Colorectal Cancer

Definition/Description

Colorectal cancer (CRC) is a rapid abnormal cell growth that affects the large intestines and/or rectum. These clusters of cells are called adenomatous polyps and develop from the tissue membrane of glandular tissue. Polyps can start as benign and non-cancerous but with time can develop and become cancerous.[1]

Prevalence

Colorectal cancer is the second leading cause of death from a type of cancer in the United States. It is also the third most common cancer among men and women. The most current statistics report 136,717 people were diagnosed in 2009 with colorectal cancer (51.26% male and 48.63% female) and 51,848 deaths (51.7% male and 48.3% female) according to the Center of Disease Control.

Data from 2009 provided by the National Cancer Institute showed that prior to January 1, 2009 1,140,161 people were living with a diagnosis of CRC in the United States. This number includes people both, currently seeking treatment for their active diagnosis, as well as, individuals who have been in years of remission. 558,648 of these individuals were male and 581,477 were female.

Other statistical facts gathered from various sources include the following:

  • The lifetime risk of developing CRC is 1/20 or 4.96%.[2]
  • The mean age of CRC diagnosis is 69 years of age. [3]
  • The mean mortality age of CRC is 74 years of age. [3]
  • Studies between 1991 and 2005 show that survival rates from CRC have increased by 30%. [4]
  • The risk of getting CRC increases with age and is greater in men than women.  [5]
  • The most common area of diagnosis is the rectum and the rectosigmoid junction, with the sigmoid resulting the most favorable outcome.  [6]

Bar Graph II.png                                                        Incidence graph.png

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Characteristics/Clinical Presentation

Colorectal cancer can present as asymptomatic and symptomatic. Asymptomatic patients are diagnosed with a fecal occult blood test are identified at an early stage and most commonly located in the cecum/ascending colon.

Symptoms differ depending on where the tumor is located.

A diagnosis is made by a Colorectal Cancer screening examination or through an evaluation for an unrelated illness.


Right Sided Tumors Left Sided Tumors
Anemia Change in Bowel Habits
Abdominal Pain Rectal Blood Loss
Weight Loss Abdominal Pain
Change in Bowel Habits
* Associated with chronic occult
bleeding linked to iron deficiency & anemia


Early Stage


Advanced Stage


Rectal bleeding, hemorrhoids Constipation progressing to obstipation
Abdominal, plevic, back or sacral pain Diarrhea with copious amounts of mucus
Back pain that radiates down the legs  Nausea and vomiting
Changes in bowel patterns Weight loss
Fatigue and dyspnea
Fever (less common)

    

Associated Co-morbidities

Approximately 51-59% of individuals with a diagnosis of CRC who are under the age of 70 do not also suffer from co-morbidities; however, in the individuals who are greater than 70 years of age, only 26-24% of them do not suffer from co-morbidities. Of this group greater than 70 years of age, the men have the highest prevalence of complicating co-morbid conditions. These conditions can have a marked impact on the treatment of the individual’s CRC diagnosis. The short-term survival is also worsened in the presence of co-morbid conditions, especially cardiovascular co-morbidities.

  • Cardiovascular disease
  • Previously diagnosed CA
  • Male – Large Bowel, Urinary Tract, Lung, and Prostate
  • Female – Large Bowel, Breast, and Female Genital System
  • Hypertension (F>M)
  • Chronic Obstructive Pulmonary Disease
  • Diabetes

             CoMorbidities.png[7]

Medications

Chemotherapy


Targeted Drug Therapy


Monoclonal Antibody Therapy: proteins engineered to help the body’s natural immune system to attack and destroy colorectal cancer cells. It can be used independently or with other chemotherapy treatment.

CRC medication.png

 

Radiation Therapy: helps to destroy cancer cells and can be used in conjunction with chemotherapy.  
Radiation options:
Intensity Modulated Radiation Therapy (IMRT)
Intraoperative Radiation Therapy (IORT)
CyberKnife®
TheraShpere®
TomoTherapy®
Trilogy™

Diagnostic Tests/Lab Tests/Lab Values[2]

Preventative Scopes

  • Flexible Sigmoidoscopy Exam: This test looks at the inner lining of the large intestine and is used for patients with abdominal pain, rectal bleeding, changes in bone, and people who are greater than 50 years of age. This is less invasive than a colonoscopy and does not require anesthesia.
  • Colonoscopy: This test is used to check for polyps and the paitent’s risk for developing CRC. It is performed by the patient ingesting a laxative that results in bowel elimination and then the patient is put under an anesthesia. A scope is then inserted into the colon for visualizing the colon. Removal and biopsies can also be done during this procedure.

