Internal Medicine Board Review 2010: Gastroenterology

Esophagus

•Dysphagia▫Mechanical vs. Motility Disorders

•Gastroesophageal Reflux Disease▫Extra esophageal manifestations

•Barrett’s Esophagus•Esophageal Cancer•Zenker’s Diverticulum

73-year-old woman presents to your office complaining of dysphagia and a 20-lb weight loss during the preceding 6 months. She has a 40 pack-year smoking history, drinks 2 -3 glasses of wine per night, and has had a longstanding history of gastroesophageal reflux disease (GERD) but has not complied with proton pump inhibitor (PPI) therapy. She has had a long standing weight problem (BMI > 35) and current weight loss is not intentional. In her medical record there is a mention of achalasia diagnosed in her 40’s. You suspect that she may have esophageal cancer. In addition to her cigarette smoking and alcohol use, which of her risk factors suggest that she has a squamous-cell carcinoma rather than an adenocarcinoma?

• Obesity • GERD symptoms • Noncompliance with PPI therapy • History of achalasia • Older age

DysphagiaMotility Structural

• As much trouble with liquids as solids

• Differential▫ Achalasia▫ Scleroderma▫ Esophageal spasm

• Progressive• Solids 1st then liquids• Differential

▫ Schatzki’s Ring▫ Stricture from damage –

GERD, Radiation▫ Malignancy

• Work-up▫ Barium Swallow▫ Upper Endoscopy▫ EUS

AchalasiaCharacterized by: Diagnostic Testing/Treatment

• Incomplete relaxation of the LES

• Lack of peristalsis in the esophageal body

• Often also see a hypertensive LES

• Pathologically see ganglionic drop-out at LES

• Classic presentation is increasing dysphagia to both liquids and solids with regurgitation▫ Often with wt loss, chest pain

• Testing▫ Manometry – diagnostic▫ EGD▫ Barium Swallow

• Treatment▫ Low Risk Patient –

Heller myotomy▫ High Risk Patient –

Botulinum Toxin injection into LES

▫ Pneumatic dilitation

Achalasia

Dilated, Bird’s BeakPlain film – no gastric bubble

EndoscopyDilated, Food

Debris

Esophageal Manometry

Low amplitude, simultaneous contractions, aperistaltic

EsophagitisClinical Presentation Epidemiology• Most commonly “Heartburn”

▫ substernal chest burning▫ often accompanied by

regurgitation, belching or dysphagia

▫ Specific, not sensitive• Not usually manifested as

abdominal pain (dyspepsia)• Sometimes “silent”• Host of other less common

symptoms, aka as extra-esophageal symptoms or “atypical” reflux▫ hoarseness, asthma, chronic

cough, sinusitis, bronchitis, bronchiectasis, erosion of dental enamel

• App 40% of adult Americans have symptoms of heartburn on a monthly or better basis▫ 15% with weekly heartburn

• Up to 20% of adults have experienced dysphagia

• Increases with age• More common in males• Other RF’s - Obesity, Pregnancy,

Smoking, Collagen Vasc Dz, EtOH use, Hiatal Hernia

EsophagitisComplications Testing

• Erosive Esophagitis 10 – 40%

• Stricture Formation• Barrett’s Esophagus

▫ Loss of Dental Enamel▫ Laryngeal Cancer▫ Aspiration Pneumonia▫ Pulmonary Fibrosis▫ Chronic Asthma▫ Vocal Cord Granulomas▫ Chronic Sinusitis▫ Bronchiectasis

• Empiric Therapy as a diagnostic test

• EGD – good for looking at complications but not as diagnostic of reflux

• pH study▫ 24 hour pH probe▫ Bravo wireless pH

monitoring system• Barium study – good for

dysphagia, bad for reflux

Endoscopy: Esophagitis

CandidaReflux

Endoscopy: Strictures/Ring

Eosinophilic EsophagitisClinical Endoscopic Image

• Eosinophilic infiltration of the esophagus

• Allergic or idiopathic• Main symptom dysphagia• Classic endoscopic

features▫ Rings, furrows,

• > 15 eosinophils per hpf despite 1-2 month acid suppression

• Treated with swallowed fluticasone

GERD Complication: Barrett’s Esophagus

• Metaplastic change of mucosa from squamous to specialized columnar

• Premalignant condition for adenoCA of esophagus

• Risk of cancer is low• Occurs in app 10% of those with

weekly GERD• May be asymptomatic• Does not spontaneously resolve• Less symptomatic than nl mucosa• Progression no dysplasia low

grade dysplasia high grade dysplasia cancer

Annual surveillance for patients with dysplasia

Epidemiology - SCCa vs. Adenocarcinoma

SCCa Adenocarcinoma

▫ More common in African-Americans

▫ More common in lower SES

▫ Associated with smoking

▫ Associated with EtOH▫ Associated with toxic

ingestions

▫ More common in Caucasians

▫ Strongly associated with reflux symptoms and the development of Barrett’s esophagus

