Colorectal Cancer

Content

Introduction ………………………………………………………………………………………..2

Actuality of the topic …………………………………………………………………………………….4

Purpose of thesis……………………………………………………………………………….……4

Objectives of thesis…………………………………………………………………………….…..4

Theoretical importance and value of the work ……………………………………………..……4

Chapter 1 ………………………………………………………………………………………………………5

1.1 General information ………………………………………………….…………….……5

1.1.1. Anatomy of the colon ……………………………………………………….……..5

1.1.2 Blood and nerve supply ……………………………………………………………10

1.2 colorectal cancers …………………………………………………………………………12

1.2.1. Etiopathology ……………………………………………………..…………………….13

1.2.2. Morphopathology …………………………………………………………….…………15

1.2.3. Epidemiology …………………………………………………………………………….17

1.2.4. Types and clinical forms ……………………………….………………………………..18

1.2.5. Stages ……………………………………………………………………………………..20

1.2.6. Signs and symptoms …………………………………………………………………….23

1.2.7. Diagnosis ……………………………………………………………………………….…24

1.2.8. Differential diagnosis ……………………………………………………………………28

1.2.9. Treatment …………………………………………………………………………………29

INTRODUCTION

Actuality of the topic:

Colorectal cancer (also known as colon cancer, rectal cancer, or bowel cancer) is the development of cancer in the colon or rectum (parts of the large intestine).[1] It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body.[2] Signs and symptoms may include blood, a change in bowel movements, weight loss, and feeling tired all the time

Colorectal cancer (CRC) represents 15% of worldwide malignancies and is the third cause of cancer in men (10% of total) and the second cause of cancer in women after breast cancer (9.4% of total). Every year there are registered around one million new cases and 500 000 deaths caused by CRC worldwide. Incidence rates are similar between men and women with cancer of the large bowel and higher for males with rectal cancer, but the overall incidence of CRC is higher in males (sex ratio M:F = 1.4/1) [1]. In Romania, according to GLOBOCAN estimated data for 2008, CRC is the second leading cause of morbidity through cancer in men (after lung cancer) and in women (after breast cancer). The number of new cases in 2008 was 8696 (22.8/100,000 population), out of which 4554 men and 4142 women

CRC incidence and mortality rates vary markedly around the world. Globally, CRC is the third most commonly diagnosed cancer in males and the second in females, with 1.4 million new cases and almost 694,000 deaths estimated to have occurred in 2012 [1]. Rates are substantially higher in males than in females.

Global, country-specific incidence and mortality rates are available in the World Health Organization GLOBOCAN database.

In the United States, both the incidence and mortality have been slowly but steadily decreasing [2]. Annually, approximately 132,700 new cases of large bowel cancer are diagnosed, of which 93,090 are colon and the remainder rectal cancers [3]. Annually, approximately 49,700 Americans die of CRC, accounting for approximately 8 percent of all cancer deaths.

Incidence — globally, the incidence of CRC varies over 10-fold. The highest incidence rates are in Australia and New Zealand, Europe, and North America, and the lowest rates are found in Africa and South-Central Asia (CRC incidence by world area) [4]. These geographic differences appear to be attributable to differences in dietary and environmental exposures that are imposed upon a background of genetically determined susceptibility.

Low socioeconomic status (SES) is also associated with an increased risk for the development of colorectal cancer; one study estimated the CRC risk to be about 30 percent increased in the lowest as compared with the highest SES quintile [5]. Potentially modifiable behaviors such as physical inactivity, unhealthy diet, smoking, and obesity are thought to account for a substantial proportion (estimates of one-third to one-half) of the socioeconomic disparity in risk of new onset colorectal cancer [5-7]. Other factors, particularly lower rates of CRC screening, also contribute substantively to SES differences in CRC risk.

Purpose of thesis

Analyze the modern aspects of colorectal cancer in dependence to its localization and severity level.

