Colorectal cancer

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Classification according to ICD-10
C18.0 Cecal carcinoma
C18.1 Appendix cancer
C18.2 Ascending colon carcinoma
C18.3 Carcinoma of the right colonic flexure
C18.4 Carcinoma of the transverse colon
C18.5 Carcinoma of the left colonic flexure
C18.6 Carcinoma of the descending colon
C18.7 Carcinoma of the sigmoid colon
C19 Carcinoma of the rectosigmoid junction
C20 Carcinoma of the rectum
ICD-10 online (WHO version 2019)
Scheme of the large intestine anatomy:
(1) Ascending colon ( ascending colon )
(2) transverse colon ( transverse colon )
(3) Descending colon ( Colon descendens )
(4) Sigma ( sigmoid colon )
(5) mast or rectum ( rectal ), and Anus .
It lacks the marker for the located in the lower left half of the cecum ( cecum ) with attached appendix ( Appendix ).

When colon cancer or bowel cancer is any malignant ( malignant ) tumors of the intestine . The colorectal carcinomas , these are the cancers of the colon and rectum (rectum), making it more than 95% of malignant colon tumors from.

Colorectal cancer is in Germany in men the second most common in women, the third most common cancer diagnosed at which more than five percent of all Germans in their lifetime. Colorectal carcinomas very rarely cause symptoms at first ; they almost always arise from initially benign intestinal polyps . The chances of recovery through surgery and chemotherapy with a 5-year survival rate at approx. 60% on average depend crucially on the stage of the disease at which the colon cancer is discovered. The health insurance companies take over in Germany for all male member from age 50 and for female insured persons aged 55 at intervals of at least ten years, the cost of a colonoscopy ( " screening colonoscopy ") to any by removing polyps colorectal cancer to prevent. The waiting period of ten years only applies to patients with normal results and no symptoms.

Tumor types and distribution

85 to 90% of malignant intestinal tumors are adenocarcinomas of the large intestine , which are derived from the glands of the intestinal mucosa. Often found in discovery of the tumor is already a central ulcer ( ulcer ) and tissue death ( necrosis ). Histologically , besides adenocarcinomas, mainly mucinous adenocarcinomas (5 to 10%) and signet ring carcinomas (1%) occur.

Other malignant (malignant) diseases of the intestine, such as the mostly low-grade carcinoids , especially in the appendix and small intestine , leiomyosarcomas and gastrointestinal stromal tumors (GIST), which are derived from the smooth muscles or the connective tissue of the intestinal mucosa, are rare and together make less than 2% of all colon cancer cases. Therefore, in the following only adenocarcinoma of the appendix (caecum) , colon (colon) or rectum (rectum) , which is referred to as colorectal carcinoma in the medical community.

The individual sections of the intestine are affected unequally, 60% of the tumors are located in the left part of the large intestine (beyond the left colon flexure) and 25% in the caecum and the rest of the right large intestine. About 55% of the left-sided malignant colon tumors are localized in the sigmoid loop (Colon sigmoideum) and in the rectum .

Occurrence

In the industrialized countries, the number of new colon cancer cases has increased significantly over the past 30 years. With an annual number of new cases ( incidence ) of less than 20 to 70 per 100,000 inhabitants, colon cancer is one of the most common malignant diseases in Central Europe. The worldwide incidence is estimated at one million new cases per year. Men are slightly more frequently affected than women, this mainly affects rectal cancer (sex ratio 60:40).

In Germany, colorectal cancer is one of the three most common forms of cancer in both new cases and deaths in men and women. Two thirds are found in the colon and one third in the rectum . More than 65,000 people in Germany contracted colon cancer in 2008, including 35,350 men and 30,040 women; In 2016 there were 32,300 men and 30,040 women. 90% of colorectal cancers occur after the age of 55. The mean age of onset is between 72 years (men) and 76 years (women). The risk of a German developing colon cancer in his lifetime is 1:17 for men and 1:20 for women. For women and men, the relative 5-year survival rates are 63% and 62%, respectively.

Out of 1,000 people between the ages of 45 and 75, around 10 have undetected colon cancer, and 300 have mostly benign polyps in the colon.

Risk factors

In addition to the factors that affect the risk of cancer in general, such as: For example, the vitamin D serum level , there are additional factors specific to colon cancer.

