Prevention colorectal mass

7/30/2019 Prevention colorectal mass

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Prevention

Most colorectal cancers should be preventable, through increased surveillance, improvedlifestyle, and, probably, the use of dietary chemopreventative agents.

Surveillance

Most colorectal cancers arise from adenomatous polyps. These lesions can be detected andremoved during colonoscopy. Studies show this procedure would decrease by > 80% the risk ofcancer death, provided it is started by the age of 50, and repeated every 5 or 10 years.[50]

As per current guidelines underNational Comprehensive Cancer Network, in average riskindividuals with negative family history of colon cancer and personal history negative foradenomas orinflammatory bowel diseases, flexible sigmoidoscopy every 5 years with fecaloccult blood testing annually or double contrast barium enema are other options acceptable forscreening rather than colonoscopy every 10 years (which is currently the gold standard of care).

Lifestyle and nutrition

The comparison of colorectal cancer incidence in various countries strongly suggests thatsedentarity, overeating (i.e., high caloric intake), and perhaps a diet high in meat (red orprocessed) could increase the risk of colorectal cancer. In contrast, a healthy body weight,physical fitness, and good nutrition decreases cancer risk in general. Accordingly, lifestylechanges could decrease the risk of colorectal cancer as much as 60-80%.[51]

A high intake of dietary fiber (from eating fruits, vegetables, cereals, and other high fiber foodproducts) has, until recently, been thought to reduce the risk of colorectal cancer and adenoma.In the largest study ever to examine this theory (88,757 subjects tracked over 16 years), it hasbeen found that a fiber rich diet does not reduce the risk of colon cancer.[52] A 2005 meta-analysisstudy further supports these findings.[53]

The Harvard School of Public Health states: "Health Effects of Eating Fiber: Long heralded aspart of a healthy diet, fiber appears to reduce the risk of developing various conditions, includingheart disease, diabetes, diverticular disease, and constipation. Despite what many people maythink, however, fiber probably has little, if any effect on colon cancer risk." [54]

Chemoprevention

More than 200 agents, including the above cited phytochemicals, and other food components likecalcium or folic acid (a B vitamin), andNSAIDs like aspirin, are able to decrease carcinogenesisinpre-clinical development models: Some studies show full inhibition of carcinogen-inducedtumours in the colon of rats. Other studies show strong inhibition of spontaneous intestinalpolyps in mutated mice (Min mice). Chemoprevention clinical trials in human volunteers haveshown smaller prevention, but few intervention studies have been completed today. The
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"chemoprevention database" shows the results of all published scientific studies ofchemopreventive agents, in people and in animals.[55]

Aspirin chemoprophylaxis

Aspirin should not be taken routinely to prevent colorectal cancer, even in people with a familyhistory of the disease, because the risk of bleeding and kidney failure from high dose aspirin(300 mg or more) outweigh the possible benefits.[56]

A clinical practice guideline of the U.S. Preventive Services Task Force (USPSTF)recommended against taking aspirin (grade D recommendation).[57]The Task Forceacknowledged that aspirin may reduce the incidence of colorectal cancer, but "concluded thatharms outweigh the benefits of aspirin and NSAID use for the prevention of colorectal cancer".A subsequent meta-analysis concluded "300 mg or more of aspirin a day for about 5 years iseffective in primary prevention of colorectal cancer in randomised controlled trials, with alatency of about 10 years".[58] However, long-term doses over 81 mg per day may increase

bleeding events.

[59]

] Calcium

The meta-analysis by the Cochrane Collaborationofrandomized controlled trials publishedthrough 2002 concluded "Although the evidence from two RCTs suggests that calciumsupplementation might contribute to a moderate degree to the prevention of colorectaladenomatous polyps, this does not constitute sufficient evidence to recommend the general useof calcium supplements to prevent colorectal cancer.". [60] Subsequently, one randomizedcontrolled trial by the Women's Health Initiative (WHI) reported negative results.[61]A secondrandomized controlled trial reported reduction in all cancers, but had insufficient colorectal

cancers for analysis.

[62]

Vitamin D

A scientific review undertaken by theNational Cancer Institute found that vitamin D wasbeneficial in preventing colorectal cancer, which showed an inverse relationship with bloodlevels of 80 nmol/L or higher associated with a 72% risk reduction compared with lower than 50nmol/L.[63] A possible mechanism is inhibition of Hedgehog signal transduction.[64]

Management

The treatment depends on the stage of the cancer. When colorectal cancer is caught at earlystages (with little spread), it can be curable. However, when it is detected at later stages (whendistant metastasesare present), it is less likely to be curable.

