Colon cancer


Colon cancer
The colon cancer develops from the lining of the large intestine or colon. In 70% of cases, the tumor grows in the sigmoid (loop located in the pit left iliac). Cancers of the colon and rectum are fairly similar, it combines them under the term of colorectal cancer. It is always a malignant tumor; liebekunien adenocarcinoma, developed from the mucosa.

This is the second cancer, in terms of frequency in women (after breast cancer) and third in men (after lung cancer and the prostate). The colon cancers have a high frequency in France: each day, 100 people learn they have colorectal cancer. More precisely, one discovers 33 000 new cases per year, and 16 000 people die. Among non-smokers, they are the second leading cause of cancer mortality. Men are slightly more affected than women (incidence rate of 40 percent and 27 thousand, respectively. In Africa and Asia, there are much fewer colorectal cancers than in Europe or North USA (up to 20 times less). Moreover, emigrants who leave a poor country to a country where the risk is important, saw their rates increase colorectal cancer in 10-20 years following their migration. These facts suggest that lifestyle, diet and physical exertion, plays an important role in cancer risk. That led to believe that an effective prevention is possible (see below).

It is essentially a cancer of the older, nearly 85% of cases occurring after 65 years. Its frequency seems to be increasing.

The hereditary forms are rare (less than 5% of cases) even if a family history is more frequently found.

Causes or risk factors

* Age: rare before fifty years, colorectal cancers are fairly frequent around 65.
* Heredity: the risk of colorectal cancer is higher if a relative has (had) colorectal cancer. The risk is even stronger there are more people living in the family, that (s) cases are close (s) (father, mother, brother, sister), and that (s) cases are young . It was identified families at very high risk, where people have a specific mutation that predisposes to cancer. These families represent only 5% of colorectal cancers:
o familial adenomatous polyposis (FAP English), where a multitude of polyps appear in all carrying the mutated gene Apc. In adulthood, one of these polyps inevitably degenerate into cancer, unless the colon is removed by surgery.
o Lynch syndrome, or hereditary colon cancer Nonpolyposis (English HNPCC). There are fewer polyps in FAP, and a lower risk of cancer, but surveillance is necessary by regular colonoscopies.
* The chronic inflammatory disease of the colon, including Crohn's disease and ulcerative colitis: after two decades, the risk of having cancer is approximately 1 / 3 if the entire colon is reached.
* The lifestyle also plays an important role, as indicated below in the "prevention". Indeed, if we can not change our age or our heredity, we can stop smoking, drink less alcohol, eat less meats but more vegetables and do more sport.

We know that environmental causes are also at stake;
A diet rich in animal fat predisposes to cancer, either directly because of the richness of it, either because of persistent toxic substances lipophilic (fat-soluble) (certain pesticides, some organochlorines, including Poly Chloro biphenyls (PCBs )...), made by the food (meat, chair of marine mammals, fatty fish or located at the top of the food pyramid).

PCBs that are not spent in the blood or who were evacuated via feces are potentially in contact with the intestinal mucosa for 1 to 2 days, leaving them time to act as carcinogens. A medical team established in 2007 that high blood levels of contaminants such PCB exposed to an increased risk of colorectal cancer. This is the conclusion in a follow-up of 208 patients with this cancer, they showed an average PCB levels double those found in the population (average). In Catalonia, the study estimated that an average adult absorbed very low doses of PCBs (3.5 pico grams of PCBs per kilogram of body weight), but these molecules are stable, low-dose active, and very bioaccumulative, they seem capable of inducing genetic mutations (This study shows a direct relationship mutation of the oncogene K-Ras and the degree of exposure to PCBs, even for the tumor suppressor gene "P53". These researchers and many others argue for a better assessment of risk induced by exposure to low doses of certain pollutants and synergies between these pollutants or between these pollutants and other molecules.

Signs functional
A colorectal cancer does not necessarily signs. That is why, after fifty years, it is recommended detection tests.

