DSA - Disorders of the Small Bowel and Colon (Completed) Flashcards
Paradoxical “diarrhea” described as liquid stool leaking around impacted feces
Overflow incontinence
You observe benign hyperpigmentation of the colon
Melanesis coli Due to chronic use of laxatives
The prescence of the following is inconsistent with medication, IBS, and lactose intolerance mechanisms of chronic diarrhea
- Nocturnal diarrhea
- weight loss
- anemia
- FOBT (fecal occult blood test)
What laboratory tests indicate inflammatory bowel disease?
- erythrocyte sedimentation rate
- C-reactive protein
What measurement determined from a fecal specimen indicates pancreatic insufficiency?
Fecal elastase less than 100 mcg/g
How might you localize a neuroendocrine tumor to visualize it’s location on imaging?
By using somatostatin receptor scintigraphy
What are four neuroendocrine tumors that all have a complication of secretory diarrhea?
- >1 L/day of high-volume watery diarrhea
- normal osmotic gap
- Diarrhea persists during fasting
- VIPoma (VIP) vasoactive intestinal peptide
- Medullary Thyroid carcinoma (calcitonin)
- Zollinger-Ellison syndrome (gastrin)
- (5-HIAA) urinary 5-hydroxyindoleacetic acid
How can small bowel bacterial overgrowth diagnosis be confirmed?
- Breath test (glucose or lactulose)
What is a non-invasive method for the diagnosis of carbohydrate malabsorption?
Hydrogen breath test
ex. Lactase deficiency —> hydrogen breath test
also can perform an elimination trial for 2-3 weeks but this takes longer
Numerous medications can cause diarrhea. What are the common offenders?
- Cholinesterase inhibiitors (-)
- SSRIs
- Angiotensin II-receptor blockers
- PPIs
- NSAIDs
- Metformin
- Allopurinol
- Orlistat (weight loss medication)
Microscopic colitis is a condition of chronic inflammation idiopathic in origin in which 15% of patients have chronic or intermittent watery diarrhea. Most commonly occurs in women between the fifth and sixth decade. What are the two types?
- Lymphocytic colitis
- collagenous colitis
What do we see histologically in microscopic colitis?
- Lymphocytes and plasma cells within the LP
- increased intraepithelial lymphocytes
normal-appearing mucosa on endoscopy
Collagenous colitis is a type of microscopic colitis. Differentiate collagenous colitis from lymphocytic colitis
Collagenous colitis:
- thickened bands of subepithleial collagen (> 10 μm)
Several medications have been implicated as the etiologic agent of microscopic colitis. What are they?
- NSAIDs
- PPIs
- ASA
- SSRI
- ACE (-)
- beta-blockers
removal of these medications resolves diarrhea within 30 days
What is osmotic gap in reference to osmotic diarrhea?
The difference between the measured osmolaltiy of the stool or serum and the estimated stool osmolaltiy
normal: less than 50 mOsm/kg
With reference to osmotic diarrhea what does an increased osmotic gap greater than 75 mOsm/kg indicate?
That the cause of the diarrhea is due to ingestion or malabsorption of an osmotically active substance
What are the most common causes of osmotic diarrhea?
- Carbohydrate malabsorption (lactose, fructose, sucrose)
- Laxative abuse (can be osmotic or secretory)
- malabsorption syndromes
What is one important and easy way you can differentiate whether a patient is havin secretory or osmotic diarrhea?
Osmotic diarrheas resolve during fasting
secretory diarrheas see little change in stool output during fasting
- volume of stool doesn’t reduce during fasting
Patients with carbohydrate malabsorption are often characterized by having chronic postprandial diarrhea. What is postprandial diarrhea?
Diarrhea occurring during or after meals (lunch/dinner)
Secretory diarrhea is a result of either increased intestinal secretion or decreased intestinal absorption. What are the defining characteristics of secretory diarrhea?