Objectives of thesis

1. Study the etiology of the colorectal cancer.

2. Study the modern diagnostic methods.

3. Study the most effective strategy of treatment and management.

4. Clinical research on patients with colorectal cancer and the relation. Between different factors with the development of the disease.

Theoretical importance and value of the work

1. Detection of the common etiology for colorectal cancer.

2. To reveal the contemporary methods used in diagnosis and treatment.

3. I participated in a surgery at the surgical department of the hospital to see the contemporary approach.

4. Presenting new methods and recent findings on early detection of the disease

5. Reveal the most common risk factors and their effect on severity of the disease

Chapter 1

General information

Anatomy of the colon:

The large intestine, also called the colon or the large bowel, is the last part of the digestive system in vertebrates. Water is absorbed here and the remaining waste material is stored as feces before being removed by defecation.[1]

Terminologia Anatomica, Medscape, and Gray's Anatomy define the large intestine as the combination of the cecum, colon, rectum, and anal canal.[2][3]Other sources, such as Mosby's Medical Dictionary and the Oxford Dictionaries of Medicine and Biology exclude the anal canal.[4][5][6] In humans, it begins in the right iliac region of the pelvis, just at or below the waist, where it is joined to the end of the small intestine. It then continues up the abdomen, across the width of the abdominal cavity, and then down to its endpoint at the anus. Overall, in humans, the large intestine is about 1.5 metres (4.9 ft) long, which is about one-fifth of the whole length of the gastrointestinal tract.

Sections

Sections of the colon

In mammals, the colon consists of four sections: the ascending colon, the transverse colon, the descending colon, and the sigmoid colon (the proximal gut usually refers to the ascending colon and transverse colon, and distal gut refers to the descending colon). The cecum, colon, rectum and anal canal make up the large intestine.[1]

Sections of the colon are:

The cecum and the appendix

The ascending colon

The right colic flexure (hepatic)

The transverse colon

The transverse mesocolon

The left colic flexure (splenic)

The descending colon

The sigmoid colon – the v-shaped region of the large intestine

The parts of the colon are either intraperitoneal or behind it in the retroperitoneum. Retroperitoneal organs in general do not have a complete covering of peritoneum, so they are fixed in location. Intraperitoneal organs are completely surrounded by peritoneum and are therefore mobile.[11] Of the colon, the ascending colon, descending colon and rectum are retroperitoneal, while the caecum, appendix, transverse colon and sigmoid colon are intraperitoneal.[12] This is important as it affects which organs can be easily accessed during surgery, such as a laparotomy.

Cecum and appendix

The cecum is the first section of the colon and involved in the digestion, while the appendix which develops embryologically from it, is a structure of the colon, not involved in digestion and considered to be part of the gut-associated lymphoid tissue. The function of the appendix is uncertain, but some sources believe that the appendix has a role in housing a sample of the colon's microflora, and is able to help to repopulate the colon with bacteria if the microflora has been damaged during the course of an immune reaction.

Ascending colon

The ascending colon is one part of four sections of the large intestine. This first section of the large intestine is connected to the small intestine by a section of bowel called the cecum. The ascending colon runs through the abdominal cavity, upwards toward the transverse colon for approximately eight inches (20 cm).

One of the main functions of the colon is to remove the water and other key nutrients from waste material and recycle it back into the body. As the waste material exits the small intestine it will move into the cecum and then to the ascending colon where this process of extraction starts. The unwanted waste material is moved upwards toward the transverse section of the colon by the action of peristalsis. The ascending colon is sometimes attached to the appendix via Gerlach's valve. The appendix traditionally seen as a vestigial organ has been shown to have a high concentration of lymphatic cells. In ruminants, the ascending colon is known as the spiral colon.[13] The cecum receives the solid wastes of digestion from the ileum via theileocecal valve.[14][15]

Transverse colon

The transverse colon is the part of the colon from the hepatic flexure to the splenic flexure (the turn of the colon by thespleen). The transverse colon hangs off the stomach, attached to it by a large fold of peritoneum called the greater omentum. On the posterior side, the transverse colon is connected to the posterior abdominal wall by a mesentery known as thetransverse mesocolon.