The most important risk factors are obesity and smoking, followed by a lack of exercise and a low-fiber diet. In addition, the occurrence of colon polyps plays a major role, as these can often degenerate. Less common risk factors are a general genetic predisposition (family members with colorectal cancer in the direct line have an approximately three-fold increased risk of the disease) and specific genetic syndromes associated with an increased risk of developing colorectal cancer ( familial adenomatous polyposis , Lynch's syndrome ).

Ulcerative colitis is also associated with an increased risk of degeneration ( facultative precancerosis ) , especially when the entire colon is affected . Patients with Crohn's disease also have a slightly increased risk of colon cancer compared to the general population.

Other risk factors

Apart from the presence of these syndromes, malnutrition is considered a risk factor for colon cancer. Be enumerated

The higher the nitrate level in drinking water, the higher the risk of colon cancer. An increase in risk can already be seen at nitrate concentrations that are well below the legally prescribed limit values. The daily consumption of red meat (such as pork and beef) or meat products apparently increases the risk of colon cancer by at least 50%, whereas daily consumption of fish reduces it to about half. (1) Modern review studies seem to suggest, however, that the increase in risk has more to do with the parallel increase in carbohydrate intake (especially sugar) and changes in behavior are associated with this increase (less exercise, more alcohol, general obesity). The connection with the consumption of red meat could not be shown with certainty. Until recently, the lack of high-fiber diet was also suspected of increasing the risk of colon cancer. However, this could not initially be confirmed with certainty in some studies. As part of the EPIC study, over 500,000 initially healthy participants from ten European countries have been looking at the dining table since 1992. In addition, their weight, height and body fat distribution are recorded and blood is drawn. For 15 years, all new cancer cases and other chronic diseases have been recorded and associated with eating habits and lifestyle . Over the years, more and more knowledge has been gained about the composition of a “healthy” diet , which could offer potential protection against cancer and other diseases. In April 2007, scientists from the study centers at the German Cancer Research Center in Heidelberg and at the German Institute for Nutritional Research (DIFE) in Potsdam-Rehbrücke drew a balance sheet: high fiber intake is associated with a reduced risk of colon cancer. Those who increase their daily consumption from 15 to 35 g can lower their risk by 40%. “Anyone who eats a lot of red meat (including beef ) and sausage products has an increased risk of stomach and colon cancer. With 100 g more red meat per day, the risk increases by 49%, an increase in 100 g sausage increases it by 70%. "

The nutritional hypothesis is also based on the increased risk of colon cancer among Japanese immigrants to the USA: While the risk of colon cancer in Japan, where traditionally high-fiber and low-meat foods are consumed, is significantly lower than in the western hemisphere, the risk of Japanese immigrants increases within 20 years the American average. In addition to the increased average age, this would also explain the increased incidence of colon cancer.

On the other hand, the risk of colon cancer also increases with age, so that the increased incidence of colon cancer could only be the result of increased life expectancy. Thirteen recent studies with nearly 750,000 participants suggest that diets low in fiber tend not to correlate with a higher incidence of colon cancer. Other factors such as the fish-rich diet in Japan with a high proportion of omega-3 fatty acids or the high zinc content of this diet must be investigated in further studies. There may be other environmental factors that could increase the risk of colon cancer. This may include a lack of sunshine : Researchers in North America and Europe noticed a noticeable north-south divide , which could only be explained by different levels of tanning in people. This relationship has been found for breast cancer , prostate cancer , colon cancer , ovarian cancer and apparently also for melanoma and bladder cancer . Obviously, vitamin D plays a key role here . 90% of the vitamin D required by the body is formed in the skin through UV-B radiation. Adults with 25-OH-D3 levels above 20 μg / ml (in blood serum ) have a three-fold reduced risk of developing colon cancer. However, it remains to be clarified which blood levels of 25-OH-D3 are optimal.

The following theory is also frequently postulated: Diets low in fiber lead to longer passage times in the intestinal tract. In this way, carcinogenic metabolic products (e.g. nitrosamines ) of the intestinal bacteria can have a longer effect on the tissue and consequently favor the development of colorectal tumors.

Long-term smoking in particular significantly increases the risk of the disease. Overweight and, to an increased extent, obesity ( obesity ) have been identified as significant risk factors for colorectal cancer in various studies.

Another hypothesis postulated by Nobel laureate Harald zur Hausen suggests an association between colorectal carcinoma and a viral cause, analogous to HPV in cervical carcinoma . A group of doctors around Andrea N. Burnett-Hartman from Seattle and Washington could not confirm this suspicion.

Infections with Streptococcus bovis are questionable risk factors .

