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ADDITIONALREADING

Cosse C, Sabbagh C, Browet F, et al. Serum value of procalcitonin as a marker of intestinal damages: type, extension, and prognosis. Surg Endosc. 2015;29(11):3132–3139.

Iacobellis F, Berritto D, Somma F, et al. Magnetic resonance imaging: a new tool for diagnosis of acute ischemic colitis? World J Gastroenterol. 2012;18(13):1496–1501.

Joo HH, Jo HJ, Jung TD, et al. Adipose-derived stem cells on the healing of ischemic colitis: a therapeutic effect by angiogenesis. Int J Colorectal Dis. 2012;27(11):1437–1443.

O’Neill S, Yalamarthi S. Systematic review of the management of ischaemic colitis. Colorectal Dis. 2012;14(11):e751–e763. doi:10.1111/j.14631318.2012.03171.x.

Yoon SY, Jung SA, Na SK, et al. What’s the clinical features of colitis in elderly people in long-term care facilities? Intest Res. 2015;13(2):128–134.

CODES

ICD10

K55.9 Vascular disorder of intestine, unspecified

K55.0 Acute vascular disorders of intestine

K55.1 Chronic vascular disorders of intestine

CLINICALPEARLS

Suspect IC in patients with multiple risk factors who present with abdominal pain and loose bloody stools.

Colonoscopy is the diagnostic gold standard.

Most often, IC is self-limited, responding well to conservative management with IV fluids, bowel rest, and empiric broad-spectrum antibiotics.

Peritoneal signs or lack of clinical improvement suggests more extensive ischemia and need for surgical intervention.

Right-sided IC is associated with higher morbidity and mortality.

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COLON CANCER

Jaine McKenzie, MD Asif Talukder, MD Daniel Albo,

MD, PhD

BASICS

DESCRIPTION

Colon and rectal cancers (CRC) are often grouped together but are two distinct clinical entities that differ in their prognosis, presentation, staging, and management.

CRC is the second leading cause of cancer deaths and is the third most common cancer in men and women in the United States.

Screening for colon cancer reduces the incidence of and mortality from colon cancer.

EPIDEMIOLOGY

Incidence

93,090 new cases of colon cancer in 2015

49,700 deaths from CRC combined were estimated in the United States in 2015 (1).

Incidence is equal between men and women.

Prevalence

The lifetime risk for developing colon cancer in the United States is about 1 in 21 (4.8%).

Incidence and death rates have been declining due to improved screening, prevention, and treatment.

ETIOLOGYAND PATHOPHYSIOLOGY

Progression from the first abnormal cells to the appearance of colon cancer usually occurs over 10 to 15 years, a disease characteristic that contributes to the effectiveness of prevention.

High-risk polyp findings include multiple polyps, villous polyps, and larger polyps.

Hyperplastic polyps are less likely to evolve into CRC.

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Multiple genetic and environmental factors have been linked to the development of CRC.

Genetics

<10% of CRC cases are linked to an inherited gene.

–APC, a tumor suppressor gene, is altered in familial adenomatous polyposis (FAP).

–Genes encoding DNAmismatch repair (MMR) enzymes are implicated in hereditary nonpolyposis colon cancer (HNPCC): MLH1, MSH2, MSH6, PMS1, PMS2, and others.

–STK11, a tumor suppressor gene, is altered in Peutz-Jeghers syndrome.

Sporadic cases of CRC have been linked to oncogenes: Kras, c-Myc, c-Src, HER-2/neu, and others.

RISK FACTORS

Age: >90% of people diagnosed with colon cancer are >50 years of age. Personal history of colorectal polyps

–Risk increases with multiple polyps, villous polyps, larger polyps, and presence of dysplasia.

Personal history of cancer

–30% increase in risk of developing metachronous (new primary tumors unrelated to the patients’previous cancers) colon cancer

–2–4% incidence of local recurrence with colon cancer, 3–5% incidence of synchronous colon cancer

History of inflammatory bowel disease (IBD)

–Prevalence of CRC in ulcerative colitis and Crohn disease is ~3%, with a cumulative risk of CRC of 2% at 10 years, 8% at 20 years, and 18% at 30 years.

Family history of CRC

–Having a single first-degree relative with a history of CRC increases risk 1.7-fold.

–Risk is more than double for those who have a history of CRC or polyps in: Any first-degree relative <60 years of age

≥2 first-degree relatives, regardless of age

Inherited syndromes

–HNPCC (formerly Lynch syndrome)

Often develops at young age (average age at diagnosis of CRC is 44 years)

Lifetime risk of CRC is 52–69%.

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Accounts for ~2% of all CRCs

–FAP

Affected individuals develop hundreds to thousands of polyps in colon and rectum.

CRC usually present by age 40 years

Accounts for <1% of CRCs

–Peutz-Jeghers syndrome

Individuals may have hyperpigmented mucocutaneous lesions (mouth, hands, feet) and large polyps in GI tract.

