Small bowel and colonic disease

Question 1

Inflammatory bowel disease

Answer 1

IBD (general):

Overview:

• IBD is a group of chronic disorders characterised by inflamed and damaged tissues in the lining of the intestinal tract.
• Thought to be due to an autoimmune process that has been triggered by a genetic predisposition, a viral illness, and/or an environmental factor.
• characterised by flare-ups (bouts of watery and/or bloody diarrhoea, abdominal pain, weight loss, fever) of active disease that alternate with periods of remission.

Labs:

• Faecal calprotectin is elevated. Fecal calprotectin levels are increased in intestinal inflammation and may be useful for distinguishing inflammatory (IBD, infections) from noninflammatory (IBS) causes of chronic diarrhea. Calprotectin is a protein released by neutrophils and monocytes (mainly a marker of neutrophil activity). Also used to monitor disease activity in IBD.
• Faecal lactoferrin test is an agglutination assay that is a marker for fecal leukocytes. Similar to calprotectin, is useful to suspect/monitor IBD.
• CRP and ESR elevated

Histopath:

• positive inflammatory markers –> proceed to ileocolonoscopy and biopsy to confirm IBD

Crohn’s disease

Ulcerative Colitis

Description:

• characterized by recurring episodes of inflammation limited to the mucosal layer of the colon. Commonly involves the rectum. Extends proximally and continuously to involve other parts of the colon.

Presentation:

• gradual, progressive symptoms over several weeks. Ranges from mild to severe disease
• Colitis: diarrhea (small volume, frequent) +/- blood due to rectal inflammation; colicky abdominal pain, urgency, tenesmus, and incontinence
• constipation accompanied by frequent discharge of blood and mucus is seen in patients with mainly distal disease
• systemic symptoms including fever, fatigue, and weight loss.
• symptoms of anaemia and malnutrition

Disease severity:

• Mild: <or></or>

<p>- <u>Moderate</u>: &gt;4 per day loose, bloody stools, mild anemia, moderate abdo pain, mild systemic syx (low-grade fever)</p>

<p>- <u>Severe</u>: ≥6 per day loose, bloody stools. Severe cramps and evidence of systemic toxicity (T &gt;37.5degC, tachycardia, anaemia, elevated ESR), rapid weight loss. </p>

<p><strong>Complications</strong>:</p>

<p>- Severe bleeding / Massive hemorrhage</p>

<p>- Fulminant colitis and toxic megacolon</p>

<p>- Perforation</p>

<p><strong>Extra-intestinal manifestations:</strong></p>

<p>- Arthritis (most common), large joints and ankylosing spondylitis </p>

<p>- osteoporosis, osteopenia, and osteonecrosis</p>

<p>- Eye: uveitis and episcleritis. Scleritis, iritis, and conjunctivitis may also occur.</p>

<p>- skin: erythema nodosum (red nodular areas) and pyoderma gangrenosum (pustular and violaceous plaque)</p>

<p>- Hepatobiliary: Primary sclerosing cholangitis, fatty liver, and autoimmune liver disease have been associated with IBD.</p>

<p>- Hematopoietic/coagulation: venous and arterial thromboembolism. Autoimmune hemolytic anemia. </p>

<p>- Pulmonary: airway inflammation, parenchymal lung disease, serositis, and thromboembolism (PE)</p>

<p><strong>Labs</strong>:</p>

<p>- anaemia, ESR &gt;or=30, low albumin, electrolyte disturbance (due to diarrhoea)</p>

<p>- raised ALP if PSC present</p>

<p>- elevated Fecal calprotectin or lactoferrin (non specific GI inflamm)</p>

<p><strong>imaging</strong>:</p>

<p>- not required</p>

<p>- CT/MRI: mucosal thickening or "thumbprinting" secondary to edema. Colonic dilation (if severe). Less sensitive than barium enema. </p>

<p>- barium enema: diffusely reticulated pattern with superimposed punctate collections of barium in micro ulcerations. In severe disease: spiculated collar button ulcers, shortening of the colon, loss of haustrae, narrowing of the luminal caliber, pseudopolyps, and filiform polyps</p>

<p><strong>Endoscopy</strong>:</p>

<p>- loss of vascular markings due to engorgement of the mucosa, giving it an erythematous appearance.</p>

<p>- The biopsy features suggestive of ulcerative colitis include crypt abscesses, crypt branching, shortening and disarray, and crypt atrophy. Epithelial cell abnormalities inc mucin depletion and Paneth cell metaplasia.</p>

<p><strong>DDx</strong>:</p>

<p>- Crohns</p>

<p>- infectious colitis </p>

<p>- radiation colitis </p>

<p>- diverticular colitis</p>

<p>- GVHD</p>

</or>

Question 2

Coeliac Disease

Answer 2

Description:

• gluten-sensitive enteropathy
• immune-mediated inflammatory disease of the small intestine caused by sensitivity to dietary gluten and related proteins in genetically predisposed individuals.