- A high-volume watery diarrhea > 1 L/day
- normal osmotic gap
- fasting = little change in stool output
Ingestion of phosphate containing compounds such as laxatives, antacids, or ingestion of magnesium and the use of fat substitute Olestra has been correlated with what?
Incidences of osmotic diarrhea
What are important causes of secretory diarrhea?
- Endocrine tumors that stimulate pancreas/intestines
- Zollinger-Ellison syndrome
- Carcinoid syndrome
- VIPoma
- Medullary thyroid carcinoma
- Bile salt malabsorption (stimulates colonic secretion)
Malabsorptive conditions are conditions in which there is disruption in digestion and nutrient absorption. What are the major malabsorptive conditions?
- Bile salt malabsorption
- Celiac Disease
- Whipple (Tropheryma whippelii, gram +)
- Lactase deficiency
Patient presents with weight loss, osmotic diarrhea, steatorrhea, and nutritional deficiency
Patient has a malabsoprtive condition
- Bilar salt malabsorption
- celiac disease
- whipple
- lactase deficiency
If a patient presents with complaints of significant diarrhea, but no complaints of weight loss what should you be thinking?
This patient most likely doesn’t have a malabsorptive condition
Patient presents with weight loss, gaseous distention, flatulence, and large greasy foul-smelling. You diagnose the patient with pancreatic insufficiency. What is causing this host of symptoms?
Due to malabsorption of triglycerides
Where are bile salts absorbed?
Bile salts are resorbed in the terminal ileum
This process is effected by certain conditions such as Crohn’s disease
While weight loss is minimally seen in bile salt malabsorption. What two things occur as a direct result of bile salt malabsorption?
- Impaired absorption of fat-soluble vitamins (ADEK)
- Can cause a watery secretory diarrhea
What occurs as a result of the impaired absorption of fat-soluble vitamins (ADEK) in bile salt malabsorption
- bleeding tendencies
- Osteoporosis
- Hypocalcemia
What are the classic symptoms seen in Celiacs disease?
- Malabsorption (steatorhea)
- Weight loss and chronic diarrhea
- dyspepsia (indigestion)
- flatulence (colonic bacterial digestion)
- abdominal distention
- muscle wasting (weakness)
- growth retardation
- infants younger than 2
A patient presents with pruritic papulovesicles over the extensor surfaces of the extremities and over the trunk, scalp, knee, and neck.
Dermatitis herpetiformis
seen atypically in Celiacs disease (typical, atypical)
What are atypical symptoms/presentations of Celiacs disease?
- Dermatitis herpetiformis
- iron deficiency anemia
- osteoporosis
What neurologic signs might you see as a result of malabsorption of vitamin B12 and vitamin E in Celiacs disease?
- Peripheral neuropathy
- ataxia
What molecules will be present in a patient with Celiacs disease?
- HLA-DQ2 (95%)
- HLA-DQ8 (5%)
Remember: if you have one autoimmune disorder you are more likely to develop others (myasthenia gravis, sjogren syndrome, Addison disease, Graves’ disease)
What is the means of diagnosis of Celiacs disease?
- abnormal serologic findings (CBC, CMP w/ GGT)
- small bowel biopsy
With serological testing of a patient with Celiacs disease what are some key findings?
- Anemia (CBC)
- Impaired calcium or vitamin D absorption (CMP)
- Imparied fat-soluble vitamin absorption
- Low serum albumin (CMP)
In a patient with Celiac’s disease one of the complications identified based off laboratory findings is anemia. What two types of anemia might you see in Celiac’s Disease?
Microcytic anemia - due to occult blood
- ferritin, iron, iron saturation, TIBC
Megaloblastic anemia - more extensive involvement
- B12, folate
Patients with Celiac’s often have impaired calcium or vitamin D absorption with osteomalacia or osteoporosis. This is identified based off collection of a CMP. What can a CMP tell us?
- Low calcium
- elevated alkaline phosphatase
- Normal GGT —> indicates bone etiology not liver
gamma-glutamyltransferase, an enyzme of the liver
What laboratory findings derived from a CMP would you indicate that a Celiac’s patient had small intestine protein loss or poor nutrition?