Blood Tests

  • Complete Blood Count (CBC): This is used to check for anemia or too few red blood cells. This can occur in CRC because of prolonged bleeding from the tumor.
  • Liver Enzymes: This is used to check the function of the live, due to the liver being a common organ for CRC to metastasize.
  • Tumor Markers: CRC cells can sometimes produce bi-products that are released into the bloodstream. Two examples of these are Carcinoembryonic Antigen (CEA and CA 19-9). Commonly the tumor marker blood tests are used in conjunction with other tests to monitor individual’s treatment progress as well as an early sign that a cancer has returned. This is not used to screen or diagnose CRC, because not all CRC’s will show a release of tumor markers and some results may show up abnormal but are due to other disease processes, such as ulcerative colitis, non-cancerous tumors of intestines, or types of liver disease or chronic lung disease, or smoking.

Biopsy

  • A biopsy is normally done if any other diagnostic test has suspected CRC. A small piece of tissue is removed through a scope during a colonoscopy. The tissue sample is tested in a lab by a pathologist under a microscope. This is the only way to determine for certain that the suspected tissue is in fact colorectal cancer.
  • Biopsied tissue can also be tested for specific gene changes in the cancer cells that have an effect on the way the cancer is treated, for example, the KRAS and BRAF genes. Those two genes specifically have a large impact on the type of cancer treatment those patients receive and respond to.
  • Biopsied tissue may be tested for changes called microsatellite instability (MSI). This is commonly present in hereditary non-polyposis colon cancer (HNPCC), as well as, some cancers not caused by HNPCC. If this is found in a cancer patient, because it is hereditary, family members may want to be tested also.

Computerized Tomography Scan (CT or CAT)

  • This imaging test is an x-ray that produces detailed cross-sectional images of the body. This machine takes many pictures of the body as they are moving and creates detailed images of the soft tissues of the body. This test is usually done to help determine if the cancer has spread to the liver or other organs.
  • CT with portography: This is done to specifically look at the portal vein or the vein that goes from the liver to the intestines to look for the spread of the cancer to the liver.
  • CT- guided needle biopsy: This is done when a suspected area of cancer lies deep within the body and a biopsy is taken using the imaging for location of the needle. This too often shows tumors in the liver.

Ultrasound

  • This imaging test uses sound waves and their echo to create a picture of internal organs or masses. These can be done to look for tumors in the liver, gallbladder, pancreas, or anywhere else in the abdomen. This test cannot be done to look for tumors of the colon.
  • Endorectal ultrasound: Specialized ultrasound used to evaluate colon and rectal cancers. The ultrasound transducer is inserted directly into the rectum. This is used to detect how far through the rectal wall the cancer has penetrated and if it has spread to nearby organs or lymph nodes.
  • Intraoperative ultrasound: This specialized ultrasound is done during surgery while the abdomen is open. The transducer is placed directly on the liver and used to detect the spread of colorectal cancer to the liver.

Magnetic Resonance Imaging (MRI) scan

  • This imaging scan provides detailed images of the soft tissues in the body. This imaging test uses radio waves and strong magnets instead of x-rays like the CT scan. A contrast material called gadolinium can also be used to see more precise images. This test is used to look at areas of the liver, where rectal cancer may have spread and also nearby structures to the colon and rectum. Endorectal MRI can also be used to improve the accuracy of this imaging test.

Chest X-ray

  • This test may be ordered by a MD to detect if CRC has spread to the lung tissue.

Positron Emission Tomography (PET) scan

  • This imaging test is done by injecting a form of a radioactive sugar (low radioactivity) into the blood. This sugar is absorbed by cancer cells because they grow rapidly in the body. A picture is then made of your body, highlighting the areas of radioactivity in your body. This test provides helpful information about your entire body. This test may be ordered to see if abnormal areas are tumors, to see if cancer has spread to the lymph nodes or if the MD feels the cancer has spread, but does not know for sure where it has spread.