Previous surgical interventions are seldom a risk factor for colorectal cancer. For example, after the urinary tract has been diverted into the large intestine ( ureterosigmoidostomy ), urinary substances such as phenols and cresols can act as mutagenic factors on the colon mucosa.

Protective factors

In 2010, a meta-study with a follow-up of 20 years concluded that the intake of acetylsalicylic acid in low doses reduced the risk of cancer of the colon by 70%. In particular, tumors of the proximal colon were less common. Implementation of the data and further studies are still pending.

Other protective factors: low-fat and low-meat, Mediterranean diet, fiber, regular physical activity, abstinence from nicotine. Regular physical activity, in particular, can reduce the risk of illness by up to 30% and is also increasingly used in supportive therapy.

Pathogenesis

Vogelstein's hypothesis of the adenoma-carcinoma sequence in colorectal cancer I.

Molecular biological knowledge about the development of colon cancer has increased enormously in the last two decades. Colorectal cancer usually develops through benign preliminary stages, the colon adenomas (so-called polyps ). Several genetic changes are required for the development of a malignant tumor. This model of the development of malignant tumors from benign precursors is called the adenoma-carcinoma sequence according to Fearon and Vogelstein. Whether a malignant tumor develops from an adenoma depends on three factors:

  • Size (adenomas with an extension of less than one centimeter practically never degenerate)
  • Histological type (in the histological examination, three types of adenomas of the large intestine are distinguished: tubular adenomas, tubulovillous adenomas and villous adenomas; tubular adenomas have the lowest risk of malignant degeneration and villous adenomas the greatest)
  • Degree of dedifferentiation ( dysplasia )

The increased knowledge about the pathogenesis of colon cancer has led to the identification of new specific molecular target structures and thus enabled the development of new pharmacological substances for therapy and prevention.

Recently, studies have been published which suggest that in addition to the genetic changes mentioned, i.e. real mutations, epigenetic changes also play a role in the development of the disease. The subject of the research is to what extent the specific pattern of genetic and epigenetic changes allows statements about the behavior of the tumor and its response to chemotherapy .

In the vast majority of cases (95%), colorectal carcinomas develop sporadically, i.e. through acquired gene mutations in the cells of the intestinal mucosa. Hereditary genesis can be demonstrated for five percent of colorectal carcinomas .

In about five percent of colon cancer cases, it is called Lynch syndrome, which is also known as hereditary non-polyposis colorectal cancer (HNPCC). In this autosomal dominant inherited disease, there is a defect in the so-called mismatch repair genes. These genes are responsible for correcting DNA mutations. If there is a defect, HNPCC occurs, which in addition to malignant colon tumors, also increases in breast cancer , endometrial cancer and ovarian cancer . Colon cancer occurs in patients with HNPCC around the age of 45 and is most often localized in the ascending part of the large intestine ( ascending colon ) . The so-called Amsterdam I criteria and Amsterdam II criteria , or the so-called Bethesda criteria, are used to make a diagnosis . The suspicion is confirmed by genetic diagnostics.

The familial adenomatous polyposis is a rare obligate precancerous condition (disease that inevitably leads to carcinogenesis), in which a very young age of the colon with colon polyps is overgrown. The incidence of hereditary colon cancer is <1%. The disease has an autosomal dominant inheritance . The cause of the development of up to 1000 polyps in the large intestine is a disruption of the normal cell cycle (the mutation of the APC tumor suppressor gene on chromosome 5). Surgical total removal of the large intestine ( colectomy ) is recommended up to the age of 20. Up to this point in time - if the diagnosis FAP has been made - a colonoscopy (colonoscopy) must be carried out for monitoring at least once a year from the age of 10.

Other syndromes with a significantly increased risk are Gardner syndrome , a hereditary disease in which benign tumors of the skin, subcutaneous tissue, bones and connective tissue occur in addition to many polyps in the intestine, and Turcot syndrome , too a rare genetic disorder that causes polyps in the intestine and brain tumors. More rarely, polyps degenerate in Peutz-Jeghers syndrome , a rare genetic disease in which, in addition to polyps in the gastrointestinal tract , pigment spots on the face and oral mucosa also occur. Polyps also rarely degenerate in juvenile polyposis , the most common type of polyp in childhood, in which the polyps are mostly located in the rectum.