Rare Cancers: 12, 000 yr in US, Equal number squamous and adenocarcinoma

Stomach

•Gastritis and PUD•Helicobacter Pylori

▫MALT Lymphoma•ZE Syndrome•Gastric Cancer

Pathophysiology of PUD

Damaging forces

-Gastric Acid-Peptic

enzymes

Defensive Forces

-mucus secretion-bicarb secretion-mucosal blood

flow-prostaglandins

-cellular regeneration

-apical surface membrane transport

Increased Damage-NSAIDS-H Pylori-Smoking-Alcohol

- Hyperacidit

y

Impaired Defense-Ischemia

-Shock-Delayed Gastric

Emptying

Normal

Disease

Ulcer

Balance between aggressive and

protective forces

Helicobacter pyloriClinical Helicobacter

• 75 % of DU• 75% of non-NSAID associated

gastric ulcers • H pylori enhances gastric acid

secretion• Infection occurs prior to

ulceration – only 10-15% will develop ulcer disease.

• Environmental factors increase risk.

• Association with MALT lymphoma

• Gram negative bacillus• Produces urease, catalase,

LPS and vacuolating cytotoxin

• Colonizes the gastric antrum

Eradication of Helicobacter Pylori infection would most likely benefit patients who present with which of the following diseases?

1. Functional (nonulcer dyspepsia)2. Gastric adenocarcinoma3. Gastric ulcer4. Gastroesophageal Reflux Disease

• A 45 year old patient with a history of duodenal ulcer and H pylori infection was treated with a 14 day course of lansoprazole, amoxicillin and clarithromycin. One year after therapy, the patient was recurrent symptoms and is found to have another duodenal ulcer by endoscopy and rapid urease testing of an endoscopically-obtained antral mucosal biopsy is positive. He is a nonsmoker and denies use of NSAIDs. Assuming excellent compliance with his prior 14 day course of antibiotic therapy, the most likely cause for the recurrent ulcer is

1. Reinfection with another strain of H pylori2. Reinfection with the original strain of H pylori3. Unsuccessful eradication of H pylori due to clarithromycin resistance4. Unsuccessful eradication of H pylori due to amoxicillin resistance5. Surreptitious NSAID use

Ables et al (2007) Am Fam Phys. 75:351-358

Intestines

•Diarrhea▫Classification secretory, osmotic, motility▫Infectious ▫C difficile colitis▫Celiac Disease

•Inflammatory Bowel Disease▫Crohn’s disease▫Ulcerative Colitis

Diarrhea Pathophysiology

•Osmotic /Malabsorption– osmotic load in the intestine resulting in retention of water in the lumen

•Secretory – excess secretion of electrolytes and water into the intestinal lumen

•Inflammatory – exudation of fluid and protein from the intestinal mucosa

•Motility – rapid transit through the colon

Osmotic DiarrheaMucosal Disease Osmotic Agents in the Lumen

• Small Intestine▫ Celiac Disease▫ Tropical Sprue▫ Whipple’s Disease

• Colon▫ Inflammatory bowel

disease▫ Infections

• Malabsorption▫ Pancreatic Insufficiency

– enzymes not available to break down food

▫ Small bowel bacterial overgrowth

• Exogenous agents▫ Osmotic laxative▫ Dietary sorbitol,

fructose, lactose in pts with lactase deficiency

Osmotic Diarrhea: Pancreatic Endocrine InsufficiencyEtiology Clinical

• Malabsorption does not occur until exocrine secretions are decreased by 90%

• Causes▫ Chronic alcoholic

pancreatitis▫ Cystic fibrosis▫ Pancreatic resection▫ Strategically placed

pancreatic cancer▫ Somatostatinoma

• Stool studies fat malabsorption

• Decrease in fat soluble vitamins D,A,K, and E

• May be helped with pancreatic enzyme supplementation.