Angiography

  • This is an imaging test that uses an x-ray procedure to look at blood vessels. This is done by injecting a contrast dye into an artery before the x-ray picture is taken. This may be done to look at the arteries that supply blood to tumors in the liver as well as helping to plan the surgical removal of a tumor in the liver.

Etiology/Causes

Colon cancer originates from rapid cell proliferation of the epithelial cells called colonocytes that line the bowel, and somatic mutations in the p53 tumor-suppressor gene. The majority of CRCs are believed to occur sporadically leaving only about 10% to 20% of CRCs to have a known hereditary component

Developing polyps is a potential risk factor for CRC, particularly if they are adenomatous (glandular hyperplasia). The age of when polyps are diagnosed can be an indicator for prognosis and risk for developing cancer. Patients with adenomatous colorectal polyps have an increased risk of 1.78 in developing CRC. The risk increases if the polyps are diagnosed before the age of 60 to 2.59. The larger the polyp the greater probability the polyp is cancerous compared to smaller polyps. Another kind of adenomatous polyp is called familial adenomatous polyposis which is an autosomal-dominant disease. This disease has an occurrence rate of 1:7000 to 1:10,000. The colon is completely covered with polyps and if medical management does not take action approximately 50-75% of patient will develop CRC.


Risks
Genetic influence of relatives who have been diagnosed with any type of cancer can increase the risk for CRC. A first-degree relative with CRC has a 2-4 times the risk. Cancer family syndrome is an autosomal-dominant disorder that puts the patient at 33% risk of developing cancer by the age of 50. Genetic changes are responsible and have an important role for hyperproliferation of carcinogenic cells which due to ulcerative colitis, acromegaly, family history of colonic neoplasia, certain professions, smoking & drinking, consumption of red or processed meat, etc.


The large intestines have an increase amount of bacteria present compared to the small intestines. This is can become problematic as it relates to an increase in proliferation of colonic carcinogens. Bile acids secreted in the intestines can act as tumor promoters and has shown to contribute to colon cancer. Inflammation of the colon and rectum are associated with an increased risk of colorectal cancer.
Twenty-five percent of patients who have inflammatory bowel disease, ulcerative colitis, have an increased risk if they’ve had the disease for over 25 years. At a lesser degree, Crohn’s disease may also have an influence of risk.

Systemic Involvement

Colorectal cancer can have an effect on the entire body. Common systemic symptoms of CRC include:

  1. Unexplained weight loss
  2. Unexplained loss of appetite
  3. Nausea or vomiting
  4. Diarrhea
  5. Anemia
  6. Jaundice
  7. Weakness or fatigue

It is important that if you experience these symptoms for you to report them to your MD to diagnose.[8]

In many cases colorectal cancer is not discovered until it has become metastatic to other locations in the body. CRC most commonly metastasizes to the liver. It will also commonly metastasize to the lung, brain and bone, but it is uncommon to find one of these metastasis without the presence of a metastatic spread to the liver as well. [6]

Medical Management (current best evidence)

National Cancer Institute at the National Institutes of Health

Cancer Advances in Focus:  Colorectal Cancer


Staging of Colorectal Cancer
If cancer is detected, it will be categorized in a stage to enable the doctor to determine the best type of treatment for the patient. Tumor size does not directly correlate with the stage of cancer. 
 CRC stages.png 


  

Colonoscopy Scopes the entire colon to look for any polyps or abnormal findings, can also be an opportunity for a biopsy
Proctocolectomy with ileostomy                                        

(with possible ileum pouch to preserve bowel function)

The large intestine and rectum is removed. Lymph nodes may be removed if needed. 

 



Colectomy with ileorectal anastomosis (IRA) Part or all of the large intestine is removed and the iluem is joined with the rectum. 

Proctocolectomy with ileal pouch-anal anastomosis (IPAA)


Also called a J-pouch

a pouch is created from the end of a patient’s small intestine and attached to the anus


 
Colostomy

Permanent. When bowel resection is not possible or colon & rectum are removed. It is a surgical procedure where an opening is made in the abdomen called a stoma or colostomy.

A disposable colostomy pouch is attached for disposal of wastes. Hygiene is important to decrease risk of infection.                 