Symptoms

Colon cancer is often symptom-free for a very long time. Symptoms only occur when the tumor bleeds to a large extent or when it significantly narrows the intestinal lumen . Typical symptoms are then blood or mucus in the stool, intestinal cramps, “pencil stool” or “goat droppings”, diarrhea and constipation and often excruciating flatulence . The loss of blood can lead to anemia ( anemia ) with the associated symptoms of decreased performance, tiredness and general weakness. As a result of the tumor disease, there is often a weight loss, possibly up to the development of tumor cachexia (emaciation).

The only early symptom is invisible (occult) bleeding, which can be detected with stool tests (e.g. Hämoccult ® ). In some countries this test is used as a screen for colon cancer.

Complications

Possible complications in colon cancer are the intestinal obstruction (ileus) caused by the tumor and the breakthrough through the intestinal wall ( perforation ) . Clinically, a perforation presents a so-called acute abdomen as to pass through the perforation air and intestinal bacteria in the abdomen and peritonitis ( peritonitis ) developed. Colorectal cancer perforations are rare and primarily affect patients with advanced tumor stages. Clinically, the abdomen of such a patient is as hard as a board, shows defensive tension ( defense musculaire) and painful knocking, which is collectively referred to as peritonism . Further tumor complications can be fistulas or the invasion of neighboring organs (T4 carcinoma), signs of liver failure due to liver metastases and compression of other organs.

Diagnosis

Adenocarcinoma of the ascending colon during a colonoscopy
PET / CT staging examination of metastatic rectal cancer. A lump in the lung is marked

First and foremost are taking a medical history ( medical history ), a general physical exam including a digital rectal exam (examining the rectum with a finger), and a test for hidden blood in the stool. So far, only the guaiac-based stool blood test (gFOBT) has been paid for by statutory health insurers, the sensitivity of which is only around 20 to 40%. Significantly more sensitive (60 to 90%) are the haematoporphyrin test and immunochemical tests (iFOT), which are 2-3 times higher detection rates for colorectal carcinomas and advanced adenomas. In addition, patient acceptance is higher because no special diet is required.

Another method for the early detection of polyps and intestinal tumors is the determination of the biomarker Tumor M2-PK in the stool. The M2-PK is a key enzyme in the metabolism of polyps and tumors. The M2-PK test detects both bleeding and non-bleeding polyps and tumors. Because of the poor specificity (correct exclusion of a tumor) of 82%, the detection of M2-PK in the stool has not yet been recommended as a routine method for the early detection of colon cancer.

In cases of suspected colon tumors a colonoscopy (will colonoscopy ) is carried out at small and is suspected tissue samples, known as biopsy specimens taken, the histological (histologically) by a pathologist to be examined. Colonoscopy is also used as a preventative measure because it can remove benign polyps that are at risk of degeneration. In Germany, therefore, regular colonoscopy for men over the age of 50 and for women over the age of 55 for colon cancer prophylaxis is paid for by statutory health insurances. In other European countries, annual occult blood tests are preferred as colon cancer screening.

Further, since less common methods of investigation are the rectocele or sigmoidoscopy , the examination of the rectum with a rigid or flexible, or the study of the end and colon with a flexible endoscope, and in the meantime by the computed tomography largely displaced enema . In the future, colonography based on spiral computed tomography or magnetic resonance tomography may replace colonoscopy as a non-invasive method, but this method is currently still in the development phase and in the case of small polyps or carcinomas it is still inferior to colonoscopy in terms of its informative value.

If the colonoscopy reveals indications of the presence of colon cancer, the following examinations are usually initiated to determine the tumor stage ( tumor staging ):

Tumor markers ( CEA and CA 19-9 ) are available for monitoring the progress . However, these are not suitable for screening examinations, as they are negative for many tumors and there are often false-positive results.

A new marker CCSA-2 (colon cancer-specific antigen 2) seems to be able to detect tumors of the colon and rectum at an early stage.

The Septin-9 test is also new . This is a blood test for early detection of colon cancer. It is based on the detection of methylated Septin-9.

There are different views on the use of positron emission tomography (PET). Contrary to several international publications that could show that the use of PET / CT with fluorodeoxyglucose had a significant influence on the staging and is superior to common methods such as CT or MRI in the diagnosis of lymph node involvement or metastases, the current German guideline of the professional associations does not see any importance in primary diagnostics. The authors of the guideline criticize the insufficient quality of the underlying studies, a point of criticism that the Institute for Quality and Efficiency in Health Care, IQWIG, had already expressed in 2011.
However, it is not yet possible for PET to be covered by the statutory health insurances, while private health insurances partially bear the costs.
In case of questionable or proven liver metastasis , the use of PET can be of benefit to the patient, recommendation grade 0, level of evidence 2b.

