Hepatitis C

• Fixed factors with poor response, genotype, RNA level, histology, race, HIV co infection, steatosis, body weight, insulin resistance, adherence IB 28b genotype.
• We cannot improve insulin resistance or elevated HOMA index are less likely to respond. Improving insulin resistance did not improve outcome in spite of improving HOMA index
• Higher dose of PEG/RBV in obese is NOT helpful
• Patients with  rs12979869 genotype are more likely to respond.  It is on chromosome 19.  (IL28B with C/C type vs. TT or T/C)
• Why are AA less likely to respond.  This is because they are less likely to have C/C genotype.  This explains for about the 50% patients.   Still unknown factors for the other 50%
• Stopping ribarvarin is associated with relapse.  Protease inhibitor + PEG is not helpful  Ribavarin is a must.
• If 1.5 gm drop in Hb in 2 weeks means patient will develop severe anemia later.
• So use dose reduction early in those patients.
• Use of EPO – be cautious because of thrombosis and PRC A.
• Anasine troposphere genetic change PROTECTS against ribavarin related anemia
• Terms used are RVR, complete EVR, partial EVR and non EVR
• See page 23 on Mayo clinic
• RVR patients with low viral load, treat only for 24 weeks. (in Europe).  In USA we still treat 48 weeks.
• Telapravir – substantial drug resistance after 14 days.  PROVE-1 and II
• Boceprevir – same results. (SPRINT-1)
• Non responders PROVE 3.  Triple therapy 35% response rate and for relapsers 70% response rate.
•  

Hepatitis B

• Types  Hep B e Ag positive (and high DNA, high ALT), Inactive carrier (neg Hep B e, normal ALT, low DNA), Hep B e Ag neg chronic hepatitis( slightly high DNA, abnormal ALT, precore mutation)
• 7 drugs, limousine, adefovir, entecavir, telbivudine, tenofovir, and 2 types of PEG
• Under evaluation are emtricitabine, clevudine, valtorcitabine and combination treatment
• So far, combination treatment with limousine is not better
• .Can effectively change from adefovir (hepsera) to viread (tenofovir)
• Mnemonic TV (tenofovir is viread), BE (baraclude is entecavir)
• Newer drugs for hepatitis B are better
• Guidelines based on DNA level of more than20,000 on adult acquiring Hep B and more than 2000 for young or childhood acquired Hep B DNA
• Current guidelines are if DNA less than 20,000 IU/ml, normal ALT, and Hep B e Ag Pos no treatment and monitor every 6 to 12 months.
• DNA more than 20,000, hep B e Ag pos, normal ALT, consider liver biopsy.  Treat if fibrosis or hepatitis treat with baraclude or viread or PEG
• If DNA more than 20,000, ALT elevated and Hep B e AG pos, treat.
• If Hep B e Ag neg patients use HBV DNA level of 2000 as cut off.   If ALT neg and less than 2000 observe ever 6 to 12 months.  If more than 2000 and normal ALT consider liver bx
• If more than 2000, ALT elevated and treat. (and hep B e ag neg)
• If patient has compensated cirrhosis, HBV DNA more than 2000, treat.  If DNA less than 2000 do not treat.  Irrespective of ALT.  DO NOT USE PEG.
• If decompensate cirrhosis, hepatitis B positive treat irrespective of DNA, or hep B e Ag pos or neg. Use Viread or baraclude
• If patient is resistant to lamuvidine, do not use baraclude. (high incidence of resistance develops eventually).
• Genotype B more likely to respond to PEG, ALT > 100 for 48 weeks
• Immune tolerant pts, less than 35, normal ALT, Hep B e Ag positive, Very high HBV DNA more than a million IU/ml should be watched!
• Immune active have abnormal ALT, HBV DNA more than 20,000 and should be treated
• Immune control : normal ALT, HBV DNA less than 20,000 and no inflammation. No treatment.
• Immune escape : abnormal ALT, HBV DNA more than 10,0000, pre core mutant, inflammation plus fibrosis and Hep B e Ag neg.
• Check HDV in IVDA, hemophilic pts.  Less likely in Asians.
• Anyone going on immunosuppressant’s or anti TNF will need treatment for Hep B.
• Anti Hbc alone positive.  Repeat lab.  Usually false positive.  It can mean window phase or late immunity.  They should be vaccinated.   4% of these patients will have HBV DNA positive. 
• Patients who fail to respond to the vaccination, if obese use longer needle to immunize and inject in deltoid.
• Liver injury occurs in immune escape and immune active.  They need treatment. 
• If adefovir resistance add lamuvdiine or switch to baraclude or viread
• If baraclude resistance switch or add hepsera or viread

HCC

• Best survival is liver transplant.  Second best is resection, third is local therapy.
• 5^thmost common cancer in the world and third leading cause of cancer death
• HCC and not cirrhosis is the leading cause of death in chronic liver disease.
• Incidence of HCC has tripled in 30 years.
• Risk factors are cirrhosis (regardless of cause), HBV, HCV, male gender, iron overload, fatty liver, hypothyroidism is a risk factor of HCC in women?
• Diagnosis can be made without biopsy. Hypervascular mass in cirrhosis is HCC till proven otherwise.
• AASLD criteria – 2 cm mass on US vascular pattern is HCC or AFP more than 200 treat as HCC
• AFP elevation is not needed to diagnose cancer.
• Screen anyone with cirrhosis, hemorchromatosis pts, HBV carriers if : African age more than 20, family history of HCC, Asian male more than 40, Asian female more than 50 or anyone with HBV DNA more than 2000 or increased AT.  USE US plus AFP or trochaic CT or MR every 6 months.
• Milan criteria for transplant for HCC 1 lesion less than 5 cm or 3 lesions less than 3 cm.
• Resection is for non cirrhotic liver if restricted to one lobe or univocal tumor.
• If pt has elevated bilirubin or overt portal HTN 5 year survival is 25% with local resection.  If none of those, local resection has 70% 5 year survival.
• TACE.  Risk includes higher MELD and portal vein thrombosis.
• RFA
• RFA plus TACE is better than either individual.
• No role of ethanol ablation and limited use of cry ablation
• Sorafenib for inoperable HCC.  It is an angiogenesis inhibitor.  Side effects include, diarrhea, bleeding, MI in 3% patients, perforation, HTN, voice change, fatigue, avoid sun exposure. Dose 400 bid.
• Secondary prevention for HCC after transplant is birdlimes or sorafenib (STORM trial)

Cholangiocarcinoma

• Ig G 4  cholangiopathy.  Treat with prednisone 40 mg  for one month and taper over 5 mg every 4 weeks.  Use level of more than 140 for Ig G 4.  Ig G 4 more than 280 is 90% specific.
• Sarcoid cholangiopathy. 
• Ig G 4 elevation can occur in cholangiocarcinoma.
• PSC life long risk of cholangiocarcinoma is 10%.
• CA 19-9 elevation cut off used is 100 U/ml.  False positive if patient has bacterial cholangitis.
• FISH (fluorescent in situ hybridization). Chromosome 3, 17, 7 and locus 9p21.  Use FISH if cytology is non diagnostic.
• Eovist MRI
• PET scan about 53% accuracy.  Positive predictive value is high 90% and neg predictive value is very low.
• If FISH negative and CA 19-9 more than 100, treat as malignancy.  If FISH neg, CA 19-9 neg, get MRI plus MRCP and EUS.
• You can survive with 30% of your liver.
• It takes about 6 weeks after stent is placed,  for bilirubin to normalize if it was more than 10.  If less than 10, it takes 3 weeks to normalize.
• Use neoadjuvant chemotherapy with liver transplant for treatment – gives best survival.

Management of complicated PORTAL HYPERTENSION

• Refractory Acites  :   Occurs in 10%.   Two types.  : Diuretic intractable ascites (cannot tolerate diuretics) 80%or diuretic resistant  in 20% of casesLV paracentesis vs. TIPS.  There is no survival benefit one over the other.
• Salt restrictions plus diuretics
• Use 6 to 8 gm of albumin with every liter fluid removed. 
• LVP is preferred.
• TIPS if patient needs LVP every 7 to 14 days.
• TIPS Contraindicated in :, age more than 70,  cardiac dysnfunction, encephalopathy, renal failure, Consider TIPS if MELD more than 20
• Hepatorenal syndrome.  Two types.  Type 1 : rapidly progressive (over days to weeks). Doubling of Cr, and halving of cr. Clearance to less than 20
• Type 2, slowly progressive, cr cl less than 40, cr. 1.5, and associated with refractory ascites.
• Hepatorenal syndrome. : No longer saline is considered as adequate for volume expansion.  Use albumin 100 gm/day for volume expansion and  urinary sodium is no longer a major criteria..  Absence of shock, cr more than 1.5, no concurrent nephrotoxic drugs and absence of renal disease.
• Use vasoconstrictors Terlipressin or octreotide + midodrine
• Use of terlipressin + albumin is best combination than just albumin.  Indefinite duration of use of terlipressin.
• Side effects of terlipressin include can be serious.
• Use CVP pressure to assess intravascular volume in patients with HRS.
• HE  : Hepatic encephalopathy.  Three types  A : acutle liver failure patients.  B associated with portosystemic bypass without cirrhosis  and type C in pateints with cirrhosis.
• Stages from confusion to drowsiness, somnolence to coma.
• Poor correlation of ammonia levels with presence or severity of HE.
• Minimal hepatic encephalopathy occurs in 30-70% patients.  Detected with psychometric and neuropsychological testing, altered hand writing.  Treatment is lacunose or symbiotic (probiotics and fermentable fiber)!
• Minimal HE is associated with imparied driving, defective visual constructive ability,, visual spacial perception impaired, attention deficits, altered handwriting
• HE is precipitated :by excess protein, GI bleeding, sedtaives TIPS, temp, diuretics, azotemia
• Protein restrction is NOT needed to treat HE
• Rifaximin for HE.  Dose is 550 mg bid.  Rifaximin was associated with 60% reduction of a subsequent HE.  Decreases hospitalization by 50%.
• Unclear if lacunose works at all for HE
• Newwer guidelines : no protein restriction.  Rifaximin will become firstline. Neomycin and flagyl of unproven value.
•  

Refer for OLT

• MELD score varies from 6 to 40
• www.ustransplant.org
• www.optn.org
• MELD more than 25 get a liver
• MELD between 15 to 24, encourage for living donor transplant
• MELD between 10-14 decreased QOL.

