a valuable addition to clinical decision-making in patients who have been diagnosed with colon or rectal carcinoma. CEA is not an appropriate screening test. Whether sampled once or serially, CEA cannot be used to help in the differential diagnosis of an unknown suspected bowel problem or malignancy. When CEA concentrations are determined before primary tumor resection, they may provide additional prognostic value, particularly for patients who have nodal involvement. However, CEA should not be used to stratify patients who are undergoing primary or adjuvant colon cancer therapy.

Serial CEA values obtained postoperatively offer an effective means of monitoring response to therapy. A postoperative CEA titer serves as a measure of the completeness of tumor resection. If a preoperative elevated CEA value does not fall to normal within 2 to 3 weeks after surgery, the resection was most likely incomplete or occult metastases are present. A rising trend in serial CEA values from a normal postoperative baseline (<5 ng/ml) may predate any other clinical or laboratory evidence of recurrent disease by 6 to 9 months.

Serial CEA values parallel either tumor regression or tumor progression during treatment for metastatic disease.Although not quantitatively related to volume of disease, CEA titers most often are highest when either liver or lung metastases are present. The vast majority of patients who respond to treatment will demonstrate a decline in CEA levels. Rising CEA values are almost always incompatible with tumor regression. Despite its accuracy in confirming the presence or absence of disease, the routine use of CEA alone to monitor response to treatment is not recommended, because its impact on survival is not clear.

The controversy regarding patient benefit when second-look surgery is performed solely on the basis of a rise in serial CEA determinations is focused more on the limited options for therapy in patients found to have recurrent disease than on the efficacy of the marker itself. When CEA is monitored correctly, surprisingly few false-positive or false-negative results are found. However, the initial enthusiasm for resection of recurrent disease and claims of durable disease-free survival have evolved to the present realization that probably no more than 10 to 15% of patients whose recurrences are defined, whether by a rise in CEA or by conventional studies, will have disease that is potentially curable with currently available surgical or nonsurgical means. In later applications of radioimmunologic scanning techniques, using either external or intraoperative gamma-scanning, the weak link will still be a lack of effective systemic therapy even when disease recurrence is found early.

When liver or lung is the first or only site of recurrence, the serial CEA rise will show the steepest slope. Specific diagnostic tests to confirm recurrence in the liver or lung are now preferable to so-called blind CEA-directed second-look procedures. At present, only patients who have recurrence of colon cancer that necessitates palliation or patients with defined isolated liver or lung metastases should undergo surgery. Therefore, it is recommended that postoperative monitoring of CEA be reserved for patients who would be potential candidates for resection of liver or lung metastases if they occur. As with other follow-up testing, the optimal frequency of serial CEA determinations has not been established.

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Screening for Colon Cancer Mon, 14 Feb 2011 15:53:49 +0000 admin Screening of symptomatic patients for colon cancer includes routine digital rectal examination and stool guaiac testing (Hemoccult), proctosigmoidoscopy and/or pancolonoscopy, and barium enema with air-contrast studies. The individual choice of test and order of test priority depend on the precise symptoms of the patient.

Rules for screening asymptomatic patients for colon cancer are empiric or dependent on data derived from statistical modeling. Major studies that attempted to determine the benefit of screening large population groups for occult blood in the stool have led to mixed results, although most studies show a reduction in colorectal cancer mortality rates.More than likely, the increased accuracy of modifications of the Hemoccult or Hemoquant tests, the new designs for testing occult blood in the stool that make application of the test more palatable to the general population, and, perhaps most important, increased communication of the algorithms for correctly interpreting the tests and correctly studying patients who have truly positive tests will all increase the cost-effectiveness of mass screening approaches in the future. Nevertheless, at the present, screening is effective only among high-risk populations (∼25% of all colorectal cancers) and is generally thought to include mandatory testing of stool for occult blood at the time of routine history taking and physical examination.

Data from the Strang Clinic study by Winawer and coworkers have shown what most people would have predicted. Patients whose colorectal tumors (polyps as well as carcinomas) are diagnosed in the asymptomatic state have more superficial lesions than do patients who present with signs or symptoms that lead to the diagnosis of colorectal cancer. The colorectal cancer mortality rate was lower in patients who underwent screening with both fecal occult blood tests and rigid sigmoidoscopy than in those who were screened with annual sigmoidoscopy alone. Although lead time bias is an issue, most thoughtful persons, given the choice, would rather have colon or rectal cancer diagnosed earlier!