 
Protoscopy (scope of the rectum): follows post 6 months colectomy to reevaluation and check for polyps.
Radiofrequency Ablation (RFA)

Intense heat to burn away tumors within the liver. Guided by a CT scan, a doctor inserts a needle-like device that delivers heat directly to a tumor and the surrounding area. This offers an alternative for destroying tumors that cannot be surgically removed.

Chemotherapy is sometimes combined with RFA for tumor destruction.

 

Physical Therapy Management (current best evidence)

Physical therapy is used after a diagnosis of CRC to help build strength and endurance to continue to perform daily activities. This is used when patients are not receiving treatment, as well as, during chemotherapy and radiation therapy. The main concept that is used is energy conservation to be able to complete tasks without becoming so fatigued that when completed they aren't able to do any more activities.

An oncology rehabilitation therapist is usually either an occupational or physical therapist; they have an expertise when treating pe
Ptpic.png
ople with cancer. These therapists create patient specific exercise programs. The goals of these treatment programs include:
  1. Minimizing fatigue 
  2. Optimizing physical function
  3. Boost their immune system
  4. Improve bowel habits 
  5. Improve flexibility                                                                                           [9]
  6. Reduce stress and anxiety
  7. Minimize depression
  8. Enhance self-image                                                                               

After a CRC surgery PT helps you through the recovery process by regaining strength, mobility and independence. With CRC and chemotherapy/radiation, physical therapy will help maintain hip and spine ROM and strength, because they are areas of negative impact for these treatments.


Evidence suggests that physical activity prevents the recurrence of colon cancer and Physical Therapists are able to provide an individualized exercise program based on this evidence with an understanding of the current treatments for cancer and how they affect a person's ability to stay active and exercise.

Read more in the article:  Impact of Physical Activity on Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803.


Physical therapists also refer to other clinical treatments to help offset side effects of the CRC medical treatment. Some of these treatment strategies include:

     Lymphadema Management- Some lymph nodes may be removed during surgery and that can interrupt the flow of lymph back to the center of the body. This treatment is used to decrease the swelling caused by this and also the pain and discomfort associated with this problem.
    ReBuilder- this is a treatment to treat chronic neuropathic pain that is a side effect from CRC chemotherapy. This treatment sends mild electrical pulses to your feet and legs. This treatment helps to reduce this pain so the limbs function better.

Physical therapy is an important piece of treatment to the independence and recovery of patients with CRC. Many times aggressive medical treatment is needed and the patient's independence, strength, range of motion, and fatigue levels are negatively impacted. Physical therapists, with an expertise in this population can have a positive functional impact on their life.[8]

Alternative/Holistic Management (current best evidence)

Nutrition Therapy

There are steps you can take to dramatically reduce your odds of developing colorectal cancer. Researchers estimate that eating a nutritious diet, getting enough exercise, and controlling body fat could prevent 45% of colorectal cancers.

The National Cancer Institute recommends a low-fat diet that includes plenty of fiber and at least five servings of fruits and vegetables per day.

Solid food may not be an option, depending on the stage and treatment.


Pain management

Naturopathic therapy: nontoxic therapy creating a healthy environment inside and out. My include clinical nutrition, botanical medicine, homeopathy, classical Chinese medicine, hydrotherapy, manipulative therapy, environment medicine and minor surgery


Mind Body Medicine

Acupuncture:this treatment helps promote the natural healing and functioning of the body. The acupuncturist inserts very small thin needles into points that stimulate energy flow in the body to promote the patient’s immune system.


Auriculotherapy:this treatment is similar to acupuncture but electrical stimulation is used instead of needles. The electrical stimulation is used on specific areas of the ear that correspond to locations on your body.

Differential Diagnosis

Colorectal cancer may present and be mistaken as other medical conditions. Some of those are including in the following list and the most common are included in the chart below, with signs and symptoms of the condition, as well as, testing that would be conducted to determine if what the patient is experiencing is colorectal cancer or the differential diagnosis.

