Colon

Acute

• SEVERE PAIN out of proportion on exam
• Small bowel or colon can be affected.  (Colon is most common)
• Symptoms:
  • Main symptom: PAIN (from mild/crampy to severe surgical emergency)
  • Suspect if PAIN on history, but abdominal exam shows less tenderness than expected.
  • ===> AKA "Pain Out of Proportion To Physical Exam"
• Causes:
  • Embolic: Usually embolic phenomenon - often SMA (either atrial embolism or thrombus in ventricle)
  • Non-Occlusive Ischemia:
    • Can get through hypoperfusion (i.e. splancnic vasoconstriction, or hypotension after acute MI)
    • "Non-Occlusive mesenteric ischemia"
• Risk Factors:
  • >50yo, underlying cardiovascular disease
  • If young (vasoactive med - cocaine use, tryptans etc.)
• Investigations:
  • Labs: Elevated WBC, Lactate, metabolic acidosis (suggests bowel compromise)
  • Abdo Xray: can be normal if early, but can show dilated loops of bowel, and "Thumbprinting" of bowel or R colon.
  • Ultrasound: Limited role, only for proximal origin of vessels.
  • CT: "Intestinal pneumotosis" (air in bowel wall)
    • Thickening of the bowel wall (Crohn's can also cause thickening)
    • (CT can be normal early, and findings can show necrotic bowel)
  • CT/MR-based Angiography
    • Better diagnose acute ischemia (earlier) - find vascular distribution.
    • Cannot treat.
  • Angiography: **Gold Standard**
    • Invasive, but best accuracy, and can intervene to re-open. 
• Management:
  • Resuscitation  (electrolytes, acidosis management, NG decompression)
  • D/C meds associated with vasoconstriction (ergots, cocaine, vasopressors, tryptans, etc..)
  • Antibiotics (high frequency of sepsis)
  • Anticoagulants: (Controversial) - usually for mesenteric vein thrombosis
    • Usually post-surgery (x7-10 days improves survival, decreases recurrence)
    • Typically bridge to warfarin x3-6mo
  • If No Peritonitis:  (usually endovascular, but can be open)
    • Interventional Radiology (Angiography - gold standard to diagnose)
      • Embolectomy/thrombectomy & revascularization (surgery or endovascular stent)
      • Local thrombolysis for incomplete embolectomy or distal embolization.
      • Papaverine (Phosphodiesterase inhibitor) - can be given at time of angiography to help open arteries.
  • If Peritoneal Signs:
    • Surgery  (to resect necrotic bowel)
  • Surgery also if there is a high index of concern for AMI despite negative imaging studies
    • Surgical revascularization is also definitive treatment for non-occlusive mesenteric ischemia.

Chronic

• Aka "Intestinal Angina" 
• Caused by intestinal atherosclerosis
• Symptoms:
  • Abdominal pain 30min after eating. (Diversion of small bowel blood flow to stomach)
    • Food avoidance - Can cause "siderphobia" - fear of eating
  • Eventually: Pain without eating
  • Rarely cause intestinal infarction
• Diagnosis:
  • Imaging + clinical history.
  • Doppler ultrasound (Screening test, cannot confirm Dx, esp poor if obsese)
  • MR + CT angiography more sensitive + specific
  • Abnormal study warrants --> confirmatory splanchnic angiography
• Treatment:
  • Surgical revascularization (like CABG)
  • Percutanous angioplasty +/- stenting (if poor surgical candidates)
    • Short-term success is high, but long-term recurrence is high (compared to surgical bypass)

