GI

odynophagia

• Oropharyngeal or neurologic.
• Needs a PEG

motility

LES

Sticture or malignancy

• EGD is the procedure of choice
• PPI is not appropriate since dysphagia usually requires more workup.
• Consider Barium Swallow if it sounds like a motility problems such as dysphagia with cold water

• Achalasia
• Diffuse esophageal spasm
• Scleroderma

• No peristalsis
• Elevated LES pressure
• Failure of LES to relax completely, thus unable to open up completely

• Dysphagia for both solids and liquids
• Delayed regurgitation
• Nocturnal cough, aspiration
• Occasional chest pain

• Barium swallow
• EGD
• Motility study

You may have to do all three of them in the order above

• Barium Swallow:
• Dilated esophagus -- degree of dilation corrlating with duration
• "Bird bead" distal esophagus
• Delay in emptying
• Retained food in esophagus

• EGD:
• Dilated esophagus/retained food
• Performed to rule out tumor at GE junction

• Motility:
• Showing no organized peristalsis
• Non-relaxing, high-pressure LES

• AKA secondary achalasia
• The presentation of achalasia due to malignancy
• Clinical features: Age > 60, short duration of semptoms, profound weight loss
• Barium swallow and manometry may be exactly the same as regular achalasis

• No medical treatment
• Standard would be pneumatic dilation -- 5% risk of rupture due to the very large balloon used.
• Surgical -- laparoscopic myotomy
• Endoscopic botox for high risk pt - relief may last 6-8 months

EGD and manometry

Esophageal spasm

• Intermittent dysphagia for solids and liquids (especeially cold liquids)
• Chest pain -- atypical for angina
• Barium swallow -- usually normal but can show "corkscrew"

Once you see "corkscrew," you have obtained the diagnosis

• EGD very low yield
• 24-hr pH probe -- some cases are due to atypical reflux
• Motility -- diagnostic criteria for DES, but also low yield
• Most of time, no additional workup needed once you see the "corkscrew" on the esophagram.

• Trial PPI
• Anti-spasm agents
• Anti-anxiety
• Calcium channel antagonists
• Reassurance - go for this first if the patient is anxious

• Lower esophageal ring
• Stricture or esophagitis
• Neoplasm

• They will show a dilated esophagus with an indentation just above the diaphragm
• Lower esophageal ring
• Intermittent solid food dysphagia
• Often for steak, chicken
• Often regurgitates for relief
• Always have hiatal hernia, but unknown if reflux plays a role, but it is becoming commonif not standard, to put on PPI after dilation
• Treatment: Dilation

• So, answer is endoscopic dilation, then PPI
• 

• Most common cause: Reflux
• Solid food dysphagia; can be progressive
• Not intermittent
• Treatment: Endoscopic dilation
• Misc. causes: Radiation, lye ingestion, NG tube trauma, pill-induced

• Esophagogram will show esophagus with smooth tapered area
• 

• Solid food dysphagia - esp food impaction
• Young males
• Often history of allergy, asthma
• EGD shows "ringed" esophagus and biopsy reveals infiltrate of eosinophils
• Treat: PPI and ingested fluticasone
• 
• 

• causes incompetent LES, poor peristalsis
• At risk for severe GERD
• Dysphagia can be due to esophagitis, stricture, or just poor motility
• Work up if dysphagia: Barium swallow and EGD - if unable to swallow, do barium swallow, otherwise go straight to EGD
• Important to assess for GERD complications -- Barretts? Esophagitis?
• Only treatment id PPI -- dilate if stricture

• Rare for common entities of stricture, i.e.,Schatzki ring
• More common causes are infections and medications
• Infections: CMV, Candida, herpes
• Medication-induced: ASA, NSAIDs, doxycycline, KCl, FeSO4, alendronate, quinidine

• LES - defective or transient relaxation
• Hiatal hernia
• Poor esophageal clearance
• Delayed gastric emptying
• Association with BMI -- Weight gain leads to more reflux

• EGD if alarm symptoms, especially dysphagia, weight loss, heme+ shools
• 24-hour pH study -- helpful in atypical cases, like refreactory symptoms and normal EGD, or atypical symptoms like cough, hoarseness

• Failure to respond to treatment
• Long history of symptoms, esp. in males
• Guide to long term treatment plan
• Alarm symptoms, like dysphagia
• Barrett's confirmation, follow-up

It confirms the diagnosis of reflux when EGD and PPI did not confirm it.

Best when taken fasting before a meal, i.e., before breakfast

• Ulcerative esophagitis
• Bleeding
• Stricture
• Barrett's esophagus

• Start with PPI qd
• Re-scope to assess healing and exclude Barrett's esophagitis in 3-6 months
• If persistent esophagitis: change PPI to bid
• Indefinite maintenance treatment

• Surgery is Fundoplication
• The following will need surgery:
• Young patient, definite GERD, intolerant of PPIs
• Any patient -- refractory regurgitation leading to cough, asthma, aspiration pneumonia

No

• Dilation can be accomplished safely
• Peptic strictures will require long-term medication use
• PPI provides better relief than standard dose histamine-2 receptor antagonists

• Change in cell type of esophagus in response to chronic injury from GERD
• Biopsy showing "Specialized intestinal epithelium" has to be present above the GE junction to call it Barrett's
• Symptoms are 2⁰ to complications like strictures, esophagitis -- this are indications for EGD
• Predominantly in white males; mean age 60
• Associated with adenocarcinoma of esophagus --which is rarely seen in absence of Barrett's
• Treat as if severe reflux -- PPI (even if asymptomatic)
• Endoscopic surveillance biopsies

Endoscopy to evaluate for Barrett's esophagus

Repeat EGD and biopsies in one year, and if still negative for dysplasia, EGD every 3 years

• Bring back in 6 months for EGD and biopsy for low grade dysplasia.
• If high grade -- look up recent recommendations

• Location in proximal 2/3 of esophagus
• Smoking and alcohol are risk factors
• Other risk factors: lye stricture, other head and neck malignancy

• Location is distal 1/3 of esophagus
• Related to reflux and Barrett's

• Start with EGD and biopsy
• Stage with both endoscopic ultrasound and CT abdomen and chest
• (endscopic u/s good for showing mets to regional nodes while CT good for showing mets to liver)
• Treat: surgery if localized
• XRT + Cistplatin + 5FU
• Then Neoadjuvant tx before surgery