The American Cancer Society now recommends that “average”-risk individuals undergo annual fecal occult blood testing and either flexible sigmoidoscopy or total colon examination for detect colon cancer (colonoscopy or air-contrast barium enema studies) every 5 years beginning at age 50.Which endoscope should be used (colonoscope, 60-cm flexible colonoscope, flexible sigmoidoscope, rigid proctosigmoidoscope), whether double-contrast enema or endoscopy is more cost effective, and precisely when screening should be applied to patients who are asymptomatic but are related to individuals with sporadic nonfamilial colon or rectal cancer would ideally be defined in clinical trials. These trials will never be done because they are extraordinarily difficult to design and prohibitively expensive. Therefore, we will likely rely on statistical modeling and commonsense empiricism for future screening rules. Asymptomatic individuals in the standard-risk group who ask for screening recommendations should be told that 60-cm flexible sigmoidoscopy should be initiated between the ages of 40 and 50 years. At the present, carcinoembryonic antigen (CEA), as well as other more experimental tumor markers, is ineffective for colon cancer screening purposes, because no marker, including CEA, is tumor specific (large numbers of false-positive and false-negative results).

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Colon Cancer Prognosis and Survival Sun, 13 Feb 2011 15:53:38 +0000 admin

The prognosis of colon cancer is related to the stage of disease at diagnosis, histologic differentiation, lymphatic invasion, and extent of tumor-free surgical resection margins. Molecular genetic markers may define subsets of patients either more or less likely to develop tumor recurrence and lead to more rational application of adjuvant multimodality treatment.Definition of subpopulations of cells in the primary tumor that have a particular predisposition to metastasize to particular sites also has exciting potential for use in the near future.

Numerous staging schemes have been defined based on the depth of bowel wall penetration by tumor and lymph node involvement. Most, however, are derived from either the original classification reported by Dukes in 1932 or the TNM staging classification originally applied by the International Union Against Cancer (UICC) in 1978 and adopted by the American Joint Committee on Cancer (AJCC) in 1982. The unified AJCC/UICC TNM staging system was updated in 1997 and is listed in Table 16-6 and illustrated along with the most widely used modified Dukes classification in Figure 16-5 . The influence of disease stages on prognosis of colon and rectal cancer is depicted in Table 16-7 . Other pathologic features, in addition to bowel wall penetration and lymph node status, that have been demonstrated to predict outcome are listed in Table 16-8 . In contrast to many other solid tumors, prognosis in patients with colorectal cancer is not influenced by the size of the primary lesion if data are corrected for nodal involvement and histologic differentiation. In fact, an inverse relationship between size and prognosis may exist.

Influence of Disease Stage on Prognosis During Two Successive 10-Year Intervals
Surgical Stage 5-yr Survival Rate (1940s and 1950s) (%) 5-yr Survival Rate (1960s and 1970s) (%)
Dukes-Kirklin A (I) 80 >90
Dukes-Kirklin B1(I) 60 80
Dukes-Kirklin B2(II) 45 70–75
Dukes C (III) 15–30 35–65

* American Joint Committee on Cancer/International Union Against Cancer TNM Staging.

Selected Pathologic Prognostic Factors in Colorectal Cancer
Adjacent organ involvement (colon)
Radial margin (rectum)
Degree of differentiation
Blood vessel invasion
Lymphatic vessel invasion
Perineural invasion
Immune response
DNA content
Proliferative index
Allelic loss of chromosome 18q (DCC)
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Colon Cancer Recurrent Rates Sun, 13 Feb 2011 15:52:45 +0000 admin

Recurrence rates of colon cancer, determined by number of involved nodes and serosal penetration, as defined by the Gastrointestinal Tumor Study Group adjuvant trial, agree with most modern single-institution series. The median survival time from the clinical detection of metastases is 6 to 8 months.However, larger reviews of patients with metastatic disease do not represent survival statistics applicable to smaller, more selected series. For instance, numerous single-institution treatment series have consistently selected smaller groups of patients with either isolated liver metastases or isolated pulmonary metastases from colon and rectal carcinoma, who have been shown to have long-term survival regardless of treatment response. If patients are diagnosed with minimal metastatic disease isolated to a single organ and have no dysfunction (so-called Eastern Cooperative Study Group [ECOG] 0 performance status), median survival without any treatment at all may be between 2 and 3 years.If these “good biology” patients are accrued to treatment protocols and compared with historic controls, whatever treatment is being examined could inappropriately be touted as effective.

Recurrence Rates by Number of Positive Nodes and Serosal Penetration of Colon Cancer
Category Total No. of Patients No. with Recurrence Recurrence (%)
Serosal penetration; negative nodes 232 47 20
No serosal penetration; 1–4 positive nodes 33 6 18
Serosal penetration; 1–4 positive nodes 205 77 38
No serosal penetration; 5 + positive nodes 16 6 38
Serosal penetration; 5 + positive nodes 85 55 65
Serosal penetration; unknown positive nodes 1 1 100
Total patients 572 192 34
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