Update in Liver transplant

• Patients develop HTN immediately post transplant.  Cirrhosis lowers the BP.
• DD for abnormal LFT post transplant
• Deceased donor Liver transplant :  two ways  duct to duct anastomosis or roux en y anastomosis.
• LDLT : here typically the right lobe of the liver is transplanted.
• Post op abnormal LFT : get an US with and without dopplers.  Must check flow esp hepatic artery flow,   Check immunosuppressive levels.  Check for CMV.  Check for HBV and HCV because of donor related viral infections.  Patients may need liver bx, ERCP.
• Rejection usually shows endothelial injury on liver biopsy.
• Most of the rejection occurs in the first 90 days.
• Early sign is elevation of alk phos but soon it is ALT and AST elevation.
• Sirolium causes hepatic artery thrombosis, interstitial pneumonitis,  elevated TG  (All of these are black box warning)
• Drug interactions with transplant drugs : A must read : calcium channel blockers, antifungal and macrolides, reglan amiodarone tagamet cause elevated level of tacrolimus and cyclosporine.
• Biliary leaks usually in 30 days but can present months later!
• First month infections are donor related infections, bacterial infection and candida.  In 1 to 6 months the infections are CMV, EBV, HIV, TB, cholnagitis, donor related
• Chronic renal disease – ESRD in 18% 5 years post op!
• Skin cancer, head and neck cancer is very common s/p OLT

Endoscopic Management of Portal HTN Bleeding

• Derma bond : off label use for GV.
• GAVE vs. Portal hypertensive naturopathy
• Transfuse to Hb of 8, use antibiotics and octreotide
• Banding every 2-4 weeks till eradiation
• EVL (band ligation ) 90% effective and better than sclerotherapy – less rebreeding, lower mortality, fewer complications,
• If actively  bleeding varix found, band it there and DO NOT band distal to it.
• If no bleeding found, start from GE junction and move proximally.
• Distal 1/3 should be ligated 5-7 cm
• PPI should be used to help promote healing.
• Sclerotherapy is second line.
• Use sclerotherapy if band ligation cannot be done.  Inject 1-2 cc at a time upto 20 cc at a session.  More complications.
• GV.  10-15% of varcieal bleeding.
• Classifications is based on location GOV 1 and 2  (1 is on lesser curvature). GOV2 are fundic.
• IGV 1 are proximal body of stomach and IGV 2 is distal body..
• Treat GOV1 : Is an extension of Esophageal Varix and treat the same EV with banding or sclerotherapy.
• Fundal GOV 2 or IGV 1.  Banding and sclera fail (90 to 100% rebleed rate).  TIPS or glue is most effective.
• IGV stands for isolated gastric varices
• Cyanoacrylate : two types : Histoacryl (must be diluated with lipoidal) or derma bond.  Dermabond is used for skin closure.  Used undiluted.   Risk of serious complications are 1-5 % include embolism, PE, CVA, severe infection and death at time of procedure.
• Avoid cyanoacrylate injection in intra pulmonary or intra cardiac shunts.
• No role for prophylactic glue injection.
• Technique.   3 cc for derma bond.   Use Wilson cook 21 gauge Macron-haber.  Use silicon at tip of scope.  1 cc over 15 seconds.  If you inject too slow – needle gets glued to varix. If too fast – causes embolism.
• You can use endoclip to buy a few minutes while you get glue ready
• String assisted retroflexion. 
• Once varix is glued repeat EGD in 4 weeks.  DO NOT remove glue cast.
• Honeycombing of antrum  is GAVE. 
• GAVE is just restricted to antrum.  GVE is diffuse and is in proximal and distal stomach.
•  Mild PHG – mosaic, with minimal to no red spot, usually in proximal stomach and usually does not bleed.
• Severe PGH is mosaic with extensive red spots, causes bleeding and treat with beta blockers and TIPS
• PHG (portal hypertensive naturopathy) and limited endo therapy.  More cobblestone than honeycombing.
• Multiple APC induced can lead to polyploidy lesions.
• Cryotherapy is emerging technique for GAVE / or GVE.  Just spray . It requires multiple sessions.  Use maximum 3 spraying per session.
• Band ligation or cry therapy for GVE if refractory to APC.  Use banding for APC induced bleeding polyposis.

Assessing patients who have cirrhosis who need surgery.

• Problems of cirrhosis on surgery include decreased liver blood flow, bleeding, increased incidence of aspiration pneumonia, pneumoperitoneum, hypoxemia and medications that are metabolized by liver.
• Pre op tests needed include MELD, Child-Pugh scores.   Check plt and INR.
• Consider stress test in patients with NASH or NAFLD.  Higher incidence of cardiovascular disease in those patients.
• Contraindications for elective surgery would be acute liver failure, acute viral hepatitis, hypoxemia, severe coagulopathy, alcoholic hepatitis.
• Child A mortality is 10 and 22 %, for B it is 30 to 38% and C it is 80% to 100% (for elective and emergency surgery)
• MELD more than 8 – high incidence of complications post cholecystectomy.  1% per MELD score in increased 30 day  mortality if less than 20.  If MELD more than 20, 2% per score increase in mortality.
• MELD is more than 14 it is superior to Childs C for predicting death / need for liver transplant.
• MELD score look up online : www.mayoclinic.com/meld/mayomodel9.htm
• Use both Chilts (CTP) and MELD.  Inform pt and surgeon.
• Correct coagulopathy with Vitamin K 10 sq for 3 days, give FFP, plt, cryoprecipitate and recombinant  Oral is not effective.  factor VIIa.  Minimize use of preop diuretics, paracentesis.
• For AIH use stress dose of steroids.
• Check albumin – consider enteral support.
• Extubate as soon as possible, minimize sedation, IV albumin as fluid replacement. 

Non endoscopicevaluation of GERD, Chest pain and dysphasia.

• Two types of motility disorders.  Inhibitory innervation disorders (achalasia, DES, transient LES relaxations) and excitatory innervation disorders (hypertensive or hypertensive peristalsis, nutcracker esophagus,)
•  High resolution manometry is faster, easier to perform and better readings.
• HRM has 36 sensors. 
• Chicago criteria for abnormalities.
• 24 hr pH should be done off medicines.
• Bravo is superior for diagnosing GERD
• Impedence measurement – when food touches catheter the impedence decreases (electric current is transmitted in the catheter)

Treatment of Dyspepsia

• FD : functional dyspepsia  :  heartburn, early satiety are 2 of the most common symptoms.
• FD patients : always related to eating in one way or the other.
• 65% of patients with UGI symptoms have FD.
• Differentiate between FD and GERD. A little heartburn does NOT mean reflux disease
• Alarm symptoms are bleeding, family history, weight loss, persistent vomiting,  etc prompt EGD is needed
• All NSAIDs cause dyspepsia. (even without ulcers)  Take a detailed medication history.
• If no alarm symptoms, emperic treatment with PPI and treat Hp. 
• Epigastric pain syndrome (EPS) and second type of FD is post prandial distress syndrome (PPDS)
• Treatment options are treatment of Hp, PPI, H2 blockers, prokinetics, antidepressants, antacids, bismuth salts, carafate, herbals.
• FD pts who are more than 40, GERD symptoms, shorter duration pts respond to PPI.
• PPDS do NOT respond to PPI but EPS pts do respond.
• If PPI does not work try H2 blockers
• Bismuth and carafate work as good as placebo!!
• Lack of fundic relaxation in FD patients causes early satiety
• Post infectious FD for eg. Salmonella gastroenteritis
• Nutrient (ensure) drink test and water load test
• Reglan does not work and lack of safety.
• Iberogast STW5 might work.  It does relax the fundus.
• Antidepressants- use as second or third line for treatment
• Venlafaxine SSRI may work
• Eosinophils in duodenum often found in pts with FD. 