The transverse colon is encased in peritoneum, and is therefore mobile (unlike the parts of the colon immediately before and after it). Cancers form more frequently further along the large intestine as the contents become more solid (water is removed) in order to form feces.

The proximal two-thirds of the transverse colon is perfused by the middle colic artery, a branch of the superior mesenteric artery (SMA), while the latter third is supplied by branches of the inferior mesenteric artery (IMA). The "watershed" area between these two blood supplies, which represents the embryologic division between the midgut and hindgut, is an area sensitive to ischemia.

Descending colon

The descending colon is the part of the colon from the splenic flexure to the beginning of the sigmoid colon. One function of the descending colon in the digestive system is to store faeces that will be emptied into the rectum. It is retroperitoneal in two-thirds of humans. In the other third, it has a (usually short) mesentery. The arterial supply comes via the left colic artery. The descending colon is also called the distal gut, as it is further along the gastrointestinal tract than the proximal gut. Gut flora are very dense in this region.

Sigmoid colon

The sigmoid colon is the part of the large intestine after the descending colon and before the rectum. The name sigmoidmeans S-shaped (see sigmoid; cf. sigmoid sinus). The walls of the sigmoid colon are muscular, and contract to increase the pressure inside the colon, causing the stool to move into the rectum.

The sigmoid colon is supplied with blood from several branches (usually between 2 and 6) of the sigmoid arteries, a branch of the IMA. The IMA terminates as the superior rectal artery.

Sigmoidoscopy is a common diagnostic technique used to examine the sigmoid colon.

Rectum

Rectum is the last section of the colon.

Blood supply :

Arterial supply to the colon comes from branches of the superior mesenteric artery (SMA) and inferior mesenteric artery (IMA). Flow between these two systems communicates via a "marginal artery" that runs parallel to the colon for its entire length. Historically, it has been believed that the arc of Riolan, or the meandering mesenteric artery (of Moskowitz), is a variable vessel connecting the proximal SMA to the proximal IMA that can be extremely important if either vessel is occluded. However, recent studies conducted with improved imaging technology have questioned the actual existence of this vessel, with some experts calling for the abolition of the terms from future medical literature.[citation needed]

Venous drainage usually mirrors colonic arterial supply, with the inferior mesenteric vein draining into the splenic vein, and thesuperior mesenteric vein joining the splenic vein to form the hepatic portal vein that then enters the liver.

Innervations :

The large intestine is innervated by intrinsic and extrinsic sources. The vagus nerve (CNX)enter the abdominal cavity via the oesophageal hiatus of the diaphragm to provide parasympathetic innervation to the large intestines. The pelvic splanchnic nerves (S2-4) also contribute to the large intestines’ parasympathetic supply. The parasympathetic fibers are responsible for increasing secretomotor activity along this segment of the digestive tract. The vagus nerve fulfil this role in the gut to the point of the transverse colon, while the pelvic splanchnic nerves carry on this function from the left colic flexure onwards. The T10-L2 thoracolumbar outflow of sympathetic fibers is responsible for the inhibitory activity along the large intestines. They form synapses at the superior and inferior mesenteric, and the inferior hypogastric plexuses. The superior mesenteric plexus provides sympathetic innervation to the cecum, appendix, ascending and transverse colon (near to the left colic flexure), while the inferior mesenteric plexus innervates the colon from the left colic flexure to the rectum. The inferior hypogastric plexus also innervates the rectum.

In addition to the extrinsic nerve supply to the gut, there are networks of nerve fibers occupying space between the longitudinal and circular muscle layers (myenteric plexus of Auerbach), and in the submucosal layer (submucosal plexus of Meissner). In addition to Auerbach’s and Meissner’s plexuses, there are additional intrinsic plexuses that collectively form the enteric nervous system. Although these networks receive postganglionic inhibitory and preganglionic excitatory fibers, they are fully functional in the absence of those contributions.

