Colon carcinoma C19

The so-called no-touch technique was first described by Barnes in 1952, when he removed the right colon of a patient due to carcinoma. Fifteen years later, Turnball et al. demonstrated a better 5-year survival rate in patients operated on using the no-touch technique (Chassin 1983).

The term "adenoma-carcinoma sequence" was introduced in 1975 (Siegenthaler 2006).

The definition of colon carcinoma is handled very differently.

-International grading system:

According to the international assessment system, rectal carcinoma is said to be present when the aboral margin of the tumor is 16 cm or less from the anocutaneous line with a rigid rectoscope. All other tumors in the colon correspond to colon carcinoma (2019 guidelines).

- Assessment in the USA:

Colon carcinoma is said to be present if the tumor is more than 12 cm from the anocutaneous line (2019 guidelines).

- Intraoperative assessment:

Intraoperative assessment is based on taeniae or the peritoneal envelope fold. These in turn depend on gender, age and other factors (2019 guidelines).

Tumor classification

The classification of colorectal cancer introduced by the UICC in 2010 :

• Stage 0: Tis, N 0, M 0
• Stage I: T 1/ T 2, N 0, M 0
• Stage II: T 3/ T 4, N 0, M 0
  • II A: T 3, N 0, M 0
  • II B: T 4 a, N 0, M 0
  • II C: T 4 b N 0, M 0
• Stage III: each T, N 1/ N 2, M 0
  • III A: T 1 / T 2, N 1, M 0
  • T 1 / N 2 a, M 0
  • III B: T 3 / T 4, N 1, M 0
  • T 2 / T 3, N 2 a. M 0
  • T 1 / T 2, N 2 b, M 0
  • III C: T 4 a, N 2 a, M 0
  • T 3 / T 4 a, N 2 b, M 0
  • T 4 b, N 1 / N 2, M 0
• Stage IV: each T, each N, M 1
  • IVA: each T, each N, M 1 a
  • IVB: any T, any N, M 1 b (2019 guidelines)

Amsterdam criteria

The Amsterdam Criteria (AC):

- AC 1: only the colon is affected

- AC 2: extracolonic manifestations are also detectable (2019 guidelines)

- 1. at least three family members are affected by an HNPCC-associated carcinoma (hereditary non-polyposis colorectal cancer [Kasper 2015]), localized in the colon, rectum, endometrium, small intestine, urothelium, renal pelvis.

- 2. at least two consecutive generations are affected

- 3. at least one family member is first-degree related to the other two.

- 4. one of the patients was younger than 50 at the time of diagnosis

- 5. familial adenomatous polyposis was ruled out (2019 guidelines)

Lymphogenous spread

Lymphogenic metastasis depends on the tumour location:

- Upper third of the rectum (12 - 16 cm from the anocutaneous line): Here there is only one metastatic route in the paraaortic lymph nodes.

- Middle third of the rectum (6- < 12 cm from the anocutaneous line): Here, there are already two metastatic metastases in the paraaortic lymph nodes and in the pelvic wall.

- Lower third of the rectum (< 6 cm from the anocutaneous line): In the lower part, in addition to the two metastatic routes mentioned above, the inguinal lymph nodes can also be added as a 3rd possibility (Herold 2021).

Hematogenous metastasis

Hematogenous metastasis occurs primarily in the lungs and liver. Other organs then follow in a cascade.

Haematogenous metastasis is already present in around 25 % of patients at the time of initial diagnosis. In the majority of cases, this occurs via the V. portae into the liver. One exception is the very distally located carcinoma. In this case, metastases can reach the lungs directly via the vena cava (Herold 2021).

The highest incidence of colon cancer in Europe is found in Germany with 70 cases per 100,000 inhabitants per year, the lowest in Greece with < 20 cases per 100,000 inhabitants per year (Herold 2021).

Colorectal cancer is the second most common cause of cancer-related death in men and the third most common cause in women. In Germany, around 25,000 patients died from colon cancer in 2014 (Herold 2021).

Around 90% of colon carcinomas occur after the age of 50. However, the incidence of those aged > 40 doubles every 10 years (Herold 2021).

The risk of carcinoma in the normal population without risk factors is 6% in > 40-year-olds. The risk in first-degree relatives of affected patients > 60 years of age is 10%, that of those < 60 years of age is 30%, that of patients with familial adenomatous polyposis coli and other hereditary polyposis syndromes is 100% (Herold 2021).