Epi:

• presents between the ages of 10 and 40 years

Pathophys:

• genetics: DR3-DQ2 (esp homozygous) and/or DR4-DQ8 gene locus present in HLA gene
• Gliadin reactive T cell (adaptive immune) cells in the lamina propria recognize gliadin peptides bound to HLA-DQ2 or -DQ8 on antigen-presenting cells.
• Tissue transglutaminase (intracellular enzyme) increases the immunogenicity of gluten peptides, enhancing their binding to HLA-DQ2 and -DQ8, which potentiates their capacity to stimulate T-cells
• Autoantibodies to tissue transglutaminase block intestinal epithelial differentiation
• Innate responses to wheat proteins (in addition to gluten-mediated activation of pathogenic T-cells) are also involved

Associated conditions / groups at risk:

• type 1 diabetes mellitus
• autoimmune thyroiditis
• Down and Turner syndromes
• Pulmonary hemosiderosis (moderate risk)

Different types/ classification

• Classic coeliac’s: diarrhea and/or signs and symptoms of malabsorption (eg, steatorrhea, weight loss, or other signs of nutrient or vitamin deficiency)

resolution of the mucosal lesions and symptoms (weeks to months) upon withdrawal of gluten-containing foods

• Atypical celiac disease: lack classic symptoms of malabsorption but may exhibit minor gastrointestinal complaints. Do have villous atrophy in duodenal biopsies and display positive celiac antibodies, prominently against tissue transglutaminase
• Subclinical or asymptomatic disease. Usu identified during endoscopy performed for other indications, or by serological screening
• Potential celiac disease: +ve celiac-specific serum antibodies but normal duodenal mucosal biopsy.
• Latent celiac disease: presented with celiac disease in the past, usually diagnosed in childhood, but who recovered completely with a gluten-free diet and remained “silent” even once a normal diet was resumed
• Refractory disease: persistence of symptoms and villous atrophy despite adherence to a gluten-free diet. Mostly due to poor dietary compliance or other underlying malabsorptive disorders.

Clinical presentation (GI and extraintestinal):

• GI manifestIations: diarrhea with bulky, foul-smelling, floating stools due to steatorrhea and flatulence
• Manifestation of malabsorption: weight loss, severe anemia, neurologic disorders from deficiencies of B vitamins, and osteopenia from deficiency of vitamin D and calcium.
• Skin: Dermatitis herpetiformis (multiple intensely pruritic papules and vesicles that occur in grouped “herpetiform” arrangements). The elbows, dorsal forearms, knees, scalp, back, and buttocks are among the most common sites for lesion development
• mucous mem: Atrophic glossitis –Oral lesions (erythema or atrophy) and a soreness or burning sensation of the tongue
• Metabolic bone disorders: osteomalacia due to vitamin D deficiency leading to secondary hyperparathyroidism
• Haem: Iron deficiency anemia, Hyposplenism
• neuropsychiatric: headache, peripheral neuropathy, ataxia, epilepsy, depression, dysthymia, and anxiety

Endoscopy:

• The histologic severity ranges from a mild alteration characterized by increased intraepithelial lymphocytes (type 1 lesion) to a flat mucosa with total mucosal atrophy, complete loss of villi, enhanced epithelial apoptosis, and crypt hyperplasia (type 3 lesion)
• Decreasing severity from the proximal to the distal small intestine.
• The severity of histologic changes in the small bowel does not necessarily correlate with the severity of clinical manifestations

Question 3

GI bleeding

Answer 3

Minimal bright red blood per rectum

• small amounts of red blood on toilet paper after wiping OR a few drops of blood in the toilet bowl after defecation. This is called ‘outlet type’ bleeding
• benign causes make up 90% of cases

Causes:

