Colorectal cancer

The last two decades have seen a progressive increase in the onset of colorectal cancers. Nonetheless this has been accompanied by an improvement in overall survival due to earlier diagnosis, based on colon cancer symptoms, and more effective therapies for the colon cancer treatment. The most common sites are the rectum (40%) and sigmoid colon (25%), although no part of the large intestine is spared. While colorectal cancer occurs equally in both sexes, rectal cancer seems to be more frequent in men with a male-female ratio of about 2:1.

STAFF

At the IEO colorectal cancer is treated by a multidisciplinary team consisting of specialists in:

• Gastrointestinal surgery
• Gastrointestinal and Neuroendocrine Cancer Medical Treatment
• Endoscopy
• New Drugs and Early Drug Development for Innovative Therapies
• Department of Pathology and Laboratory Medicine
• Department of Medical Imaging and Radiation Sciences

There are many risks related to colorectal cancer, only a few of them are known and have appropriate procedures in place for prevention.

Genetic factors. Colorectal cancer risk can be inherited. This happens if there have been repeated cases of colorectal cancer in the family of origin (especially if the affected subjects were under the age of 50) or if hereditary diseases predisposed to this colorectal cancer have occurred (of note are hereditary adenomatous polyposis and hereditary colorectal carcinomatosis on a non-polyposis basis, also called HNPCC or Lynch syndrome). It is estimated that the risk of colorectal cancer increases 2-4 times in first-degree relatives with colorectal cancer or polyps of the large bowel. Total colonoscopy as a screening test is recommended in patients with a documented genetic risk. At the IEO, genetics and cancer prevention programmes are active for the diagnosis and the prevention of many hereditary colorectal cancers.

Nutritional factors and lifestyles. Many studies show that a diet high in calories, proteins and animal fats and low in fibre is associated with an increase in colorectal cancers and the develop of colon cancer symptoms. Conversely, diets high in fibre (characterised by a high consumption of fruit and vegetables) appear to exert a protective role avoiding the presence of colon cancer symptoms. The adoption of the so-called Mediterranean diet – with its high content of vitamins, fibre and antioxidants - is a tool for prevention for colon cancer, avoiding symptoms of colon cancer, as are weight monitoring and moderate physical and sporting activity (it only takes 20 minutes a day of walking briskly to significantly reduce the risk). In addition, abstention from smoking and avoiding alcohol abuse has a favourable impact.

Non-hereditary factors. Chronic inflammatory of colorectal cancers (including ulcerative colitis and Crohn's disease), a past medical history of colon polyps or a history of colorectal cancer are important. Not to be forgotten is age; incidence is 10 times higher among people aged between 60 and 64 compared with incidence in those who are 40-44.

Occult blood in the stool is the most widely-used screening tool; an annual check-up from the age of 50 is strongly recommended. Thanks to the good specificity and sensitivity of the new generation immunoassays, the test can detect colorectal cancers before colon cancer symptoms arise. If the patient has a positive faecal test, colonoscopy should be performed. Colonoscopy is indicated as the first test for early diagnosis in subjects with documented risk factors (family history, previous polyps or colorectal cancers, idiopathic colitis).

Early diagnosis based on colon cancer symptoms is very important. Five-year survival is 75-90% in the early stages and drops to less than 10% in metastasized colon cancer.

Nutritional prevention for colorectal cancer

Based on a thorough evaluation of the results of scientific research, specific risk factors and protective nutritional factors have been identified for specific types of colorectal cancer. Experts have classified the results into four levels: "convincing evidence", "probable evidence", "limited evidence" and one final level that includes effects for which evidence of association with the cancer is “highly unlikely". The following probable and convincing evidence forms the basis for the recommendations:

According to the Worldwide Fund for Research on Cancer, convincing nutritional risk factors for increasing the risk of colorectal cancer are:

• red meat (convincing evidence)
• processed and preserved meat (convincing evidence)
• alcoholic beverages (convincing evidence for men - probable evidence for women)
• overweight and obesity (convincing evidence)
• abdominal fat (convincing evidence)

The protective factors that have shown convincing evidence in lowering the risk for colorectal cancer are regular physical activity and the consumption of foods rich in fibre such as whole grains, legumes, vegetables and fruits. The consumption of garlic and milk has shown probable evidence for the prevention of this type of colorectal cancer.

Colon cancer symptoms

Signs and symptoms of colon cancer vary. They are influenced by several factors such as the site of the cancer, its size and the presence or absence of obstruction or bleeding. Colon cancer symptoms include intestinal irregularities, loss of blood in the faeces, abdominal pain, anaemia, unintentional weight loss and fatigue.

Diagnosis of colorectal cancer

Since the majority of colorectal cancers derive from the malignant transformation of polyps or small benign mucosal expansion due to the proliferation of the cells in the intestinal mucosa, the removal of benign polyps is an effective prevention. Not all polyps are at risk of colorectal cancer. Only adenomatous polyps are really considered precancerous, therefore it is necessary that evaluations of pre-cancerous lesions through endoscopic and histological diagnosis are performed in well-equipped centres and with high volume of cases.