IBS and constipation

• 5HT4 agonists : prucalopride
• Prucalapride – approved in Europe for constipation

Pelvic floor dysfunction

• Manometry and Balloon expulsion are adequate to make diagnosis.
• Defecography to be done if only one of them is positive.  Or get MRI.
• Biofeedback
• If biofeedback not available – use suppositories, enemas, regular bowel habits, avoid straining.
• Fecal incontinence : Obstetric injury is anterior wall of anal sphincter.
• Post surgical injury is posterior defect of anal sphincter.
• MRI is better test to identify anal sphincter abnormality.
• Diarrhea related fecal incontinence – can use colesevelam (welchol) or cholestyramine

Short Bowel

• Less than 200 cm of small bowel remaining
• Three types : jejunal resection, jejunal and ileal resection or end jejunostomy where colon is also removed.
• Complications include malabsorbption, diarrhea, fluid imbalance, oxalate nephropathy, bacterial overgrowth, metabolic bone disease, peptic ulcer dis.
• Lactose free diet is not recommended for SBS.  However, patients should have a high CHO, low fat diet, oxalate restricted and hyperosmolar fluid restriction
• Do not use questran in SBS

Nutrition in ESLD

• PEM is common.  This is due to insulin resistence, anorexia, dietary restrictions, leptin levels, increased cytokines, dietary restrictions, nutrient malabsorbption, medications

Celiac disease

• Bx second and third part of duodenum.
• There is an ultra short celiac disease which just affects the bulb of duodenum.
• Can have only abnormal changes in proximal jejunum
• It tends to be patchy
• It can mimic acute SBO, perforation, intussuception,
• Skin rashes,  dental hyperplasia, short stature, osteopenia, delayed puberty, infertility, mouth ulcers, arthritis, seizures.
• Fertility can recover after treatment of celiac.  Warn the patient they can become pregnant.
• Raised alk phos, check sprue.
• Celiac can cause hepatitis with ALT and AST of 300-400
• Hep C treatment can precipitate celiac
• It is world wide.  It occurs in Indians too
• Must have bx and serology. 
• No role of stool testing for celiac antibodies
• Keep tropical sprue in mind for DD
• You need an expert dietitian
• Family support is crucial
• Increases mortality if patient is non compliant to diet
• No wheat, rye or barley.  Also avoid lipstick, balms, mouthwash, toothpaste, play dough, OTC medications, mineral preparations, stamps and envelope glues.
• Refractory sprue – type 1 and type 2 immunity. Type 2 immunity is associated with 40% mortality!!

Biologic therapy in IBD

• Severe UC : cyclosporine and Infliximab combination – THINK twice.  Higher incidence of death and infection compared to surgery
• For UC only TNF approved is infliximab
• Post op prevention of recurrence of Crohns – Infliximab is very successful
• Combination of methotrexate and infliximab – no advantage for crohns
• Infliximab plus AZA is better than infliximab is better than AZA
• Serious infection rate is NOT higher in using combination of Infliximab plus AZA
• Top down therapy for complex perianal disease, after any colonic resection or more than 2 SB surgery or stoma within 5 years of diagnosis.
• Prevention of transmigration of neutros through the cell layer – natalizumab. 
• Natalizumab is alpha integrin monoclonal Ab for crohns
• Other drugs down the pipeline are Glomma (anti TNF), anti interleukin Ustekinumab, anti selective adhesion molecule vedolizumab,  anti CTLA-4 abatacept
• Discuss risk of infection, hepatitis B, lymphoma with use of these drugs
• Methotrexate pneumonitis
• Highest risk of infection in patients on prednisone plus AZA plus infliximab.
• Use of prednisone and narcotics associated with higher risk of mortality
• Don’t forget  hepatosplenic T cell lymphoma
• Progressive multimodal leukoencephalopathy in alpha 4 integrin Ab

Older drugs vs. newer drugs in IBD

• Aggressive crohns in pts with fistula, young age onset, smoking, early need for steroids, deep ulcers and high serologic titers
• Budesonide for right colonic CD or ileal disease
• AZA can be effective in avoiding surgery and is better than steroids in that regard
• TPMT predicts early but not late leukopenia
• Side effects of AZA include infections (7%), lymphoma risk if 4 times general population (in general population risk is 1 in 10,000),  hepatitis (10% dose dependent), nausea, dyspepsia, elevation of uric acid,
• Methotrexate maybe helpful if AZA is not tolerated or fails. 25 mg/week IM
• 3 types of UC – proctitis, left sided and pan colitis
• Canasa 1000 mg very effective for proctitis
• Oral and topical therapy for distal UC is the best.  Esp for induction remission

Complicated Crohns Management

• Refractory IBD – evaluate for celiac, bacterial overgrowth, giardia, ischemic colitis, medication colitis, PUD, gastro duodenal crohns,
• Treatment options consider – Thalidomide, tacrolimus, nataluzimab
• Vitamin A acutane can cause colitis. 
• Infections that mimic refractory IBD – TB, basidioboles, lymphoma and adenoca
• Reasons for refractory are – inadequate dose, insufficient duration, medication side effect, unrealistic expectations, medication non adherance
• Truly refractory Crohns – consider surgery.  Consider nataluzimab, AZA plus remicaide, Don’t forget methotrexate, off label use of tacrolimus or thalidomide or investigational drug
• It is better to increase dose than lower frequency of use of infliximab
• Added infections to consider with infliximab plus AZA are herpes, candida, cmv, EBV, blasto, histo, crypto, TB, strepto, e coli ?
• Higher risk of lymphoma in pts on TNF plus AZA?
• Herpes – pain occurs before rash.  Pain could be in back, chest etc
• Adalumimab – 40 mg every week is better than every other week
• If crohns more than 3 years cimzia response is 60% if less than 3 years cimzia is 70%
• Cimzia – relapse, give an extra dose in between and that should be adequate
• Tysabri (natalizumab) risk of PML black box warning
• Headache is a sign of PML.  If the patient has headache, needs a spinal tap and MRI of head  Other signs are back pain,
• Also monitor for urine for JC virus and CD34 count in blood
• Tacrolimus (Prograf) can be helpful in CD. 
• clinical trials.gov or ccfa.org for trials for CD treatment. Or contact IBD centers and ask.

Newer surgical approaches for UC

• Single incision laparoscopic colostomy
• Interest in NOTES surgery
•  

Newer Tests for IBD

• Fecal tests for IBD are calprotectin and lactoferrin
• Measured by ELISA.  NOT disease specific but elevated in colon inflammation.
• Fcal levels are more than 219 in IBD and more than 132 in colorectal cancer
• Fcal more than 150 – relapse likely and less than 150 is less likely to relapse in CD.  It is better than even endoscopy.
• Uses include response to treatment, predicting relapse, post op recurrence, monitoring mucosal healing
• CE (capsule endoscopy) : SB CD is more than suspected.  Average lag between symptoms and diagnosis is 3 years.
• CE : Apthous ulcers in early CD can occur in celiac, ischemia, drug induced, auto immune, allergic, immune deficiency
• Capsule retention is 5 to 13% in known crohns.  Risk of capsule retention in obscure bleeding it is 1.5 %
• No role of CE in UC pts
• CE can help in demonstrating mucosal healing in CD
• Perforation rate is higher in DBE, esp rectal DBE.

Dysplasia in IBD

• Backwash ileitis pts are more likely to have dysphasia
• Minumum 32 bx for pan colitis
• Chemoprevention for dysphasia – folic acid, unsocial for PSC? Mesalamine???,
• Dysplasia has to be confirmed by second pathologist
• Begin survellience immediately if patients have PSC.
• Apply same recommendations for pts with CD as UC
• If patient has colorectal cancer and in pan colitis is 1% per year after 10 years of disease (for dysphasia)
• DALM or high grade colostomy risk of cancer is 43%
• Low grade dysphasia is 19% risk of cancer
• If polyp is removed, bx area around polyp to identify colits in the area
• Adenoma like DALM lesions can be followed by colonoscopy yearly if it looks like polyp, no pSC, short disease duration, no dysplasia around polyp.
• Chromoendoscopy – indigo carmine vs. methlene blue
• Indigo carmine 0.1%.  Mayo uses 0.2%
• In Mayo, they mix it in the wash bottle
• Meth blue can cause DNA damage?
• Chromo endoscopy increases procedure time by 10 min

Post op Management of CD

• Post op CD 30% by 3 years and 60% by 10 years
• Endoscopic recurrence after surgery it is 70-90%
• 60-75% pts of CD will need intestinal resection
• Op scoring based on ulcers seen I0 to I4
• I0 and I1 very rare chance of disease recurrence
• I2 20% recurrence
• I3 and I4 – 50-100% chance of disease
• Using AZA in post op pt is only 8% better than placebo in early disease
• In severe disease I3 or I4, AZA is not helpful at all in preventing disease
• Infliximab is the best way to prevent post op recurrence. (small study)
• Perform colonoscopy in 1 year after surgery

Pouchitis

• J pouch is the most common pouch
• Usually 2 stage surgery
• Two types of anastomosis – hand sown with mucosectomy vs. double staple.
• Hand sown has a higher risk of leak and pudendal nerve injury
• Average stool frequency after a pouch is 6-8 / day including 2 at night
• Pouchitis rate is more than 20%
• Sexual dysfunction occurs in 4% and SBO in 13%
• Pouchitis – increased frequency, liquid stools, urgency, tenesmus, fever, bleeding, EIM
• RF for pouchitis include extensive UC, PSC,backwash ileitis, pANCA +, non-smoking, NSAIDs
• Treatment includes metronidazole, cipro, budesonide, steroids, mesa amine, VSL 3, combination antibiotics
• J pouch – owl eye appearance.  Cuff looks like Schatzkis ring.  Avoid bx of suture line or cuff.
• Flagyl – 1200mg/day
• Cipro and flagyl both work – cipro has fewer side effects and better
• Rifaximin results were not impressive – not helpful
• Pouchitis – think is this crohns?
• Also think of C diff, NSAID use, celiac, disease, CMV infection
• Maintenance antibiotics for chronic pouchitis