• Hemorrhoids 27-95 % of cases. Painless bright red bleeding at the end of defecation, drip into the toilet or stain toilet paper
• Anal fissures: tearing pain with the passage of bowel movements, bright red small PR bleeding on the toilet paper or on the surface of stool. Occasional perianal itch.
• Distal polyps (inc adenomatous polyps): asymptomatic, mostly detected by CRC screening tests. Colorectal neoplasms (mostly adenomas) are found in 16 % of pts who were concurrently diagnosed with an anorectal source of bleeding
• proctitis or proctosigmoiditis: gradual onset, intermittent rectal bleeding, mucus, and mild diarrhea (<4 x per day)
• Rectal ulcers: bleeding, mucus, straining during defecation, a sense of incomplete evacuation
• symptomatic Colorectal cancer: hematochezia, abdominal pain, and/or a change in bowel habits. Can have pain with defectation.

Work up:

• DRE / PR exam and ask pt to bear down (may induce prolapse of haemorrhoid)
• FBE, ferritin if >40yo, coags
• CT colonography: when colonoscopy is contraindicated
• flexible sigmoidoscopy (distal 60cm of colon). It can be done without sedation. There is potential need for a colonoscopy if a source of bleeding is not found or if a distal adenomatous polyp is found.
• Colonoscopy is the definitive tool for evaluating the entire colon for neoplastic lesions and is also a sensitive tool for the detection of all other bleeding lesions in the lower gastrointestinal tract. Requires full bowel prep and conscious sedation.

Malena

• Indicates upper GI source
• Present with coffee ground vomit, malena, haemodynamic instability

Causes:

• bleeding peptic ulcer
• slow proximal colonic bleed

Work-up:

• elevated urea
• check coags

Intermixed bright red blood and maroon stools (haematochezia):

Causes:

• acute proximal (Right side) colonic bleed e.g. due to diverticular bleed, vascular (angiodysplasia, ischemic, radiation-induced), inflammatory (infectious, inflammatory bowel disease), and neoplastic.
• small intestinal source
• upper GI source should be considered in severe haematochezia. Esp with elevated urea, haemodynamic instability

Work-up:

• FBE shows normocytic anaemia
• urea is normal (unlike upper GI bleed)
• check coags

Question 4

C.Diff enterocolitis

Answer 4

Epidemiology:

• c.diff infection is one of the most common hospital-acquired (nosocomial) infections
• Pseudomembranous colitis refers to swelling or inflammation of the large intestine (colon) due to an overgrowth of Clostridioides difficile (C difficile) bacteria. This infection is a common cause of diarrhea after antibiotic use.

Pathophys:

• C. difficile colonizes the human intestinal tract after the normal gut flora has been disrupted (frequently in association with antibiotic therapy)
• Frequently associated antibiotics: Fluoroquinolones, Clindamycin, Cephalosporins (broad spectrum), Penicillins (broad spectrum)
• Occasionally associated: Macrolides, Trimethoprim-sulfamethoxazole

Consequences:

• antibiotic-associated diarrhea and pseudomembranous colitis

Diagnosis:

• The diagnosis of C. difficile infection should be suspected in patients with acute diarrhea (≥3 loose stools in 24 hours) with no obvious alternative explanation (such as laxative use), particularly in the setting of relevant risk factors (including recent antibiotic use, hospitalization, and advanced age)
• The diagnosis of C. difficile infection is established via a positive laboratory stool test for C. difficile toxin(s) or C. difficile toxin B gene.

The GDH antigen test uses antibodies to test for the presence of the GDH enzyme, a protein present in all C. difficile isolates (has high sensitivity but poor specificity, as it can’t distinguish between toxigenic and nontoxigenic strains of C. diff).

The toxin test uses antibodies to detect the presence of C. difficile toxin A and/or toxin B (testing for both toxins is preferred). The toxin test has high specificity, but low sensitivity, so there is a high rate of false negatives.

The NAAT tests for the presence of toxigenic C. difficile organisms in stool by amplifying one or more genes specific to toxigenic strains; the critical gene is tcdB, which encodes for toxin B. This test is specific for toxigenic strains but does not test for active toxin production and also detects asymptomatic carriers of toxigenic C. difficile.