Colonic Ischemia

• Vast majority of intestinal ischemia (75%) is colonic ischemia
  • Severity from mild transient reversible colitis --> gangrene fulminant colitis (high mortality)
• Most common sites: "watershed regions" at splenic flexture + retrosigmoid junction (desc. colon + sigmoid)
  • Rectum has dual supply, rarely affected.
• Causes:
  • Arterial - Hypoperfusion (decreased output - arrhythmias, sepsis, shock, thrombotic, embolic - cholesterl arterial etc...)
  • Drug-induced
    • Cocaine, digoxin, estrogen, pseudoephedrine
  • Post-operative
    • CABG, Abdominal aortic surgery
  • Vasculitis - SLE
  • Hypercoagulable state - Protein C/S deficiency, AT3, FVL, etc..
• Symptoms:
  • Acute onset mild crampy abdo pain, with tenderness on exam over affected colonic region.
    • Can get colonic bleeding, if it's a few days of onset.
• Diagnosis:
  • Abdomen Xray  or CT (can be normal), look for Thumbprinting
  • Flexible Sigmoidoscopy or Colonoscopy (***Gold Standard***)
• Treatment:
  • Supportive Care
    • IV Fluids
    • Broad spectrum abx.
  • Treat causative agent (stop drugs, etc..)
  • Peritoneal findings / shock requiring colectomy is very rare
    • (usally patients recover well)

Diverticulitis

• 1 in 5 at least one episode.
• Clinical Features:
  • Leukocytosis, Fever, LLQ pain
  • Other: Loss of appatite, nausea, vomiting, dysuria, abdo mass, guarding, rebound tenderness
• DDx: Appendicitis, crohn's, colorecal cancer, ischemic colitis, ovarian cyst (abscess/torsion), ectopic pregnancy.
• Diagnosis:
  • If not obvious clinically:
    • Abdominal-Pelvic CT is test of choice
  • Colonoscopy or Flexible Sigmoidoscopy relatively contraindicated --> procedure induced perforation
• Management

  • Natural History / Management of Diverticulitis

    Subgroup	Features	Management
    Isolated, uncomplicated	Solitary episode of acute diverticulitis	Antibiotics, bowel rest, analgesia
    Recurrent, uncomplicated	Multiple discrete episodes of acute diverticulitis	Surgical resection on a case-by-case basis
    Complicated	Acute diverticulitis with abscess, fistula, obstruction, perforation, or stricture	- Antibiotics - Percutaneous drainage - Endoscopic stent  (temporizing measure, to make surgery elective) - Surgical resection
    Smoldering	Acute diverticulitis with ongoing, chronic symptoms	Antibiotics, surgical resection
    - Abx should cover gram-negative rods and anaerobic bacteria.     - Outpatient abx for mild symptoms     - Inpatient IV therapy for severe symptoms or complicated disease Source: MKSAP 16 - Gastroenterol Clin North Am. 38(3). Touzios JG, Dozois EJ. Diverticulosis and acute diverticulitis; 513-525.

    
     
  • Once acute diverticulitis has resolved --> Need to scope to r/o other dx (Crohn's, Adenocarcinoma)
  • Surgery offered to immunocompromized patients even after one episode (high risk of complications)
  • NOTE: Nuts, popcorn, corn, etc... does not cause diverticulitis (from large cohort studies)
• Outpatient Management of Mild Diverticulitis

1. Liquid Diet
2. Broad Spectrum Antibiotics
3. Analgesia

Types of Polyps

• NOTE: Serrated Colorectal Polyps (WHO classification):

  • 1.  Hyperplastic Polyps 

  • 2.  Sessile Serrated Polyps

  • 3.  Traditional Serrated Adenomas

• Polyp Type	Prevalence	Appearance	Malignancy Risk	Notes
  Hyperplastic Polyps	VERY COMMON	Sessile/Flat	NO!
  Sessile Serrated Adenoma	COMMON	Sessile/Flat		15% of colorectal ca starts as SSP
  No Dysplasia			LOW
  Dysplasia			YES
  Traditional Serrated Adenomas			YES