Enhanced Imaging

• Chromoendoscopy now endorsed by AGA and replace random survellience bx for IBD.  3 x detection rate
• Chromo endoscopy for polyp detection by 1.5 to 3 x!
• Dysplasia in IBD detection is 0.14% but with chromoendoscopy it is 8%
• NBI and FICE : Doug Rex did not find NBI better in detection.  But his polyp detection rate is 60%!!!
• Polyp miss rate is 42% with white light and 16% in NBI. 
• High Def scope : higher polyp detection!
• Paris Classification : based on  shape. 1-p, I s, II a, b, and c, and III.  Depressed lesions are worse
• Kudo Classification : pit pattern.  Requires NBI. 1, II, III L, III S, IV, V.  Loss of pit is bad / cancer.
• Confocal endo microscopy :  available
• NBI classification : Amsterdam or Kansas.  NBI is superior – targeted bx .
• 2 gm of powder indigo carmine, add to 1 liter water and put in the water bottle.  Spray on the side opposite of gravity
• Methylene blue – theory DNA damage
• Use split bowel preps. 
• ASA guideline 2 hour NPO.
•  

Capsule Imaging :

• Human body communication technology : takes 3 images per second compared to given which is 2 per second
• Sayaka capsule : no battery internal. It gets charged by external battery via RF.  The camera is on the side, rotates along long axis
• Occult and Overt bleeding
• Deep endoscopy for overt bleeding esp if bleeding scan is positive
• 6-12% tumor detection rate with capsule (a lot of them are false positive. Real tumor detection is 4%)
• PJ : routine capsule endoscopy should be done
• Celiac disease with alarm symptoms should undergo CE or if they are not responding
• Contraindications to CE include ICD, or pill dysphasia
• Avoid in pt CE (poor prep).  If it must be done, ambulate pt, use pro kinetics
• Retained capsule.   Usually at occurs at sight of pathology
• Agile patency capsule : the capsule gets self destroyed
• Capsule CT colography : 

Deep Enteroscopy

• Single, Double balloon or spiral arthroscopy
• DBE can cause pancreatitis!, pain perforation
• Spiral endoscopy may need 2 physicians but it maybe faster

GI Obscure bleeding

• Perform endoscopy or deep endoscopy within 48 hours
• Consider repeat routine endoscopy prior to doing deep endoscopy
• Deep Enteroscopy for lesion suspected in upper 3/4^th of small bowel should be done orally or anterograde

Nutrition in post gastric bypass

• Give patients gummy bear vitamins 2 of them daily, iron and folic acid to all patients after bypass and also check b12, folic, iron, and zinc 3 months post surgery.  Other deficiencies include chromium, cadmium, selenium

Barretts Ablation

• Best response to ablation in less than 8 cm, normal P51 and no modularity

Post bariatric complications

• Three types : Malabsorbptive, restrictive or mixed
• RYGB : roux en Y gastric bypass.  Most common, it is mixed  It has 4 things, roux limb, gastric pouch, biliopancreatic limb and blind limb
• Sided to side will have 3 openings and end to side will have 2 openings.  Side to side has 3 openings for afferent and efferent limb and the biliopancreatic limb
• Gastric band :Band is placed in proximal stomach and a tubing to the band and the tubing to a reservoir.
• Vertical band gastroplasty : It is fallen out of favor. Inferior long term weight loss.
• Biliopancreatic diversion plus duodenal switch : It is reserved for extreme obesity.
• RYGB : If you want to see the RY limb you need the enteroscope.
• Complications of RYGB.  Marginal ulcer, stenosis
• Marginal ulcer in 16% of patients
• Causes of marginal ulcer : Gastro gastro fistula NSAID use, Hp +, ischemia, gastric acidity and gastric pouch size.
• If marginal ulcer found check Hp, and look for gastro gastro fistula, use PPI, liquid carafate, stop smoking and NSAID. May need revision surgery
• Stomal stenosis  : more common in lap RYGB surgery.  Size less than 1 cm.
• Stenosis : use TTS and dilate to 12 to maximum 15 mm size.  Do not dilate if there is marginal ulcer.  Over stretching can lead to dumping syndrome.  Perforation rate Is 2-3%
• Staple line dehiscence : or gastro gastro fistula.  Can appear like a gastric diverticulum!
• Complications of gastric banding include pouch dilation, band erosion and GERD
• Other complications of RYGB : gallstones in CBD, food impaction

Stents

• Uncovered stents are not removable and covered stents are removable

Screening for Pancreatic Cancer

• 85% pancreatic cancer not respectable at presentation.  Back pain, jaundice and anorexia is associated with irresectable disease
• PJ patients have 36% chance of pancreatic cancer
• HNPCC pts have <5% of pancreatic ca
• Hereditary pancreatitis have 40% chance of PaC
• New onset DM less than 3 years associated with PaC
• New onset DM past age of 50, identify a unique biomarker for PaCDM
• Type 2 DM – usually onset associated with weight gain.  However, if type 2 DM associated with weight loss can be suggestive of PaC

Pancreatic Imaging

• CT angio Pancreas or MRI pancreas
• 8 ml/second, advanced 3 D imaging and ASIR (suppresses noise an advanced algorithm) (adaptive statistical iterative reconstruction)
• In Mayo, they start 2 IV and inject 4 ml/sec in each arm
• MRI – diffusion restriction technique
•  

Barrett's Esophagus :

• Define Barretts's as C2M5
• 5% with Long BE and 8% with Short BE
• There maybe other causes of BE besides reflux
• Study by Doug Rex – free EGD with colonoscopy.
• ? role of EGD with screening colonoscopy
• 4 quadrant biopsy.  After each bx, suction the air!
• Adherence 51% to the 4 quad bx
• BIT – Barrett's inspection time!  Higher BIT more the detection.
•  3 min versus 5 min versus 7 min. At 7 min 69% detection rate
• Capsule endoscopy is not ready for Barrett's diagnosis.
• Capsule that dissolved in the stomach and then use brushings.   Trial from UK

Eosinophilic Esophagitis

• S/S dysphagia, odynophagia, Food impaction
• IN children vomiting, feeding intolerance, failure to thrive feeding aversion
• IN adults epigastric pain, chest pain, refractory GERD
• Ringed esophagus, white specks, linear furrows, stricture.  NOT Pathognomonic
• Dx more than 15 eosinophils per HPF and basal zone hyerplasia and dilated intercellular spaces.  Again NOT pathognomonic.  Rule out GERD then the above is acceptible as diagnosis and EoE
• New definition – chronic immune antigen mediated eso disease.
• Remember GERD and EoE now thought to be mutually exclusive.
• High eosinophils present both in GERD and EoE.  Some patients with GERD have more than100 eos per HPF
• Trial of PPI is recommended for all EoE
• PPI responsive EoE (confirmed by bx and neg 24 hr pH)
• Is it possible that PPI have an anti inflammatory response besides controlling pH

Whats new in GERD and motility

• Non responders to PPI – Medications don't help regurgitation
• Dyspeptic symptoms – pain in epigastric area or burning
• Regurgitation – acid taste in mouth or unpleasant movement of material from the stomach
• Cough – top 3 causes are sinusitis, asthma and GERD. (60%, 60% and 40%)
• Efficacy of GERD relief is 60-75% with NERD and esophagitis
• Chest pain with neg pH response is 25%
• Chronic cough response rate with PPI is less than 10 %
• PPI does not work for regurgitation, wheeze, globus or throat clearing.
• GERD plus epigastric pain – 20% response rate less (?)  Usually additional symptoms makes response rate lower to PPI
• Lastly concept of hypersensitivity of esophagus.
• LNF works best for volume reflexurs – even if partial response to PPI.
• Hypersensitivity esophagus DO NOT DO Laproscopic fundoplication (LFP)

Newer Techniques for Barrett's Ablation

• EMR but associated with stricturing
• Phobar trial for PDT – 52% complete eradication of Barrett's
• "Buried Barrett's" – 25% of patients have  sub-squamous intestinal metaplasia.
• Cryotherapy machines for BE.  There are different kinds of cryotherapy machines including balloon based. Liquid nitrogen.  Efficacy is 97% complete response.
•  Esophagectomy 30 day mortality is 18% to 8% (depending on skills and number of surgeries done by surgeon).
• Endoscopic therapy is therapy of choice of HGD Barrett's.
• If EMR shows submucosal invasion – needs surgery.
• Even after ablation – regular follow up is needed  – every 3 months of HGD and 6 months to a year for LGD. 
• EMR for nodular lesions.
•  