• Findings of pseudomembranous colitis (purulent inflammation of the inner lining of the bowel) on radiographic or endoscopic examination are highly suggestive of C. difficile infection

Disease severity and treatment:

●Nonsevere CDI – White blood cell count ≤15,000 cells/mL and serum creatinine <1.5 mg/dL (~130micromol/L). Treat with oral vancomycin (bacteriostatic) 125mg QID for 10days OR oral fidaxomicin (bacteriocidal) 200 mg bd for 10 days OR oral metronidazole (bacteriostatic) 500 mg orally TDS for 10 days (note, the use of metronidazole has been associated with treatment failure)

●Severe CDI – White blood cell count >15,000 cells/mL and/or serum creatinine ≥1.5 mg/dL (~130micromol/L). Treat with oral vancomycin or oral fidaxomicin

●Fulminant colitis (previously referred to as severe, complicated CDI) – Hypotension or shock, ileus, or megacolon. Treat with oral vancomycin + IV metronidazole. Consider surgery if serum lactate >2.2

● recurrent infection. Depends on whether first or subsequent recurrence. Treat with tapering oral vancomycin, OR fidaxomicin. Rifaxamin can be used as an option for subsequent recurrent C.diff infection.

Management/Rx:

• discontinuation of the inciting antibiotic agent(s) as soon as possible, due to increased risk of prolonged diarrhoea and recurrent c.diff infection
• contact precautions for patients with suspected or proven C. difficile infection. Hand hygiene with soap and water is more effective than alcohol-based hand sanitizers since C. difficile spores are resistant to killing by alcohol.
• antibiotic treatment [refer above] is warranted for patients with typical manifestations of C. difficile infection (≥3 loose stools in 24 hours), with no obvious alternative explanation, and a positive diagnostic laboratory assay. Treatment not indicated in the absence of diarrhoea as asymptomatic carriage is common.
• consider surgery if serum lactate >2.2 after a few days, signs of sepsis, significant abdo distension, WCC >20, admission to ICU, end organ failure, failure to improve after 3-5days. Suspect toxic megacolon.
• Faecal microbiota transplantation (FMT) is an alternative to colectomy and has been associated with reductions in mortality in some observational studies, but further study is warranted.
• Antimotility agents (eg, loperamide, opiates) have traditionally been avoided in CDI, but the evidence that they cause harm is equivocal
• correction of fluid losses and electrolyte imbalances
• may have regular diet as tolerated

Question 5

Colorectal cancer

Answer 5

Presentation:

Patients who are symptomatic at diagnosis typically have more advanced disease and a worse prognosis

●Change in bowel habits (most common 74 %)

●Rectal bleeding in combination with change in bowel habits (51% of all cancers and 71 % of those presenting with PR bleeding)

●Rectal mass (24.5 %) or abdominal mass (12.5 %)

●Iron deficiency anemia (9.6 %)

●Abdominal pain as a single symptom (3.8 %)

● distant metastatic disease at the time of presentation (20%). The most common metastatic sites are the regional lymph nodes, liver (given the portal venous drainage of the bowel), lungs, and peritoneum.

● constitutional symptoms

Risk factors:

• inflammatory bowel disease
• history of abdominal radiation
• positive family history of CRC - higher risk with 1st degree relative, higher if diagnosed <55yo. Refer to table of categories: https://wiki.cancer.org.au/australia/Clinical_question:Family_history_and_CRC_risk
• predisposing inherited syndrome.
• increasing age (rare before 40yo, then incidence increases steadily with age). Anyone >or= 50yo needs colonoscopy for PR bleeding.

Labs:

• CEA (carcinoembryonic antigen, specificity 89% for CRC, can be elevated in gastritis, PUD, diverticulitis, liver disease, COPD, DM, inflammatory states, smokers), CA 19-9 (carbohydrate antigen 19-9)
• LFT derangement with liver mets

Imaging:

• contrast CT or MRI to detect liver metastases. MRI is more sensitive.
• FDG-PET esp for extrahepatic metastases

Colonoscopy

• Colonoscopy is the most accurate and versatile diagnostic test for CRC, since it can localize and biopsy lesions throughout the large bowel, detect synchronous neoplasms, and remove polyps.

PILLCAM 2

• A colon capsule for CRC screening is approved for use in patients who have had an incomplete colonoscopy. While its role in screening for CRC is still uncertain, it could be considered in a patient with an incomplete colonoscopy who lacks obstruction.