- Low serum albumin
- low zinc
- low vitamin B
What two serological tests will identify Celiac’s disease in a patient?
IgA tissue transglutaminase antibody (IgA tTG)
Anti-DGP (IgG antibodies to delaminates gliadin peptides)
- useful for patients who are IgA deficient
- second choice, tTG still number 1
(True/False) Anti-DGP is the preferred method for diagnosing Celiacs because it will indicate prescence of the disease even if the patient is IgA deficient
False
IgA tTG is more specific/sensitive and is number one choice
(True/false) next to IgA tTG and anti-DGP, IgA anti-endomysial antibodies can also be used in the diagnosis of Celiac’s disease
False
IgA endomysial antibodies are no longer used due to failure for labs to standardize to their use
You’re presented with a patient who has all the hallmark typical symptoms of a patient with Celiac’s disease, he even has Dermatits herpetiformis! However when you perform both a IgA-tTG (top choice) and anti-DGP (second choice) you observe that there are no antibodies present? Explain this
Levels of all antibodies become undetectable after 3-12 months of dietary gluten withdrawal. Your patient shouldn’t be on a gluten free diet if you want to check these antibodies.
however, this is a way to check to see if your patient is being compliant once Celiac’s is diagnosed
The standard method for confirmation of Celiacs after serological testing is a mucosal biopsy of what?
Proximal duodenum (bulb) and distal duodenum
What would you see on endoscopy of the proximal and distal duodenum in a Celiacs patient?
Atrophy or scalloping of the duodenal folds
What will you see on histology of a Celiac’s patient?
- intraepithelial lymphocytosis
- extensive infiltration of the LP w/ lymphocytes and plasma cells
- hypertrophy of intestinal crypts
- loss of intestinal villi
Once a CMP is obtained from your patient with Celiacs disease you observe a low serum calcium and elevated alkaline phosphatase. However, a GGT reads normal and you become concerned that your patient may have osteoporosis. What test can be performed to verify whether or not your patient has osteoporosis?
Dual-energy x-ray densitometry (DEXA)
Will indicate whether or not the patient has osteoporosis
Celiac patients must avoid all wheat, rye, and barley. What other complications due Celiac patients tend to have?
Most Celiac patients also have lactose intolerance (either temporarily or permenantely)
(True/false) The most common reason for treatment failure of Celiac’s disease is incomplete removal of gluten
True
What is Whipple disease?
A rare multi-system disease caused by gram positive bacillus tropheryma whipplei
What are the hallmark signs/symptoms of Whipple disease. Which sign/symptom was mentioned in the CIS?
- Lymphadenopathy (LAD) - CIS
- Fever
- Arthralgias*
- Weight loss*
- Malabsorption
- Chronic diarrhea
- abdominal pain
What stain can be used to identify Whipple disease and by what means?
Duodenal biopsy w/ periodic acid Schiff (PAS) positive for macrophages with characteristic bacillus
Source of the infection is unknown
Clinically, what is typically the first symptom seen in Whipple disease and what is the most common presenting symptom?
Non-deforming arthralgias - first symptom
weight loss - most common presenting symptom
What physical exam findings might you see in a patient with Whipple disease?
- Hypotension - late finding
- heart murmurs due to valvular involvement
- peripheral joint inflammation and enlargement (non-deforming arthlragias)
Whipple disease is established (diagnosed) 90% by endoscopic biopsy of the duodenum w/ histological evaluation. What do you see on endoscopy?
- Infiltration of the LP w/ PAS+ macrophages that contain gram (+) bacilli (the bacilli are not acid fast)
- dilation of lacteals
Describe the appearance of Whipple disease on electron microscope?
Trilamellar wall appearance on electron microscopy
What is the prognosis of Whipple disease?
If untreated, the disease is fatal
Goal is to prevent progression of neurologic signs
Diagnosis of bacterial overgrowth is suggested by glucose/lab tulles/14C-xylose breath tests. What confirms the diagnosis?