Probiotics

• Coined by  IlieMetchinikoff in 1907 and got a nobel prize in 1908 – Longer survival in Bulgaria which he thought was from probiotics.
• It may help in constipation, C diff, H pylori eradication, lactose intolerance, antibiotic associated diarrhea, infectious diarrhea in children (best data) and IBD.
• Bacteria in GUT can cause pro or anti inflammatory effects in colon.
• It enhances barrier function – increased mucos, increased surface cell effects and can produce chemicals that are antibiotic like substances, serotonin like substances.
• Unfortunately it is NOT held to any standards in production. 
• So, many of the products may not be viable after it passing through stomach pH, or viable in the capsule etc.
• On the packaging there is "no claims" they make.
• Constipation benefits – B lactis DN shortens colonic transit, L rhamnosus, B lactis and inulin stimulate bowel motility.  It should be considered investigational. 
• Lactobacillus paracasei (published in Alim. Pharm) – 20 patients 15 day trial (L. paracasei enriched with artichokes) statistically significant benefit with chronic constipation.
• VSL # 3 decreased bloating.
• Funnel plot asymmetry – trial bias
• Bifidobacterium, Lactobacillus, Streptococcus, by themselves no study has shown clear benefit but pooled study shows a trend that to benefit.
• Bifidobacterium infantis 35264 is beneficial for IBS.
• Lactobacillus salivarius 4331 is not helpful in IBS
• Bifidobacterium infantis 35264 improved pain, bloating, incomplete evacuation, straining.
• B. infantis 35264 – for non-patients with mild symptoms – there was no benefit.
• VSL # 3 slows bowel motility and improved flatulence
• Bifidobacterium lactis (animalis or rapidis) – has shown some benefits in IBS-C.
• Another study showed Lactobacillus paracasei helped IBS-D in another trial not IBS-C!
• Probiotics are supplementary.
• Results with one strain cannot be applied to another.
• Combination can be additive in some cases and antagonistic in other situations.
• Get medication from good supplier and stick with evidence.
• Chronic constipation – L paracasei, B lactis DN (activia)
• IBS – D/M B. infantis 35264 (align)
• IBS-C B. lactis DN 1 container 3 times a day for 3 weeks before effect or benefits is seen.
• Gas and bloating – VSL #3, B. infantis 25624?
• Probiotics in IBD -
•  Body weight is 1-2 kg is from 100 trillion bacteria.
• 400-500 species.
• Most bacteria is in colon – 10 to the power 11 and in distal ileum 10 raised to 8.
• Active probiotic should contain more than 100 million per dose but less than a trillian bacteria.
• Extremely rare but infections have occurred in immunosuppressed pts.
• Pouchitis VSL # 3, helpful in maintenance.
• UC – VSL # 3 probably helpful and E coli Nissle maybe helpful in induction but helpful in maintenance. (as adjunctive Rx)
• Crohns – uncertain if E coli Nissle or S. boulardii, LGG is helpful.

Future of GI

• New generation stool DNA tests 100% sensitivity and specificity.  (2 meth markers) (for cancer detection)
• Detection rate was 64 % sensitivity for 1 cm, 79% for 2 cm and 91% for 3 cm polyps.
• No difference between proximal or distal location
• Screening is suggested q 2 years and after 3 years of screening the detection rate is 95%
• DNA markers in Plasma – plasma septin 9.  CRC sensitivity is 50-90% (58%) but not good for polyps.  (ARUP lab)
•  ANother blood test is sDNA (Exact Sciences lab)
• Conceptual model – Large pre-cancerous polyp best test would be stool makers.
• Stage 4 cancer – blood test is better.
• Role is "interval test" for every 10 year colonoscopy screening.

Surveillance Colonoscopy

• Reason is Interval cancer
• New fast growing lesions, incomplete removal occurs in 20 to 27% as cause
• Missed lesions occurs in 17% of polyps – polyps greater than 1 cm.  Even when done by expert colonoscopists.  Thus it underestimates the rate of missed lesion in general population
• Risk of interval cancer is -  1.7-2.8 cancers /100 person years or 0.3-0.9% in 3-5 years
• 2-9 % of cancers were interval cancers in Canadian registry
• Interval cancers were more likely to be proximal, in women and advanced stage.
• Interval cancers have high micro-satellite instability and are more aggressive.
• 30% of GI physicians suggested repeat colonoscopy even in hyper-plastic polyps
• Advanced adenomas and  more than 3 adenomas need more frequent colonoscopies
• 2006 Guidelines, 3 adenomas, 3 year colonoscopy, more than 1 cm, repeat in 3 years, villous adenoma 3 year colonoscopy,
• If adenomatous or villous adenomas surveillance guideline is 3 years.
• Cancer surveillance is 1 year.
• Serrated polyp is 20% of CRC.  Hard to detect esp. if sessile and often covered with mucous.  During colonoscopy – look carefully for synchronous polyps. 
• Hyperplastic polyposis syndrome more than 5 and 2 of them more than 1 cm – repeat in 1 year
• serrated polyp with dysplasia or more than 1 cm – 3 cm
• So high risk polyps, continue every 3 years and if neg after 1 – change to 5. 
• Poor prep colonoscopy – repeat colonoscopy.
• If FOBT + after colonoscopy  – individualized approach.
• Above is proposed but not approved (all the above guidelines)

New approaches for better colonoscopy

• Spend at least 6-8 min, look behind folds and attentive to flat mucosal changes
• Colonoscopy reduces it by 76-90% reduction rather than 100%.  Reason is MISSED lesion
• Canadian study shows there is no reduction in right colon cancer but substantial reduction in left CRC.   However it was done by non – GI and 66-83 % cecal intubation rate. Cecal intubation should be more than 95%
• German study showed reduction in both left and right colon cancer but more in left colon compared to right colon.
• 15% and 25 % detection rate for female and males.  % screening / surveillance
• Low adenomatous detection rate is associated with higher colon cancer in next 5 years.
• New technology improves polyp detection rate by 3-4%
• cap assisted colonoscopy, look behind folds
• Increasing WT does not improve polyp detection.  What is needed is better visualization.
• Use Peer pressure by having statistics on display of detection rate.
• Yellow golden mucous suggests sessile serrated polyp under it.
• Fold deformity suggests polyp behind it, lack of vascular marking and yellow mucous suggests it.
• High definition colonoscopy – 3.5% increase in polyp detection based on meta-analysis.
• NBI – if there is any advantage it is very slight.
• clear caps – studies are very variable to helpful, no help and worsens polyp detection.
• MAKE A COMMITMENT TO IMPROVE YOUR PERFORMANCE
• Experience of nurse in room helps to improve polyp detection rate.

HNPCC

• Risk of cancer with Lynch is 70-80%
• Autosomal dominant
• 40-50 years old, 2 generations, and usually in proximal colon.
• MSH2, MLH1, MSH6, PMS2
• stomach cancer 13% life time risk, endometrial cancer is 4-60% risk renal is less than 5%,  Surveillance for stomach cancer every 1-4 years
• Muir_Torre syndrome – Lynch plus kerato-acanthomas and sebaceous neoplasms.
• Anyone with CRC before 50 think Lynch.
• Start screening at 20-25 and interval is 1-2 years.  AFter 40 every year.
• CRC repeat colon in 1 year and then 3 years and then every 5 years.
• De Novo germ line mutation occurs in 30% of patients for FAP / Gardeners.

IBD

• 70% endoscopic healing with immunomodulators vs 14% on imuran
• The healing was maintained at 3 and 4 years.
• Top down is better than conventional (73% vs 30% remission)
• Optimizing Imuran therapy
• 30-40% rates of remission overall
• It may alter course of CD natural history.
• Syngergistic effect of imuran with immunomodulators.
• SONIC study – advantage is 10% added benefit
• He believes infliximab level guided therapy makes sense
• SONIC was only 26 week study (that was published)
• Advantage of imuran is lower CRP and higher trough of infliximab.
• Loss of response to IFX with time.  22.9% for IFX, 20% for adalimumab,
• Do not use episodic treatment and combination is better.

IBD and Pregnancy

• Fertility is NOT affected by IBD.
• Fertility is dropped by 30% with creating pouch
• Disease should be in remission before they conceive.
• If active disease and they get preganant – 1/3 get better, 1/3 no change and 1/3 get worse
• Higher change of prematurity, low body weight and need for C section.
• Active perianal disease or active CD – go for C section
• Safe medications in pregnancy -
•          Azathioprine or 6 MP is a category B.
•          The greatest risk to pregnancy is active disease not the medications
•          Asacol is a category C, but other aminosalicylates are category B.
•          Steroids are category B/C – higher incidence of oral clefts, overall risk of malformations is low., adrenal suppression in newborn, premature rupture of membranes. Entocort does not share these problems.
•          Immunomodulators are all category B.
•          DO NOT GIVE ANY LIVE VACCINE – TO ANY BABIES BORN OF MOTHERS WHO RECEIVED IMMUNOMODULATORS. (ROTAVIRUS, MMR, BCG)
• Breast feeding contraindicated with flagyl cipro, methotrexate and cyclosporine
• Post partum period is when they often have flareup of CD / IBD

Toxicity of IBD Medications

• Bad prognostic markers of IBD – onset at young age, fistulizing disease, perianal disease, early need for steroids, severe endoscopic disease, positive serologies for CD are more likely to need surgery.
• Combination therapy is much better!
• Recurrent use of steroids or use of steroids is associated with twice the mortality.
• In contrast – IFX or Mtx or 6 – MP does not increase mortality.
• 6 MP can cause allergic reaction, nasuea, hepatitis, pancreatitis, serious infections and non hodgkins lymphoma.
• Patients with low tPMT have EARLY leukopenia
• Any drop in WBC even if in normal range, WARNING sign of low TPMT activity.
• NHL 2-4% on imuran.  It is discovered within 8 weeks of treatment.
• Best study for risk of NHL is the French study.
• Cesame trial – Old men pass the age of 50 get NHL. 
• Risk of NHL on anti TNF – 6.1 per 100,000 pt years.  Usually it is in older patients
• HSTCL _ hepatosplenic T cell lymphoma from anti TNF
• Quality measures – if patient on steroids more than 60 days, check C diff, TB, Hep B screening, and yearly BDM, pneumonia and flu vaccination.
• HPV vaccination in young women
• Avoid varicella and MMR vaccination.

Surgery in IBD

• 1/3 patients with UC need surgery
• 2/3 of patients with CD need surgery.
• Surgical rate has not changed in spite of newer medications between 1-2% however the trend is you may need it less likely.  Probably because they already had tissue damage by the time they started treatment.
• Post op IFX – endoscopic recurrence was 0-10% versus it was 85-100% in placebo at 1  year
• Post op anti TNF works the best is the most effective. 
• Mucosal healing is the most important. 
• Data suggests that start treatment after surgery even if no endoscopic mucosal lesions.  Waiting for disease to come back after surgery is probably not the best thing.