Osmotic Diarrhea: Bacterial OvergrowthPathophysiology Diagnosis

• Decreased transit results in overgrowth of bacteria in the small bowel▫ deconjugation of bile

acids▫ damage to small bowel

mucosa▫ absorption of vitamin B12

• Causes▫ Motility disorders, small

bowel diverticulae▫ strictures, post-surgical

• Small bowel X-Rays▫ SBFT

• Hydrogen breath test▫ Sucrose

• quantitative culture of fluid from duodenum

• empiric trial of an appropriate antibiotic▫ Xifaxin, tetracycline,

ciprofloxacin

Secretory Diarrhea•Stimulated secretion of intestinal cells

•Usually characterized by substantially elevated stool volumes and associated hypokalemia

•This continues despite fasting.

Increased SecretionActive Secretion Other

• Bacterial Toxins▫ Vibrio cholerae,

clostridium difficile, Escherichia coli O157:H7, shigella

• Endocrine Tumors▫ VIPoma, gastrinoma,

carcinoid• Villous adenoma

• Inflammatory cell products▫ Prostaglandins and

leukotrienes, platelet activating factor, histamine, serotonin

Clostridium DifficileEpidemiology Clinical

• C diff colonizes the intestinal tract after normal gut flora have been altered.

• One of the most common health-care infections

• Significant cause of morbidity and mortality among elderly patients

• Up to 50% carriage rate in hospitalized patients.

• Watery diarrhea• Range in severity from

asymptomatic carrier to severe fulminant disease with toxic megacolon.

• Cramping, diarrhea, low grade fever and leukocytosis

• C diff toxins in stool toxins A and B – mutation in toxin A may give false negative EIA

Clostridium difficileEndoscopy Treatment

• Stop the offending antibiotic

• Oral metronidazole or oral vancomycin

• Can’t use IV vanco – does not get to the gut – can use IV metronidazole

• Toxic dilation with progression urgent surgical therapy

• Recurrent disease in up to 25%

Endoscopic findings range from patchy erythema to the classic pseudomembranes

•A 44 year old woman presents with abdominal pain and anemia. During the work-up a small bowel biopsy was performed and a PAS stain was done. This stain revealed foamy PAS+ macrophages. What is this patients diagnosis?

▫ Whipple’s disease▫ Chronic Pancreatitis▫ Zollinger-Ellison syndrome▫ Celiac Sprue▫ Eosinophilic Gastroenteritis

Histology to Recognize

•Whipple’s Disease•Celiac Disease•Giardia•Collagenous Colitis•CMV•Cryptosporidiosis•Eosinophilic Gastroenteritis

WEB Path

Giardiasis

•Sources: contaminated water, fecal-oral transmission.

•Incubation: 1 - 4 weeks•Symptoms: sudden onset of explosive

watery diarrhea, cramps, nausea, bloating, flatulence

•Duration: weeks, relapses are common•Treatment: Metronidazole 250 tid x 5 - 7

days

Celiac Disease• Gluten sensitive enteropathy• Incidence is 1 in 133 people in the US• Among people with 1st degree relative with CD –

1 in 22 may have the disease• More common in Down’s syndrome and Turner’s

syndrome• Absence of HLA-DQ2 or HLA-DQ8 has a NPV

close to 100%• Serologic testing anti-endomesial antibody

(EMA) or anti-tissue Tranglutaminase AB (anti-tTGA)

Celiac Disease Pathogenesis1. Gliadin is absorbed into the

lamina propria and presented in conjunction with HLA-DQ2 or HLA-DQ8 cell-surface antigens by antigen-presenting cells, probably dendritic cells, to sensitized T cells expressing the α/ß-cell receptor.

2. Tissue transglutaminase deamidates gliadin peptides, generating acidic, negatively charged residues of glutamic acid from neutral glutamines. Because negatively charged residues are preferred in positions 4, 6, and 7 of the antigen-binding groove of HLA-DQ2, deamidated gliadin elicits a stronger T-cell response

 

Farrell RJ, Kelly CP in N Engl J Med 2002;346:180-8).

Celiac Disease and Dematitis Herpetiformis

• 15- 25 % of patients with celiac disease will have DH

• IGA deposition in the upper papillary dermis

• 90% of DH will have Celiac Disease

• Affects elbows, kness, buttocks and back

Inflammatory Bowel DiseaseUlcerative Colitis Crohn’s Disease

• Colon only• Diffuse, contiguous• Mucosal• Non-smoker

• Any GI Segment• Focal, asymmetric• Transmural inflammation• Smoker• +/- Perianal• +/- Fistula• +/- Granuloma

Etiologic Factors in CD

•Genetics•Antigenic triggers

▫Microbial pathogens▫Dietary factors▫Autoantigens

•Other environmental factors▫Smoking▫Use of oral contraceptives, NSAIDs?