Colorectal cancer

Colorectal cancer (also known as colon cancer, rectal cancer, or bowel cancer) is the development of cancer in the colon or rectum (parts of the large intestine).[1] It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body.[2] Signs and symptoms may includeblood in the stool, a change in bowel movements, weight loss, and feeling tired all the time.[3]

Risk factors for colorectal cancer include lifestyle, older age, and inheritedgenetic disorders.[4][5] Other risk factors include diet, smoking, alcohol, lack ofphysical activity, family history of colon cancer and colon polyps, presence of colon polyps, race, exposure to radiation, and even other diseases such asdiabetes and obesity.[4][5] Genetic disorders only occur in a small fraction of the population. A diet high in red, processed meat, while low in fiber increases the risk of colorectal cancer.[4] Other diseases such as inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis, can increase the risk of colorectal cancer.[4] Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of cases.[4][5] It typically starts as a benign tumor, often in the form of a polyp, which over time becomes cancerous.[4]

Bowel cancer may be diagnosed by obtaining a sample of the colon during asigmoidoscopy or colonoscopy.[3] This is then followed by medical imaging to determine if the disease has spread.[1] Screening is effective for preventing and decreasing deaths from colorectal cancer.[6] Screening is recommended starting from the age of 50 to 75.[6] During colonoscopy, small polyps may be removed if found. If a large polyp or tumor is found, a biopsy may be performed to check if it is cancerous. Aspirin and other non-steroidal anti-inflammatory drugs decrease the risk.[4][7] Their general use is not recommended for this purpose, however, due to side effects.[8]

Etiopathology:

Greater than 75–95% of colon cancer occurs in people with little or no genetic risk.[14][15] Other risk factors include older age, male gender,[15] high intake of fat, alcohol or red meat, obesity, smoking, and a lack of physical exercise.[14] Approximately 10% of cases are linked to insufficient activity.[16] The risk for alcohol appears to increase at greater than one drink per day.[17] Drinking 5 glasses of water a day is linked to a decrease in the risk of colorectal cancer and adenomatous polyps.[18]

Inflammatory bowel disease

People with inflammatory bowel disease (ulcerative colitis and Crohn's disease) are at increased risk of colon cancer.[19] The risk increases the longer a person has the disease,[20] and the worse the severity of inflammation.[21] In these high risk groups, both prevention with aspirin and regular colonoscopies are recommended.[20] People with inflammatory bowel disease account for less than 2% of colon cancer cases yearly.[21] In those with Crohn's disease 2% get colorectal cancer after 10 years, 8% after 20 years, and 18% after 30 years.[21] In those with ulcerative colitis approximately 16% develop either acancer precursor or cancer of the colon over 30 years.[21]

Genetics

Those with a family history in two or more first-degree relatives (such as a parent or sibling) have a two to threefold greater risk of disease and this group accounts for about 20% of all cases. A number of genetic syndromes are also associated with higher rates of colorectal cancer. The most common of these is hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) which is present in about 3% of people with colorectal cancer.[15] Other syndromes that are strongly associated with colorectal cancer include Gardner syndrome,[22] and familial adenomatous polyposis (FAP). For people with these syndromes, cancer almost always occurs and makes up 1% of the cancer cases.[23] A total proctocolectomy may be recommended for people with FAP as a preventative measure due to the high risk of malignancy. Colectomy, removal of the colon, may not suffice as a preventative measure because of the high risk of rectal cancer if the rectum remains.[24]

Most deaths due to colon cancer are associated with metastatic disease. A gene that appears to contribute to the potential for metastatic disease, metastasis associated in colon cancer 1 (MACC1), has been isolated.[25] It is a transcriptional factor that influences the expression of hepatocyte growth factor. This gene is associated with the proliferation, invasion and scattering of colon cancer cells in cell culture, and tumor growth and metastasis in mice. MACC1 may be a potential target for cancer intervention, but this possibility needs to be confirmed with clinical studies.[26]

Epigenetic factors, such as abnormal DNA methylation of tumor suppressor promoters play a role in the development of colorectal cancer

