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Colorectal cancer ( CRC )

Colorectal cancer ( CRC ) or Bowel cancer – cancer arising from the epithelium
 of the colon or rectum

 

Third most deadly and 4th most commonly diagnosed cancer worldwide 4th most common cancer in UK accounting for 11 % of all new cancer cases in 2017 Slightly ↑ common in men More common in the developed than developing world Incidence ↑ es with age ( except familial colorectal cancer ) in the UK during 2015-17 on average each year more than 4 in 10 new cases were in people aged 75 and over Highest rate are in 85-89 age group Incidence increasing worldwide and mortality decreasing ( Western way of life ) Almost always adenocarcinoma

 

What happens -almost always arises from benign neoplasms called tubular adenomas and serrated polyps which evolve into CRC over several years ie polyp-cancer progression is slow many adenomas begin as small polyps which enlarge and become dysplastic and eventually cancerous environmental factors are important in the aetiology of the disease CRC arises from epithelial lining most often as a consequence of mutations in the signaling pathways Underlying molecular changes have largely been identified Most CRC are localized with or without lymph node metastases

 

Risk factors -Majority of CRC are sporadic Increasing age Family history
○ strong family history of CRC and or polyps
○ early age at diagnosis of CRC
○ Inherited conditions as Famililal adenomatous polyposis Lynch syndrome ( Hereditary non polyposis colon cancer HNPCC) most common cause of hereditary bowel cancer ( represent minority of cases < 8 % )
☼ All patients with colorectal cancer should be tested for Lynch syndrome – NICE advice
○ BRCA1 gene mutation →possibly ↑ risk in women under 50 of CRC Benign polyps in bowel
○ most bowel cancers develop from an adenoma ○ slow growing Ulcerative colitis and Crohn’s disease
○ risk ↑ by 70 % Previous h/o CRC or h/o other cancers as
○ lymphoma
○ oesophageal cancer ○ renal or bladder cancer ○ breast cancer ○ uterine or cervical cancer ○ head and neck cancer ○ prostate cancer Radiation exposure eg
○ previous radiotherapy treatment
○ diagnostic background radiation Other comorbid conditions as
○ type 2 diabetes ○ gallstones ○ acromegaly Alcohol ,Smoking tobacco
○ risk ↑es with number of cigarettes smoked/ day Obesity – risk 33 % higher compared to people with normal BMI Diet
○ link with eating too much red and processed meat
○ high fat and low fiber diet Lack of physical activity
○ particularly in men.

 

Assessment -Presentation depends upon the site of the cancer and its ability to metastasize
 Screening – now often detects CRC before it starts to cause symptoms
 Traditionally sited features of CRC include
○ change in bowel habit
○ iron deficiency anaemia
○ rectal bleeding 
○ abdominal pain
○ intestinal obstruction or perforation
 Based upon which part of the bowel is involved
○ right side of the colon ( ascending colon & cecum ) usually cause severe faecal obstruction & anaemia
○ left sided tumours ( ie descending colon ) cause constipation
 Constitutional symptoms
○ wasting 
○ loss of appetite , weight and strength
 Emergency presentation and surgery is associated with poor short and long term outcomes

 

NICE Guidelines

 

Refer 2 weeks USC -aged 40 and over with unexplained weight loss and abdominal pain OR aged 50 and over with unexplained rectal bleeding OR aged 60 and over with
○ iron deficiency anaemia OR
○ changes in their bowel habit OR tests show occult blood in their faeces

 

Consider a two weeks USC referral -rectal or abdominal mass adult < 50 with rectal bleeding and any of the following unexplained symptoms or findings
○ abdominal pain
○ change in bowel habit
○ weight loss
○ iron deficiency anaemia

 

FIT test -Quantitative faecal immunochemical test to guide
 referral for CRC in primary care – adults without rectal bleeding
 age 50 and over with unexplained
○ abdominal pain OR
○ weight loss OR
 aged under 60 with
○ changes in bowel habit OR
○ iron deficiency anaemia OR
 aged 60 and over and have anaemia even in absence of iron deficiency.

 

Anal cancer -Consider a suspected cancer referral pathway for people with an unexplained anal mass or unexplained anal ulceration.

 

Bowel screening 60-74 every 2 yrs.

CRC ( many forms ) can be prevented through early and routine screening 
( early adenomas are detectable & treatable ) Several screening modalities are available
○ FOBT ( guaiac- based fecal occult blood )
○ FIT ( has greater sensitivity for detecting advanced adenomas and CRC than FOBT ) 
These are based on the concept of detecting blood or shredded cell debris by vascularized polyps

○ CT- colonography
○ Colonoscopy
○ Others as ColonSentry , SEPT-9 based tests , Cologuard
 Colonoscopy is the gold standard screening test with a high sensitivity and specificity ( allows simultaneous biopsy sampling and can be therapeutic )

 

Capsule endoscopy-Wireless capsule allows for examination of the whole GI tract for patients who refuse conventional colonoscopy or a complete colonoscopy is not possible due to anatomical reasons

 