• Test and treat H. pylori
• DC NSAIDs
• Trial PPI
• EGD if with alarm sx, failure of tx, or over 55 and new-onset sx

• Spiral, flagellated GNR
• Lives in mucous layer
• Mucosal invasion rare
• Chronic, nonspecific gastritis
• Infiltration PMN + lymphocytes
• Has urease

MALT lymphoma of the stomach

• Gastritis
• PUD
• gastric adenocarcinoma
• gastric B-cell lymphoma
• MALT lymphoma

• any prior history of PUD
• EGD shows gastritis, or ulcer
• MALT lymphoma
• Family history of gastric cancer
• Dyspeptic symptoms -- test and treat, if age less than 50 and no alarm symptoms

• if doing a scope anyway, do CLOtest or mucosal biopsy
• If no need for EGD: H. pylori ELISA, breath test, stool antigen test

Breath test and stool antigen are best test for eradication

• If patient is taking a PPI, this suppresses the bacteria. The CLOtest may be false negative, and the same for the breath test.
• Stool test should still be accurate.
• Use the stool test if patient cannot be taken off PPI

Patient has to be off PPI for 2-3 weeks if doing breath test.

Reflux symptoms may worsen secondary to increased acidity (H. pylori reduces gastric acidity)

• H. pylori
• NSAIDs
• Zollinger-Ellison syndrome

• first 3 months of admintistration
• Advanced age
• History of ulcer disease
• Concomittant steroids

• Empiric treatment with PPI
• H. Pylori ELISA and treat if positive
• Endoscopy if with alarm symptoms

• Dysphagia and odynophagia
• Suspected ulcer
• Follow-up healing of gastric ulcer
• UGI bleeding
• Abnormal UGI series or CT
• Epigastric pain
• Anemia, iron deficiency (start workup from below)
• Some occulrt GI bleeding
• Follow-up gastric adenoma, carcinoid

• PPI + bismuth + metronidazole + tetracycline
• PPI + amoxicillin + clarithromycin
• PPI + metronidazole + clarithromycin
• PPI should be bid

follow-up in few months for stool test to check for eradication

after stabilization

• 50%
• 30%

Use for 72 hours in any patient with endoscopic therapy

• Hereditary Hemorrhagic Telengiectasia
• Telangiectasia of fingers and nasal and oral mucosa
• History of nosebleeds
• Familial

• Pt presents with perioral pigmentation
• Hamartomas of GI tract can bleed

• Gastrinoma
• Chronic diarrhea accompanied either by bad esophagitis or peptic ulcer disease
• Ulcer disease of UGI tract
• Due to non-beta islet cell tumor or pancreas or duodenal wall
• Marked increase gastric acid and elevated serum gastrin
• 20% has MEN-1
• Workup: Somatostatin-receptor scintigraphy and endoscopic ultrasound (EUS)

chronic diarrhea + bad esophagitis or bad peptic ulcer disease

• Somatostatin-receptor scintigraphy
• Endoscopic ultrasound (EUS)

Surgical exploration if can't find lesion

achlorhydria - no acid means no inhibition of gastrin secretion

• Recurrent ulcer and no other factors
• Recurrent complicated ulcer
• Duodenal ulcer and big folds in stomach
• Duodenal ulcer and diarrhea combination
• Chronic diarrhea and gastritis despite omeprazole

• Carcinoid
• Adenocarcinoma
• Lymphoma
• GIST-stromal tumor

• Single or multiple polypoid lesions in fundus or body of stomach
• Common gastrin elevation
• Benign behavior
• Least common GI site
• Very rare to have carcinoid syndrome with this

• Usually diagnosed after symptoms
• Most with symptoms are advanced
• Abdominal pain, nausea, satiety, wt. loss
• Most common of the gastric neoplasms -- with recent trend of increase in proximal stomach near junction of esophagus and stomach

• Most common form is Diffuse Histiocytic Lymphoma
• Better prognosis than adenocarcinoma
• MALT - related to H. pylori

• omeprazole/amoxicillin/clarithromycin and F/U
• Repeat endoscopy in a few months

• Endoscopy, brush, and biopsy
• -- CT and EUS for staging
• -- most have regional nodes or direct invasion

• Surgical resection if possible
• - node-negative: 5-year survival 85-90%
• - node-positive: 5-10%
• Chemotherapy

• Gastric emptying scan
• Always exclude obstruction with EGD
• More prevalent in DM type 1

• Improve diabetes control
• Diet: liquid if severe, low fiber
• Reglan
• E-mycin -- not indicated, but does cause strong gastric contractions (only good for 1 or 2 uses)
• Gastric pacemaker?

• Symptom onset in 20s
• Overt bleeding is unusual
• Perirectal symptoms or lesions
• Symptoms often prolonged, diagnosis delayed
• Family history in 10-20%, association with smoking

• Colonoscopy
• - patchy disease, aphthous and deep ulcers, strictures, fistula
• - Colonic disease -- rectal sparing, skip lesions, perirectal disease
• - ileal disease
• CT or CT enterography: shows small bowel or colonic inflammation or thickening
• UGI with small bowel: String sign -- ileal disease
• Granulomas not common, but diagnostic

Wide claw-shaped ulcers found only in Crohn's

• Calcium oxalate kidney stones
• Pigment gallstones
• B12 deficiency
• Hypocalcemia and Vit D malabsorption
• Bile acid induced diarrhea (seen if less than 100 cm resected) Tx: cholestyramine
• Steatorrhea 2⁰ to depleted bile acids (more than 100 cm resected, Tx: low-fat diet and medium-chain triglycerides)

• Less than 100 cm resected causes "bile acid-induced diarrhea.
• Tx: cholestyramine

• More than 100 cm resected causes Steatorrhea 2⁰ to depleted bile acids.
• Tx: low-fat diet and medium-chain triglycerides

Mesalamine

• Mild disease : mesalamine, sulfasalazine, budesonide
• Acute flares: prednisone
• Immunocompromisint drugs?