Surgery remains the primary treatment, while chemotherapy and/or radiotherapy may berecommended depending on the individual patient's staging and other medical factors.
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Because colon cancer primarily affects the elderly, it can be a challenge to determine howaggressively to treat a particular patient, especially after surgery. Clinical trials suggest"otherwise fit" elderly patients fare well if they have adjuvant chemotherapy after surgery, sochronological age alone should not be a contraindication to aggressive management.[65]

Surgery

Surgeries can be categorised into curative, palliative, bypass, fecal diversion, or open-and-close.

Curativesurgical treatment can be offered if the tumor is localized.

Very early cancer that develops within apolypcan often be cured by removing the polyp

(i.e., polypectomy) at the time ofcolonoscopy. In colon cancer, a more advanced tumor typically requires surgical removal of the section

of colon containing the tumor with sufficient margins, and radical en-bloc resection ofmesenteryand lymph nodesto reduce local recurrence (i.e., colectomy). If possible, the

remaining parts of colon are anastomosedto create a functioning colon. In cases whenanastomosis is not possible, a stoma(artificial orifice) is created.

Curative surgery on rectal cancer includes total mesorectal excision (lower anterior

resection) orabdominoperineal excision.

In case of multiple metastases, palliative (noncurative) resectionof the primary tumor is stilloffered to reduce furthermorbidity caused by tumor bleeding, invasion, and its catabolic effect.Surgical removal of isolated liver metastases is, however, common and may be curative inselected patients; improved chemotherapyhas increased the number of patients who are offeredsurgical removal of isolated liver metastases.

If the tumor invaded into adjacent vital structures, which makes excision technically difficult, thesurgeons may prefer to bypass the tumor (ileotransverse bypass) or to do a proximal fecaldiversion through a stoma.

The worst case would be an "open-and-close" surgery, when surgeons find the tumorunresectable and the small bowel involved; any more procedures are thought by some to do moreharm than good to the patient. This is uncommon with the advent of laparoscopy and betterradiological imaging. Most of these cases formerly subjected to "open and close" procedures arenow diagnosed in advance and surgery avoided.

Laparoscopic-assisted colectomy is a minimally invasive technique that can reduce the size ofthe incision and may reduce postoperative pain.

As with any surgical procedure, colorectal surgery may result in complications, including

wound infection, dehiscence (bursting of wound) or hernia,

anastomosis breakdown, leading to abscess or fistula formation, and/or peritonitis,

bleeding with or without hematomaformation,
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adhesions resulting inbowel obstruction. A 5-year study of patients who had surgery in

1997 found the risk of hospital readmission to be 15% after panproctocolectomy, 9%after total colectomy, and 11% afterileostomy[66]

adjacent organ injury; most commonly to the small intestine, ureters, spleen, or bladder,

and

cardiorespiratory complications, such as myocardial infarction,pneumonia,arrythmia,

pulmonary embolism, etc.

Chemotherapy

Chemotherapy is used to reduce the likelihood of metastasis developing, shrink tumor size, orslow tumor growth. Chemotherapy is often applied after surgery (adjuvant), before surgery(neoadjuvant), or as the primary therapy (palliative). The treatments listed here have been shownin clinical trials to improve survival and/or reduce mortality rate, and have been approved for useby the US Food and Drug Administration. In colon cancer, chemotherapy after surgery is usually

only given if the cancer has spread to the lymph nodes (Stage III).

Adjuvant (after surgery) chemotherapy

o 5-fluorouracil (5-FU) orcapecitabine (Xeloda)

o Leucovorin (LV, folinic Acid)

o Oxaliplatin (Eloxatin)

Chemotherapy formetastatic disease. Commonly used first line chemotherapy regimensinvolve the combination of infusional 5-fluorouracil,leucovorin, and oxaliplatin

(FOLFOX) withbevacizumab or infusional 5-fluorouracil, leucovorin, and irinotecan(FOLFIRI) withbevacizumab or the same chemotherapy drug combinations withcetuximab in KRAS wild type tumors

o 5-fluorouracil (5-FU) or capecitabine

o UFT or Tegafur-uracil

o Leucovorin (LV, folinic Acid)

o Irinotecan (Camptosar)

o Oxaliplatin (Eloxatin)

o Bevacizumab (Avastin)

o Cetuximab (Erbitux)

o Panitumumab (Vectibix)

In clinical trials for treated/untreated metastatic disease.[67]
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o Bortezomib (Velcade)

o Oblimersen (Genasense, G3139)

o Gefitinib and erlotinib (Tarceva)

o Topotecan (Hycamtin)