Jejunal aspiration with quantitative bacterial cultures
What causes the increased flatulence, osmotic and secretory diarrhea seen in bacterial overgrowth?
Malabsorbed bile acids and carbohydrates located in the colon
Malabsorptive condtion that arises secondary to removal of significant segments of the small intestine
Short Bowel Syndrome
What are the most commons causes of Short Bowel Syndrome?
- Crohns disease
- mesenteric infarction
- radiation enteritis
- volvulus
- tumor resection
- trauma
What are the main concerns with a Terminal Ileal (TI) Resection?
- Malabsorption of bile salts (< 100 cm resection)
* Leads to watery diarrhea - Malabsorption of vitamin B12 (> 50cm resection)
- Reduction in bile salt pool (> 100 cm resection)
- steatorrhea (tx: low fat diet)
- malabsorption of ADEK (tx: vitamin supplement)
- cholesterol gallstones
- oxalate kidney stones
How do oxalate kidney stones form when over 100cm of the ileum is removed?
malabsorption of fats leads to free fatty acids that bind with calcium enhancing the absorption of oxalate
What complication is associated with ileocolonic valve resection?
bacterial overgrowth leading to malabsorption
(True/False) Resection of up to 40-50% of the total length of the small intestine is usually well tolerated
True
What is required in a patient with no colon + less than 100-200 cm of jejunum left?
Need parenteral nutrition
After colon resection what is the minimal amount of proximal jejunum needed to maintain oral nutrition?
No colon + at least 200 cm of proximal jejunum required to maintain oral nutrition
With loss of the duodenum due to resection what are our main concerns?
Iron, folate, or calcium malabsorption
How do we confirm a lactase deficiency?
Hydrogen breath test
What kind of diarrhea will result with a higher lactose ingestion in a lactase deficient patient?
osmotic diarrhea
What is the most common cause of chronic diarrhea in young adults?
Irritable bowel syndrome (IBS)
also the most common GI disease in clinical practice
IBS patients will present with altered bowel habits and abdominal pain, but what is one strong characterization that lets us know this is IBS and not another pathology?
Absence of detectable organic pathology
In IBS pathophysiology the reported anatomical abnormalities include…
- Altered colonic motility (at rest, in response to stress)
- Altered small intestine motility
- enhanced visceral sensation (lower pain threshold)
What are the clinical manifestations of IBS?
- Abdominal pain (crampy/lower abd)
- Irregular bowel habits (increased freq. w/ pain)
- abdominal distention
- bowel movement relieves abdominal pain
- Mucus in stools
- sense of incomplete evacuation
In addition to the main clinical presentations we see with IBS, what are the associated findings? What is the most important clinical finding?
- Pencil-thin stools (most important)
- Pasty stools
- heartburn
- urinary frequency
When can IBS be defined as chronic? How long do symptoms have to be present before we consider it in our differential?
Chronic > 6 months (symptoms for at least 3 months before considering it in differential)
“Alarm symptoms” are symptoms that suggest a diagnosis other than irritable bowel syndrome and warrant further investigation? What are these symptoms?
- Nocturnal diarrhea
- hematochezia
- weight loss
- acute onset of symptoms (raises likelihood of organic disease)
IBS is a diagnosis of exclusion. What does this mean?
It means organic causes must be excluded first
IBS can be diagnosed using the ROME criteria. Define this criteria.
- Improvement with defecation
- onset associated with a change in frequency of stool
- onset associated with a change in form (appearance) of stool
Historically, in the treatment of IBS dietary bulk (fiber, psyllium extract) has been used. Describe the efficacy of this treatment.
Appears to be of little value
Little change in bowel frequency
IBS patients with diarrhea, bloating, and flatulence are placed on a low FODMAP diet. What is this?
Dietary restriction of fermentable carbohydrates:
- oligosaccharides
- disaccharides
- monosaccharides
- polyols
(ex. Lactose, fructose, corn syrup, sorbitol)
A number of disorders may present with similar findings to irritable bowel syndrome, but must be differentiated from this disease. What are these diseases?