• Only use in Crohn's disease of the colon
• Split by colonic bacteria to 5-ASA and sulfpyridine
• Not very effective in small bowel, only in colon
• Use in acute or maintenance
• Sulfa portion can cause side effects and allergy -- leukepenia, oligspermia

• Oral and enema preparations
• Oral forms have delayed absorption
• -- Useful for Crohn's even if small bowel disease and UC, or Crohn's of the colon
• -- Use in acute or maintenance

Interstitial nephritis

• Use in ileal Crohn's
• For mild to moderate disease
• This is an option to mesalamine

• Azathioprine, 6MP and methotrexate
• Value as steroid-sparing
• Maintenance agent
• Takes 3-4 months to start working
• Probably more useful for Crohn's disease, but can be used in UC
• Side effect: BM suppression, esp. WBC -- follow the CBC

• Infliximab, adalimumab and certolizumab
• Indications: Fistulous Crohn's, moderate-to-severe active Crohn's and refractory UC
• Generally requires ongoing treatment
• Screen for TB before treating
• Arthralgias are very common after start of treatment

• Crohn's: Perianal abscess, fistula
• UC: Only if peritonitis, toxic megacolon, pouchitis

Side effects, especially neuropathy limits long term use

• Infliximab is most helpful
• If symptoms weren't severe, could also use Flagyl and 6MP, but would take longer to respond
• Mesalamine and steroids would never help fistulous disease

Mesalamine, also sulfasalazine

• Mesalamine
• Budesonide

• Infliximab
• Metronidazole
• 6MP

Corticosteroids

• 6MP (or azathioprine)
• Infliximab

Uniform, continuous, mucosal inflammation, may be shallow ulcers, nothing deep

• Bloody diarrhea and abdominal pain - main symptoms
• Variable extent
• -- Proctitis - Rectum only
• -- Proctosigmoiditis
• -- Extensive colitis (pancolitis)
• Contstitutional symptoms are common

• Peripheral polyarthritis (RF negative)
• Ankylosing spondylitis (HLA-B27)
• Skin lesions (E. nodosum, pyoderma)
• Eye: Iritis, episcleritis, uveitis
• *HLA association tends not to improve with colitis treatment
• *Not unique to UC, seen with Crohn's

• Primary Sclerosing Cholangitis
• -- this can occur even after colectomy

Order ultrasound or MRCP

Colonoscopy q 2 years after 10 years, and q 1 year after 20 years

• High grade dysplasia -- colectomy
• Any mass lesion or cancer -- colectomy

Sulfasalazine, 5-ASA, topical

Steroids

• Hospital
• IV fluids
• Steroids
• Antibiotics

Sulfa and 5-ASA decrease recurrence

Azathioprine or 6-MP

• Cyclosporine
• Infliximab
• Don't forget surgery

• a. Suppository mesalamine
• b. Enema (hydrocortisone or mesalamine)

After topical treatment, may still need oral maintenance

• Intractable disease
• Growth retardation in children
• Perforation
• Toxic megacolon
• Massive hemorrhage
• Suspected cancer, high-grade dysplasia
• Stricture

C. diff

Crohn's: Lesions are focal, skip, deep; granulomas are present (not always there, but pathognomonic); with rectal sparing, and absecess or fistula on perianal disease.

UC: Lesions are shallow, continuous; no granulomas, always involve the rectum, no perianal disease

• Colonoscopy is usual method to assess
• Very little role for barium enema
• Never BE in acute illness
• Crohn's patients should quit smoking
• Most UC patients are non-smokers

• acute -- up to 14 days
• persistent -- 14-30 days
• chronic -- 30 days

• Definition: Occurs during or within 10 days of travel
• Attack rate: up to 40%
• Most common organism: Enterotoxigenic and enteroadherent E. coli (ETEC and EAEC)
• Lasts 3-5 days
• Prevention is key
• Prevent with bismoty subsalicylate or lactobacillus
• Treat: Bactrim, doxycycline, fluroquinolone, rifaximin
• No treatment needed after acute phase

• Salmonella (sickle cell, achlorhyrida)
• Campylobacter (most common)
• Shigella
• Yersinia (joint pains, rash)
• E. Coli 0157:H7

Yersinia

Salmonella

• Most common bacterial colitis
• 90% with diarrhea and fever
• Abdominal pain and bloody stools are common
• Assoc with Guillain-Barre
• Tx: E-mycin and azithromycin preferred. Cipro works but increasing resistance
• No treatment if mild

• Same sx as campylobacter - bloody diarrhea
• Treat if severe sepsis or underlying medical or immune disorder
• Resistance in ampicillin and Bactrim (but ok to use if sensitive)
• Ciprofloxacin effective, higher relapse
• Tx: Levofloxacin for 5-7 days

• Very bloody diarrhea
• Only small inoculum is needed
• Tx: ampicillin unless PCN-allergic or community has resistance
• Bactrim effective
• Fluoroquinolone good choice if acquired in developing country

• Contaminated beef
• Sporadic and epidemic disease
• Bloody diarrhea, often n/v
• Right colon involved
• Associated with complicated HUS and TTP
• Don't treat with antibiotics -- patients treated with antibiotics can develop HUS
• Tx: supportive measures only

• Empiric antibiotic treatment if severe: > 8 stools per day, bloody. fever, volume depletion, severe enough for admit, immunocompromised
• Empiric tx -- flouroquinolone

• Metronidazole + iodoquinol
• Then add paronomycin afterwards to get rid of the luminal phase of any amoeba remaining

• most common extraintestinal manifestation
• Usually a traveller or recent immigrant who presents with Fever, RUQ pain, WBC > 10,000
• Concurrent diarrhea in approx 1/3
• Abnormal LFTs common; alk p in 75%
• Rare increase in bili
• Multiple abscesses
• Complications: Rupture into chest, peritoneum

• Scenario: Travel (mountain streams), daycare workers
• Presentation: Acute, sub-acute, and chronic. Foul-smelling diarrhea, bloating, diarrhea, cramps, malabsorption, weight loss
• Giardia is hardy in cold water and resistant to chlorine

• Tx: Metronidazole and tinidazole
• Dx: Stool antigen
• No eos
• No systemic symptoms
• No fecal leucocytes

Secretory: Daily stool volume > 1 L daily, continues even if pt fasts, solute gap <50

Osmotic: daily stool volume < 1L/day, stops when pt fasts, solute gap > 50

• Resolves with fast, gap > 50
• Lactose intolerance is a common cause
• Assoc with Nutrient malabsorption -- pancreatic disease or celiac disease

• Enteral feeding is the preferred route of providing nutrition in patients with severe acute pancreatitis
• Imipenem therapy is only helpful in acute pancreatitis when there is evidence of pancreatic necrosis.
• Pancreatic necrosis is diagnosed by a contrast-enhanced CT scan that shows nonenhancing pancreatic tissue.
• In patients with noninfected pancreatic necrosis, antibiotics may decrease the incidence of sepsis, systemic complications (for example, respiratory failure), and local complications (for example, infected pancreatic necrosis or pancreatic abscess).
• Prospective trials have shown no benefit from antibiotic use in acute pancreatitis of mild to moderate severity but may lead to development of nosocomial infections with resistant pathogens.
• Pancreatic débridement is recommended only in patients with pancreatitis and infected pancreatic necrosis.