Differential diagnosis

Different diseases can cause a clinical picture similar to that of colon cancer. In addition to the chronic inflammatory bowel diseases, Crohn's disease and ulcerative colitis , these include absorption disorders such as sprue or lactose intolerance . Only when these diseases and a tumor of the intestine have been ruled out, the diagnosis of irritable bowel syndrome can be made. A colonoscopy with the acquisition of histological material serves to confirm the diagnosis of irritable bowel syndrome.

pathology

Histological examination of a well-differentiated adenocarcinoma of the colon
Moderately differentiated adenocarcinoma of the rectum

Macroscopic and microscopic pathology of colon cancer

From a morphological point of view, there are three macroscopic growth forms in colon cancer:

  • polypous-exophytic type: cauliflower-like tumor that is sharply demarcated from the healthy intestinal mucosa
  • Bowl-shaped-ulcerated type: with central ulceration and crater-like raised edges
  • diffuse infiltrating type

Histologically, an adenocarcinoma is present in 95% of colon cancer cases, which consists of tubular, cribriform, acinar and papillary structures and, depending on the degree of differentiation of the tumor, also exhibits mucus secretion. Two special forms of colon cancer are mucinous adenocarcinoma , which is characterized by massive mucus production, and signet ring carcinoma , which is characterized by an intracellular accumulation of mucus in diffusely adjacent cells.

metastasis

Metastases refer to the settlement of a tumor in distant tissue. There are several ways in which metastases can get to other organs.

Per continuitatem

Per continuitatem , d. H. Starting directly from the primary tumor, the tumor infiltrates the adjoining pericolic (next to the colon ) or perirectal (next to the rectum ) fatty tissue . Infiltration into the neighboring organs only rarely occurs.

Lymphogenic metastasis

Lymphogenic metastasis describes the spread of the disease through the lymphatic system . Colon cancer has a unipolar metastasis path in the ascending and transverse colon along the superior mesenteric artery and in the descending colon along the inferior mesenteric artery , i.e. H. Lymph node metastases initially appear in the lymph nodes along the course of these arteries. The middle area of ​​the transverse colon is an exception : due to the double arterial supply of this area through the superior mesenteric artery and the inferior mesenteric artery , carcinomas can metastasize in both directions ( Riolan's anastomosis , Cannon-Böhm point ).

Hematogenous metastasis

Haematogenic metastasis is understood as the settlement of metastases via the bloodstream. Deep-seated rectal carcinomas show a metastatic behavior of the cava type, which means that hematogenous metastases occur here first in the lungs, since the venous outflow from this area takes place via the inferior vena cava . The tumor cells are carried over the inferior vena cava to the right heart and from there to the lungs. All other colorectal carcinomas show a metastatic behavior of the portal vein type, hematogenous metastases first appear in the liver. The reason for this is that the venous outflow and thus the tumor cells are primarily carried over the portal vein into the liver. In a second step, tumor cells can pass from the liver via the liver veins into the inferior vena cava and from there into the lungs.

UICC TNM Classification of Colon Cancer

The TNM classification is a forecast-oriented classification system of the UICC , which has been published in its 7th edition since 2010. The aim is to classify the prognosis of different tumor stages and to be able to compare treatment results from different clinics. The "TNM formula" characterizes the tumor in the context of so-called staging . In colorectal carcinoma (as with other solid tumors), this staging is performed pretherapeutically (based on computed tomography ) (clinical TNM = cTNM) and postoperatively (based on the histopathological examination of the resected tissue (pTNM)).

TNM is an abbreviation for the following categories of classification:

  • T = tumor: primary tumor (the depth invasion is assessed here, explicitly NOT the tumor size)
  • N = Nodus: lymph node involvement (nodal status - i.e. there are lymph node metastases or not)
  • M = metastases: absence or presence of distant metastases
TNM classification
T0 No infiltration
T1 Infiltration of the tela submucosa
T2 Infiltration of the muscular tunica
T3 Infiltration of the subserosa
T4 Infiltration of neighboring organs or the peritoneum ( peritoneum viscerale )
N0 No metastases in the lymph nodes
N1 Metastases in one to three pericolic (perirectal) lymph nodes
N2 Metastases in more than three pericolic (perirectal) lymph nodes
N3 Metastases along a named vascular trunk and / or apical lymph node metastases
M0 No distant metastases
M1 Distant metastases (usually liver and lymph nodes followed by the peritoneum , lungs , less often the skeleton , adrenal glands or brain )