Modern endoscopic techniques can cure pre-cancerous forms and many types of initial colorectal cancer. Surgery plays a fundamental role in colorectal cancer treatment when the cancer is localised. The integration of surgery with chemotherapy, radiotherapy and recently-introduced biological therapies has successfully treated many patients who would, until a few years ago, have had an unfavourable prognosis, including those with metastasized colon cancer.

Diagnosis is initially based on clinical examination, which consists of palpation of the abdomen to look for any masses, and rectal exploration (approximately 70% of rectal cancer can be discovered with this operation). The diagnosis is confirmed by performing colonoscopy and biopsy.

Treatment of colorectal cancer

Surgery - integrated with medical care - is the main treatment tool in localised forms of the colorectal cancer, while the type of medical care chosen - integrated with surgery, interventional radiology and radiotherapy - plays an important tool in the treatment of advanced form metastasized colon cancers. Endoscopic therapy, with removal of the polyp in the course of the rectal-colonoscopy, is an effective treatment and replaces surgery in its very initial forms and in the pre-cancerous forms.

It is fundamental that surgery and integrated medical-surgical treatments are performed at centres that can document a high number of patients treated each year for colorectal cancers, where there is an optimal and constant integration between the different groups of specialists involved in the process of diagnosis and care of colorectal cancers. All of this expertise has been present at the IEO since its foundation. The Ministry of Health data (AGENAS 2013) rank the IEO among the top national centres and at the top in Lombardy for the number of patients annually treated for colorectal cancer, with a high proportion of surgeries performed with minimally-invasive laparoscopic or robotic techniques.

Surgery is the treatment of choice for the colorectal cancer, being indicated in all the localised forms of the disease. In the majority of patients, surgery relies on extensive use of minimally-invasive techniques (laparoscopy and robotics) with an appreciable advantage in postoperative recovery times. The numbers of interventions performed put the IEO General Surgery Unit at the forefront in the national rankings. In particular, interventions for the treatment of rectal cancer through robotic techniques have exceeded 300, which represents one of the largest caseloads for a single centre in the world.

Rectal cancer surgery has become increasingly conservative over time. Integration with advanced chemo-radiotherapy methods in the preoperative period and the adoption of innovative surgical techniques allows us to minimise the number of interventions with demolition of the anal sphincter (which would lead ultimately to the opening of a stoma), now limited only to cases of direct colorectal cancer infiltration of the anal sphincter.

In some cases, chemotherapy and/or radiotherapy for preventing metastasized colon cancer in patients at risk are associated with surgery (adjuvant therapies) or they are an alternative to surgery in preventing the development of metastasized colon cancer that may have already spread around the cancer or to other parts of the body through the blood and lymphatic circulation.

Treatment for metastasized colon cancer

The first line of therapy for colon cancer stage 4 metastasized to liver is s .

However, instead of surgery of liver metastases from colorectal cancer, the patient can benefit of other local therapies aimed at ablation of liver metastases as a thermal ablation or radiotherapy . These techniques can offer a valuable tool in the treatment of metastasized colon cancer contributing to increased chances of cure and prolonging survival. The main cause of death is due to the patients with colon cancer stage 4 metastasized to the liver and/ or to other sites. Most often, patients with colorectal cancer develop liver and bone metastases (liver 66%), bone (1.9%) and the following locations in the order of frequency being peritoneal (15%) and pulmonary (10%). In the past three decades, it has been found that for patients with colorectal hepatic-only metastases, the treatment that provides the longest survival (and even the cure in some patients) is hepatic resection associated with adjuvant oncologic treatment.

Most recently, ablative therapies based on needle-delivered thermoablation or radiation therapy have become additional weapons for effective treatment. Overall, the recent combined advances in surgery, radiation therapy, ablative therapy, and chemotherapy have provided more patients with a chance for long-term survival.

Trials in progress at IEO are aimed at:

• identifying earlier and more reliable endoscopic diagnostic tools (such as Confocal Laser Endomicroscopy)
• defining the criteria for the objective assessment of the quality of the endoscopic examination
• establishing the benefits of minimally-invasive robotic surgery in rectal cancer
• studying the prognostic factors in radically operated colorectal cancer
• finding new biomarkers
• defining the lymphatic basin of colorectal cancers
• clarifying the role of Diffusion MRI in the surgical treatment of rectal cancer undergoing robotic surgery
• investigating the prognostic role of circulating cancer cells and circulating DNA in peripheral venous blood of patients with rectal cancer.

An important part of studies and research is dedicated to prevention based on the study of the genetic risk. In addition, major efforts are focused on aimed at clarifying the role of adjuvant and palliative chemotherapy and radiotherapy in cases where they are indicated, through specific dedicated studies.