- Colonic neoplasia (inflammatory bowel disease + Crohn’s disease)
- psychiatric disorders
- women w/ refractory symptoms
Neurogenic failure or loss of peristalsis in the intestine in the absence of any mechanical obstruction
Acute paralytic ileus
Acute Colonic Pseudo-Obstruction (Ogilvie Syndrome)
Spontaneous massive dilation of cecum or right colon w/o mechanical obstruction
What are the clinical findings of Acute Colonic Pseudo-obstruction (Ogilvie Syndrome)?
- Abdominal distention (first sign)
- absent bowel movements
- Colonic distention (plain film radiograph)
Acute colonic pseudo-obstruction (ogilvie syndrome) is associated with colonic dilation of the cecum. What are the limitations of the diameter of the cecum? How continuously does the diameter of the cecum need to be monitored?
Upper limit of normal cecal size is 9 cm
A cecal diameter greater than 10-12 cm is associated with an increased risk of colonic perforation
cecal size should be assessed by abdominal radiographs every 12 hours
How successfully can acute colonic pseudo-obstruction (ogilvie syndrome) be treated with oral laxatives?
Oral laxatives are not helpful and may cause perforation (pain) and electrolyte abnormalities
What are the two toxins seen in antibiotic-associated colitis, C diff
- TcdA (enterotoxin)
- TcdB (cytotoxin) - PCR
How is C diff commonly acquired?
- Patients hospitalized for 3+ days
- Patients who have received antibiotics 10+ days (ex. Ampicillin, clindamycin)
- handwashing required (no hand sanitizers)
- patients on PPIs
How would a patient with C diff present clinically with regards to patients stool?
- Mild to moderate greenish, foul-smelling diarrhea 5-15 times per day w/ lower abdominal cramps
- stools without blood
How would a C diff patient present serologically?
- WBC count > 15,000/mcL (>30,000/mcL = severe)
- unexplained leukocytosis
- albumin < 2.5 g/dL
- elevated lactate
- rising creatinine
In the diagnosis of C diff two tests: EIAs and PCR can be used to identify the toxins. Which test is better?
- EIAs (toxin A & B)
- PCR - toxin B only 97% sensitive
PCR is able to detect NAP1 hypervirulent strain
You see a patient that you believe has a severe case of C diff. You decide to perform flexible sigmoidoscopy.What should you see?
True pseudomembranous colitis which shows as epithelial ulceration with a classic “volcano” exudate of fibrin and neutrophils
What is a severe consequence/complication of C diff?
Megacolon as a result of severe colitis
Where is diverticular disease most commonly found?
In the sigmoid colon
Patients with abnormal connective tissue are disposed to development of diverticulosis. What patients is this in reference to?
- Ehlers-Danlos Syndrome
- Marfan Syndrome
- Scleroderma
90% of patients with diverticular disease have…
Uncomplicated diverticulosis
Diverticulitis is a condition marked by rupture of diverticuli. This is the more severe of two forms of diverticular disease. Describe the main signs and symptoms of diverticulitis. (Not the progression, just symptoms)
- Acute abdominal pain/tenderness (LLQ)
- Possible mass in sigmoid or descending colon
- Fever
- Leukocytosis
Describe the progression of diverticulitis. What is seen first and what comes after
Constipation reported first —> loose stools —> liquid stools (inflammation inhibits solid stool)
What is the best way of confirming diagnosis and staging of diverticulitis and what method is recommended against?
CT with contrast is method of choice
Endoscopy (sigmoidoscopy or colonoscopy) is contraindicated during initial stages of an acute attack because of the risk of perforation
If you were to look under a microscope at the descending colon and sigmoid colon what would you see macroscopically?