Morphopathology :

Colorectal cancer is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract, most frequently as a result of mutations in the Wnt signaling pathway that increase signaling activity. The mutations can be inheritedor acquired, and most probably occur in the intestinal crypt stem cell.[28][29][30] The most commonly mutated gene in all colorectal cancer is the APC gene, which produces the APC protein. The APC protein prevents the accumulation of β-cateninprotein. Without APC, β-catenin accumulates to high levels and translocates (moves) into the nucleus, binds to DNA, and activates the transcription of proto-oncogenes. These genes are normally important for stem cell renewal and differentiation, but when inappropriately expressed at high levels, they can cause cancer. While APC is mutated in most colon cancers, some cancers have increased β-catenin because of mutations in β-catenin (CTNNB1) that block its own breakdown, or have mutations in other genes with function similar to APC such as AXIN1, AXIN2, TCF7L2, or NKD1.[31]

Beyond the defects in the Wnt signaling pathway, other mutations must occur for the cell to become cancerous. The p53protein, produced by the TP53 gene, normally monitors cell division and kills cells if they have Wnt pathway defects. Eventually, a cell line acquires a mutation in the TP53 gene and transforms the tissue from an benign epithelial tumor into an invasive epithelial cell cancer. Sometimes the gene encoding p53 is not mutated, but another protective protein named BAX is mutated instead.[31]

Other proteins responsible for programmed cell death that are commonly deactivated in colorectal cancers are TGF-β and DCC (Deleted in Colorectal Cancer). TGF-β has a deactivating mutation in at least half of colorectal cancers. Sometimes TGF-β is not deactivated, but a downstream protein named SMAD is deactivated.[31] DCC commonly has a deleted segment of a chromosome in colorectal cancer.[32]

Some genes are oncogenes: they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS,RAF, and PI3K, which normally stimulate the cell to divide in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important. If a previous APC mutation occurred, a primary KRAS mutation often progresses to cancer rather than a self-limiting hyperplastic or borderline lesion.[33]PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated.[31]

Comprehensive, genome-scale analysis has revealed that colorectal carcinomas can be categorized into hypermutated and non-hypermutated tumor types.[34] In addition to the oncogenic and inactivating mutations described for the genes above, non-hypermutated samples also contain mutated CTNNB1, FAM123B, SOX9, ATM, and ARID1A. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of ACVR2A, TGFBR2, MSH3, MSH6, SLC9A9,TCF7L2, and BRAF. The common theme among these genes, across both tumor types, is their involvement in WNT and TGF-β signaling pathways, which results in increased activity of MYC, a central player in colorectal cancer

Epidemiology:

CRC incidence and mortality rates vary markedly around the world. Globally, CRC is the third most commonly diagnosed cancer in males and the second in females, with 1.4 million new cases and almost 694,000 deaths estimated to have occurred in 2012 [1]. Rates are substantially higher in males than in females. Global, country-specific incidence and mortality rates are available in the World Health Organization GLOBOCAN database.

In the United States, both the incidence and mortality have been slowly but steadily decreasing [2]. Annually, approximately 132,700 new cases of large bowel cancer are diagnosed, of which 93,090 are colon and the remainder rectal cancers [3]. Annually, approximately 49,700 Americans die of CRC, accounting for approximately 8 percent of all cancer deaths.

Incidence — Globally, the incidence of CRC varies over 10-fold. The highest incidence rates are in Australia and New Zealand, Europe, and North America, and the lowest rates are found in Africa and South-Central Asia (CRC incidence by world area) [4]. These geographic differences appear to be attributable to differences in dietary and environmental exposures that are imposed upon a background of genetically determined susceptibility.