Stenson W. In: Yamada T (ed). Textbook of Gastroenterology. 1999:1775.Sandler et al. In: Kirsner JB (ed). Inflammatory Bowel Disease. 2000: 98.

Crohn’s DiseaseDifferential Diagnosis Location and Extent

• Primary diseases of the ileum ▫ Neoplasms▫ Vascular diseases▫ Infections▫ Miscellaneous (eg,

eosinophilic gastroenteritis)• Right-lower-quadrant

inflammatory diseases▫ Acute appendicitis▫ Periappendiceal abscesses▫ Cecal diverticulitis▫ Tubo-ovarian disorders▫ Endometriosis

40%Ileocolitis

25%Colitis

30%Ileitis/

Jejunoileitis

5%Gastroduodenitis

Crohn’s DiseaseClinical Presentation Evaluation

• Abdominal Pain• Diarrhea• Weight Loss• Growth retardation in

children• Fever• Perianal disease

• Stool studies to R/O fecal pathogens

• Blood studies to include:▫ CBC (anemia)▫ CRP or sedimentation rate

(elevated in inflammation)▫ Albumin (drops with

increasing disease activity “leaky gut”)

• Imaging studies▫ SBFT, CT, CT enterography

• Endoscopy▫ Colonoscopy with ileal

intubation, Capsule endoscopy, EGD for upper symptoms

Crohn’s Disease Evaluation

SBFTCT Enterography

Endoscopic Appearance: CD

Stricture with ulcer in colon

Linear serpingenous ulcers in the small bowel

Punched out colonic ulcer

Capsule Endoscopy Linear ulcers in SB

Crohn’s Disease

Skip Areas

Transmural Disease: Wall Thickening of

Terminal Ileum

Crohn’s Disease: Clinical Features

Inflammation Obstruction Fistulization

Pain Tenderness Diarrhea

Cramps Distention Vomiting

Diarrhea Damage to skin Air/feces in urine Types

– Enteroenteric– Enterovesical– Retroperitoneal– Enterocutaneous

Crohn’s Disease

Perianal Disease

Crohn’s Disease: Bile Salt Diarrhea and B12 deficiency

• The terminal ileum has specialized receptors for absorbing bile salts and B12. With inflammation or resection of the TI patient may develop B12 deficiency and bile salt diarrhea (choleretic diarrhea)

• Resection > 100cm Fat malabsorption

Ulcerative Colitis

Differential Diagnosis Location and Extent

• Crohn’s Colitis• Radiation damage to the

colon• Ischemic colitis• Infections: Shigella,

Salmonella, E. histolytica, E coli, C. difficile

• Antibiotic effects• NSAIDS• Diversion Colitis• Diverticular Colitis.

Ulcerative ColitisClinical Presentation Evaluation

• Bloody diarrhea• Tenesmus• Crampy abdominal pain

with bowel movements• Weight Loss• Fever• Growth retardation in

children

• Stool studies to R/O fecal pathogens

• Blood studies to include:▫ CBC (anemia)▫ CRP or sedimentation rate

(elevated in inflammation)▫ Albumin (drops with

increasing disease activity “leaky gut”)

• Imaging studies▫ Plain film of the abdomen to

R/O toxic dilation• Endoscopy

▫ Sigmoidoscopy or Colonoscopy

Endoscopy: Ulcerative Colitis

Contiguous, mucosal disease with superficial ulceration and

exudate. In patients with limited disease – sharp cut off

to normal mucosa.

Complications of UC

Toxic MegacolonSurgical Emergency: High risk of perforation.

Colorectal Cancer• Start dysplasia screening

with colonoscopy and biopsy 8-10 yrs post diagnosis

• 5-ASAs ? protective

Aminosalicylates/Antibiotics

Immunomodulators

Corticosteroids

Surgery

Treatment for IBDDisease Severity

Mild

Severe Infliximab/Tysabri

Cyclosporin (UC)

• A 28 y/o female has been treated for 6 years for Crohn’s disease of the ileum. Her main symptoms have been diarrhea and abdominal pain. She has continued to have active disease over the past year. Despite the use of mesalamine, she has required frequent course of corticosteroids. In fact, she has been unable to get completely off prednisone for the past 4 months.