• Malabsorption due to small bower atrophy of villi
• Presentation
• -Dermatitis herpetoformis
• -Iron deficiency anemia
• -Diarrhea, wt loss, malabsorption, osteoporosis, infertility, unexplained LFTs
• Dx:
• - Tissue transglutaminase*
• - Antiendomysial Ab*
• - Antigliadin Ab
• Treatment: Gluten-free diet
• 

• Tropheryma Whipplii
• Sx: weight loss, arthralgias, abdominal pain, diarrhea, malabsorption
• Dx: endoscopy with small bowel biopsy
• Bx: Foamy macrophages, bacterial remnants stain with PAS stain
• Tx: Ceftriaxone, then TMP for 1 year
• May relapse with CNS sx

• Steatorrhea: the best indicator
• Sudan Stain: best screening test
• Serum carotene: less specific
• Quatitative fecal fat is gold standard (> 14 g/day)
• Pancreatic insufficiency has the most fat.

• Celiac
• Crohn's if B12 def

• Normal D-xylose excludes small bowel disease (urine > 5 gm after 25 gm oral dose)
• Low D-xylose: small bowel disease, poor gastric emptying, bacterial overgrowth, ascites, renal insufficiency, old age
• Biopsy if low D-xylose

If normal D-xylose, do trial of pancreatic enzymes

• Structural abnormalities: Diverticula, prior surgery
• Motility disorders: Diabetes, scleroderma
• Symptoms: diarrhea, steatorrhea, abdominal distension, wt. loss
• Diagnosis: Lactulose breath test,
• Empiric tx: Tetracyclline, Augmentin, or rifaximin 400 mg tid for 7 days
• Pearl: Increased folic acid but high MCV from B12 deficiency

• Characteristics:
• -abdominal pain relieved by defecation
• -altered stool frequency
• -altered stool form
• -abdominal distention
• -no organic symptoms
• -no nocturnal symptoms
• -symptoms more than 3 months
• -no iron deficiency or anemia

Do a colonoscopy. IBS onset is usually in the early 20's.

• Chronic, watery diarrhea
• Middle-aged to elderly female
• Associations: NSAIDs, autoimmune disease
• Know how to make diagnosis: need colonoscopy or sigmoidoscopy of normal looking mucosa
• Does not evolve into UC or Crohn's

• Age > 50
• Hx adenoma
• 1st degree relatives
• Familial polyposis
• UC or Crohn's (after they've had the disease for 10 years or more)
• Hereditary nonpolyposis: HNPCC
• Diet of High-fat, low fiber

• Adenoma
• Risk of cancer: size > 2 cm, sessile base, multiple polyps, villous
• No malignant potential: hyperplastic polyps
• Tx: Remove at colonoscopy and follow closely

• If no polyp, or hyperplastic, can f/u in 10 years.
• One or two adenomas, then 5 years

• Repeat colonoscopy in three years for any of the ff:
• 3-10 adenomas found
• Any adenoma larger than 10 mm
• Any adenoma with villous eratures
• Any adenoma with high-grade dysplasia

• Autosomal dominant
• Hundres of adenomas
• 100% cancer risk
• -scope to confirm diagnosis
• -Elective proctocolectomy by age 20
• Gardner Syndrome: Same as FAP except bone lesions -- osteomas, soft tissue tumors
• After proctocolectomy, recommend UGI endoscopy every few years to evaluate for duodenal polyp. Duodenal cancer -- the second most common cause of death
• Screen family members

• Peutz-Jeghers syndrome
• -Hamartomatous polyps GI tract
• -Pigmentation on lips
• -Can bleed or obstruct
• -Main clinical problem early: Small bowel obstruction from intussusception
• -Clinical problems later: At risk for different malignancies

• HNPCC or Lynch syndrome
• Colon Ca in three 1st degree relatives over 2 generations, one with dx < 50 years old
• Right sided colon cancers
• Screen for other malignancies: endometrial, renal, ureteral, gastric
• Start screening early -- Colonoscopy at 25

• Cancer confined to the mucosa and submucosa
• About a quarter of cases
• 5-year survival -- 93%
• No treatment after resection, but careful follow-up
• Colonoscopy followup after a year

• Cancer extends into or through the muscularis, but no lymph node involvement
• About 30% of cases
• 5-year survival: 72 to 85%
• Chemo if locally advanced

• Cancer extends into lymph nodes
• 26% of cases
• 5-year survival: 44 to 83%
• Treat with FOLFOX: 5FU + leucovorin + oxaplatin

• Spread into liver
• Poor prognosis

• Occult bleeding
• Iron-deficiency anemia
• Gross lower GI bleeding (not hemorrhoidal in young)
• Abnormal barium enema
• Adenomatous polyp on flexible sig or in past
• History of colon ca
• Family history of colon ca
• Bacteremia; Strep bovis, Clostridium septicum
• Ischemic colitis
• After an acute attack of diverticulitis: 4-8 weeks later

• Most frequent congenital GI anomaly
• Cause of half of GI bleeds in children and young children
• Can cause obstruction, intussusception
• Not seen on barium enema, rarely on UGI series
• Dx: technetium scan

• Diverticulosis - most common, painless
• AVM
• Colon cancer or polyp (and post-polypectomy)
• Ischemic colitis: Always with pain
• Upper source; duodenal ulcer
• Meckel diverticulum - in young patient
• Anorectal source

• Telangiectasias on physical exam and family history
• History of epistaxis
• Family history of GI bleeding or epistaxis
• AVMs (multiple) of GI tract -- more upper than lower

Video capsule

• Severe abdominal pain followed by severe bloody diarrhea
• Usually pain in the LLQ
• Involves watershed area -- splenic flexure
• Low-flow state, not embolic
• At risk: CHF, hypovolemic
• Treatment: Bowel rest, IV fluid, possible antibiotics
• Usual resolution > 50%
• Dx: colonoscopy
• No angiogram
• Young patients: workup for Protein C deficiency, Antithrombin III def
• Females: oral contraceptives
• Cocaine use
• Pseudoephedrine users
• Long-distance runners