Macroscopic inflammation of a diverticulum
Leads to
local inflammation of that area around diverticulum
Leads to
Microperforation w/ localized paracolic inflammation
Leads to
Macroperfortation w/ abscess or generalized peritonitis
Diverticulosis is the formation of outpouchings usually in the sigmoid colon. Diverticulitis is the inflammation due to bacteria of these outpouchings. Which of these types of diverticular disease would you expect to see hemorrhage?
Hemorrhage usually in the abscence of diverticulitis (ascending colon and typically self-limited)
meaning this occurs in diverticulosis not diverticulitis
How do we treat diverticulosis?
Periumbilical pain out of proportion to tenderness accompanied by GI bleeding and altered bowel habits
acute mesenteric ischemia
Acute mesenteric ischemia on x-ray shows bowel distention, air-fluid levels, and what other hallmark radiologic sign?
Thumbprinting (submucosal edema)
Differentiate Acute mesenteric ischemia from Chronic mesenteric ischemia
Acute Mesenteric Ischemia:
- periumbilical pain out of proportion to tenderness
- Thumbprinting (submucosal edema)
Chronic Mesenteric Ischemia:
- Abdominal angina - dull, crampy periumbilical pain 15-30 min after a meal lasting for several hours
- patients will have food fear
Differentiate acute mesenteric ischemia from ischemic colitis
Acute Mesenteric Ischemia
- Periumbilical pain out of proportion to tenderness
- Thumbprinting (submucosal edema)
Ischemic Colitis (superior mesentary artery syndrome)
- First part of duodenum compressed between aorta and superior mesenteric a.
- Severe lower abdominal pain followed by rectal bleeding
- thumbprinting - colonic dilation on x-ray
What does BRBPR stand for?
Bright Red Blood Per Rectum
- hemorrhoids (not always hemorrhoids!)
- anal fissure/fistula
- UC
- CD
- neoplasms (distal colon or rectum)
External hemorrhoids (anorectal disease) can be visualized through inspection. How are internal hemorrhoids observed?
Anoscopic examination
An exquisitely painful, tense, and bluish perinatal nodule covered with skin of acute onset. Can be precipitated by coughing, heavy lifting, or straining at stool
Thrombosed external hemorrhoid
How do you treat the pain from a hemorrhoid?
- Laxatives
- stool softeners
- Sitz bath (hips and buttocks submerged only)
What anorectal Infection causes lymphogranuloma venereum?
Chlamydia trachomatis
What is lymphogranuloma venereum?
proctocolitis (anorectal discomfort, constipation, tenesmus, bloody/mucus discharge) w/ fever and bloody diarrhea
- painful perianal ulcerations
- anorectal strictures/fistulas
- inguinal lymphadenopathy (buboes)
What are the important take-aways from the American Cancer Society Guidelines for Colorectal Cancer Screening?
- Start regular screening at 45 and continue to 75
- 76-85 screening based on preference and goals
- over 85 should not receive screening
What individuals are at above average risk for colorectal cancer?
- Hx of colorectal cancer or certain types of polyps
- family hx of colorectal cancer
- Inflammatory bowel disease (ulcerative colitis/Crohns disease)
- family adenomatous polyposis (FAP)
- Lynch syndrome
- Hx of radiation to abdomen or pelvis for other cancers
What are the screening recommendations for individuals who are above average risk for colorectal cancer?
- colonoscopy every 5 years starting at 40 (or 10 yrs before the age of the youngest affected relative)
What is the recommendation for an individual who has a family history of familial adenomatous polyposis?
Genetic testing to annual sigmoidoscopy beginning at age 10-12
What is the colorectal cancer screening recommendation for a patient with a family history of hereditary non polyposis colorectal cancer (HNPCC)?
Refer for genetic testing
Colonoscopy:
- every 1-2 years beginning at age 20-25 -or-
- 10 years younger than youngest age of colorectal cancer diagnosis in family
What are the four major pathological groups of polyps of the colon?
- Mucosal adenomatous polyps
- Mucosal serrated polyps
- Mucosal nonneoplastic polyps
- Submucosal lesions
Tubular, tubulovillous, and villous (70%) colon polyps fall under what category?