At the 2008 annual meeting of the American Society of Clinical Oncology, researchersannounced that colorectal cancer patients that have a mutation in the KRAS gene do not respondto certain therapies, those that inhibit theepidermal growth factor receptor(EGFR)--namelyErbitux (cetuximab) and Vectibix (panitumumab).[68]Following recommendations by ASCO,patients should now be tested for the KRAS gene mutation before being offered these EGFR-inhibiting drugs.[69] In July 2009, the US Food and Drug Administration (FDA) updated thelabels of two anti-EGFR monoclonal antibody drugs (panitumumab (Vectibix) andcetuximab(Erbitux)) indicated for treatment of metastatic colorectal cancer to include information aboutKRAS mutations.[70]

However, having the normal KRAS version does not guarantee these drugs will benefit thepatient.[68]

The trouble with the KRAS mutation is that its downstream of EGFR, says Richard Goldberg,MD, director of oncology at the Lineberger Comprehensive Cancer Center at the University ofNorth Carolina. It doesnt matter if you plug the socket if theres a short downstream of theplug. The mutation turns [EGFR] into a switch thats always on. But this doesnt mean thathaving normal, or wild-type, KRAS is a fail-safe. It isnt foolproof, cautions Goldberg. If youhave wild-type KRAS, youre more likely to respond, but its not a guarantee. Tumors shrink inresponse to these drugs in up to 40 percent of patients with wild-type KRAS, and progression-

free and overall survival is increased.

The cost benefit of testing patients for the KRAS gene could potentially save about $740 milliona year by not providing EGFR-inhibiting drugs to patients who would not benefit from the drugs."With the assumption that patients with mutated Kras (35.6% of all patients) would not receivecetuximab (other studies have found Kras mutation in up to 46% of patients), theoretical drugcost savings would be $753 million; considering the cost of Kras testing, net savings would be$740 million."[71]

Radiation therapy

Radiotherapy is not used routinely in colon cancer, as it could lead to radiation enteritis, and it isdifficult to target specific portions of the colon. It is more common for radiation to be used inrectal cancer, since the rectum does not move as much as the colon and is thus easier to target.Indications include:

Colon cancer

o pain relief and palliation - targeted at metastatic tumor deposits if they compress

vital structures and/or cause pain
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Rectal cancer

o neoadjuvant - given before surgery in patients with tumors that extend outside the

rectum or have spread to regional lymph nodes, to decrease the risk of recurrencefollowing surgery or to allow for less invasive surgical approaches (such as a lowanterior resection instead of an abdominoperineal resection). In locally advancedadenocarcinoma of middle and lower rectum, regional hyperthermia added tochemoradiotherapy achieved good results in terms of rate of sphincter-sparingsurgery.[72]

o adjuvant - where a tumor perforates the rectum or involves regional lymph nodes

(AJCC T3 or T4 tumors or Duke's B or C tumors)

o palliative - to decrease the tumor burden to relieve or prevent symptoms

Sometimes chemotherapy agents are used to increase the effectiveness of radiation by sensitizingtumor cells, if present.

Immunotherapy

Bacillus Calmette-Gurin (BCG) is being investigated as an adjuvant mixed with autologoustumor cells in immunotherapy for colorectal cancer.[73]

Cancer Vaccine

TroVax, a cancer vaccine,[74]produced by Oxford BioMedica,[75] is in Phase III trials for renal

cancers, and phase III trials are planned for colon cancers. [76]

Treatment of liver metastases

According to the American Cancer Society statistics in 2006,[77]over 20% of patients presentwith metastatic (stage IV) colorectal cancer at the time of diagnosis, and up to 25% of this groupwill have isolated liver metastasis that is potentially resectable. Lesions which undergo curativeresection have demonstrated 5-year survival outcomes now exceeding 50%.[78]

Resectability of a liver metastasis is determined using preoperative imaging studies (CT or MRI),intraoperative ultrasound, and by direct palpation and visualization during resection. Lesions

confined to the right lobe are amenable to en bloc removal with a right hepatectomy (liverresection) surgery. Smaller lesions of the central or left liver lobe may sometimes be resected inanatomic "segments", while large lesions of left hepatic lobe are resected by a procedure calledhepatic trisegmentectomy. Treatment of lesions by smaller, nonanatomic "wedge" resections isassociated with higher recurrence rates. Some lesions which are not initially amenable to surgicalresection may become candidates if they have significant responses to preoperativechemotherapy or immunotherapy regimens. Lesions which are not amenable to surgical resection
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for cure can be treated with modalities including radio-frequency ablation (RFA), cryoablation,and chemoembolization.

Patients with colon cancer and metastatic disease to the liver may be treated in either a singlesurgery or in staged surgeries (with the colon tumor traditionally removed first) depending upon

the fitness of the patient for prolonged surgery, the difficulty expected with the procedure witheither the colon or liver resection, and the comfort of the surgery performing potentially complexhepatic surgery.