Low socioeconomic status (SES) is also associated with an increased risk for the development of colorectal cancer; one study estimated the CRC risk to be about 30 percent increased in the lowest as compared with the highest SES quintile [5]. Potentially modifiable behaviors such as physical inactivity, unhealthy diet, smoking, and obesity are thought to account for a substantial proportion (estimates of one-third to one-half) of the socioeconomic disparity in risk of new onset colorectal cancer [5-7]. Other factors, particularly lower rates of CRC screening, also contribute substantively to SES differences in CRC risk

Types of colorectal cancer:

Mucinous adenocarcinoma : is made up of approximately 60 percent mucus. The mucus can cause cancer cells to spread faster and become more aggressive than typical adenocarcinomas. Mucinous adenocarcinomas account for 10 to 15 percent of all colon and rectal adenocarcinomas.

Signet ring cell adenocarcinoma :accounts for less than one percent of adenocarcinomas. Named for its appearance under a microscope, signet ring cell adenocarcinoma is typically aggressive and may be more difficult to treat.

Gastrointestinal carcinoid tumors: This slow-growing cancer forms in the neuroendocrine cell (a nerve cell that also creates hormones) in the lining of the gastrointestinal tract. These tumors account for just 1 percent of all colorectal cancers, but half of all of the cancers found in the small intestine.

Primary colorectal lymphomas: A type of non-Hodgkin lymphoma (NHL), lymphomas are cancers that develop in the lymphatic system from cells called lymphocytes. Lymphocytes are a type of white blood cell that helps the body fight infections. NHL can develop in many parts of the body, including the lymph nodes, bone marrow, spleen, thymus and the digestive tract. Primary colorectal lymphomas account for just 0.5 percent of all colorectal cancers, and about 5 percent of all lymphomas. The disease usually occurs later in life, and is more common in men than women.

Gastrointestinal stromal tumors: Also known as GISTs, this is a rare type of colorectal cancer that starts in a special cell found in the lining of the gastrointestinal (GI) tract called interstitial cells of Cajal (ICCs). More than 50 percent of GISTs start in the stomach. While most of the others start in the small intestine, the rectum is the third most common location. GISTs are classified as sarcomas, cancers that begin in the connective tissues, which include fat, muscle, blood vessels, deep skin tissues, nerves, bones and cartilage.

Leiomyosarcomas: Another form of sarcoma, leiomyosarcomas essentially means “cancer of smooth muscle.” The colon and rectum have three layers of the type of muscle that can be affected, which all work together to guide waste through the digestive tract. This rare type of colorectal cancer accounts for about 0.1 percent of all colorectal cases.

Melanomas: Though most commonly associated with the skin, melanomas can occur anywhere, including the colon or rectum.

Squamous cell carcinomas: Some parts of the GI tract, like the upper part of the esophagus and the end of the anus, are lined with flat cells called squamous cells. These are the same type of cells that are found on the surface of the skin. Cancers starting in these cells are called squamous cell carcinoma.

Stages of colorectal cancer:

Signs and symptoms:

Colorectal cancer might not cause symptoms right away, but if it does, it may cause one or more of these symptoms:

A change in bowel habits, such as diarrhea, constipation, or narrowing of the stool, that lasts for more than a few days

A feeling that you need to have a bowel movement that is not relieved by doing so

Rectal bleeding

Blood in the stool, which may make it look dark

Cramping or abdominal (belly) pain

Weakness and fatigue

Unintended weight loss

Colorectal cancers can often bleed into the digestive tract. While sometimes the blood can be seen in the stool or make it look darker, often the stool looks normal. But over time, the blood loss can build up and can lead to low red blood cell counts (anemia). Sometimes the first sign of colorectal cancer is a blood test showing a low red blood cell count.

Diagnosis :

Diagnosis of colorectal cancer is via sampling of areas of the colon suspicious for possible tumor development typically done during colonoscopy or sigmoidoscopy, depending on the location of the lesion. The extent of the disease is then usually determined by a CT scan of the chest, abdomen and pelvis. There are other potential imaging test such as PET and MRIwhich may be used in certain cases. Colon cancer staging is done next and based on the TNM system which is determined by how much the initial tumor has spread, if and where lymph nodes are involved, and the extent of metastatic disease.[15]

The microscopic cellular characteristics of the tumor are usually reported from the analysis of tissue taken from a biopsy or surgery. A pathology report will usually contain a description of cell type and grade. The most common colon cancer cell type is adenocarcinoma which accounts for 98% of cases.[53] Other, rarer types include lymphoma and squamous cell carcinoma.