Hepatitis C

• Anemia is more severe in triple therapy and more serious.   Recommend ribavarin ? role of epo.  Reducing ribavarin dose dos not affect SVR
• Rash use topical steroids and antihistamines
• Stop statins, sildefnafil, versed, rifampin, ergots cisapride, st. Johns wort,
• Largest increment in SVR is for CT/TT patients
• Modest increase in SVR in CC naives
• IL28B use for fine tune discussions and more useful in naive patients than non responders.
• HCV resistance in patients who fail triple therapy.  They are V36, T54, R155, A156 types.
• End of IFN era / – DAA-1 plus DAA-2.   NS5A plus Protease inhibitor  works well even in null responders
• Next step will be quad combo and then interferon free regimen. DAA protease inhibitor and DAA polymerase inhibitors.

Strategies for Hep B treatment

• High viral load associated with higher chance of hepatoma.
• Type C is associated with highest chance of hepatoma
• Older the age higher the chance of hepatoma
• ALT more than 45 – risk of hepatoma is higher
• Cirrhosis also higher chance of hepatoma
• New concept is HBsAg level than HBV DNA level correlates better with ccc DNA in liver.
• Use HBsAG levels (<1000) and HBV DNA (<2000) gives best result of inactive carrier validation.
• HBsAg loss after 2-5 years of treatment is less common (less than 5%.  One study showed 11%)
• Traditionally we start treatment based on elevated ALT, inflammation on liver biopsy and presence of serum HBV DNA level.
• AASLD guidelines suggests Rx when ALT > 2 x ULN and HBV DNA > 20,000 level.  Exception Lower threshold for pt > 4, active fibrosis and clinical evidence of cirrhosis. Then start treatment earlier.  Borderline ALT or HBV DNA do liver biopsy and monitor.
• Resistance more likely in nucleosides or tides and no mutations in interferon treatment.
• TDF and ETV should be initial Rx choice (entecavir or tenofovir). 
• Genotype A favor interferon treatment.
• HBe Ag neg – Lack of HBsAG and HBV DNA decline at week 12 – futility rule for genotype D-HBV.  Hb e Ag+ pt, decline in HBs AG at week 12 and 24 predicts sustained response.
• PEG treatment for 1 year.  May need longer for Hbe Ag neg.
• Likelihood of HBeAg seroconversion 50% after 5 years treatment

NASH

• 2 types Micro and Macro
• NAFLD  – 30% of the US population has it
• NASH occurs in up to 10% of US population
• NAFLD increases risk of death – from liver, cardiovascular and cancer causes.
• Fat in liver is an independent risk factor for CV death!
• Nash with high activity score, DM, obesity and fibrosis have worse prognosis.
• Caspase-3 generated fragments are seen in NASH.
• CK-18 level in blood -? Diagnostic value for NASH
• Rx for NASH – lifestyle changes
• PIVENs study – vitamin E 800 IU/day was helpful and pioglitazone was not helpful
• TONIC is other study which showed vitamin E helped. But weight loss is most important
• Pioglitazone associated with risk of fracture and CV risk.
• Rx of Vitamin E can increase risk of prostate cancer and 0.04% increase in risk of mortality from all causes.
• ? role of gastric bypass.
• Pentoxyfylline maybe helpful for NASH
• PUFA on NASH – data is pending could be helpful.

HCC

• AASLD slide recommendation
• If mass is less than 1 cm, repeat US every 3 months. If it remains stable repeat every 6-12 months.  If it grows follow 1-2 cm recommendation
• If more than 2 cm – dynamic CT or or MRI.  If typical for HCC – proceed with treatment for HCC WITHOUT bx.  Most transplant centers recommend proceed without bx
• If between 1-2 cm, get CT and MRI. If concordant proceed accordingly.  If findings not concordant proceed with bx.
• Staging based therapy – number, size, symptoms of HCC, cirrhosis presence and
• If one lesion, less than 2 cm, and no cirrhosis, surgery is curative.
• Look at slides in book.
• RF ablation has 50% 5 year survival.
•  

Biliary dyskinesia

• Biliary and pancreatic SOD
• SOD evaluation – invasive and non invasive
• Hopkins scintographic score for biliary SOD dynfunction.  100% sensitivity and specificity.  Drawback is does not evaluate pancreatic SOD.
• Secretin stimulated MRCP – 0.5 cm increase in PD size suggests pancreatic SOD.
• ERCP 30% of patients will develop pancreatitis in SOD.  DO NOT DO ERCP.
• Chronic abd. pain – 60% of them had SOD.  10% isolated biliary SOD, 20% had ioslated pancreatic SOD and 30% had both.
• Rx is antispasomodics – smooth muscle relaxants, botox injections, CCBs
• Gold standards is biliary sphincterotomy.
• Type 2 and type 3 biliary – do sphincterotomy. 
• Causes of pain after sphincterotomy – residual SODor pancreatic SOD or chronic pancreatitis or non pancreaticobiliary cause.
• Should patients get pancreatic sphincterotomy with biliary sphincterotomy ?  On going study.

Cysts of Pancreas

• 1.2% of general population has it on routine imaging.
• serous cystadenoma, mucinous cystic neoplasm, IPMN, cystic islet cell tumor, pseudocyst, solid papillary neoplasm
• IPMN in male, head of pancreas, variable malignancy risk, All other cysts are more common in women.
• Pseudocyst – may not always have history of pancreatitis. It is 15-30% of all cysts
• Islet cell tumor – 17% is cystic and more common in MEN 1
• Serous cystadenoma – usually large, innumerable small cysts with central calcification.  There is a macrocystic variant, usually females in 6th or 7 th decade and can be symptomatic, frothy, and very bright on EUS, low malignant potential.
• Mucinous cystic neoplasm – has ovarian stroma in it, malignant potential and usually in women
• IPMN – 29% malignant risk in 10 years. Can present as unexplained pancreatitis with dilated PD, jaundice and diabetes. Cancer risk is if size more than 3 cm,mural nodules.  Fish mouth appearance of IPMN – with mucous. Amylase in pseudocyst in cystic fluid is more than 250. CEA less than 5 unlikely to be cancer and more than 800 in fluid is probably malignant.
• PANDA study – DNA analysis of cystic fluid.  Moderate accuracy and does not add much to current tests
• Mucinous cysts – inject with ethanol or paclitaxel.  Cyst resolution is 33-79%.  10% pancreatitis risk and 20% abd. pain.
• Cyst more than 1 cm and symptomatic consider surgery. If more than 1 cm and no symptoms do EUS.
• If cyst less than 1 cm, repeat imaging in 1 year.

Chronic Pancreatitis

• Pain occurs from PD obstruction or ischemia of pancreas or pseudocyst formation or inflammation or duodenal and CBD obstruction.
• Mx from enzymes, analgesics, octreotide, antioxidants, nerve blocks, endoscopic therapy, ESWL and surgery.
• Pancreatic surgery – islet autotransplantation.
• Endoscopic treatment involves ESWL, EUS and ERCP.  Pancreatic and biliary sphincterotomy.  Often needs a screw dilator, shock wave lithotripsy and then stone extraction
• Pancreatic stone extraction – less than 30-40% extraction rate

Familial Pancreatic Cancer

• 2 or more patients with pancreatic cancer in family.
• 10% of all pancreatic cancers are familial.
• High risk FPC.  Families with > 3 members with cancer.
• Hereditary Pancreatic cancer BRCA1/2, p16 mutations or FAMMM, Lynch syndrome, PJ syndrome, hereditary pancreatitis (cationic trypsinogen gene)
• Hereditary breach and ovarian cancer HBOC BRCA 1 and BRCA2
• PJ syndrome higher risk of colon cancer and should be monitored for pancreatic cancer also.  Moreover risk of gastric cancer, ovarian, breast, cervical and endometrial cancer
• FAMM (familial atypical multiple mole melanoma). p16/CDKN2A gene.  They have atypical melanocytic nevi, autosomal dominant
• Lynch – SB cancer, ureter cancer, renal pelvis cancer, brain, ovary and pancreatic cancer.  Age 50 1.3% and Age 70 4% risk of pancreatic cancer
• HBOC syndrome – autosomal dominant.  Some patient family may have pancreatic cancer but no breast or ovarian cancer !!!!
• BRCA mutation in Jewish patients.
• PALB-2 Multiple family members with pancreatic cancer.  Also increased risk of breast cancer
• Johns Hopkins, Mayo clinic, Creighton Univ, Mt Sinai, Anderson CC,  – sites for familial  cancers
• Screening with EUS, dedicated MRI / MRCP or dedicated pancreatic protocol CT, aggressive evaluation of cysts. ????prophylactic pancreatectomy.
• PanINs lesions – intraepithelial neoplasia (similar to colon cancer from adenoma).  High grade PanIN3 and more dense, different Kras mutations.
• Thus 2 ways to develop pancreatic cancer PanIN or IPMN.
• 3 D reconstruction for pancreatic neoplasm
• MRI has no radiation advantage.
• EUS not widely available and high inter observer variability.  Requires extra training.
• Start screening at 50 or 10 years younger.  PJ start at 35

Celiac disease

• Best combo is t Tg Ig A and DGP.
• neg serology in 15% of patients
• Hemolysis reduces anti tTG titer
• Bx is gold standard.
• Marsh Classification
• Patchy disease. 
• Need 4-6 biopsies during endoscopy.
• Bulb biopsies increased diagnosis of celiac by 13%
• 4-6 bx from SB and 2 bx from duodenal bulb
• Genetic testing DQ2/DQ8 – 100% of patients with celiac disease have this genotype.
• Thus genetic has 100% negative predictive value.
• Gluten free diet.  Support groups  CDF, GIG, CSA/USA
• Increased mortality in celiac is from lymphoma (T and B lymphoma and extraintestinal), other cancers are also increased.   Increased breast, cervical endometrial cancer also.  They should get pneumovaccine also.
• Gluten free diet is protective against malignancy
• Poorly responsive celiac disease – wrong diagnosis, bacterial overgrowth, lactose or fructose intolerance, microscopic colitis, pancreatic insufficiency and refractory celiac disease.
• Refractory celiac disease – type 1 and 2 based on intra epithelial immunohistochemistry.  Intra epithelial lymphocytes do not have surface markers then it is type 2 refractory celiac disease.  Type 2 is poor prognosis.  ALso can do flow cytometry and PCR to differentiate. Type 1 use immonomudolators including steroids, imuran etc.   Do not use steroids in type 2 because it increases risk of lymphoma.
• Children should get gluten when being breast fed to reduce their chance of developing celiac disease.