• See "high risk screening" section

Summary

• If Average Risk -->
  • Screen at 50yo (90% of colon ca. occur after age 60)
    • Colonoscopy q10y
    • Flex sig q5y
    • FOBT q1y
  • Two categories:
    • Detection of pre-malignant CRC
      • Flex-sig, Barium Enema, Colonoscopy, CT colonography
    • Detection of CRC
      • Fecal Assays
• If Higher Risk:
  • 1st deg. relative with CRC  --> screen at 40yo or 10y prior to diagnosis q5y Colonoscopy
  • IBD involving 1/3 of colon --> Screen 8y post-diagnosis, colonoscopy q1-2y
    • If PSC diagnosed --> Screen right away, q1y

Polyp Follow-Up

• 1 or more adenomas detected during CRC screening evaluation --> increased risk of advanced CRN
  • Low Risk (1-2 adenomas, <1cm, tubular morphology, and low-grade dysplasia) --> colonoscopy in 5 years
  • High Risk (≥3 adenomas, ≥1cm, villous morphology, or high-grade dysplasia) --> colonoscopy in 3y
  • IF >10 ademonas --> repeat colonoscopy in <3y, consider hereditary syndrome.
  • LARGE adenomas --> repeat in 2-6mo to ensure complete resection.
  • IF small, hyperplastic, rectal polyps (not hyperplastic polyposis syndrome) --> average screening.

• AGA Guidelines 2012:

• 

Screening - Average Risk

• Colorectal Cancer Screening Guidelines for Average-Risk Persons

  Screening Option	ACP	ACS-USMSTF-ACR	USPSTF	Screening Intervala
  Guaiac fecal occult blood testing	Recommended	Recommended if >50% sensitivity for CRC	Recommended	1 year
  Fecal immunochemical test	Recommended	Recommended if >50% sensitivity for CRC	Recommended	1 year
  Stool DNA test	Recommended	Recommended if >50% sensitivity for CRC	Not recommended owing to insufficient evidence	Uncertain
  Flexible sigmoidoscopy	Recommended	Recommended if sigmoidoscope is inserted to 40 cm of the colon or to the splenic flexure	Recommended, with fecal occult blood test every 3 years	5 years
  CT colonography	Uncertain	Recommended, with referral for colonoscopy if polyps ≥6 mm in diameter are detected	Not recommended owing to insufficient evidence	5 years
  Colonoscopy	Recommended	Recommended	Recommended	10 years
  Barium enema	Not recommended	Recommended, but only if other endorsed options are not available	Not recommended	5 years
  ACP = American College of Physicians ACS-USMSTF-ACR = American Cancer Society, U.S. Multi-Society Task Force on Colorectal Cancer, and American College of Radiology; USPSTF = U.S. Preventive Services Task Force. Reprinted from Gastroenterology. 138(6). Lieberman D. Progress and challenges in colorectal cancer screening and surveillance; 2115-2126.

  
   