There are various factors that play a role in colorectal carcinoma:

• 1. genetic factors: they play a role in about 10 %, including:
  • FAP: so-called familial adenomatous polyposis. Occurs in approx. 1% of those affected (Herold 2021). If left untreated, colon carcinoma develops almost without exception (Guidelines 2019).
  • Family history of known colorectal carcinomas
  • Lynch syndrome: Also known as hereditary non-polyposis colon carcinoma syndrome (NPCC). It is found in around 5% of all affected people and is inherited in an autosomal dominant manner. Up to 70% of men are affected and up to 60% of women. The age of onset is usually around 45 years and the right colon section is primarily affected. In addition, there is an increased risk of 50% for endometrial cancer, <10% for gastric, ovarian and urothelial cancer, rarely for carcinomas in the small intestine, bile ducts and pancreas (Herold 2021)
• 2. nutritional factors:
  • High meat diet
  • Diet low in fiber
  • Avoidance of vegetables and fruit
  • High alcohol consumption (Herold 2021)
• 3. risk diseases:
  • Long-standing chronic inflammatory bowel disease, especially ulcerative colitis with high grade IEN (Herold 2021)
  • Colorectal adenomas, especially multiple adenomas, i.e. > 3 or > 1 cm adenomas (2019 guidelines)
  • Z. after ureterosigmoideoscopy
  • History of known carcinomas of the uterus, corpus uteri or ovary
  • Schistosomiasis (Herold 2021)
• 4. other risk factors:
  • Obesity
  • Age > 40 years
  • Long-term cigarette smoking
  • High alcohol consumption
  • Ignoring the screening examinations (Herold 2021)
• Colon carcinomas are familial in approx. 20 - 30 % of those affected, i.e. there is an increased incidence of malignant disease, but genetic causes cannot be specifically identified. In first-degree relatives such as parents, siblings and children, the average risk is 2 - 3 times higher. If colon carcinoma occurs before the age of 60, the risk for affected first-degree relatives increases 3-4-fold (2019 guidelines).

Pathogenetically, a distinction is made between:

• Adenoma/dysplasia-carcinoma sequence:

This is found in approx. 70-80 % of colon carcinomas. Carcinomas develop from intraepithelial neoplasia, the so-called IEN. These IEN occur in the form of adenomas. Tumor regression from normal tissue to adenoma to carcinoma takes approx. 10 years (Herold 2021).

• Serrated carcinogenesis pathway:

These account for approx. 20 - 30 % of colon carcinomas. An initial mutation plays a role here (Herold 2021).

• Chromosomal instability pathway (CIN)

The pathogenesis of sporadic colorectal carcinoma is characterized by detectable progression and led to the introduction of the term adenoma-carcinoma sequence (Siegenthaler 2006).

Colon carcinoma is localized 50% in the rectum as so-called rectal carcinoma, 30% in the sigmoid colon and 10% in the coecum, ascending colon and the rest of the colon (Herold 2021).

The symptoms are completely uncharacteristic. They can consist of:

• Blood impurities in the stool, most frequently in rectal cancer, but only in 1/6 of patients with right colon cancer (colon cancer can also be present without blood impurities, so never be satisfied with the diagnosis "hemorrhoids", as more than half of patients with colon cancer have hemorrhoids )
• Any sudden change in bowel habits in patients > 40 years of age such as "false friend", persistent foul wind odors, etc.
• General symptoms such as:
  • Fatigue, weight loss, fever, reduced performance
  • Chronic bleeding anemia
  • Symptoms of ileus as a late symptom (Herold 2021)

Every patient with conspicuous symptoms (see above under "Clinical picture") should be palpated rectally. Furthermore, colonoscopy and additional examinations (see "Imaging" below) to assess the spread of the tumor (Herold 2021).

• High quality colonoscopy

Quality-assured colonoscopy has the highest sensitivity and specificity with regard to the detection of colorectal carcinomas and adenomas (2019 guidelines).

However, the colonoscopy should be performed at least up to the bottom of the coecum (Herold 2021).

• 3D spiral CT

This is also known as a "virtual colonoscopy". It should always be performed if the colonoscopy was only incompletely possible (Herold 2021).

• Supplementary diagnostics

These include: rectal endosonography, MRI of the pelvis, in case of unclear sonographic findings: spiral CT of the abdomen, in case of suspected bladder infiltration: cystoscopy of the urinary bladder, gynecological examination in case of suspected infiltration of the uterus, vagina or adnexa (Herold 2021).

• Search for metastases:

For a metastasis search are indicated:

• Chest X-ray
• Abdominal sonography or CT, possibly also MRI of the liver
• Thoracic CT in the presence of rectal carcinoma (Herold 2021)

The following should be determined:

• Carcino-embryonic antigen (CEA):

However, this is not tumor-specific and is more important in follow-up care after radical surgery. If the values are elevated preoperatively, they normalize postoperatively and rise again in the event of a recurrence (Herold 2021).

