Table of contents
- 1. Microscopic Colitis
- 2. Mesenteric Ischemia
- 2.1. Acute
- 2.2. Chronic
- 2.3. Colonic Ischemia
- 3. Toxic Megacolon
- 4. Notes on Constipation
- 5. Diverticular Disease
- 5.1. Diverticulitis
- 6. ALARM Features requiring Colonoscopy
- 7. Colorectal Cancer
- 7.1. Types of Polyps
- 8. Colon Cancer Surveillance Guidelines
- 8.1. Summary
- 8.2. Polyp Follow-Up
- 8.3. Screening - Average Risk
- 8.4. Screening - Increased Risk
- 8.4.1. IBD Screening
- 8.5. Hereditary Non-Polyposis Colorectal Ca
.
Microscopic Colitis
- Definition:
- Histologic inflammation in endoscopically normal-appearing colon.
- Features of fat malabsorption, and vitamin deficiencies should not be seen.
- Mild weight loss, dehydration
- Pathology:
- Intra-epithelial lymphocytes in colonic mucosa.
- Two types: Lymphocytic colitis, and collagenous colitis (collagenous band)
- Causes:
- Medications
-
Drugs That May Cause Microscopic Colitis
High Likelihood
Acarbose, Aspirin, Lansoprazole (possibly other PPIs),
NSAIDs, Ranitidine, Sertraline, Ticlopidine
Intermediate Likelihood
Carbamazepine, Flutamide, Lisinopril, Levodopa
with benserazide, Paroxetine, Simvastatin
Low Likelihood
Cimetidine, Gold Salts
Source: Beaugerie L, Pardi DS. Review article: drug-induced
microscopic colitis - proposal for a scoring system and review
of the literature. Aliment Pharmacol Ther. 2005;22(4):277-284. PMID: 16097993
-
- Systemic Disease
- Medications
- Clinical Features:
- Hallmark: "Painless watery diarrhea, no bleeding"
- Often referred for chronic large-volume diarrhea.
- **nocturnal stools**.
- Not as much abdominal pain.
- Diagnosis:
- Colonoscopy with random biopsies.
- Treatment:
- Review Medications (over counter + rx)
- R/O Celiac Disease
- Medical Therapy:
- Mild Disease:
- Loperamide
- Diphenoxylate
- Moderate Disease
- Bismuth subsalicylate
- Severe Disease:
- Budesonide (Delayed-release)
- Stopping budesonide has high recurrence rates > 80%. Sometimes may need to continue low-dose budesonide or steroid sparing (azathioprine, etc..)
- Mild Disease:
Mesenteric Ischemia
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.
- Interventional Radiology (Angiography - gold standard to diagnose)
- 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
- Abdominal pain 30min after eating. (Diversion of small bowel blood flow to stomach)
- 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.
- Acute onset mild crampy abdo pain, with tenderness on exam over affected colonic region.
- 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)
- Supportive Care
Toxic Megacolon
- Diagnosis:
-
Diagnostic Criteria for Toxic Megacolon
1. Radiologic Evidence of Colonic Distension
(Usually cited >6cm colon, usually transverse)
2. PLUS (3 of following)
- Fever > 38°C
- Heart Rate > 120 bpm
- Neutrophils > 10,500/uL
- Anemia
3. PLUS (ONE of following)
- Dehydration
- Altered sensorium
- Electrolyte Disturbances
- Hypotension
-
- Management:
- Resuscitation & Monitoring (NPO!)
- NG tube decompression (only if vomiting, or gas-filled stomach)
- Consider broad-spectrum antibiotics (ulcerated colonic mucosa can cause invasion of bacteria)
- cipro flagyl, pip-tazo, carbapenems.
- If concerned for C.Diff --> PO vanco + IV flagyl (or fidaxomicin)
- Consider IV Steroids in Inflammatory Colitis
- Does not increase rate of colonic perforation, but can mask it.
- Taper after resolution.
- Surgery!
- If no improvement in 24-48hrs of conformed dx --> indication for surgery
Notes on Constipation
- Slowly introduce fibre, fluids.
- PEG is superior to other osmotic agents (more frequency, form).
- Magnesium antacids helpful, but careul if impaired renal function.
- Methylnaltrexone - chronic opioids
- Biofeedback therapy (dyssynnergic defecation, pelvic floor dysfunction)
Diverticular Disease
- Colonic diverticulosis is common:
- 40% by age 60, 60% by age 80
- Distal colon most often affected (sigmoid + descending) (in Asians --> more proximal + Cecal)
- 1 to hundreds of diverticuli (5-10mm in diameter)
- Pathophysiology:
- Anatomic factors (weakness in vaso-recta penetration of colon wal)
- Motility factors (poor haustral contractions)
- Dietary causes (Decreased fiber intake)
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
- If not obvious clinically:
- 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
- Liquid Diet
- Broad Spectrum Antibiotics
- Analgesia
ALARM Features requiring Colonoscopy
- Blood in stool
- Weight loss
- Sudden change in bowel habits
- FHx of Colon Ca
- New Constipation age >50
Colorectal Cancer
- Worldwide 3rd in cancer incidence and 4rth in mortality
- Black patients have higher colorectal cancer incidence + mortality.
- Risk Factors:
- Environmental:
- Red meat consumption (Especially when charred - high temperature cooking)
- Cigarette Smoking
- Alcohol >30g/day (3 drinks/day)
- Predisposing Conditions:
- BMI > 30 (growth hormone mediated)
- IBD (duration important, and amount of colitis - pancolitis vs. left-only)
- Famiy History (esp if <50yo)
- Type II DM (high insulin + insulin-like growth factors) - 30% higher risk.
- Cholecystectomy (changes in bile secretion)
- Ureterosigmoidostomy (500x)
- Nonsyndromic Family History
- Complex, ask about polyps too (relationship of family members, age of dx, number of relatives)
- Environmental:
- Reducing Risk:
- Physical Activity
- Calcium supplements --> modest favourable effect (but toxicity common)
- Diets high in fruits, vegetables, fiber --> reduced risk (prevention benefits not demonstrated)
- Folate --> limited data for potential benefit (query accelerated tumor growth)
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
Colon Cancer Surveillance Guidelines
- For overview of genetic risk factors (FAP/HNPCC, etc..) visit: Oncology > Mutations 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
- Detection of pre-malignant CRC
- Screen at 50yo (90% of colon ca. occur after age 60)
- 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:
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)
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