• Exam	Notes
  Guaiac fecal occult blood testing (GFOBT)	Changes color in presence of peroxidase: Found in human blood Found in incompletely cooked meat + other dietary sources Proper collection: 2 samples from 3 consecutive stools (6 total) - at home, mail to clinical lab. Must use "High Sensitivity" GFOBT test RCTs: Statistically significant reductions in CRC (incidence 17-20% reduction, mortality 15-33% reduction) Limitations: Low sensitivity for advanced adenomas, diet/medication interacttions (FP + FN), annual testing, needs diagnostic f/u if positive. If any positive ---> colonoscopy
  Fecal Immunohistochemical Test (FIT Assay)	Antibodies directed against human globin protein (improves specificity over GFOBT) Advantages: No Pre-test dietary restrictions Single test is ok
  Stool DNA Test (sDNA testing)	- Unlike FOBT< sDNA assays target molecular alterations directly from the lesion. - Entire stool specimen (30g minimum) must be submitted - Two prospective screening studies --> moderate sensitivity for (25-58%) for CRC. - Not routinely available in US.
  Flexible Sigmoidoscopy	- Lower colorectum, up to 60cm. - Limited bowel prep required (2 enemas), no conscious sedation (can have sedation though). - If find adenomas any size or polyps larger than 5mm --> should get full colonoscopy. - Screening benefits only in examined segment (mortality down 60%) - Proximal neoplasia more common in black patients and older women --> often need direct colonoscopy for those pts. - Bowel perforation <1 in 20,000 exams.
  CT Colonography	- Entire colorectum, + limited extra-colonic structures - Dietary restrictions + oral contrast required. - During exam - small catheter placed to insufflate colon with room air or CO2 (no sedation) - Compared with colonoscopy, estimated Sens >90% for CRC, and 85-93% for polyps ≥1cm - Bowel perforation possible <1:10,000 exams
  Colonoscopy	- Entire colorectum - Dietary restrictions + full prep required prior  + Sedation - Theraputic polypectomy can be done.  - q10years if ideal visualization      - If poor or suboptimal prep --> should repeat ASAP before planning longer term suveillance Miss rates are 5% for CRC, 2-12% for polyps ≥1cm, ≥20% polyps ≥6mm - Risks:    - bleeding (2-6:1000), bowel perforation (1:1000)

Screening - Increased Risk

• Colorectal screening guidelines provided...

• NOTE: Serrated Colorectal Polyps (WHO classification):

  • 1.  Hyperplastic Polyps 

  • 2.  Sessile Serrated Polyps

  • 3.  Traditional Serrated Adenomas

  • Polyp Type	Pre-Malignant?	Notes
    Hyperplastic Polyps	NO!
    Sessile Serrated Polyps	YES	15% of colorectal ca starts as SSP
    Traditional Serrated Adenomas	YES

• Colorectal Cancer Surveillance for Patients at Increased Risk

  Patient Group	Preferred Test	Onset	Surveillance Interval	Other Considerations
  Inflammatory Bowel Disease (as long as 1/3 of distal colon is involved)
  UC, pancolitis	Colonoscopy	IBD duration >8 years	1-2 years
  UC, distal colitis	Colonoscopy	IBD duration >8 years	1-2 years
  UC, proctitis	Colonoscopy	IBD duration >8 years	10 years
  Crohn disease, ≥1/3 of colon involved	Colonoscopy	IBD duration >8 years	1-2 years
  With PSC	Colonoscopy	At PSC diagnosis	1 year
  Nonsyndromic Family History
  1 first-degree relative with CRC	Colonoscopy	Age 40 years or age 10 years before youngest age at CRC diagnosis in the family, whichever is younger	5 years
  Hereditary Cancer Syndromes
  Lynch syndrome	Colonoscopy	Age 20-25 years	1-2 years	Transvaginal ultrasound or endometrial aspirate at age 25-30 years, repeat every 1 year (women) Urine cytology at onset of CRC screening, repeat every 1 year Upper endoscopy screening may be offered in families with gastric cancer
  Familial CRC type X	Colonoscopy	Age 5-10 years before youngest age at CRC diagnosis in the family	3-5 years
  Familial adenomatous polyposis, classic	Flexible sigmoidoscopy - Only one with flex sig (distal bowel  in classic)	Age 10-12 years	1 year	Abdominal ultrasound and serum α-fetoprotein, age 0-6 years, repeat every 1 year Upper endoscopy (with side-viewing examination of the duodenal papilla) when CRN detected or by age 25 years, repeat every 1-3 years Palpation of thyroid gland, repeat every 1 year
  Familial adenomatous polyposis, attenuated	Colonoscopy	Age 5-10 years before youngest age at CRC diagnosis in the family	1 year
  MYH-associated polyposis	Colonoscopy	Age 25-30 years	3-5 years	Upper endoscopy (with side-viewing examination of the duodenal papilla) at age 30-35 years, repeat every 3-5 years
  Peutz-Jeghers syndrome	Colonoscopy	Age 25 years	2-3 years	Upper endoscopy and small-bowel radiography at age 10 years, repeat every 2 years Testicular exam at age 10 years, repeat every 1 year (men) Pelvic exam with cervical smear at age 20 years, repeat every 1 year (women) Mammography at age 25-35 years, repeat every 1 year (women)
  Juvenile polyposis	Colonoscopy	Age 12 years	3 years	Upper endoscopy by age 15 years, then repeat every 1-3 years
  Hyperplastic polyposis	Colonoscopy	Age 40 years	5 years
  CRC = colorectal cancer; CRN = colorectal neoplasia (adenoma or adenocarcinoma); IBD = inflammatory bowel disease; PSC = primary sclerosing cholangitis; UC = ulcerative colitis. Source: MKSAP 16