CT Colonography-low dose CT scanning to obtain an interior view of the colon requires full bowel prep , air inflation and change in position

 

Double contrast barium enema –the colon is studies through X-Rays once the mucosa is coated with Ba and distends the colon with air , both of which are inserted PR poor sensitivity and false positive results – now replaced by novel imaging methods

 

 

CEA is the most frequently examined marker – it is a glycoprotein produced by cells of the large intestine 
○ it is highly specific in CRC but its sensitivity and validity are not sufficient for early cancer recognition
○ CEA in serum may also occur in inflammatory conditions as hepatitis , inflammatory bowel disease , pancreatitis or obstructive pulmonary disease
 CA19-9 ( carbohydrate antigen ) can be used in diagnostic of pancreatic , gastric & CRC ( ie GI tract tumours )
○ it is not specific for a particular histological type of neoplasm or which organ its coming from

Simultaneous CEA & CA 19-9 have role in obtaining pre-operative prognostic factor in evaluation of tumour stage and survival rate

 

Treatment –Surgery is the main and curative treatment for CRC New treatments for primary and metastatic CRC have emerged for e.g
○ laparoscopic surgery for primary disease
○ more aggressive resection for metastatic disease ( such as liver and pulmonary metastases )
○ radiotherapy for rectal cancer
○ neoadjuvant and palliative chemotherapies
But these interventions did not improve the outcome – hence the focus on early detection and treatment ie screening
 Cancer Research UK figures report
○ 53 % survive bowel cancer for 10 or more years ( 2013-17 , England )
○ survival has more than doubled in the last 40 yrs
 Screening is vital as 5 yr survival rates for patients with early stage cancer is about 90 % compared to 10 % for patients diagnosed with advanced stage metastatic disease
 Following factors have played an important role in improved survival
○ removal of polyps and other early detection efforts as colonoscopies , flexible sigmoidoscopies , CT colonography , FIT and FOB testing
○ screening programme

References

  1. Diagnosis and management of colorectal cancer SIGN Guideline 126 Aug 2016
  2. Oxford Handbook of Oncology Oxford university Press Aug 2015
  3. ABC of Colorectal Cancer -BMJ Books 2011
  4. NICE Pathways Suspected Cancer recognition and referral https://pathways.nice.org.uk/pathways/suspected-cancer-recognition-and-referral/suspected-cancer-recognition-and-referral-site-or-type-of-cancer#content=view-node%3Anodes-gastrointestinal-tract-lower-cancers
  5. CKS NHS Gastrointestinal tract ( lower ) cancers- recognition and referral NICE Nov 2015
  6. Colorectal cancer overview NICE Pathways
  7. Cancer Research UK ; Bowel cancer Colon Cancer https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bowel-cancer
  8. Medscape Tomislav Dragovich et al March 2017
  9. Clinical features of bowel disease in patients aged < 50 years in primary care : a large case-control study Br J Gen Pract March 2017 http://www.haveigotbowelcancer.com/
  10. Kuipers, Ernst J et al. “Colorectal cancer.” Nature reviews. Disease primers vol. 1 15065. 5 Nov. 2015, doi:10.1038/nrdp.2015.65
  11. Bray C, Bell LN, Liang H, Collins D, Yale SH. Colorectal Cancer Screening. WMJ. 2017 Feb;116(1):27-33. PMID: 29099566. ( Abstract )
  12. Baer C, Menon R, Bastawrous S, Bastawrous A. Emergency Presentations of Colorectal Cancer. Surg Clin North Am. 2017 Jun;97(3):529-545. doi: 10.1016/j.suc.2017.01.004. PMID: 28501245. ( Abstract )
  13. Weitz J, Koch M, Debus J, Höhler T, Galle PR, Büchler MW. Colorectal cancer. Lancet. 2005 Jan 8-14;365(9454):153-65. doi: 10.1016/S0140-6736(05)17706-X. PMID: 15639298. ( Abstract )
  14. Haraldsdottir S, Einarsdottir HM, Smaradottir A, Gunnlaugsson A, Halfdanarson TR. Krabbamein í ristli og endaþarmi [Colorectal cancer – review]. Laeknabladid. 2014 Feb;100(2):75-82. Icelandic. doi: 10.17992/lbl.2014.02.531. PMID: 24639430. ( Abstract )
  15. Rawla, Prashanth et al. “Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors.” Przeglad gastroenterologiczny vol. 14,2 (2019): 89-103. doi:10.5114/pg.2018.81072
  16. Haggar, Fatima A, and Robin P Boushey. “Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors.” Clinics in colon and rectal surgery vol. 22,4 (2009): 191-7. doi:10.1055/s-0029-1242458
  17. Colorectal Cancer e An Update for Primary Care Nurse Practitioners
    Cyndy Simonson, MS, ANP-BC https://www.npjournal.org/article/S1555-4155(18)30003-5/pdf
  18. Swiderska, Magdalena et al. “The diagnostics of colorectal cancer.” Contemporary oncology (Poznan, Poland) vol. 18,1 (2014): 1-6. doi:10.5114/wo.2013.39995

 

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