• Classic triad:
• 1. Abdominal pain after meals - 30 min. after meals
• 2. Decreased pain with smaller meals and weight loss
• 3. Abdominal bruit
• Diagnosis: mesenteric angiogram -- CT angiogram, or MR angiogram

• Acute, severe abdominal pain
• Symptoms out of proportion to exam
• Vomiting, diarrhea, occult blood (not gross)
• Acidosis, elevated amylase
• Dx: Angiogram

Cholecystectomy

• Amylase 3X normal
• Lipase peaks later
• Hemoconcentration - a bad indicator
• Leukocytosis
• Bili > 3 and increased ALT suggest common bile duct stone

• NPO, aggressive IV fluids
• NG tube if ileus or vomiting
• Tx: Imipenem if necrosis on CT, otherwise no antibiotic
• Feed: jejunal feeding is superior and safe

• Can be seen in acute or chronic
• Usually 2 to 4 weeks after acute episode
• Can spontaneously resove
• Size > 5 cm unlikely to resolve, need drainage or surgery after acute episode
• Size ≤ 5 cm can be observed rather than surgery, etc.
• Can be complicated -- infection, hemorrhage
• Consider if delayed recurrence of pain with another elevation of amylase

• Early ony if ongoing biliary sepsis, biliary obstruction, cholangitis, rising bili
• Later for other cases; suspected due to CBD stone, unknown cause, Ca of pancreas
• Timing of lap chole -- can be done early but wait until pancreatitis has subsided

• Early: recurrent pain episodes
• Late: Steatorrhea and diabetes (80-90% function lost)
• Fecal fat can be very high (40-100 gm/d)
• Increased risk of pancreatic cancer
• Dx: calcification on KUB - not usually seen, but significant if present
• CT and EUS: Best second step
• Classic diagnostic triad: Pancreatic calcifications, diabetes, steatorrhea
• MRCP: visualizes pancreatic and bile ducts. Order before the invasive ERCP if suspicious of CBD stone

• Risk factors: Smoking, chronic pancreatitis, DM
• 5th leading cause of cance deat in U.S.
• Presentation: Jaundice, abdominal or back pain, and weight loss
• Most located at head of pancreas
• Elevated CA 19-9
• If mass: CT-guided biopsy, or needle biopsy at EUS
• If no mets: Consider eval for surgery.
• Resectable if: no mets, no encasement of vessels. If either of these are present, then non-resectable.
• If mets or local vascular invasion: ERCP + stent to give palliation of the jaundice.
• Gemcitabine: Improves survival, reduces pain and improves QOL

• Can occur in bile duct with chronic infection: Clonorchis, strictures, cholangitis
• Can occur in gallbladder with hemolysis
• Can occur in Crohn's pts, with ileal disease or ileal resection
• 50% radio-opaque
• Symptoms: Pain is epigastric or RUQ. Constant for 20-60 minutes. Nausea and vomiting. (dyspepsia, heartburn, and fatty food are not sxs)
• Ultrasound: 90% sensitive
• HIDA for acute cystic duct obstruction

• Treatment if symptomatic: cholecystectomy
• If asymptomatic: no treatment. Bile acid never used
• Common duct stones: ERCP

• Cholangitis: Charcot's triad -- abd pain, fever and chills, jaundice
• Pigmented stones or cholesterol
• Management: Antibiotics, endoscopic sphincterotomy, surgery if ERCP unable to pull out stone

• Pain and increased LFT's
• Immediate post-op: Think bile duct leak
• Any delay (think months to years later): Think Choledocholithiasis, need ERCP

• MR cholangiography: Sensitivity for CBD stones about same as ERCP
• Use when index of suspicion is low to moderate -- i.e., if pt with pancreatitis, CBD stone mildly dilated but bili is normal
• If high index of suspicion, go straight to ERCP

• Middle-aged women
• Main symtoms: Fatigue, pruritus, often suspected based on symptoms alone
• Often asymptomatic
• Autoimmune disorders are common (Sjogren's, CREST, thyroiditis)
• PE: Xanthelasma, skin hyperpigmentation, hepatomegaly, other signs of liver disease
• Diagnosis:
• -Increased alk phos (can be marker) and GGT
• -Anti-mitochondrial Ab
• -Increased cholesterol (HDL)
• -Increased IgM
• -Bili usually normal
• Liver biopsy required to establish dx
• - nonsuppuratie destruction of small bile ducts
• - reduced biliary excretion
• - accumulation of bile acids and copper
• - early stage: (I) chronic inflammatory cells and granulomas adjacent to damaged bile ducts
• Natural History
• - Asymptomatic: survival 10-16 years
• - Asymptomatic: Survival 7 years
• Symptom treatment:
• - Pruritus: Cholestyramine
• - Metabolic bone disease: Calcium, Vit D, estrogen, bisphosphonates
• - Malabsorption: Restrict dietary fat, medium-chain triglycerides
• Complications:
• - Steatorrhea
• - Wt. loss
• - At risk for deficiency of fat-soluble vitamins -- most importanc clinically is D
• - Liver failure
• Treatment for PBC: UDCA (Ursodeoxycholic acid)
• Poor prognosis if Bilirubin increasing -- refer for liver transplant
• Best test for diagnosis: anti-mitochondrial antibody

• Primary biliary cirrhosis: Anti-mitochondrial Ab 90% pos; anti-smooth muscle Ab neg
• Autoimmune chronic active hepatitis: Anti-smooth muscle Ab pos; anti-mitochondrial Ab occ pos at low titers
• Drug-induced chronic active hepatitis: Anti-mitochondrial Ab occ pos; Anti-smooth muscle Ab neg

• Phenothiazine
• Steroids
• Bactrim

• Male to female 2:1
• Average age: 45
• 75% have IBD, esp UC
• No relation to severity of colitis
• Often asymptomatic at first
• Later Sx: Weakness, fatigue, itching, jaundice, cholangitis
• Labs:
• -increased Alk Phos
• -Mild increase AST and ALT
• -Bili usually normal
• -Positive pANCA
• Tests: MRCP and ERCP show multiple strictures of intra= and extrahepatic bile ducts. Do MRCP first with suspected PSC

• Slow, indolent course
• 5-year survival: 60-70%
• Most will progress to liver failure
• Cholangiocarcinoma in 10%
• Liver transplant for end-stage disease
• Ursodeoxycholic acid may help pruritus
• Stricture dilation
• No benefit from colitis treatment or colectomy
• These pts have significant colon cancer risk, more than just colitis -- go to every year colonoscopy