Complications:

• liver metastases
• Residual tumor after definitive therapy is an adverse prognostic factor. The completeness of resection is largely dependent on the status of the circumferential (radial) resection margin

Management:

• For hepatic flexure tumors, we typically perform a standard right colectomy unless there is evidence of nodal disease beyond the right branch of the middle colic artery, in which case we perform an extended right colectomy.
• Liver resection for hepatic metastases in appropriate patients. Usually performed prior to colorectal resection. Post op complications inc bile leak, blood loss
• Adjuvant chemotherapy (prior to resection of liver mets)

Case report of an elderly man with intrabiliary colorectal metastasis: https://academic.oup.com/jscr/article/2018/1/rjx259/4812593

84 M with Hx metastatic CRC and R) hemicolectomy 4years prior, presents with obstructive jaundice. MRCP demonstrated obstruction of the biliary tract transitioning at the ampulla. Samples taken during ERCP confirmed malignant cells consistent with adenocarcinoma that were (CK-7) negative and CK-20 positive, favouring an intrabiliary colorectal metastasis over a new primary bile duct carcinoma.

Question 6

Irritable bowel syndrome

Answer 6

Labs:

• Fecal calprotectin is normal/negative

Question 7

Bacterial overgrowth - small bowel

Answer 7

Description:

Small intestinal bacterial overgrowth (SIBO) is a condition in which the small bowel is colonized by excessive aerobic and anaerobic microbes that are normally present in the colon (esp streptococci, Bacteroides, Escherichia, and Lactobacillus)

Risk factors:

• Small intestinal stasis: Anatomic abnormalities (Small intestinal diverticulosis; Surgically created blind loops i.e. end-to-side anastomosis; Strictures i.e. Crohn disease, radiation, surgery)
• Abnormal small intestinal motility (Diabetes mellitus, Scleroderma, Idiopathic intestinal pseudo-obstruction, Radiation enteritis, Crohn disease)
• Abnormal communication between the proximal and distal gastrointestinal tract (Gastrocolic or jejunocolic fistula, Resection of the ileocecal valve)
• Associations usually with multifactorial causes (Hypochlorhydria due to atrophic gastritis or medications, Immunodeficiency states inc AIDS, Chronic pancreatitis, Cirrhosis, Alcoholism, End-stage kidney disease, Advanced age, TPN use in children)

Consequences of small intestinal bacterial overgrowth (SIBO):

• Inflammation, injury to the intestinal surface
• malabsorption due to enterocyte damage esp of Carbohydrates, Fat (and fat-soluble vitamins), Protein, Vitamins (esp B12, thiamine, nicotinamide)
• elevated folate and vitamin K produced by bacteria
• D-lactic acidosis is a rare neurologic syndrome in patients with SIBO associated with short bowel syndrome or a prior jejunoileal bypass

Symptoms/features:

• bloating, flatulence, abdominal discomfort, or chronic diarrhea

Diagnosis:

• positive carbohydrate breath test (using 10g lactulose or 75g glucose). The substrate is metabolised by bacterial flora leading to the production of an analyte (hydrogen, methane), which is absorbed and ultimately excreted in the breath within 2-3hours (breath is sampled every 15mins for 2hrs). Antibiotics, laxatives, prokinetics, complex carbs, food (8-12hrs prior), smoking, strenuous exercise should all be avoided prior to the test.
• OR bacterial concentration of >103 colony forming units/mL in a jejunal aspirate culture

Substrates used in the hydrogen breath test:

• Lactulose is a ‘control’ sugar that is 100% malabsorbed. Commonly, 15g of lactulose is used. An early rise in breath hydrogen (before 90 minutes) after lactulose has been used as a marker for small intestinal bacterial overgrowth (SIBO). however, this is more likely to reflect rapid small intestinal transit than SIBO. Glucose is the preferred sugar for detection of SIBO. Glucose is rapidly absorbed and only causes a rise in breath hydrogen if it meets bacteria in the small bowel before absorption.

DDx:

• celiac disease
• crohns
• IBS

Endoscopy and histopath:

• most commonly is normal.
• can show non-specific findings of colitis and ileitis associated with severe SIBO include mucosal edema, loss of normal vascular pattern, patchy erythema, friability, and in rare cases, ulceration
• Sources:*
• UpTodate - SIBO (https://www.uptodate.com/contents/small-intestinal-bacterial-overgrowth-clinical-manifestations-and-diagnosis?search=hydrogen%20breath%20test&source=search_result&selectedTitle=1~1&usage_type=default&display_rank=1)*
• RACGP (states that multiple substrates can be used) https://www.racgp.org.au/afp/2012/may/fructose-and-lactose-testing/#:~:text=Breath%20hydrogen%20testing%20can%20be,and%20related%20functional%20gut%20disorders.*