  • Colon lymphoma
  • Colon polyps, benign
  • Crohn’s disease
  • Diverticular disease
  • Gastrointestinal tuberculosis
  • Hemorrhoids
  • Infectious colitis
  • Inflammatory bowel disease (IBD)
  • Irritable bowel syndrome
  • Ischemic colitis
  • Ulcerative colitis


Condition
Differentiating signs/symptoms
Differentiating tests
Irritable bowel syndrome (IBS)
A clinical diagnosis is based on the Rome III Criteria that specify at least 3 months' duration, with onset at least 6 months previously, of recurrent abdominal pain or discomfort associated with 2 or more of: improvement in abdominal pain with defecation, change in frequency of stool, change in form (appearance) of stool.
• There is no specific diagnostic test for IBS.
• Patients who fulfil the clinical criteria for IBS and have no alarm features have a very low probability of organic disease. Colonoscopy or colonic imaging is recommended for patients older than 50 years of age due to higher pre-test probability of colorectal cancer.

Ulcerative colitis
Average age of onset of inflammatory bowel disease (20 to 40 years) is younger than with colorectal cancer. Patients with inflammatory bowel disease frequently have watery diarrhoea. However, patients with colitis are at higher risk of colorectal cancer and may need reassessment if symptoms are atypical or do not respond to treatment.
• Colonoscopy will show rectal involvement, continuous uniform involvement, loss of vascular marking, diffuse erythema, mucosal granularity, normal terminal ileum (or mild 'backwash' ileitis in pancolitis).
Crohn's disease
Average age of onset of inflammatory bowel disease (20 to 40 years) is younger than with colorectal cancer. Patients with inflammatory bowel disease frequently have watery diarrhoea. Patients with colitis are at higher risk of colorectal cancer and may need reassessment if symptoms are atypical or do not respond to treatment.
• Colonoscopy with intubation of the ileum is the definitive test to diagnose Crohn's disease and will show mucosal inflammation and discrete deep superficial ulcers located transversely and longitudinally, creating a cobblestone appearance. The lesions are discontinuous, with intermittent areas of normal-appearing bowel (skip lesions).
Hemorrhoids
Causes bright red rectal bleeding that is separate from the stool. There is no abdominal discomfort or pain, altered bowel habits, or weight loss.
• Colonoscopy or colonic imaging is recommended in patients with abdominal symptoms in addition to rectal bleeding and in those older than 50 years of age.
Anal fissure
Severe pain on defecation. Blood is usually on wiping. There is no abdominal discomfort or pain, altered bowel habits, or weight loss.
• Colonoscopy or colonic imaging is recommended in patients with abdominal symptoms in addition to rectal bleeding and in those older than 50 years of age.
Diverticular disease
Diverticular stricture or inflammatory mass may be clinically indistinguishable from colorectal cancer.
• Colonoscopy with biopsies and CT imaging will usually differentiate.

[10]

Case Reports/ Case Studies

Case Study #1: From the Cancer Therapy & Supportive Care from John Hopkins Advanced Study in Nursing


• 52yo F presented to her PCP with c/o weakness & fatigue.
• Attributed changes due to menstrual cycle/menopause
• Rapid wt loss of 10lbs with in the past 6 months

PMHx:
• Chronic constipation & hemorrhoids
• Mild dyspnea on exertion
• Chronic arthritis in knees/hands
• No screening for colposcopy or sigmoidscopy
• Not currently receiving hormone therapy, took contraceptives for 10yrs


Family/social Hx:
• Father died age 60 of MI.
• Owns & manages interior design firm
• Divorced, 2 grown children & lives alone
• Active tennis player


Physical examination
• Body type, thing 5’6” 128lbs
• Normal BP, HR, RR

Lab work:
• Found she was anemic and prescribed iron pills
• Anemia was unresolved, she became constipated, denied melena
• Unable to take a stool sample for fecal occult blood testing due to constipation
• Later referred for a colonoscopy which a mass was found (6cm in ascending colon) and a biopsy was taken
• Mass was found to be poorly differentiated invasive adenocarcinoma with ulceration. A CT scan later confirmed the lesion found from the colonoscopy


Treatment:
• With a prior blood transfusion she had a Right hemicoloectomy followed by 6 months of chemo
• Patient was diagnosed with Stage 3C colon cancer
• Issue was resolved and her iron levels were carefully monitored and normalized


Case Study #2: Cardiac metastasis from colorectal cancer: A case report

• 70 yo F presented with bloody stools & admitted to hospital
• Experienced SOB and lost 8.8lbs in the past 3 months
• Colonoscopy showed an adenocarcinoma mass of the sigmoid colon