• Associated PSC: more commonly men
• -Lifetine risk of cancer: 10%
• -Time with PSC before Ca: Variable
• Other associations: choledochal cysts, clonorchis sinensis
• Sx: painless jaundice, pruritus
• Labs: Alk phos, GGT > transaminases
• - CA 19-9 > 100% in 80%
• ERCP: brush cytology 50% yield
• Use CT, MRI, EUS if needed
• If mass found early and procedures above non-diagnostic, may have to do surgery

• ALT more liver-specific than AST
• Alcohol AST:ALT 3:1
• Viral hepatitis ALT > AST
• Workup for increased ALT: full set biochemical -- Alk phos, direct and indirect bili, albumin, PT, CBC
• Persistent increase: Hepatitis panel, Fe, TIBC, Ferritin

• Only hepatitis DNA virus
• Incubation 1-6 mos
• Transmission: Sexual contact, IV drugs, vertical mother to newborn
• Activates cellular immune response
• Vigor of immune response determines course
• Acute HBV:
• - Usually acute infection asymptomatic
• - Can present as serum sickness due to immune complex disease with fever, urticaria, arthralgias
• - Glomerulonephritis, vasculitis, PAN
• Chronic HBV:
• - nonspecific sx
• - malaise, fatigue, anorexia

• Initial rise HBsAg
• Later anti-HBc
• HBsAg usually becomes undetectable
• Window period: Anti-HBc IgM
• HBeAg correlates with intact virus and infectivity
• Risk of chronic HBV inversely related to age
• - 90% infants infected at birth
• - 25-50% children age 1-5
• - 1-5% oder children and adults
• Development of clinical disease relates to age:
• - 10% of children have sxs
• - 30% adults over 30 have sxs

• Acute infection: HBsAg
• Acute infection and Chronic, carrier: HBsAg and HBcAb
• Remote infxn, immunized: HBsAb
• Remote infection: HBcAb, HBsAb
• Window, remote infection, false pos: HBcAb
• More than one infection: HBsAg, HBcAb, HBsAb

• Most have HBsAg
• Usually HBeAg (in the U.S.)
• Positive HBcAb IgG
• High levels of HBV DNA

• Termed non-replicative state
• HBsAg persists
• HBcAb present
• HBV DNA present at low levels
• Inflammatory response minimal

• Recombinant vaccines
• Indicated pre- and post-exposure: prophylaxis
• Post exposure: Give HBIG too
• Check HBsAb for effect
• Reduced response in cirrhosis, chronic renal failure, immunosuppressed
• Immunocompetent patients: 90-95% develop Ab
• Chronic hemodialysis patients: 50-60% develop Ab

HBIG and vaccine at birth

• Any HBeAg+, and eAg- with HBV DNA, and compensated cirrhosis with HBV DNA greater and 2000
• Options for treatment: Interferon, lamivudine, adefovir, entecavir, telbivudine
• Lamivudine has highest risk of developing resistance

• Liver failure with Hep B is an indication for liver transplant
• High rate of recurrent infection (up to 100%)
• Give long-term HBIG, lamivudine

• Lifetime risk HCC around 20%; therefore screen with alpha-fetoprotein and US q 6 months
• Risk of HCC varies with viral load: increased risk with HBV DNA > 10,000 copies/ml

• RNA virus
• Incubation 15-50 days
• Acute infection: Anti-HAV IgM

• Travel or working in high-risk contries
• Children in communities with high rates of disease (> 2 yr)
• Individuals with high-risk behavior
• Patients with chronic liver disease

• Single-stranded RNA
• Genotype 1: 70% U.S. infection
• Prone to mutation - genetic diversity

• Sexual transmission is low. Monogamous relationship 10-20 years -- 5%
• Household contact -- extremely low
• Maternal infant transmission: < 5%
• Health care worker needle stick: 5-10% from known infected pt. No treatment needed after needle stick

• Acute infection: only 25-35% have sxs
• Rare, fulminant liver failure
• Incubation period: 7 weeks (range 3-20)
• Chronic phase
• - 30% carriers: no sxs and normal LFTs
• - 50% no sxs and abnormal LFTs
• - 20% clinical liver dz with sx

• Small vessel vasculitis
• Most common cause:
• - Essential mixed cryoglobulinemia
• - Skin rash: Purpura, vasculitis, urticaria
• - Joint, muscle aches
• - Porphyria cutanea tarda
• - Neuropathy and glomerulonephritis associated with cryoglobulinemia

Porphyria Cutanea tarda which is associated with Hepatitis C

• If positive in low-risk pt, confirm with Recombinant Immunoblot Assay or HCV-RNA
• HCV-RNA by PCR: Useful in response to tx, confirm diagnosis
• Liver bx: Assess severity, presence cirrhosis
• ALT usually > AST

• Pegylated interferon with weight-based ribavirin
• Indication: Abnormal LFTs, moderate fibrosis on bx
• Adverse effects: Flu sx, leucopenia, low platelets, fatigue, depression*
• *Be careful with pt with depression before treatment. Do not give interferon. Depression has to be under good control for fear of suicide.
• Genotype I: most common in U.S., has lowest response to treatment, treat for 1 year
• Genotype II and III: has better response, treat typically shorter for 24 weeks
• Follow HCV-RNA for treatment
• Overweight pt has poor response
• Best response: Female, less than 40, less fibrosis on biopsy
• Ribavirin side-effect: Hemolytic anemia
• Can use EPO if respoding but Hgb < 10
• Vaccinate for HBV and HAV

• Tx: PEG interferon and ribavirin
• Only 27% sustained virologic response at 72 weeks
• No co-administration of didanosine

• Known complication
• Median interval: 30 years
• Surveillance: US and alpha-fetoprotein q 6 months

• RNA virus, requires HBV
• found in IV drug abuse, high-risk HBsAg carriers
• Can be severe if superinfects HBV carrier
• Diagnosis: Anti-HDV IgM

• Fecal-oral spread like HAV
• Far East, Africa, Central America
• Contamination of water supply
• No chronic state
• High-risk fulminant in pregnancy (mortality 20%)

• Young women, 50% autoimmune disease
• Acute, fulminant, or indolent
• Can be asymptomatic or nonspecific sx
• Anti-smooth muscle Ab -- 80%
• Low titer AMA, ANA
• Elevation of gamma globulin
• Tx: Prednisone and azathioprine