UICC stages of colon cancer

A stage classification ( UICC stages ) can be made from this information . This was introduced by the "Union internationale contre le cancer" (UICC) and is based on statistical studies that prove, for example, that the prognosis of the disease worsens from a certain size of a tumor. The classification of a tumor disease therefore allows prognostic statements and often also determines further therapy. The Dukes classification of the British pathologist Cuthbert Dukes (1890–1977) from 1932, the stages of which are given in the table, is no longer in use and has been replaced more and more by the UICC classification.

UICC classification
Stage Ia Restriction of tumor infiltration to the mucosa and tela submucosa (Dukes A)
Stage Ib Restriction of tumor infiltration into the tunica muscularis propria (Dukes A)
Stage II T3 or T4 without lymph node metastasis (Dukes B)
Stage III Lymph node metastasis (Dukes C)
Stage IV Distant metastases (Dukes D).

Differentiation degrees ("Grading") according to WHO

The histological (tissue) differentiation of the degree of differentiation in colorectal carcinomas follows the so-called grading system of the WHO (World Health Organization) - see also figure.

  • G1: well differentiated tumors
  • G2: moderately differentiated tumors
  • G3: poorly differentiated tumors
  • G4: dedifferentiated / undifferentiated tumors

WHO grading has prognostic relevance: the lower the degree of differentiation, the worse the prognosis is to be assessed (G1 has a better prognosis than G4).

therapy

As with many cancers, therapy is primarily based on the tumor location and stage. As a rule, a complete surgical resection (removal) of the tumor-bearing intestinal section with removal of the associated lymphatic drainage area is sought. The chances of recovery are very good in the early stages. The operation is usually performed with open surgery , but now there are also techniques for minimally invasive laparoscopic or laparoscopic-assisted surgical treatment of colon cancer.

surgery

The surgical removal of the tumor is in colorectal cancer in advanced stage or in the presence of metastases, the treatment of choice, even to the emergence of agonizing complications such as bowel obstruction ( ileus ) should be avoided. In some stages, chemotherapy is used beforehand as part of so-called neoadjuvant therapy concepts , possibly in combination with radiation therapy, in order to achieve a preoperative reduction in size of the tumor (downsizing or downstaging).

As standardized procedures, tumors of the ascending colon are removed as a right-sided hemicolectomy and of the descending colon as a left-sided hemicolectomy. These operations can also be carried out as an extended hemicolectomy if the transition to other sections is affected. An artificial anus does not normally have to be created. Removal of the cross colon by so-called. Distance of the transverse colon may only be performed if the tumor is located right in the middle of the transverse colon. Tumors in the area of ​​the colonic flexures are operated on in an oncologically correct manner using an extended hemicolectomy on the right or left. The extent of the resection (extent of the operation) depends on 1. the location of the tumor 2. the required safety distance 3. the blood supply to the intestinal segment and 4. the lymphatic drainage area. The operation always includes the removal of the tumor-bearing section of the intestine, together with the lymph nodes belonging to this section of the intestine (lymphadenectomy).

For rectal cancer (rectal cancer), an artificial anus had to be created just a few years ago. Today modern surgical procedures such as B. Transanal Endoscopic Microsurgery (TEM) or Total Mesorectal Excision (TME) often prevent this artificial anus in rectal cancer in the early stages.

The most serious complication of colorectal surgery is anastomotic leakage (suture breakage). It can lead to serious infections in the abdomen. In rectal surgery, in 50% of cases it leads to a permanent artificial anus ( anus praeternaturalis ). In addition to technical causes, the anastomotic leakage is bacterial. It can be prevented by perioperative antimicrobial prophylaxis (decontamination).

In the case of the precancerous diseases of familial adenomatous polyposis and Gardner syndrome, which have already been explained above , a prophylactic colectomy should be performed, if possible with an ileoanal pouch . To protect this deep reconstruction (connection directly to the anus), a so-called protective ileostomy is always temporarily connected upstream for protection. This can then be relocated back after 1 to 3 months - after evidence that the anastomosis has healed.