It may be manifested by:

* Blood in the stool (fecal blood, apparent or hidden, in this case detected by a test);
* Constipation still emerging. Sometimes a complete obstruction, or diarrhea persistante.A extreme, a blockage can occur, or perforation of the tumor with peritonitis. The presence of digestive signs emerged in the months preceding the accident acute guide to cancer of the acute complications;
* Abdominal pain

The symptoms are often less specific, with, for example:

* Anaemia which gives a persistent fatigue and a dyed increasingly pale (due to intestinal bleeding). It is typically by iron deficiency (low iron and serum ferritin blood). The search for a hidden bleeding in this case led to a diagnosis of colon cancer in approximately 10% of cases.
* An unexplained weight loss;
* Belatedly, liver metastases can give a huge liver to palpation.

Clinical examination
It is, as a rule, disappointing. The rectal examination, through a gloved finger into the anus, looking for possible anomalies rectal. Quick and inexpensive, this review only detects anomalies around the rectum.

Search fecal blood
The search for fecal occult blood (see above) is made all 3 - 5 years by Hemoccult test: It spreads itself a little fecal matter on a "cardboard" special, two days later. Folded, this card is sent to the laboratory to detect blood even in very small quantities. It can thus detect the bleeding of an intestinal polyp (not necessarily cancer). If this test is positive, we resurfaced, and if it is confirmed positive, a colonoscopy must be done. The Hemoccult test is 1 diagnostic tool used in the screening campaigns. However, this test has limits: the patient must refrain from eating meat just cooked, black pudding, and any external source of blood in the three days preceding the test. It is too little specific and sensitive to the topic at risk where one prefers propose initially colonoscopy.

The analysis spectrometer (spectroscopy) a stool sample through a magnetic resonance spectrometer. This technique (SRM) would be "capable in 95% of cases to identify both the presence of cancer and precancerous polyps" according to the Institute for Biodiagnostics in Winnipeg (Centre National de Recherches Canada). "This test is for us a method of screening. Only those whose tests are positive SRM should undergo a colonoscopy. This preliminary test should be less unpleasant for the patient and less costly for the hospital." This technique is being evaluated in humans.

The colonoscopy (or colonoscopy) is the consideration of reference: a probe (long flexible plastic coating) is inserted through the anus and then slid gradually in the intestine, most often during a general anaesthetic. It allows to observe the lining of the anus to the junction ileo-colic, at the caecum and the appendix, and taking samples. If there is a polyp, it is removed entirely and will be analysed at a laboratory histology, and his surgery reduces the risk of cancer (see below paragraph Prevention). The sigmoidoscopy, an examination faster and less complete, use a short semi-rigid probe that allows exploration of the rectum and sigmoid colon, but not the remainder of the colon.

The tissue samples is included in a block of paraffin to extract cuts fines of a few micrometers. After colouring, these cuts are microscopically examined by a doctor specialized in anatomical pathology (or histology). This examination will classify the levy following the shape of the tumor and the type of cells.

It found most often in the intestines of adenomas (= adenomatous polyps). Regarded as benign, the polyp might evolve into cancer if left in place, it is large (more than one centimeter in diameter), and / or is villous (= with villus). The small polyps and tubular polyps present less risk. There are also hyperplastic polyps considered virtually risk-free. Finally, you can find in côlons of adenocarcinomas, which are the real cancers whose cells dysplastic crossing the lamina propria. The first stage of the invasion may evolve to spread to other organs and lead to the emergence of liver metastases in most cases, causing death more frequently than the initial tumor.


* Enema X-ray after the barium sulphate (commonly called barium enema): barium, very heavy, is opaque to X-ray By contrast, we see the contours of the colon, and can identify polyps on the photos. This system, less invasive than colonoscopy, is also less sensitive. It is greatly improved by using computed tomography (scanner, called in this case coloscanner) with the help of powerful computers that allow a virtual colonoscopy in which the entire colon is displayed in 3D high definition, almost real time. This technique is still not as sensitive than colonoscopy and can not remove polyps. If a polyp is detected, it must make a colonoscopy to remove it. The coloscanner is nevertheless preferred if the patient is considered fragile because does not require general anesthesia.

Other types of examinations are little used, too expensive, too new or too specific or sensitive (vidéocapsule, PET, CEA…).