• mRNA of the tumor-specific antigen HL- 6

This is more sensitive than CEA (Herold 2021).

• Postoperatively for the diagnosis of local recurrences should be determined:
  • Radioimmunoscintigraphy (RIS) with 99m Tc-labeled CEA antibodies
  • PET with fluorodeoxyglucose (Herold 2021)

Histologically, 80 - 90 % are adenocarcinomas, less frequently mucinous adenocarcinomas, lymphomas, squamous cell carcinomas, undifferentiated carcinomas and signet ring carcinomas (Buchta 2019).

According to the WHO, a distinction is made between:

• Low-grade carcinomas

Here the degeneration rate is low (Krams 2010).

• High-grade carcinomas (Herold 2021).

High-grade carcinomas have an increased risk of degeneration (Krams 2010).

• Ulcerative colitis
• M. Crohn's disease
• Diverticulitis
• Benign colon polyp
• Benign colon tumor
• Carcinoid (Buchta 2019)

• Stenosis with subsequent ileus
• bleeding
• Perforation (Buchta 2019)

Possible complications of radiation can be:

• Shrunken bladder
• stenosis
• Chronic radiation proctitis
• Fistulas (Herold 2021)

pT1 carcinomas

If the histological examination of an endoscopically R0- removed polyp reveals a pT1 carcinoma, oncological resection can be dispensed with if the situation is low-risk and the base of the polyp is free of carcinoma. Endoscopic follow-up should then take place after six months in the form of a local endoscopic examination and a complete colonoscopy after 3 years (2019 guidelines).

In the high-risk situation, however, radical surgical treatment is recommended (2019 guidelines).

Neoadjuvant therapy:

Neoadjuvant therapy is recommended for advanced rectal cancer of the distal two thirds of the rectum in UICC stages II and III, as this reduces the risk of local recurrence and may enable sphincter preservation, which did not appear possible based on the preoperative diagnosis (Herold 2021).

This is a:

• Preoperative short-term radiotherapy
• Radio / chemotherapy (RT / CT)

The actual operation then takes place 6 - 8 weeks after RT / CT (Herold 2021).

Adjuvant therapy:

In UICC stage III, the 5-year survival rate can be improved by 15 - 20 % with postoperative chemotherapy:

• Oxaliplatin

plus

• 5- fluorouracil

plus

• folinic acid

for 4 - 6 weeks p.o. for a total of 3 - 6 months (Herold 2021)

For tumors in stages T 1 - 3, N 1, the significantly better tolerated 3-month administration of:

• oxaliplatin

plus

• capecitabine

This can achieve a 5-year tumor-free rate of approx. 70 % (Herold 2021).

For tumors in UICC stage II, adjuvant therapy is only recommended if there are risk constellations such as tumor perforation, emergency surgery, removal of less than 12 lymph nodes (Herold 2021).

Conversion therapy for potentially resectable metastases

First, technically unresectable (liver) metastases are treated with chemotherapy (doublets or triplets with or without antibodies over a total of 2 - 6 months). This can achieve resectability in up to 40% of cases. The actual operation then takes place 4 weeks after the end of chemotherapy (Herold 2021).

Palliative therapy

Palliative therapy is planned as part of an interdisciplinary tumor conference (Herold 2021).

• Colon carcinoma:

In colon carcinoma, either a bypass anastomosis is placed or an anus praeter is created (Herold 2021)

• Rectal carcinoma:

This involves endoscopic stent placement or local, endoscopic argon laser therapy (Herold 2021)

• Metastatic: colorectal carcinoma

- If the patient is in a good AZ, polychemotherapy with e.g. 5 FU or prodrug capecitabine plus oxaliplatin and/or irinotecan can be carried out.

- Combination with a targeted substance. Molecular biological diagnostics are required beforehand to identify therapy-relevant mutations.

- Antibodies such as bevacizumab, aflibercept and ramucirumab, which have shown a therapeutic effect in several randomized studies (2019 guidelines), are used in cases of reduced general condition and also in second-line therapy, which can be given to around 70 % of patients.

- Sonography- or CT-guided local therapy procedures or stereotactic radiotherapy can be carried out for individual liver metastases to improve quality of life (Herold 2021).

Treatment can be curative-surgical:

I. Rectal carcinoma:

• Restorative resection procedure

A sphincter- (continence-) preserving restorative resection procedure is recommended. An anterior rectal resection with total mesorectal excision is performed for carcinomas in the lower two-thirds.

The limit for continence-preserving surgery is 5 cm between the anocutaneous line and the distal edge of the tumor. This applies to approx. 85% of all rectal cancers (Herold 2021).