Minimally Invasive Surgery

In the era of minimally invasive surgery (so-called keyhole surgery ), more and more complex interventions with this minimized access trauma (without a large abdominal incision) are being tackled. The principle possibility has been shown and the results suggest an oncological equivalence compared to open surgery (e.g. Jayne DG, Thorpe HC, Copeland J, Quirke P, Brown JM, Guillou PJ. Five-year follow-up of the Medical Research Council CLASICC trial of laparoscopically assisted versus open surgery for colorectal cancer. Br J Surg. 2010; 97: 1638-1645.). This applies to colon carcinoma, but now also to rectal carcinoma.

Multimodal therapy

In the case of locally advanced colorectal carcinomas, therapy is now usually carried out as a so-called multimodal therapy. This means that chemotherapy (CTx) and / or radiochemotherapy (RCTx) are administered in addition to the operation .

Nowadays, modern cytostatics are usually administered in combinations. In this way, the individual active ingredients can be dosed in lower amounts and the effectiveness increased. There are essentially three therapeutic goals:

For colon cancer, adjuvant therapy with 5-fluorouracil (5-FU) in combination with folinic acid has been administered since the 1990s if lymph node involvement is demonstrated in the surgical resection (UICC stage III). This standard has changed due to the so-called MOSAIC study. Now the so-called FOLFOX -4 protocol is the current standard of treatment (5-FU / folinic acid and additionally oxaliplatin), which can also be found in the current guidelines of the DGVS and is valid for all certified intestinal centers in Germany.

In rectal cancer, the principle of neoadjuvant therapy is favored due to the narrow anatomical conditions in the small pelvis in locally advanced tumors. Since the study by Sauer et al. Pretreatment with a combination of radiation therapy and the administration of 5-FU is standard for locally advanced tumors in the lower and middle third of the rectum. The aim of this therapy is to reduce the size of the tumor (“downsizing”) or even to reduce its stage (“downstaging”) in order to achieve better resectability (surgical removal).

  • In neoadjuvant treatment, chemotherapy is used to reduce the size of a large tumor or metastasis before resection and thus to be able to operate better (downstaging, downsizing) .
  • In adjuvant (that is, supportive or preventive) treatment, chemotherapy is used to kill any cancer cells that may have remained in the body after an operation, thereby preventing relapse. Adjuvant chemotherapy should be in
    • UICC stage III must always be carried out (i.e., to put it simply, when there are already lymph node metastases but no distant metastases).
    • In UICC stage II, adjuvant chemotherapy is not generally recommended, but only for so-called risk constellations (T4 tumor, emergency surgery, insufficient histopathological examination of the lymph nodes).

The adjuvant chemotherapy is based on the drug 5-fluorouracil (5-FU) in combination with folinic acid. More recent studies show a lower relapse rate when a combination therapy consisting of 5-FU, folinic acid and oxaliplatin (so-called FOLFOX scheme) is carried out. In stage III, the combination of 5-FU and oxaliplatin is now standard for patients under 70 years of age. However, the range of side effects of oxaliplatin should be noted; In particular, the drug triggers side effects on the nervous system in the form of polyneuropathy . The use of monoclonal antibodies in the adjuvant therapy situation is the subject of current research (clinical studies, phase III)

  • The palliative (d. E. Complaints palliative) chemotherapy in advanced disease (eg. As inoperable metastases) are used to preserve the quality of life and prolong life.

Common treatment regimens include FOLFOX and FOLFIRI . The combination with the VEGF (Vascular Endothelial Growth Factor) blocking monoclonal antibody bevacizumab (Avastin ® ) has been approved since spring 2004. The XELOX and 5FUFS schemes as well as a combination therapy with the monoclonal antibody cetuximab (Erbitux ® ) offer alternative therapy options . Treatment with cetuximab should only be given if the K-ras gene is not mutated in the tumor tissue. The K-Ras testing, which is standardized today, is carried out on tumor tissue that has already been removed and takes a few days. Since December 2007, the monoclonal antibody panitumumab (Vectibix ® ) has also been approved for the treatment of tumors with non-mutated K-Ras genes that were previously treated with 5-FU-based chemotherapy.

In combination with chemotherapy or cancer immunotherapy, radiation therapy has a firm place in the palliative, adjuvant and neoadjuvant treatment of rectal cancer. It is used to shrink tumors before surgery and, in the case of advanced tumors, after surgery to prevent recurrence. The current standard of chemotherapy is 5-FU; alternative chemotherapeutic agents in combination with radiation are e.g. B. Capecitabine .

There is evidence that exercise during chemotherapy for colon cancer can improve survival by up to 50% compared to drug-only cancer therapy.