Bariatric surgery in Obesity

• Roux – en – Y(RYGP). 
• Endoluminal bariatric interventions.
• Complications of bariatric surgery – gallstones, PUD, GERD, food impaction, band displacement, band erosion.  RYGP compllications includes biliopancreatic diversion
• Gastric bypass – late complications are stomal stricture, stomal ulceration, marginal ulcer, stomal ulcer, staple line disruption, internal hernia.  Pouch is 3-5 cm long. 
• Anastomotic ulcer in RYGP – 3-20% of patients.  They have nausea, vomiting and epigastric pain.  Ulcers on jejunal side usually. Remember to wash well.  Anastomotic ulcer can occur within a few cm of the anastomosis also.
• Treatment PPI high dose, carafate, eradicate Hp.  Use carafate suspension not tablet.  Rare cases will require resection.
• Anastomotic stricture – less common than ulcer.  Non wire guided dilatation with balloon.  Try to dilate to 1 cm. Usually diagnostic scope will not traverse. 
• RYGP – staple line fistula or disruption.  Fistula is between gastric pouch and gastric remnant.  (gastro gastric fistula).  S/S weight gain and reflux are symptoms.  Contrast radiologic study.
• Cutaneous fistulas can also occur.
• May need to remove anastomotic suture material with applying traction and cutting suture material.  This way you can see the ulcers etc better.
• GI bleeding is uncommon in RYGP fortunately.  If DU, can be hard to reach it endoscopically.
• Laproscopic adjustable gastric banding – dome seen on retroflexion.  Complications include food impaction, band displacement or slippage, band erosion, gastric pouch dilatation, esophageal dilatation.
• Sleeve gastrectomy complication  – Long staple line 10-12 cm long!
• Endoscopic Mx of post bariatric surgery – CBD stone,  Can be very difficult to remove the stones.
• If EGD does not give answer – then do CT, SBFT and MRCP or EUS.  Role of WCE is questionable.  Consider Agile patency capsule.
• Suture scissors maybe needed.

IBS

• ROME 3 – change in frequency / consistency and pain relieved with BM and occuring 3 times in a year
• IBS -C , IBS – D, mixed, IBS – U
• Patients with IBS migrate from C to D to A(lternating)or mixed.
• Physical activity helps improve IBS! Encourage patients to exercise. 
• Food intolerance – 2/3 of patients associate IBS triggered by some foods! 
• Also fermentation plays a role.  Gas handling is different in IBS patients than normal patients.
• Later on patients have a conditioned response to food later on – Psychological factors.
• Food elimination helps reduce IBS symptoms.
• Gluten sensitivity – Consider that in patients. 
• Lactose intolerance.  More likely to be carbohydrate intolerance.
• FODMAPs diet – fermentable oligo, di, monosaccharides and polyols.  Avoid fructose, fructan containing vegetables, wheat based products, sorbitol and lactose containing foods, raffinose containing foods (legumes, lentils,cabbage, brussels sprouts).
• FODMAPs diet – you must have a trained dietitian.
• Patients with severe symptoms will follow FODMAPs diet.  This information is from UK and Australia.  No US data yet.
• Consider anti depressants in some patients with IBS – TCA and SSRI. 
• No data for IBS-C for using PEG or miralax ! 
• Rifaximin – 10% therapeutic gain with treatment.  Improvement is it related to SIBO?

Allergies and EoE

• Physiological food reaction – large volume leads to distension and regurgitation.
• Fatty food delay gastric emptying
• Legumes, cruceferous vegetables, garlic, onions, leads to flatus.
• Non absorbable or poorly absorbed sugars and carbohydrates can lead to diarrhea, bloating, flatulence etc.
• Normal flatus is 14 x/day !!!!
• Gas becomes a problem in crohns, gastroparesis etc.
• Food hypersensitivities, celiac, hypersensitivity to food protein enteropathies (usually in pediatrics)
• Food allergy – 4-5% of patients have it. 50% of anaphylaxis in USA is due to food!
• ARF (adverse reaction to food) occurs in IBS, IBD also.
• Big 8 foods – milk, soy, eggs, wheat, peanuts, tree nuts, fish and shelfish.
• Outgrows in egg, milk and peanuts by the age of 5.   Milk – they outgrow in 80% of cases by 5.
• Increased risk on those taking b blockers and Ace Inhibitors. (for food allergies)
• Oral allergy symptoms – cross reactivity between raw fruit and vegetables and pollens.  Itching and swelling and tingling on lips.  Patients with seasonal rhinitis are more likely to get it.
• Latex food allergy syndrome – Foods are kiwi, potato, tomato, avocado, chestnut and banana.
• GI disorders associated with eosinophilia – EoE, E gastritis, enteritis, colitis. 
• Lactose intolerance – secondary lactase insufficiency occurs after gastroenteritis, crohns and celiac.  Genetic usually more common in asians, africans, native NA and mediterranean areas.
• Lactose intolerance – can tolerate upto 12-15 g lactose (8oz milk a day).  Yogurt, hard cheese are lactose free.  Better if you take it in small frequent amounts.  Lactase supplements are helpful.  Triacylglycerol content of many milk products can cause GI symptoms unrelated to lactse insufficiency or cows milk protein allergy.
• (FODMAPs diet) (see table).
• 3 types of ARF (food hypersensitivity, food  protein enteropathy and food intolerance).
•  

Update on new treatments for IBS

• Rifaximin is helpful in IBS – bloating associated symptoms.  Rx is 550 mg tid for 2 weeks.
• Linaclotide – submitted for approval. Effective for IBS-C.  guanylate cylcase -C agonist.
• Others in the same class of GC-C is guanilib.
• 5-HT3 antagonist – ramostron.
• Crofelemer CFTR inhibitor
• Asimadoline – k opiod receptor agonist
• Tryptophan hydroxylase 1 inhibitor.

The study did not show any benefit with using Selenium.

Fatal infections have occured with Legionella and Listeria.  This is especially true with patients on TNF plus another immunusuppresant.

Simvastatin has drug warnings with interactions with amidarone, diltiazem, verapamil, antifungals including diflucan and other drugs.  Dose reduction or NOT using them at the same time is strongly recommended. Also dose of 80 mg is associated with a higher drug toxicity.  Talk with your cardiologist or primary care for the same.

Heartburn:

            Avoid irritants such as tomato sauce, spicy and fatty foods, fried foods, citrus fruits, chocolates, alcohol, coffee, caffeine, and cigarettes. Eat small frequent meals. Do not lie down immediately after meals. Avoid tight fitting clothes. Medicines work best if taken 30 mins. before a meal.

Bloating:

Avoid milk, cheese, fruits, potatoes, broccoli, cabbage, asparagus, cauliflower, beans, potatoes and corn.

Avoid artificial sweeteners (like that present in sugar free candies, chewing gum) soda and high fructose corn syrup.

            Avoid mouth breathing.

            Soluble fibers like that present in oats, barley, legumes, etc can cause more bloating.

            Peppermint Tablet (To be swallowed not sucked on – available at GNC stores)           

            Align or VSL #3 (probiotics)

         Iberogast    Iberogast 20 drops tid.  It is available online from amazon and other web pages.  This has been shown to be helpful by anecodatal reports and is not FDA approved.  I have discussedthis with the patient.  It has been helpful for bloating.  The side effects of Iberogast include allergic reaction to Chamomile (including anaphylaxis) and side effects of Liquorice which includes myocardial infarction, water retention, pseudohypoaldosternoism, headaches, fatigue and hypertension.  Moreover it contains some alcohol. 

Side effect of medications used for GERD / Heartburn treatment.

This is far from complete. Please contact your pharmacist or physician for additional information.

PPI: The drugs included in this is Nexium, Prevacid (Lansoprazole), Prilosec, Omeprazole, Protonix, and Aciphex. The new concerns with these medications include: increased incidence of wrist and hip fractures from osteoporosis (thinning of the bone), increased chance of pneumonias, bowel infection called C-Diff and low magnesium levels. Anyone on the medication for more than one year should get their magnesium level checked. Please contact your primary care for evaluation of osteoporosis.

Diflucan: Do not take cholesterol lowering agents with this medicine. It can cause rare serious liver failure.

New Medication Ordered:   All RX’s are faxed to the pharmacy of your choice after 4:30pm

X-Rays Ordered                                                          EGD                 Colonoscopy

Blood Test Ordered

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Reducing Your Risk of Colon Cancer:

            Take multivitamin with Selenium. Eat a high fiber diet. Avoid red meats. Exercise and Aspirin is helpful as well.