The adenocarcinomas account for 95% of cases, of which 17% of adenocarcinomas colloids or mucineux.

The only classification used in preoperative east TNM classification whose 6th version dates from 2002.

Classification TNM

T (tumor)

* Tis intra-epithelial or chorion
* T1 sub-mucosal
* T2 muscle
* T3 through the muscularis propria in the sub-serous or in the tissues péricoliques non péritonealisés.
* T4 organ or structure neighbourhood and / or perforation of visceral peritoneum

N (node)

* N0 no lymph node metastasis
* Nx nodes have not been evaluated or less than 8 nodes examined
* N1 1 to 3 metastatic regional lymph nodes

* N2 4 regional lymph nodes or metastatic plus M (metastasis)

* M0 no metastasis
* M1 metastases distance (nodes above claviculaires)

A data from the TNM classification, colon cancers are classified into 4 stages. The chances of recovery vary considerably Stage I to Stage IV. For each stage is noted in parentheses survival rates five years after treatment. The therapeutic strategy is also tailored to each of these stages.

* Stage I (93.2%): pT1-T2 N0 M0
* Stage II: pT3-T4 N0 M0
o Stage IIA (84.7%): pT3 N0 M0
o stage IIB (72.2%): pT4 N0 M0
* Stage III: all T N1-N2 M0
o stage IIIA (83.4%): pT1T2N1M0
o Stage IIIB (64.1%): pT3T4N1M0
o stage IIIC (44.3%): all T N2M0
* Stage IV (8.1%): metastases distance

The prognosis is worse in case of obstruction or perforation, cancer or indiscriminate colloid mucous. It is best if phenotype RER + (MSI).

When cancer is detected at an early stage on the heals (90% of healing for stage I). If the cancer is discovered late, the chances of recovery are much lower (less than 5% of the healing stage IV). The first treatment is surgery, which allows you to remove the tumor and surrounding lymph nodes (lymph node flushing). (Cancers are sometimes very superficial totally endoscopic réséqués through without surgery necessary when there is no crossing of the muscle lining). It combines adjuvant treatment: chemotherapy, if the flushing contains lymph node metastases or if there are liver or lung metastases; radiotherapy if exerèse surgery could not be total, with remaining tumor individualized on a vital organ.

In the case of low rectal cancer, the presence of lymph visible on the scanner or échoendoscopie is an indication of radio-preoperative chemotherapy.

Methods therapeutic

Any polyp removed by endoscopy is considered a pathology. The presence of dysplasia (pre-state) or cancerous very superficial (no invasion of the muscular lining, ie stage Tis) that the endoscopic resection is curative. The presence of cancer on a bank of surgery or flooding in depth (stage T1 or more) results in an additional indication of systematic surgery (unless the general condition of the patient does not allow it).

The goal of surgery is to remove the tumor and lymph nodes are swelling around by flushing. The ganglia accompanying blood vessels irrigating the colon (in the mésocôlon, lame fat lying between the aorta and colon), it is therefore to remove a segment of colon and not just the tumor. The surgery, to be sufficient, must win at least 5 cm colon on both sides of cancer, and at least 12 lymph nodes in the flushing.

As a result of the vascular anatomy of the colon, the most commonly used are:

* Hémicolectomie right, with anastomosis ileo-transverse, carrying all mésocôlon right to the edge of the superior mesenteric artery;
* Hémicolectomie left true, with anastomosis between the transverse colon and rectum high. The flushing lymph node wins the inferior mesenteric artery, which is linked to 1 cm from its origins on the aorta and its branches. ;
* Sigmoïdectomie with vascular ligation after emergence of the artery colic top left;
* Transverse colon resections are more atypical and depend on the vascular anatomy highlighted in preoperative.

Remove the tumor is the fastest and most effective way to eliminate cancer. However, if the tumor has already sent metastases far colon, exerèse surgery is not enough to heal the sick.

These interventions can be made by laparotomy (open belly) or cœlioscopie (working in a belly swollen by CO2 through instruments introduced through holes 1 cm. The cancer escaped through a small incision at the end of 'intervention).