Macroscopy

Cancers on the right side of the large intestine (ascending colon and cecum) tend to be exophytic, that is, the tumor grows outwards from one location in the bowel wall. This very rarely causes obstruction of feces, and presents with symptoms such as anemia. Left-sided tumors tend to be circumferential, and can obstruct the bowel lumen, much like a napkin ring, and results in thinner caliber stools.

Microscopy

Adenocarcinoma is a malignant epithelial tumor, originating from superficial glandular epithelial cells lining the colon and rectum. It invades the wall, infiltrating the muscularis mucosae layer, the submucosa, and then the muscularis propria. Tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Sometimes, tumor cells are discohesive and secrete mucus, which invades the interstitium producing large pools of mucus/colloid (optically "empty" spaces). This occurs in mucinous (colloid) adenocarcinoma, in which cells are poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery. This occurs in "signet-ring cell." Depending on glandular architecture, cellular pleomorphism, and mucosecretion of the predominant pattern, adenocarcinoma may present three degrees of differentiation: well, moderately, and poorly differentiated.[54]

Immunochemistry

Most (50%) colorectal adenomas and (80–90%) colorectal cancer tumors are thought to over express the cyclooxygenase-2(COX-2) enzyme.[55] This enzyme is generally not found in healthy colon tissue, but is thought to fuel abnormal cell growth.

Macroscopy

Appearance of the inside of the colon showing one invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor)

Gross appearance of acolectomy specimen containing twoadenomatous polyps(the brownish oval tumors above the labels, attached to the normal beige lining by a stalk) and one invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor located above the label)

Endoscopic image of colon cancer identified in sigmoid colon on screening colonoscopyin the setting of Crohn's disease

PET/CT of a staging exam of colon carcinoma. Besides the primary tumor a lot of lesions can be seen. On cursor position: lung nodule.

Micrographs (H&E stain)

Lab tests :

Genomic tumor assessment: Genomic testing examines a tumor on a genetic level to find the DNA alterations that are driving the growth of cancer. By identifying the mutations that occur in a cancer cell's genome, we can better understand what caused the tumor and tailor treatment based on these findings. Learn more about genomic tumor assessment.

Tumor molecular profiling: If you have a solid tumor, we’ll try to get a sample of tissue during a biopsy or surgery. Then, we’ll test for the presence of a variety of enzymes, proteins and genes to identify which therapies are likely to be most effective. Learn more about tumor molecular profiling.

CBC test: Complete blood count (CBC) tests determine the numbers of the different types of cells in the blood. A CBC test can be particularly helpful in determining whether you have too few red blood cells, which causes anemia. This can be a concern for colorectal cancer patients, as they may have a tumor that’s been bleeding for some time.

Liver function tests: These blood tests may be done to assess the function of the liver, an organ to which colorectal cancer can spread. These blood tests may be done to assess the function of the liver, an organ to which colorectal cancer can spread.

Tumor marker tests: This blood test may be used in addition to other tests for people who have already been diagnosed with colorectal cancer and are being treated for the disease. The tumor marker tests check for two substances in the blood that colorectal cancer may produce: carcinoembryonic antigen (CEA) and CA 19-9. The tests can help determine the effectiveness of treatment and, sometimes, disease recurrence.

Differential diagnosis:

Treatment :

Six types of standard treatment are used:

Surgery:

Surgery (removing the cancer in an operation) is the most common treatment for all stages of colon cancer. A doctor may remove the cancer using one of the following types of surgery:

Local excision: If the cancer is found at a very early stage, the doctor may remove it without cutting through the abdominalwall. Instead, the doctor may put a tube with a cutting tool through the rectum into the colon and cut the cancer out. This is called a local excision. If the cancer is found in a polyp (a small bulging area of tissue), the operation is called a polypectomy.