81–93% risk for CRC and increased risk for other cancers Race and ethnicity

–African Americans have the highest CRC incidence and mortality rates in the United States. It is unclear whether this is biologic or due to lower rates of access to screening.

–Colonoscopy is underutilized, particularly in minorities.

–Several different gene mutations have been identified among Ashkenazi Jews.

Lifestyle factors that increase risk

– Smoking, obesity, diet high in fat and low in fiber

GENERALPREVENTION

Optimal screening method for colon cancer is unclear. Stool based testing such as guaiac fecal occult blood test (gFOBT) and fecal immunochemical test (FIT), or FIT-DNAtests are less invasive, but endoscopic testing such as flexible sigmoidoscopy or colonoscopy offers ability to provide intervention if polyp discovered.

Compared to no endoscopic screening, screening colonoscopy has been associated with 67% relative risk reduction in death from any colorectal cancer.

Lifestyle factors that may reduce risk:

–Low-fat, high-fiber diet (rich in fruits and vegetables)

–Supplementation with vitamin D, calcium, folate, and fiber may lower CRC risk; more research is needed to understand how diet affects risks of CRC.

ALERT

The U.S. Preventive Services Task Force (USPSTF) strongly recommends screening adults, beginning at age 50 years and continuing until age 75 years and gives this an “A” Grade, meaning screening’s benefits far outweigh its harms.

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Screening methods include

–Colonoscopy every 10 years

–Flexible sigmoidoscopy every 5 to 10 years (2)[C]

–FIT annually (1)[C]

–Fecal occult blood testing annually (1)[A]

–Stool DNAtest (sDNA) every 3 years (2)[C]

–Note: The USPSTF does not recommend barium enema as a screening test and concludes the evidence is insufficient to assess the benefits and harms of CT colonography and stool DNAtesting as screening modalities for CRC. The USPSTF also recommends AGAINST screening routine screening for CRC in adults 76 to 85 years of age but acknowledges there may be considerations that support screening in certain patients and

recommends AGAINST screening those age >85 years.

American Cancer Society recommends screening with colonoscopy every 10 years. For those patients refusing colonoscopy, an alternative cancer detection tests method is recommended.

Screening in high-risk groups:

–The American Gastroenterology Society recommends screening African American patients starting at age 45 years.

–People with a history of polyps need frequent colonoscopy screening, depending on risk.

–People who have a first-degree relative or two second-degree relatives with CRC or adenomatous polyps before age 60 years should begin colonoscopy at age 40 or 10 years younger than the age of relative at cancer diagnosis, whichever is earlier.

–People with IBD should have regular surveillance colonoscopy with biopsies to detect dysplasia; guidelines generally indicate starting surveillance by 8 to 10 years of onset of symptoms followed by surveillance every 1 to 2 years.

–Genetic testing may be appropriate for individuals with a strong family history of CRC or polyps:

Family members of a person affected by HNPCC should start colonoscopy surveillance at age 25 years.

Individuals with suspected FAPshould have yearly flexible sigmoidoscopy beginning at age 10 to 12 years; those who test positive for the gene linked to FAPmay consider colectomy.

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DIAGNOSIS

HISTORY

Most patients with colon cancer are asymptomatic.

Microcytic anemia in men of any age and postmenopausal women is CRC until proven otherwise, evaluation must include diagnostic colonoscopy. Symptoms may indicate advanced disease. Common presenting symptoms include:

–Abdominal pain or cramping

–Change in bowel habits (constipation, diarrhea, narrowing of stool)

–Rectal bleeding, dark stools, or blood in stool

–Weakness or fatigue

–Unintentional weight loss

Other presentations may include symptoms due to the presence of metastatic lesions (lymph nodes, liver, lung, peritoneum), fever of unknown origin, and

Streptococcus bovis or Clostridium septicum sepsis.

PHYSICALEXAM

Signs of anemia

Weight loss

Palpable abdominal mass (late presentation)

Must include digital rectal exam

DIFFERENTIALDIAGNOSIS

>95% of colon cancers are adenocarcinomas. Other colonic tumors include carcinoid tumors, lymphomas, and Kaposi sarcoma in HIV.

Many conditions can mimic CRC, including other cancers, hemorrhoids, IBD, infection, and extrinsic masses (i.e., cysts, abscesses).

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

Should any screening method identify an increased risk, colonoscopy must be performed as it can be both diagnostic and therapeutic.

For confirmed colorectal cancer, obtain:

–CBC, ferritin to evaluate iron deficiency anemia

–CEA, LFTs

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Follow-Up Tests & Special Considerations

If CT chest, abdomen, and pelvis to evaluate presence of metastatic disease

Intraoperative US may be used to evaluate solid organs (e.g., the liver) after tumor resection.

In selected cases, positron emission tomography (PET) may be used to detect metastatic disease.

Biopsy is usually performed (most often during colonoscopy) if cancer is suspected.

CT-guided biopsy may be needed to evaluate a suspected tumor or metastasis. Staging of colon cancer

–The American Joint Committee on Cancer (AJCC) TNM staging is preferred.