• PMH: CD x 6 years, no prior surgery, ileal involvement• Meds: Mesalamine – 4 g/day, Prednisone 20 mg/day

What is the most appropriate treatment at this time?1.Admit to the hospital for IV cyclosporin2.Increase mesalamine from 4 grams per day to 6 grams per day3.Initiate therapy with azathioprine4.Evaluate for surgical resection as a patient is a treatment failure5.Admit to the hospital for TPN

Colon

•Colon Cancer Screening•Polyposis Syndromes•Lower Gastrointestinal Bleeding•Ischemic Colitis

A 68-year-old man undergoes colonoscopic evaluation as part of a workup for microcytic anemia. A friable mass is found in the descending colon, but the study could not be completed because of inadequate bowel preparation. The biopsy results confirm that the mass is an adenocarcinoma. The patient exhibits no signs or symptoms of obstruction from the mass. What is the most appropriate next step in management?

▫ Full-body positron-emission tomography (PET) scanning ▫ CT scan of the abdomen and pelvis and measurement of carcinoembryonic

antigen level ▫ Surgical resection ▫ Repeat colonoscopy to evaluate the entire colon ▫ Initiation of neoadjuvant chemotherapy

USPSTF Recommendation for CRC Screening• Regular screening, beginning at age 50, is the key to

preventing colorectal cancer.1 The U.S. Preventive Services Task Force (USPSTF) recommends screening for colorectal cancer using high-sensitivity fecal occult blood testing, sigmoidoscopy, or colonoscopy beginning at age 50 years and continuing until age 75 years.1

• Recommended screening tests and intervals are:2

▫ High-sensitivity fecal occult blood test (FOBT) - Annually▫ Flexible sigmoidoscopy – Every 5 years▫ Colonoscopy – Every 10 years

A healthy 53-year-old male undergoes routine screening colonoscopy. He has no family history of colon cancer and no symptoms of any gastrointestinal illness. A single 0.7-cm polyp found at the rectosigmoid junction is successfully removed. Pathologic examination shows a tubular adenoma with low-grade dysplasia. What is the most appropriate follow-up?

A. None; schedule repeat colonoscopy in 10 years B. Flexible sigmoidoscopy in 1 year C. Colonoscopy in 1 year D. Colonoscopy in 3 years E. Colonoscopy in 5 years

Polyp F/U Recommendations• surveillance colonoscopy in 5 years for patients

with 1 or 2 small (<1 cm) tubular adenomas and no family history of colon cancer.

• Patients with multiple adenomas (>3), a large adenoma (>1 cm), villous histology or high-grade dysplasia, or a positive family history of colon cancer should undergo repeat surveillance colonoscopy in 3 years

• Hyperplastic polyps – routine CRC in 10 years , no increased surveillance.

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Polyposis Syndromes

Familial adenomatous polyposis (FAP) Mutations in the AFP gene, autosomal

dominant, 100% chance of CRC Associated with adenomatous polyps of

duodenum, periampullary carcinoma, hamatomatous polyps of the stomach

Gardner’s syndrome: soft tissue tumors, osseous abnormalities, endocrine tumors, abnormal dentition, autosomal dominant, variant of FAP

Jasperson KW, et al. Gastroenterology. Jun 2010. 138(6):2044-58.

Polyposis Syndromes

▫Turcot’s syndrome—polyposis with brain tumors

▫Peutz-Jeghers Syndrome—multiple intestinal hamartomatous polyps with mucocutaneous pigmentation autosomal dominant STK11 gene (19p13.3) 15-fold increase in intestinal cancer

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Jasperson KW, et al. Gastroenterology. Jun 2010. 138(6):2044-58.

Polyposis Syndromes Hereditary non polyposis colon

cancer (HNPCC, “lynch syndrome”) Autosomal dominant Due to mutations of DNA mismatch

repair genes CRC at young age Associated with endometrial and ovarian

Ca

64

Jasperson KW, et al. Gastroenterology. Jun 2010. 138(6):2044-58.

Colon Cancer Screening

• Familial syndromes▫ HNPCC

Begin at age 20–25, or 10 years earlier than youngest age of colon CA dx in the family, whichever comes first

Colonoscopy every 1–2 years▫ FAP

Begin at age 10–12 and continue until age 35–40 if negative

+/- genetic counseling and testing

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Dominic OG, et al. Am J Gastroenterol. Oct 2009. 104(10):2626-7.