The presence of a non-curable anal incontinence, complications of cancer type of obstruction or perforation, or the inability to retain the anal sphincter, leading to practise a stoma (or artificial anus): the colon is the abouché skin of the abdomen, and feces are collected in a pocket that the patient positioning itself every day or every 3 days. The equipment currently available provide comfort.

If there is discovery of metastatic liver surgery for colon cancer, resection is envisaged: a synchronous (at the same time operating) if the surgery is easy, so métachrone (later) if multiple metastases. Recent studies have shown that the size and number of injuries had little influence on survival after surgery. Some techniques such as ultrasound preoperative, chemotherapy néoadjuvante (before liver surgery) and the embolization of the branch of the portal vein segment reached, the radio, can increase the number of operable patients of their metastases and precision of surgery.

If the patient is not operable, alternatives exist: chemotherapy and more recently the application of physical treatment on metastases (radiofrequency ablation, heat treatment). The lung metastases of colorectal cancer should also be made whenever possible. Otherwise, here too chemotherapy and physical treatments are possible.

It sometimes radiates the tumor to kill cancer cells before or after surgery. Radiation therapy may be associated with chemotherapy, which sensitizes the tumor to the lethal effect of radiation. Radiation therapy is most often used for cancers of the rectum, sometimes preoperatively. In colon cancers, it may be useful if the cancer can not be réséqué entirely due to flooding (ureter, iliac vessels).

Nutritional support
Any resection of colon cancer can cause diarrhea, sometimes disabling. Likewise, chemotherapies used, often causing an acceleration of transit. Patients are therefore propose a no residue more or less restrictive: avoid eating raw vegetables, fibre-rich vegetables or meat sauce can improve the comfort of life. Similarly, thickeners digestive type Smecta humps or transit type loperamide can help.

Colon cancer located
The treatment of colon cancer is located a cure. The first step is to remove the tumor, usually during surgery. Then, adjuvant treatment with chemotherapy is offered if the risk of relapse is important.En 2008 chemotherapy is proposed systematically where there are lymph node metastases (Stage III). In the absence of lymph node metastases, adjuvant chemotherapy is proposed in the following cases:

* T4N0
* Emboli lymph
* Occlusion,
* Perforation
* Number of lymph nodes removed insufficient
* Aneuploidy

In both cases the protocol of chemotherapy most frequently used is the protocol FOLFOX4, an injection every two weeks for 6 months.

Prevention of colorectal cancer
The majority of cancers of the colon and rectum could be prevented by increased surveillance, a way of life and, probably also take oral products chemoprevention.

1. Surveillance: most colorectal cancers arise in polyps (adenomas). These lesions can be detected and removed during a colonoscopy. Studies show that this procedure could decrease by 80% the risk of death by cancer if intestinal examinations began at around 45, then every 5 or 10 years.
2. Lifestyle: comparing the incidence of colorectal cancer in different regions of the world suggests that physical inactivity, excess calories ingested and perhaps also a regime too rich in red meat and sausages could increase the risk of cancer. Conversely, physical activity and a diet rich in fruits and vegetables, would lower the risk of cancer, probably because the plants contain micronutrients protectors. By changing his lifestyle, could therefore reduce the risk of cancer by 60 to 80%. In addition, a diet promoting fruit and vegetables, fish and poultry, could reduce the risk of recurrence and mortality of cancer.

1. Chimioprévention: more than 200 products, including micronutrients cited above, as well as other nutrients such as calcium or folic acid (vitamin B), and drugs like aspirin inhibit carcinogenesis in preclinical models ( In animal). In some studies, it inhibits completely chemically induced tumors in the colon of rats. Other studies show significant inhibition of spontaneous intestinal polyps in mice mutated (Min mice). Clinical trials of chemoprevention in human volunteers have been less successful, but few products have been tested so far. Some calcium supplements or given aspirin each day for 3 to 5 years after the removal of a polyp, have reduced the recurrence of polyps in the volunteers (15 to 20%). The database of chemoprevention of INRA gives the results of all studies published on chemoprevention agents in humans and in rodents.

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