Lab work:
• All lab work was normal except a routine transthoracic echocardiography showed an enlargement of the right atrium and a mass adjacent to the right atrium.
• A chest x-ray and CT confirmed supporting findings of the echo


Treatment:
• Planned surgery of colon followed by cardiac surgery 4 weeks post
• Anterior Resection with colorectal anastomosis was performed, diagnosed with T4N2 (Stage 3)
• 2wks post op SOB became worse, and immediate cardiac surgery took place
• Mass was removed and identified as adenocarcinoma identical to the one found in the colon.
• Due recurrent cardiac bleeding, pt did not survive treatment 3 days post op


Conclusion:
• Cardiac metastais is more common than what is discovered and documented
• Further evaluation and diagnostic testing due to predicted increase in colorectal cancer metastasizing in the cardiac region is needed.

Case Study #3: Colonic Carcinoma in a Young Adult Presenting as an Intussusception

  • 32 yo F presented with a 15 day history of intermittent abdominal pain and nausea
  • One episode of diarrhea with no blood or mucus
  • initial examination revealed diffuse tenderness in the epigastrium and left upper quadrant


Lab Work:

  • Patient developed tachycardia and pain that had to be controlled with analgesia
  • Patient had developed anemia
  • Ultrasound scan was unremarkable
  • CT scan suggested a large bowel intussesception with a probable mass lesion


Treatment:

  • An extended right hemicolectomy was performed
  • Histology revealed an intussusception around a tubulovillous adenoma with moderately differentiated adencarcinomatous changes
  • She was discharged without complications 10 days after surgery


Conclusion:

  • Clinical presentation may include a palpable mass, nausea and vomiting, abdominal colic, change in bowel habit and occult blood per rectum.
  • It is important during a patient's initial visit to ask challenging questions if they present with an abnormal presentation.
  • Early referral for these patients is critical because this cancer is repidly progressive.
  • MD's in this report that though this women was referred and diagnosed quickl, she would have benefited more had she been diagnosed even quicker.
  • A high index of suspicion and an early CT scan may prevent delayed diagnosis and the development of complications.


Resources

Center of Disease Control

American Cancer Society

Cancer Treatment Centers of America

National Cancer Institute 

National Institute of Health 

Recent Related Research (from Pubmed)

References

  1. 1
  2. 2.0 2.1 Colorectal Cancer Overview [Internet]. American Cancer Society. 2013 [updated 2013 Jan 17]. Available from: http://www.cancer.org/cancer/colonandrectumcancer/overviewguide/colorectal-cancer-overview-key-statistics.
  3. 3.0 3.1 Seer Stat Facts Sheets: Colon and Rectum [Internet]. National Cancer Institute. 2012 [updated 2011 Nov]. Available from: http://seer.cancer.gov/statfacts/html/colorect.html.
  4. Enzinger PC, Benson AB, Mitchell EP, et al. Medical Update on Colorectal Cancer Understanding KRAS [pamphlet]. New York: Elsevier Oncology; 2010.
  5. Colorectal (Colon) Cancer [Internet]. Center for Disease Control. 2012 [updated 2012 Oct 22]. Available from: http://www.cdc.gov/cancer/colorectal/index.htm.
  6. 6.0 6.1 Tidy, Colin MD. Colorectal Cancer [Internet]. Patient.co.uk; 2012 [updated 2012 July 19]. Available from: http://www.patient.co.uk/doctor/colorectal-adenocarcinoma.htm.
  7. De Marco MF, Janssen-Heijnen ML, Van Der Heijden LH, et al. Comorbidity and colorectal cancer according to subsite and stage: a population-based study. Eur J Cancer. 2000 Jan; 36(1): 95-9
  8. 8.0 8.1 Colorectal Cancer: Integrative Treatment Program [Internet]. Cancer Treatment Centers of America. 2012. Available from: http://www.cancercenter.com/colorectal-cancer.cfm.
  9. http://cedarhillpt.com/2010/01/stretch-yourself-a-2010-challenge-from-cedar-hill/clipart-illustration-of-an-orange-man-sitting-on-a-gym-floor-and/
  10. Colorectal Cancer [Internet]. BMJ Publishing Group. 2011 [updated 2013 Feb 4]. Available from: http://bestpractice.bmj.com/best-practice/monograph/258/diagnosis/differential.html.