• Transanal local excision:

This can only be performed for low-grade T1 carcinomas without lymph vessel invasion (Herold 2021).

• Abdominoperineal rectal extirpation:

This involves the creation of a terminal anus praeter sigmoidalis. This surgical procedure is suitable for tumors in the lower third of the rectum where a tumor-free distal safety margin is not available (Herold 2021).

Nowadays, the abdominal part of the operation can also be performed laparoscopically (Herold 2021).

II Colon carcinoma

This usually involves surgical or laparoscopic en bloc resection of the tumor-bearing section of the colon while maintaining a sufficient safety zone plus removal of the regional lymph nodes. A so-called no-touch technique is used to keep the risk of intraoperative spread of tumor cells as low as possible (Herold 2021).

The no-touch technique includes:

• Dissection of the vessels from central to peripheral
• The tumor is not manipulated until all lymphatic vessel connections have been isolated (Chassin 1983)

III. liver and lung metastases

Both liver and lung metastases can now be removed with curative intent (Herold 2021)

IV. Peritoneal carcinomatosis

A multimodal treatment concept with surgical removal of all foci, systemic and hyperthermic intraoperative chemotherapy is recommended here (Herold 2021).

After curative treatment, locoregional recurrences occur in approx. 10 - 30 % depending on the surgical method and tumor stage (Herold 2021).

The prognosis depends, among other things, on the tumor location; the more distal the tumor, the less favourable the prognosis (Herold 2021).

Statistically, the 5-year survival rate for:

• Rectal carcinoma:
  • UICC stage I at 95 %
  • UICC stage II at 85 %
  • UICC stage III at 55 %
  • UICC stage IV at 5 %
• Colon carcinoma:
  • UICC stage I at 95
  • UICC stage II at 85
  • UICC stage III at 65
  • UICC stage IV at 5 % (Herold 2021)
• The 5-year survival rate after resection of liver metastases is now 40% (Herold 2021)

Protective are:

• Low-fat and low-meat diet
• A diet rich in salad and vegetables
• Fast stool passage
• Cereal fiber
• Physical activity
• Abstinence from nicotine
• Medication such as ASA and NDAR
• Treatment with 5- ASA for ulcerative colitis (Herold 2021)

Screening:

• Non-risk persons should have a colonoscopy from the age of 50. Adenomas should be removed as premalignant changes. If the findings are normal, a colonoscopy is recommended every 10 years (Herold 2021).
• The previously performed guaiac-based fecal occult blood test (gFOBT) has now been replaced by the significantly more sensitive quantitative immunological test (iFOBT) for the detection of non-visible blood in the stool (Herold 2021). The specificity is > 90 % (Guidelines 2019).
• In first-degree relatives, the first colonoscopy should be performed before the onset of colon cancer or from the age of 40 if adenomas occur before the age of 50. If no polyps are found, a follow-up colonoscopy every 10 years is sufficient (Herold 2021).
• In the case of hereditary non-polyposis colorectal cancer (HNPCC), the first colonoscopy is recommended 5 years before the first manifestation in the family or at the latest at the age of 25. In addition, annual checks for extracolonic tumors should be performed (Herold 2021).
• If familial adenomatous polyposis (FAP) is present or FAP cannot be ruled out, annual rectosigmoidoscopies should be performed from the age of 10. If adenomas are detectable, annual colonoscopies are recommended. Screening examinations for extracolonic tumors should also be performed (Herold 2021).

• If 1 or 2 adenomas < 1 cm are detected without high-grade intraepithelial neoplasia, a follow-up colonoscopy is recommended after 5 - 10 years (2019 guidelines).
• If 3 to 4 adenomas are detected or an adenoma of > 1 cm or an adenoma with predominantly villous histology or with high-grade intraepithelial neoplasia with complete ablation, a follow-up colonoscopy should be performed after 3 years (2019 guidelines).
• In the case of histologically unactivated complete removal of adenomas > 5 mm, a follow-up colonoscopy should be performed after 6 months (2019 guidelines).
• After complete removal of a pT1, low grade carcinoma, the first follow-up should take place after six months, a complete colonoscopy after 3 years (2019 guidelines).
• For patients with UICC stage II and III, regular follow-up examinations are indicated after 6, 12, 18, 24, 36, 48 and 60 months. A complete colonoscopy every 6, 12, 60 months and a rectosigmoidoscopy every 6, 12, 18, 24 months (2019 guidelines).

Follow-up examinations should be performed depending on the tumor stage and include:

• CEA / medical history
• colonoscopy
• Chest X-ray
• Sonography of the liver
• Rectoscopy (guidelines 2019)
• Spiral CT for rectal cancer (Herold 2021)

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