Relieving Constipation:

            Gradually increase the fiber in your diet to 20-30 grams daily. Fiber supplements such as Benefiber, Citrucel, or Metamucil can be used.

Miralax (Glycolax)      We generally recommend taking it at 8 pm mixed with a drink or water of your choice. If you need the medicine more than once we recommend taking second dose 30 min later at 8:30 pm  

MOM 30cc (2 tbsp.) as needed.  Take MOM 2 tbsp on any day that you skip a BM.  (This is in addition to miralax).

Bloating:   Avoid milk, cheese, fruits, potatoes, broccoli, cabbage, asparagus, cauliflower, beans, potatoes and corn.

Avoid artificial sweeteners (like that present in sugar free candies, chewing gum) soda and high fructose corn syrup.

            Avoid mouth breathing.

            Soluble fibers like that present in oats, barley, legumes, etc can cause more bloating.

            Peppermint Tablet (To be swallowed not sucked on – available at GNC stores)           

            Align or VSL #3 (probiotics)

            Iberogast    Iberogast 20 drops tid.  It is available online from amazon and other web pages.  This has been shown to be helpful by anecodatal reports and is not FDA approved.  I have discussedthis with the patient.  It has been helpful for bloating.  The side effects of Iberogast include allergic reaction to Chamomile (including anaphylaxis) and side effects of Liquorice which includes myocardial infarction, water retention, pseudohypoaldosternoism, headaches, fatigue and hypertension.  Moreover it contains some alcohol. 

Diverticular disease:              Eat more fiber. Chew your food carefully. Currently, seeds or nuts are NOT thought to cause complications like inflammation or diverticuli or bleeding. Diverticulitis is inflammation of the diverticuli and can lead to complications.  Patients need antibiotics when it is inflamed.  They may need surgery.

Diverticular disease (just having the pockets but there is no inflammation or complication) is common and generally requires no intervention unless infected or if it bleeds.

New Medication Ordered: All RX’s are faxed to the pharmacy of your choice after 4:30pm

X-Rays Ordered                                                          EGD                 Colonoscopy

Blood Test Ordered      Check us out on the web: www.mygastrodr.com. Facebook Us: GI Consultants Community

Medication Side Effects

This is far from complete. Please contact your pharmacist or physician for additional information.

Cipro or Levaquin: Tendon rupture (Achilles tendon) and liver toxicity.

Pramine or Bentyl: Dry mouth, drowsiness, racing of the heart, urinary retention, and constipation.

Flagyl or Metronidazole: Do not drink alcohol with this medication. This includes alcohol from mouth wash rinses ect. Long term use can cause neuropathy.

Amitizia: Nausea. You can avoid this by taking it with food. Abortions. Patients are advised to use birth control pills or contraceptive measures prior to using it. Do not share this medication with anyone.

Food Serving Grams of fiber

Crohns Disease or Ulcerative Colitis

This can often be a lifelong disease associated with multiple complications and may require surgery also.  Side effects of the medications commonly used to treat it are listed here.

Remicade, Humira, Cimzia: Life threatening infections including fungal infections, TB, hepatitis B reactivation. Patients are advised to get a yearly PPD and immunized against hepatitis A and B. It can also cause life threatening cancers. Other side effects include CHF, anemia, skin rashes, serious neurological problems, sensitivity to the sun, worsening lupus, sarcoidosis. Moreover, it should be avoided during pregnancy and lactation.

While on these medications, we recommend

1)      Yearly flu shot

2)      Evaluation for hepatitis A and B.  You should get immunized against both

3)      Yearly PPD

4)      Immunization against Pneumonia.

5)      Call your physician IMMEDIATELY if you develop fever.

Mesalamine (like Lialda, Asacol, Apriso, colazal etc): Generally very safe.  Some patients may develop inflammation of the liver, lungs, kidneys. 

Imuran  : This medication can cause life threatening drop in blood counts.  You WILL NEED blood tests frequently – initially every week or other week to later on once every 2-3 months INDEFINATELY.  Moreover it can cause liver problems, pancreatitis, fever, and a higher chance of cancers like lymphomas.

Prednisone:  Anxiety, insomnia, irritability, cataracts or glaucoma , facial swelling,  high blood sugar, increased risk of infections, changes in body fat distribution, skin changes (acne, stretch marks, slow healing), osteoporosis (weakened bones and possible fractures), avascular necrosis of joints, joint pain, muscle weakness, and weight gain.

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Hepatitis C and Telaprevir

Telaprevir

·      Safe to use in COMPENSATED liver disease.  Do not use in patients which Childs score more than 7. 

·      It can only be used on Type 1 HCV pts

Contraindications

·      Cannot use in men or women who are planning pregnancy

·      Must use 2 contraceptives while on treatment and for 6 months after treatment

·      2 contraceptives needed because the drug decreases BCP efficacy

·      After 2 weeks of stopping Telaprevir, you can switch to one form of contraception

·      Solid organ transplant patients

·      HIV and HBV co infected patients

·      Nursing mothers.

·      Age more than 65 – use with caution.

·      Renal impairment.

Caution and Drug Interactions

·      It is contraindicated in pts on drug metabolized by CYP3A for metabolism

·      Eg include rifampin, atorvastatin, lovastatin, simvastatin, sildenafil, tadalafil, midazolam, triazolam, St. Johns wort,  ergot derivatives, alfuzosin. Pimozide

·      Long list of drugs for which it is not recommended and use with caution.  It includes methadone, seboxon, etc.

Response Guided Therapy

·      This is a new term used for treatment. Basically it means that treatment duration depends on how the patient responds initially to treatment.

Dose

·      Telaprevir needs fat for better absorbption.  Take food (not low fat food) with the medicine

·      Dose MUST be given every 8 hours (range 7-9 hours)

·      Dose is 375 mg . Take 2 tablets three times a day.

·      The dose MUST NOT be reduced or interrupted.

Treatment Regimen

·      If HCV RNA > 1000 at week 4 – STOP treatment

·      If HCV RNA > 1000 at week 12 – stop treatment

·      If patients have cirrhosis and are negative at week 12, treat for 48 weeks

·      If patients are prior relapsers, partial or null responders and are negative at week 12, treat for 48 weeks.

·      If patient is less than 1000 at week 12, check at 24. If neg, treat till 48 weeks.  (basically 36 after undetectable).

Monitoring

·      Use CMP, CBC, TSH uric acid every 2 weeks, week 4, week 8 and week 12

·      Check PCR at weeks 4 and 12. 

Studies

·      Advance, Illuminate and Realize.

·      2/3 treatment naïve patients will need treatment only for 24 weeks.

·      Response rate in compensated cirrhosis is 62%

·      Response rate in AA is 62%

·      Overall response rate is 79%

·      Response rate for Hispanics is 74%

·      Relapse rate overall is 4%

·      Results for prior relapsers is 86%, partial responders is 59% and for null responders 32%.  Treatment in this group was for 48 weeks.

Side Effects

·      Rash, fatigue, pruritis, nausea, anemia, diarrhea, vomiting, hemorrhoids, anorectal discomfort, dysgeusia and anal pruritis

·      Rash occurs in first 4 weeks.  Occurs in 56% of patients

·      Difficult to differentiate between rash of ribavirin or Telaprevir.

·      DRESS – drug related eosinophilia and systemic symptoms (may develop hepatitis, nephritis, facial edema and may or may not have eosinophilia)

·      Steven Johnsons syndrome and TEN can occurs in 1%

·      General care includes – no fragrances, Dove soap, no sun exposure, High SPF (>45),  oral antihistamines (zyrtec, Benadryl, Claritin) topical steroids.

·      Rashes – mild (local or just one area), moderate (diffuse) severe (diffuse plus systemic)

·      Hb usually decreases at week 4.  Lowest Hb is at week 12.

·      Anorectal symptoms – treat analpram cream, tucks. 

There are a fair number of patients who display gluten sensitivity – this means they do not test positive for gluten but feel better when they are on a gluten free diet. 

2) Melatonin 6 mg/ day maybe helpful in treating GERD

3) Sacchromyces Cervasae was found to have visceral analgesia (Pain killer) in mice.  Studies show promise in treating IBS

4) Linaclotide is a new drug that is being evaluated for IBS with chronic constipation.  Works in a novel way

5) Rifaximin maybel helpful in treating bloating.  It is not FDA approved for it

6) Pregnant women should not eat high carbohydrate or fructose.  Higher chance of biliary sludge and stones

7) Some physicians routinely check for IL28 polymorphism.  Only the patients with genotype CC benefit with treatment for hepatitis C type 1 (for cure)

Babies who were exposed to monoclonal antibodies during utero (Remicaide, Humira and cimzia? ) should not get live vaccine for first 6 months

9) Patients exposed to thiopurines should have be checked for skin cancers.  All patients should get an annual dermatological evaluation past the age of 60 by dermatologist and by regular physicians otherwise

10) Suboptimal pap smear evaluation in patients with IBD.  Patients should be warned

11) Consider double dose HBV vaccine in patients with IBD

12) Budosenide MXX 9 mg works in patients with ulcerative colitis also.

13) Red meat ingestion leads to a higher chance of Barretts

14) Patients with extraesophageal symptoms of GERD are more likely to have Barretts

15) NHANEs suggests that the ALT be readjusted to 29 as upper limit of normal for men and 19 for women. 

The medicine will be used for the first 3 months of the treatment.