Aspirin

A study published in 2009 found that aspirin reduces risk of colorectal neoplasia in randomizedtrials, and inhibits tumor growth and metastases in animal models. The influence of aspirin onsurvival after diagnosis of colorectal cancer is unknown.[79] Several reports, including aprospective cohort of 1,279 people diagnosed with stages I-III (nonmetastatic) colorectal cancer,[80] have suggested a significant improvement in cancer-specific survival in a subset of patients

using aspirin.[81]

Cimetidine

Cimetidine is being investigated in Japan as an adjuvant for adenocarcinomas, [82] including forstage III[83]and stage IV[84] colorectal cancers biomarked with overexpressed sialyl Lewis X andA epitopes. Multiple small trials suggest a significant survival improvement in the subset ofpatients with the sLeX and sLeA biomarkers that take cimetidine treatment perioperatively,through several mechanisms[3].

Support therapies

Cancer diagnosis very often results in an enormous change in the patient's psychologicalwellbeing. Various support resources are available from hospitals and other agencies, whichprovide counseling, social service support,cancer support groups, and other services. Theseservices help to mitigate some of the difficulties of integrating patients' medical complicationsinto other parts of their lives.

Prognosis

Survival is directly related to detection and the type of cancer involved, but overall is poor forsymptomatic cancers, as they are typically quite advanced. Survival rates for early stagedetection is about 5 times that of late stage cancers. For example, patients with a tumor that hasnot breached the muscularis mucosa (TNM stage T1-2, N0, M0) have an average 5-year survivalof approximately 90%. Those with a more invasive tumor, yet without node involvement (T3-4,N0, M0) have an average 5-year survival of approximately 70%. Patients with positive regionallymph nodes (any T, N1-3, M0) have an average 5-year survival of approximately 40%, whilethose with distant metastases (any T, any N, M1) have an average 5-year survival ofapproximately 5%.[85]
http://en.wikipedia.org/wiki/Neoplasiahttp://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-78http://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-79http://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-80http://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-81http://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-82http://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-82http://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-83http://molpharm.aspetjournals.org/content/70/2/450.full.pdfhttp://molpharm.aspetjournals.org/content/70/2/450.full.pdfhttp://en.wikipedia.org/wiki/Counselinghttp://en.wikipedia.org/wiki/Cancer_support_grouphttp://en.wikipedia.org/wiki/Cancer_support_grouphttp://en.wikipedia.org/wiki/Muscularis_mucosahttp://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-agabegi2nd-84http://en.wikipedia.org/wiki/Neoplasiahttp://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-78http://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-79http://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-80http://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-81http://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-82http://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-83http://molpharm.aspetjournals.org/content/70/2/450.full.pdfhttp://en.wikipedia.org/wiki/Counselinghttp://en.wikipedia.org/wiki/Cancer_support_grouphttp://en.wikipedia.org/wiki/Muscularis_mucosahttp://en.wikipedia.org/wiki/Colorectal_cancer#cite_note-agabegi2nd-84


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CEA level is also directly related to the prognosis of disease, since its level correlates with thebulk of tumor tissue.

Follow-up

Micrograph of a colorectal villous adenoma. These lesions are considered pre-cancerous. H&Estain.

The aims of follow-up are to diagnose, in the earliest possible stage, any metastasis or tumorsthat develop later, but did not originate from the original cancer (metachronous lesions).

The U.S.National Comprehensive Cancer Networkand American Society of Clinical Oncologyprovide guidelines for the follow-up of colon cancer.[86][87]A medical history andphysicalexaminationare recommended every 3 to 6 months for 2 years, then every 6 months for 5 years.Carcinoembryonic antigen blood level measurements follow the same timing, but are onlyadvised for patients with T2 or greater lesions who are candidates for intervention. A CT-scan ofthe chest, abdomen and pelvis can be considered annually for the first 3 years for patients whoare at high risk of recurrence (for example, patients who had poorly differentiated tumors or

venous or lymphatic invasion) and are candidates for curative surgery (with the aim to cure). Acolonoscopy can be done after 1 year, except if it could not be done during the initial stagingbecause of an obstructing mass, in which case it should be performed after 3 to 6 months. If avillous polyp, a polyp >1 centimeter or high grade dysplasia is found, it can be repeated after 3years, then every 5 years. For other abnormalities, the colonoscopy can be repeated after 1 year.

Routine PET orultrasound scanning, chest X-rays, complete blood count orliver function testsare not recommended.[86][87]These guidelines are based on recent meta-analyses showingintensive surveillance and close follow-up can reduce the 5-year mortality rate from 37% to30%.[88][89][90]

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