• Chronic hepatitis: Methyldopa, nitrofurantoin, phenytoin
• Cholestasis: Oral contraceptives, anabolic steroids, chlorpromazine, erythromycin
• Fulminant hepatitis: Ketoconazole, INH
• Indolent cirrhosis: Methotrexate

• Acetaminophen:
• - Glutathione reduces toxic metabolite
• - Glutathione depletion-- toxin accumulates- treat with N-acetylcysteine acutely after checking acetaminophen level
• Chronic, moderate-to-heavy alcohol induces cytochrome p450 and depletes glutathione. Therefore, at risk for toxicity at relatively low levels; e.g., dose < 4 gm a day
• Other risks: dieting, weight loss, gastric bypass, malnutrition

• Young women
• Oral contraceptives and Glycogen Storage Disease
• Typically solitary lesion
• Can cause RUQ pain and rare complications like rupture/hemopritoneum

• Macrovesicular fat accumulation
• Women more susceptible
• GGT disproportionately high
• AST:ALT = 3:1
• AST less than 300

• Also known as Non-alcoholic steatohepatitis (NASH)
• Typical pt: Obese, diabetic female, hyperlipidemia
• Can cause hepatomegaly, RUQ pain
• Mild increase: ALT > AST
• Ultrasound: Fat, diffuse
• Can cause fibrosis, cirrhosis

• Hepatomegaly, RUQ bruit
• Labs: High alk phos, hypercalcemia, high alpha-fetoprotein
• 75% prior cirrhosis - any type
• Developing countries: HBV acquired at birth
• Highest risk: non-whites
• Rising incidence overall
• Leading U.S. causes: HCV, HBV, ETOH
• HCV with cirrhosis: Cancer develops 1-4% per year
• INF Tx may decrease risk of HCC
• Surveillance: AFP (alpha-fetoprotein) and ultrasound q 6 months
• Criteria for liver transplant

• Common causes: ETOH, HBV, HCV
• Uncommon causes: Post-necrotic (drug), biliary disease, R-sided CHF, A1AT, hemochromatosis, Wilson's, schistosomiasis

• Variceal hemorrhage
• 30% mortality, 30% cirrhotics bleed
• Risk of bleeding higher for larger varices
• Primary prevention: beta blockers
• Acute treatment: Banding (or sclero) and ocreotide infusion
• Treatment failure: TIPS
• Antibiotics to prevent SBP (if with ascites)
• Hepatic encephalopathy
• Hepatorenal syndrome
• -Oliguric renal failure
• -Renal vasoconstriction
• -Often iatrogenic, poor survival
• -Urinary Na < 10
• -Attempt volume expansion
• -Midodrine

• Many precipitating factors: GI bleed, pneumonia, high protein intake, low K, sedatives, alkalosis
• Hyperreflexia, asterixis
• Treat: Lactulose, antibiotics -- neomycin or metronidazole

• Appearance:
• - Bloody: Ca
• - Cloudy: infection
• - Milky: lymphatic obstruction
• Serum albumin - Ascitic albumin
• - Difference > 1.1 = portal hypertension
• - Difference < 1.1 = TB, nephrotic syndrome, pancreatitis, peritoneal carcinomatosis

• Cirrhosis
• Portal HTN
• Liver failure
• Budd-Chiari syndrome
• Right heart failure

• TB peritonitis
• Nephrotic syndrome
• Pancreatitis
• Peritoneal carcinomatosis

• Dietary Na restrictionis vital
• Cirrhosis is most common vause
• Spironolactone is diuretic of choic
• Avoid NSAID, ASA, aminoglycosides

• CHF, encephalopathy are contraindications
• Low platelets, transplant candidate are not contraindications

• Risk factors: Prior SBP, bili > 2.5, fluid protein < 1, UGI hemorrhage
• Criteria for diagnosis: > 250 neutrophils on paracentesis
• Common organisms: E. coli, S. pneum, Klebsiella
• Initial treatment: Cefotaxime
• Give IV albumin: less renal impairment and lower mortality

• Fever
• Unexplained leukocytosis
• Unexplained renal failure
• Hepatic Encephalopathy
• Abdominal pain not always present
• *Have a low threshold for doing paracentesis on pt with tense ascites and any sx such as confusion, fever

• Unconjugated hyperbilirubin (indirect, without bilirubinuria)
• Jaundice after physical stress, fasting
• Common, hereditary condition
• Autosomal dominant

• Genetic or acquired
• C282Y mutation 0.44% of U.S. non-Hispanic white population
• Autosomal recessive
• Abnormal increased intestinal Fe absorption
• Fe deposition: Liver, heart, pancrease, pituitary
• Associated with arthritis
• Sx: Hepatomegaly 95%, hyperpigmentation 90%, diabetes 65%, arthropathy 40%, Cardiac 15%
• Dx: Fe saturation, ferritin, HFE gene (use if Fe sat and ferritin are positive)
• Screen family members
• Treat with phlebotomy, try to get ferritin level around 50

• Autosomal recessive
• Presents: Adolescents with liver, neuro, personality change
• Impaired excretion of copper
• Hemolysis
• Serum Ceruloplasmin is low
• Urinary copper is high
• Slit lamp exam show Kayse-Fleisher ring
• Liver biopsy: high copper, but this is also seen in PBC and PSC

• Hyperemesis: Mild increase AST/ALT first trimester
• Intrahepatic cholestasis of pregnancy: Itching, late in pregnancy, increased ALT/AST, ↑↑Alk Phos, and Bili
• Gallbladder and CBD stones: Pain, abnormal U/S, 2nd trimester is best for surgery
• Viral hepatitis E can be severe

• Microvesicular fat deposition
• Occurs in last trimester
• Abdominal pain, nausea, vomiting
• Encephalopathy, hypoglycemia -- due to rapid liver failure
• Pruritus is rare
• Complications: Fulminant liver failure, encephalopathy, jaundice, hypoglycemia, coagulopathy
• Modest elevation of AST/ALT/Bili
• Tx: Prompt delivery

• Consider for any pt with end-stage, acute/chronic disease or with HCC
• End-stage disease: Bili > 10, Alb < 2.5, INR 2
• Refractory sx: pruritus, encephalopathy, ascites
• Assess with MELD: Includes bilie, INR, and creat

Sclerosing cholangitis

Staphylococcus aureus produces illness indirectly via a specific enterotoxin. Patients present with rapid onset of symptoms, usually within 30-60 minutes of ingestion. Patients typically experience nausea and cramps followed by vomiting. Duration of symptoms is short, usually 24-48 hours. Since humans are the principal reservoir for Staphylococcus, uncooked foods that require extensive handling, such as salads, eggs, dressings and sandwich meat, are the most common sources. Staphylococcus aureus also causes dermatologic lesions, such as pustules and abscesses, which, when present on the skin of food handlers, can be a source of contamination. In addition, Staphylococcus aureus is present in cows; therefore, milk and cheese products that are not adequately refrigerated can also cause illness.