Mucosal adenomatous polyps
What are the various subtypes of mucosal serrated colonic polyps?
- Hyperplastic
- Sessile serrated polyps (sessile - non mobile)
- Traditional serrated adenoma
Over 95% of cases of adenocarcinoma of the colon are believed to arise from adenomas and serrated colonic polyps. What defect causes this?
Adenomas —> Inactivation of APC gene
Serrated:
- Kras mutation (traditional)
- BRAF oncogene activation (sessile serrated)
Most patients with adenomatous and serrated polyps are ___________ ____________
Completely asymptomatic
What are the sample obtaining diagnostic tests by which CRC (colorectal cancer) is screened?
- FOBT (Fecal Occult Blood Test)
- FIT (Fecal Immunochemical Test for hemoglobin)
- Cologuard
Test combining a fecal DNA test with a fecal immunochemical test (FIT) for stool hemoglobin that is approved by the FDA
Cologuard
What are the radiologic tests by which colorectal cancer (CRC) can be diagnosed?
- Barium enema examination = NOT RECOMMENDED
- CT colongraphy = only okay for low risk individuals
Why is CT colongraphy for diagnosis of colorectal cancer only acceptable for low risk individuals?
- Can only detect polyps > 10mm
- diagnostic but not therapeutic
- accuracy for detection of polyps 5-9mm significantly lower (advanced carcinoma can be found in these)
All patients who have positive FOBT, FIT, fecal DNA tests or iron deficiency anemia are subjected to what and why due to the increased prevalence of colonic neoplasms in these individuals?
Colonoscopy
remains the best test in most patients to detect and treat colorectal polyps (polypectomy)
How do we treat colonic polyps? What are the complications?
Colonoscopic polypectomy
- removal of polyps by biopsy forceps or snare cautery
Complications include perforation and clinically significant bleeding
What are the essential considerations, genetic testing, and treatment for Familial Adenomatous Polyposis (FAP)
- Early development of hundreds to thousands of colonic adenomatous polyps and adenocarcinoma
- 90% mutation in APC (AD)
- 8% mutation in MUTYH gene (AR)
- prophylactic colectomy recommended to prevent otherwise inevitable colon cancer
What are the essential considerations, clinical findings, genetic testing, and treatment of Lynch Syndrome (Hereditary nonpolyposis colon cancer - HNPCC)?
- Lifetime risk of colorectal cancer 22-75%
- rapid transformation over 1-2 yrs from normal tissue to adenoma to cancer
- Thorough family cancer hx needed (Bethesda criteria)
- (AD) autosomal dominant
- defect in genes for detection and repair of DNA base-pair mismatches: MLH1, MSH2, MSH6, and PMS2
- women should undergo ovarian cancer screening
- prophylactic hysterectomy and oophorectomy at 40
- gastric cancer upper endoscopy screening
How is diagnosis suspected and diagnosis confirmed in Lynch Syndrome (hereditary nonpolyposis colon cancer - HNPCC)?
Diagnosis suspected:
- tumor tissue immunohistochemical staining for mismatch repair proteins or testing for microsatelite instability
Diagnosis confirmed:
- by genetic testing
What are the important points of understand in Peutz-Jeghers syndrome (Hamartomatous Polyposis Syndrome)?
- Hamartomatous polyps throughout GI tract
- Intussusception (among other abnormalities)
- Mucocutaneous hyper pigmented maculoes on the lips, buccal mucosa, and skin
What are the important points to understand about Familial Juvenile Polyposis (Hamartomatous Polyposis Syndromes)?
- > 10 juvenile Hamartomatous polyps located in colon
- 50% increased risk of adenocarcinoma
What are the important points to understand about PTEN multiple Hamartomatous syndrome (Cowden Disease) (Hamartomatous Polyposis Syndromes)?
- Hamartomatous polyps and lipomas throughout the GI tract
- Trichilemmomas (lips)
- Increased rate of malignancy is demonstrated in the thyroid, breast, and urogenital tract