Aftercare

After a curative operation on patients in stage II-III (T3 / 4 or N +, M0), for whom relapse or metastasis therapy is generally possible due to their age and general condition, standardized follow-up care is an interdisciplinary task of Aimed at family doctor and specialist doctors, on which the participating medical societies have agreed.

It includes biannual, after two years annual controls of tumor markers in serum (CEA), colonoscopy, computer tomography and, in the case of rectal carcinoma, rectosigmoidoscopy and endosonography. A British study from 2014 shows that follow-up care using CT or CEA or both increases the number of curatively operable recurrences, but there was no apparent effect on overall survival.

forecast

Course of mortality (y-axis in deaths per 100,000 inhabitants) in colorectal cancer as a function of age (x-axis)

The prognosis depends on the depth of the infiltration into the intestinal wall and the presence of lymph node and distant metastases as well as the degree of differentiation of the tumor cells; the mean 5-year survival rate is around 40 to 60%. The most common finding is T3 N +, i.e. stage III.

5-year survival rates by UICC stage
Stage I. approx. 80-100%
Stage II approx. 60-80%
Stage III approx. 30–60%
Stage IV approx. 0-57%

The 5-year survival rate in stage IV depends on factors such as lymph node status, number and size of metastases, CEA (tumor marker,> 200 ng / dl unfavorable) and the disease-free interval (<12 months unfavorable). Based on these numbers, preventive examinations are offered for early detection.

Screening exams

For the prophylaxis or early detection of colon cancer there is the possibility of participating in early detection examinations. A digital rectal examination is carried out regularly. Since more than half of the tumors are located in the rectum or rectum, colon cancer can often be “felt” through the anus ( rectal examination ).

The examination of the stool for hidden blood every one to two years is a recognized screening method in many European countries , as colon cancer can be detected early on by small bleeding that cannot be seen with the naked eye. According to one study, seven out of 1,000 people who were screened died from colon cancer while eight out of 1,000 people died from colon cancer who didn't screen.

A new biomarker that detects both bleeding and non-bleeding polyps and tumors is the determination of the M2-PK tumor in the stool. This marker detects a key enzyme in the energy metabolism of polyps and tumors ( M2-PK test ). According to the medical service of the Central Association of Health Insurance Funds (MDS), there are no studies on the extent to which the M2-PK stool test can help prevent colon cancer deaths. There are no scientifically reliable indications that the M2-PK stool test is more useful than the blood stool test, which is why its use should be assessed as "unclear".

In Germany, since 2002, the cost of a colonoscopy as an early diagnosis examination has been covered by health insurance companies for all people aged 55 and over and for patients from risk families from 35 years of age. This is based on the knowledge that colon cancer almost always develops from benign polyps over a longer period of time , in the so-called adenoma-carcinoma sequence . The results of the preventive colonoscopy up to 2005 were published in 2006. According to this, adenomas are found in 20% of the people examined and carcinomas in 0.7%. Most of the tumors (70%) were in the favorable stage UICC I and II. The complication rate of the screening colonoscopy was very low. The perforation rate (breakthrough of the intestinal wall) was only 0.02% with simple diagnostic colonoscopy and 0.1% with polyp removal. In the first three years, 8.8% of men and 10.2% of women took part in examinations ( stool blood test or colonoscopy ) for the prevention of colorectal cancer. The annual stool blood test is offered to men and women from the age of 50, the colonoscopy from the age of 56. The stool blood test has been shown to save people from death from colon cancer; however, on the one hand it overlooks many cancer cases, on the other hand it often delivers false positive results. The colonoscopy is considered to be the most informative procedure and therefore the so-called gold standard of colorectal cancer screening because it is very accurate and can already detect precancerous stages that can be removed relatively easily.

A large-scale study in Saarland showed that people who had already undergone a colonoscopy within a period of ten years before a colonoscopy had significantly less advanced cancer than those in a comparison group who underwent a colonoscopy for the first time ( 6.1% to 11.4%).

Whether people who are younger than 55 years and whose families already have a member with colon cancer can benefit from an early detection examination is currently the subject of an investigation by the Institute for Quality and Efficiency in Health Care (IQWiG). The institute published the preliminary results in September 2012. Accordingly, the benefits and harms of such screening remain unclear because there are no relevant studies.

There are now a number of chemoprevention studies around the world that have tested whether various drugs or dietary supplements can prevent colon cancer or its precursors, adenomas.

literature

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Web links

Individual evidence

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