Bacillus cereus is another organism that causes illness via the production of enterotoxins. 2 enterotoxins are produced by these spore-forming bacteria, 1 that is heat stable and another that is inactivated by heat (heat labile). The heat stable species causes primarily vomiting, while the heat labile form results predominantly in diarrhea. Intoxication caused by Bacillus cereus is most commonly associated with foods - classically rice - that have been reheated after having been left at room temperature. Illness usually occurs within a few hours of ingestion and usually resolves within 24 hours.

• Gram-positive, rod-shaped, anaerobic
• Clostridium perfringens is also a toxin-producing organism. Cramping and diarrhea are the most common symptoms of illness caused by C. perfringens. Nausea also occurs, but vomiting is rare. Inadequately heated meat products are the most common source. Onset of symptoms occurs within 12 hours of ingestion, and symptoms usually abate in a day.

Giardia lamblia is a protozoon that causes upper intestinal enteritis marked by fatigue, chronic diarrhea, steatorrhea, colicky abdominal pain, and bloating. Infection can occur with ingestion of a single cyst, and symptoms generally appear within 1 week of exposure. Fecal contamination of drinking water is a common source of infection, as is person-to-person infection via hand-to-mouth contact with the feces of an infected individual. Outbreaks have occurred in institutional facilities such as day care centers by this method. Diagnosis of Giardia lamblia can be made by visualization of trophozoites or cysts in appropriately prepared fecal specimens.

• Primary biliary cirrhosis is a chronic progressive cholestatic liver disease of unknown cause.
• Occurs predominantly in women (80% to 90% of cases) between 40 and 60 years of age.
• The diagnostic triad associated with primary biliary cirrhosis includes a cholestatic liver profile, positive antimitochondrial antibody titers, and compatible histologic findings on liver biopsy.
• Serum alkaline phosphatase level is usually elevated ten times or more above normal.

Chronic intestinal pseudo-obstruction is characterized by chronic or recurrent episodes of abdominal pain, distention, nausea, vomiting and obstipation; the disorder may be due to myopathic causes (such as scleroderma) or neuropathic causes (such as amyloidosis, diabetes mellitus, and paraneoplastic syndromes).

Sorafenib is beneficial in treating patients with unresectable hepatocellular carcinoma.

• Ursodeoxycholic acid therapy is indicated for early-stage primary biliary cirrhosis and may reduce the rate of liver transplantation and prolong survival in affected patients.
• Treatment with ursodeoxycholic acid improves the biochemical profile, reduces pruritus, decreases progression to cirrhosis, and delays the need for liver transplantation if begun at an early stage of disease. The data are more conflicting for later stages of disease. Therapy is usually continued indefinitely.

Patients at low risk of colonic neoplasia may undergo evaluation for hematochezia with flexible sigmoidoscopy rather than colonoscopy.

• a liver biopsy is indicated to distinguish between rejection and recurrent HCV infection
• HCV is known to recur in the transplanted liver almost immediately after surgery if the patient was viremic at the time of transplant. As a result, some degree of inflammation is to be expected and in some patients early histologic injury as the HCV establishes itself in the new liver. In a small percentage of patients, the HCV can recur very quickly and aggressively a few months after liver transplantation, a condition termed rapidly recurring cholestatic hepatitis C, which carries a poor prognosis. Fortunately, most patients have a much more benign course, with approximately 30% still developing recurrent cirrhosis within 5 to 10 years after transplantation. Identifying those patients who show histologic injury in the liver graft and initiating therapy in these patients is important.

Most patients with HNPCC are identified from their medical history. The diagnosis should be suspected in persons who have multiple family members with cancers of the colon, endometrium and ovaries, small bowel, ureter, renal pelvis, and pancreaticobiliary system. The Amsterdam II clinical criteria for HNPCC use the 3-2-1 rule: three relatives with an HNPCC-associated cancer, two generations affected, one person diagnosed before age 50 years.

• Management of patients with HNPCC or those who are considered at risk for the disease consists of colonoscopy every 1 to 2 years beginning at age 20 to 25 years or 10 years before the age at diagnosis of the youngest family member diagnosed with colon cancer.
• Annual colonoscopy is recommended after age 40 years.
• The risk for gynecologic malignancies is greatly reduced in affected women who undergo prophylactic hysterectomy and salpingo-oophorectomy, and many physicians advocate surgery for women who no longer wish to bear children.
• Women who do not choose prophylactic surgery should have a pelvic examination with endometrial sampling, transvaginal ultrasonography, and measurement of serum CA-125 every 1 to 2 years from age 30 years. Screening for urinary tract cancers with urine cytology and renal ultrasonography should also be performed every 1 to 2 years beginning at age 30 years.

The annual cancer risk is estimated to be 1% to 2% per year after 8 years of disease, and, therefore, colonoscopic surveillance should be started in patients who have had inflammatory bowel disease for 8 years or longer. For patients with inflammation limited to the left colon, recommendations vary, with some authorities initiating surveillance after 15 years' duration of disease. If dysplasia is detected on biopsy in a patient with colitis, the risk for colon cancer is markedly increased even at sites distant from the site of biopsy; colectomy should, therefore, be considered even in the absence of a preoperative cancer diagnosis.

• Abdominal pain that is usually mid-epigastric
• Postprandial diarrhea
• DM secondary to pancreatic endocrine insufficiency

a marker for celiac disease

Upper endoscopy is often the first test performed to establish the diagnosis. CT scanning is often the next step to evaluate for metastatic involvement, but it cannot accurately assess the depth of disease in early lesions. Conversely, endoscopic ultrasonography is the most reliable preoperative test for assessing depth of invasion, but it is poor at determining distant metastases. Positron emission tomography may be used preoperatively to follow-up suspicious but nondiagnostic abnormalities detected on CT scan

Patients with metabolic syndrome and persistently elevated liver enzyme concentrations, despite adequate treatment of its components, should undergo liver biopsy.