Stage 0: limited to the mucosa (carcinoma in situ or intramucosal carcinoma (Tis, N0, M0)

Stage I: invades mucosa (T1) or muscularis propria (T2); no invasion of lymph nodes or distant sites (T1, N0, M0 or T2, N0, M0)

Stage IIA: invades pericolorectal tissues; no lymph nodes or distant sites (T3, N0, M0)

Stage IIB: penetrates to surface of visceral peritoneum; no lymph nodes or distant sites (T4a, N0, M0)

Stage IIC: directly invades or adherent to other organs or structures (T4b, N0, M0)

Stage IIIA: invades submucosa or muscularis propria with spread to 1 to 3 lymph nodes; no distant sites (T1, N1, M0 or T2, N1, M0)

Stage IIIB: invades pericolorectal tissues or surface of visceral peritoneum + spread to 1 to 3 lymph nodes; no distant sites (T3, N1, M0, or T4a, N1, M0)

Stage IIIC: invades pericolorectal tissues or peritoneum or other organs and to ≥4 nearby lymph nodes; no distant sites (any T3 or T4, N2, M0)

Stage IVA: any level of invasion with spread to one organ or site (any T, any N, M1a)

Stage IVB: any level of invasion with spread to more than one organ or site or peritoneum (any T, any N, M1b)

TREATMENT

Colon cancer is typically treated with surgery and chemotherapy.

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Data suggest multidisciplinary communication among providers of colon cancer patients can improve cancer survival.

SURGERY/OTHER PROCEDURES

Surgery is the primary treatment for localized colon cancer.

–Minimally invasive (i.e., laparoscopic) surgery has fewer complications, less blood loss, shorter hospital stay, less time to bowel movement, and lower 30-day mortality when compared to open surgery with equivalent oncologic outcomes. This approach allows patients to have less pain and faster recovery. For health systems, decreased length of stay and fewer complications improves the cost of care (3).

–There are no significant differences between minimally invasive and open

colorectal surgery in long-term survival and recurrence rates (3).

Radiation therapy is most often used for peritoneal cancers; it may also be used to relieve symptoms.

ADDITIONALTHERAPIES

Adjuvant chemotherapy is most clearly beneficial for stage III (node-positive) disease, in which improvements of 30% can be achieved in both disease recurrence and overall survival, compared with untreated controls. Chemotherapeutic regimens for metastatic disease may extend overall survival from 6 months to 2 years (2)[B].

First-line therapy includes combination chemotherapy with oxaliplatin, irinotecan, fluorouracil, leucovorin, and capecitabine.

Targeted therapies may be used alongside first-line agents or alone if first-line agents are ineffective.

Bevacizumab (Avastin) is a monoclonal antibody that targets vascular endothelial growth factor (VEGF); inhibits angiogenesis

Cetuximab (Erbitux) and panitumumab (Vectibix) are monoclonal antibodies that target epidermal growth factor receptor (EGFR).

Aflibercept and regorafenib are newer agents with actions on VEGF.

ONGOING CARE

FOLLOW-UPRECOMMENDATIONS

Patient Monitoring

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Risk of recurrence is greatest in the first 2 to 4 years after treatment; 80% occur in first 2.5 years from date of surgery.

H&Pand CEAshould be performed every 3 to 6 months for 5 years.

Annual CT scan of chest, abdomen, and pelvis for 3 years

Surveillance colonoscopy 1 year after initial surgery. Subsequent colonoscopies should generally be every 5 years if findings are normal.

In obstructive colon cancer precluding from preoperative colonoscopy, recommend colonoscopy within 3 to 6 months after surgery to detect synchronous cancer and complete resection of precancerous polyps.

CEAis used to detect recurrences after resection of primary colon cancer. CEAlevels decrease and normalize within 4 to 6 weeks after surgery. Persistent elevation of CEAlevels can suggest incomplete resection or occult metastasis. Elevated CEAshould raise suspicion for recurrent disease, and adjustments of routine surveillance program should be undertaken (4,5).

PROGNOSIS

5-year relative survival rate after surgical resection alone (6):

Stage I: 85–95%

Stage II: 60–80%

Stage III: 30–60%

Stage IV: 25–40% following resection of hepatic metastases with clear margins

COMPLICATIONS

Surgery: pain, deep vein thrombosis (DVT), anatomic leaks, wound infection, incisional hernia. Incidence complications are lower with minimally invasive (i.e., laparoscopic) approach.

Chemotherapy: hair loss, nausea, vomiting, bruising, fatigue, increased risk for infections

Radiation therapy: skin irritation, nausea, rectal pain, incontinence, bladder irritation, fatigue, and sexual problems

PATIENT EDUCATION

NIH: Colorectal Cancer: http://www.nlm.nih.gov/medlineplus/colorectalcancer.html

NCI: Colorectal Cancer: http://www.cancer.gov/types/colorectal

AAFP: Colorectal Cancer: http://www.aafp.org/afp/2015/0115/p93-s1.html

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