Resection of the colon with anastomosis: If the cancer is larger, the doctor will perform a partial colectomy (removing the cancer and a small amount of healthy tissue around it). The doctor may then perform an anastomosis (sewing the healthy parts of the colon together). The doctor will also usually remove lymph nodes near the colon and examine them under amicroscope to see whether they contain cancer.ENLARGE

Resection of the colon with anastomosis. Part of the colon containing the cancer and nearby healthy tissue is removed, and then the cut ends of the colon are joined.

Resection of the colon with colostomy: If the doctor is not able to sew the 2 ends of the colon back together, a stoma (an opening) is made on the outside of the body for waste to pass through. This procedure is called a colostomy. A bag is placed around the stoma to collect the waste. Sometimes the colostomy is needed only until the lower colon has healed, and then it can be reversed. If the doctor needs to remove the entire lower colon, however, the colostomy may be permanent.ENLARGE

Colon cancer surgery with colostomy. Part of the colon containing the cancer and nearby healthy tissue is removed, a stoma is created, and a colostomy bag is attached to the stoma.

Even if the doctor removes all the cancer that can be seen at the time of the operation, some patients may be givenchemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiofrequency ablation

Radiofrequency ablation is the use of a special probe with tiny electrodes that kill cancer cells. Sometimes the probe is inserted directly through the skin and only local anesthesia is needed. In other cases, the probe is inserted through an incision in theabdomen. This is done in the hospital with general anesthesia.

Cryosurgery

Cryosurgery is a treatment that uses an instrument to freeze and destroy abnormal tissue. This type of treatment is also called cryotherapy.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into thecerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy).

Chemoembolization of the hepatic artery may be used to treat cancer that has spread to the liver. This involves blocking the hepatic artery (the main artery that supplies blood to the liver) and injecting anticancer drugs between the blockage and the liver. The liver’s arteries then deliver the drugs throughout the liver. Only a small amount of the drug reaches other parts of the body. The blockage may be temporary or permanent, depending on what is used to block the artery. The liver continues to receive some blood from the hepatic portal vein, which carries blood from the stomach and intestine.

The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or cathetersthat are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.

Types of targeted therapies used in the treatment of colon cancer include the following:

Monoclonal antibodies: Monoclonal antibodies are made in the laboratory from a single type of immune system cell. Theseantibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

Angiogenesis inhibitors: Angiogenesis inhibitors stop the growth of new blood vessels that tumors need to grow.

Treatment according to stages:

Stage 0 (Carcinoma in Situ)

Treatment of stage 0 (carcinoma in situ) may include the following types of surgery:

Local excision or simple polypectomy.

Resection and anastomosis. This is done when the tumor is too large to remove by local excision.

Stage I Colon Cancer

Treatment of stage I colon cancer usually includes the following:

Resection and anastomosis.

Stage II Colon Cancer

Treatment of stage II colon cancer may include the following:

Resection and anastomosis.

Stage III Colon Cancer

Treatment of stage III colon cancer may include the following:

Resection and anastomosis which may be followed by chemotherapy.

Clinical trials of new chemotherapy regimens after surgery.

Stage IV and Recurrent Colon Cancer

Treatment of stage IV and recurrent colon cancer may include the following:

Local excision for tumors that have recurred.

Resection with or without anastomosis.

Surgery to remove parts of other organs, such as the liver, lungs, and ovaries, where the cancer may have recurred or spread. Treatment of cancer that has spread to the liver may also include the following:

Chemotherapy given before surgery to shrink the tumor, after surgery, or both before and after.

Radiofrequency ablation or cryosurgery, for patients who cannot have surgery.

Chemoembolization of the hepatic artery.

Radiation therapy or chemotherapy may be offered to some patients as palliative therapy to relieve symptoms and improve quality.

Chemotherapy and/or targeted therapy with a monoclonal antibody or an angiogenesis inhibitor.

Clinical trials of chemotherapy and/or targeted therapy