Hereditary Non-Polyposis Colorectal Ca

• Most common type of hereditary colorectal cancer. (2-3% of cases)
• Autosomal dominant.
• Lifetime risk of colorectal Ca is 80% (mean dx 44yo)
• Types of Malignancies:
  • Colorectal Cal (Lifetime risk 80%)
  • Endometrial Cancer (30-60%) - 2nd most common
  • Gastric
  • Biliary tract
  • Urinary tract, Ovarian, Small bowel cancer.
• Diagnosis:
  • Pedigree analysis +/- molecular testing
  • Amsterdam criteria III

  • Criteria for Hereditary Nonpolyposis Colorectal Cancer Screening

    Amsterdam Criteria II Suspect HNPCC if all criteria are met. Used to identify families likely to represent HNPCC.
    ≥3 relatives with an HNPCC-associated cancer
    ≥2 successive generations affected
    ≥1 first-degree relative of at least 2 other cancer cases
    ≥1 cancer diagnosed before age 50 years
    Revised Bethesda Guidelines Proceed with microsatellite instability testing if any criterion is met. Used to select colorectal cancer cases for molecular analyses of the DNA mismatch repair system.
    Colorectal cancer diagnosed in a patient less than 50 years of age
    Presence of synchronous, metachronous colorectal or other HNPCC-associated tumors, regardless of age
    Colorectal cancer with the MSI-H (Microsatalite instability high) histology diagnosed in a patient less than 60 years of age
    Colorectal cancer diagnosed in one or more first-degree relatives with an HNPCC-related tumor, with one of the cancers diagnosed under age 50 years
    Colorectal cancer diagnosed in two or more first- or second-degree relatives with HNPCC-related tumors, regardless of age
    Gastroenterology. 116(6). Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC; 1453-1456.  Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96(4):261-268

  •  
  • Others:
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  Syndrome	Notes
  Hereditary Non-Polyposis Colorectal Ca (HNPCC)	- Most common - 80% risk of lifetime colorectal cancer
  Familial Adenomatous Polyposis (FAP)	- APC gene (autosomal dominant) mutations - Hundreds to thousands of polyps (16yo mean) --> almost all get CRC (mean 39yo) - Duodenal carcinoma (4-12%), Gastric Ca, papillary thyroid ca, etc... - Mutational analysis to confirm diagnosis
  Attenuated familial adenomatous  polyposis (AFAP)	- <100, proximal colorectal adenomas - Cumulative CRC (70%) rather than 100% in FAP
  MYH-Associated Polyposis	- Heterozygous or homozygous mutation in MYH gene (base excision repair) - Autosomal recessive - Resembles AFAP, and broader extra-colonic neoplasia - Genetic testing not yet routinely performed.
  Peutz-Jeghers Syndrome	- Autosomal Dominant  - Mucocutaneous melanocytic macules, usually peri-oral and buccal mucosal and  GI hemartomatous polyps  (abdo pain, bleeding obstruction, intususception) - Genetic test exists
  Juvenile Polyposis Syndrome
  Hyperplastic Polypsosi (HPP)