Gi newsletter

1 To earn CME credit complete the posttest and evaluation at www2012GIHepUpdatecom

T his CME newsletter based on the 2012 GastroenterologyHepatology Update meeting will provide expert perspectives from Indiana University School of Medi-cinersquos distinguished faculty on new developments in gastroenterology and hepa-

tology These insights will help busy gastroenterologists internists family practice physi-cians and other primary care providers evaluate results of recent breakthrough research for their implications for todayrsquos clinical practice

Key features of the 2012 program include presentations on new and updated clinical information as well as treatment and management updates for gastroenterologic and hepatologic diseases A review of potentially practice-changing studies will be provided in a number of areas such as upper and lower gastrointestinal tract diseases liver disease and pancreatobiliary disease Finally clinical recommendations will be offered to help improve practice and ultimately patient outcomes

Update in Colorectal Cancer Screening

Douglas K Rex MD Distinguished Professor of Medicine and Chancellorrsquos Professor presented an update on colorectal cancer screening including a discussion about the criteria by which the quality of colonoscopy can be evaluated

Every colorectal cancer (CRC) is unique from a molecular standpoint and has its own unique genetic profile of muta-tions However gene mutations in 3 general pathways define the molecular basis of CRC the chromosomal insta-bility pathway (CIN tumor suppressor and oncogene mutations) the Lynch pathway (mutations in mismatch repair genes) and the CpG island meth-ylator phenotype (CIMP) pathway (hypermethylation of genes) which accounts for about 30 of colorectal cancers The precursor for CIMP-positive tumors is not the traditional adenomatous polyp but a different sort of polyp called a serrated lesion The serrated lesions are classified as hyperplastic polyp (HP) sessile serrated adenomapolyp (SSAP) which can be with cytological dysplasia or without cytological dysplasia and traditional serrated adenoma (TSA) SSAP is the main precursor of CIMP-high CRC Presently there is no reli-

able way to distinguish HP from SSAP endoscopically1 Most large serrated lesions in the proximal colon are SSAP In particular SSAP with cytological dysplasia is a dangerous lesion

The commonly used CRC screening tests in the United States are the guaiac-based fecal occult blood test (gFOBT) fecal immunochemical test (FIT) and colonoscopy Although not commonly used the most promising stool test may be the fecal DNA test because hypermethylated genes can be easily detected in the stools A large-scale randomized controlled trial of FIT versus gFOBT in 20623 participants showed better adherence and positivity rate for FIT (596 and 55 respec-tively) compared with gFOBT (469 and 24 respectively)2 Septin 9 is a new blood test not yet approved by the US Food and Drug Administration (FDA) that tests for hypermethylation of the septin 9 gene When compared with the fecal DNA test the septin 9 test performed poorly in terms of specificity as well as sensitivity for stage I to stage III cancer and large adenomas3 Computed tomographic (CT) colonography is another screening technique that is seldom used in CRC surveillance It is not approved by the US Preventive Services Task Force because of the radiation risk and likeli-

Highlights from the 15th Annual GastroenterologyHepatology Update

ChairDouglas K Rex MD

Distinguished Professor of MedicineChancellorrsquos ProfessorIndiana University-Purdue University IndianapolisIndianapolis IN

Learning ObjectivesThis activity is designed for specialists in gastroenterology internal medicine family practice and primary care There are no prerequisites for this activity At the conclusion of this activity participants should be able to

bull Identify and screen patients with average and high risk for colorectal cancer to prevent colorectal cancer and reduce cancer mortality based on the American College of Gastroenterology guidelines

bull Examine patients for Barrettrsquos esophagus based on American College of Gastroenterology guidelines and conduct cost-effective surveillances

bull Usemanagementstrategiesforgastroesophagealrefluxdisease(GERD)recommended by the American College of Gastroenterology to improve qualityoflifeinpatientswithGERD

bull Evaluate and treat patients with abnormal liver test results and patients with viral hepatitis using American Association for the Study of Liver Diseasesscreeningguidelinestopreventcirrhosisinpatients

bull Optimize outcomes of treatment for hepatitis C by considering the use of new protease inhibitors

bull Employ current guidelines regarding screening in a consistent manner so as to identify and screen all patients at risk for hepatitis B infection

bull Apply current guidelines to identify patients at high risk for hepatocel-lular carcinoma screen using recommended modalities and follow up with appropriate treatment or referral

bull DescribetheimplicationsforclinicalpracticeofrecentadvancesinthemanagementoflowergastrointestinaltractdiseaseGERDandpancreaticandpelvicfloordisorders

CME InformationReleaseDateAugust152012ValidforcreditthroughAugust142013

This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing MedicalEducation(ACCME)throughthejointsponsorshipofIndiana Univer-sity School of Medicine and Heath Focus Inc Indiana University School of Medicine is accredited by the ACCME to provide continuing medical education for physicians

Indiana University School of Medicine designates this enduring activity for a maximumof2AMA PRA Category 1 Creditstrade Physicians should claim only the credit commensurate with the extent of their participation in the activity

To receive credit participants must read this newsletter and submit the activityevaluationformandposttest(passingscore=75orhigher)Lengthoftimetocompletetheactivity2hours

Disclosure InformationCommercial SupportIndiana University School of Medicine and Health Focus Inc gratefully acknowledge the unrestricted educational grant provided by Vertex

Faculty DisclosureIn accordance with the Accreditation Council for Continuing Medical Education (ACCME)StandardsforCommercialSupporteducationalprogramssponsoredbyIndianaUniversitySchoolofMedicine(IUSM)mustdemonstratebalanceindependenceobjectivityandscientificrigorAllfacultyauthorseditorsandplanning committee members participating in an IUSM-sponsored activity are required to disclose any relevant financial interest or other relationship withthemanufacturer(s)ofanycommercialproduct(s)andorprovider(s)ofcommercial services that are discussed in an educational activity Dr Rexreported that he has received consulting fees andor honoraria from American BioOptics Braintree Boston Scientific CheckCap Epigenomics ExactSciences Given Imaging and Olympus

Staff Hassan Danesh PhD Monica Armin and Dr Deborah Teplow havedisclosedthattheyhavenopotentialoractualconflictsofinterest

Note Although it offers CME credits this activity is not intended to provide extensivetrainingorcertificationinthefield


hood of extracolonic findings It is also not approved by Centers for Medicare amp Medicaid Services because of insuf-ficient data in the elderly and because it is less cost-effective than colonoscopy Capsule colonoscopy which requires extensive bowel preparation is yet another nonndashFDA-approved screening method with a sensitivity greater than 80 for polyps 6 mm and smaller and a specificity of less than 80

The adenoma detection rate (ADR) the primary measure of the quality of colo-noscopy varies greatly among gastro-enterologists the lowest ADR ranges from 7 to 155 and the highest ADR ranges from 327 to 44 Some of the factors that may underlie the variable detection rate are training (eg lesion recognition withdrawal technique and withdrawal time) personality visual gaze patterns and withdrawal time A prospective study demonstrated that adequate bowel preparation results in a detection rate of 294 for any adenoma and a detection rate of 64 for large adenomas (gt1 cm) when compared with inadequate bowel preparation which showed a detection rate of 239 for any adenoma and a detection rate of 43 for large adenomas (P lt 05)4 In bowel preparation split-dosing has been shown to provide more satisfactory results than traditional dosing5 Thus the components of good detection are a good bowel preparation adequate time and a sound technique

Barrettrsquos Esophagus Screening Surveillance Diagnosis and TreatmentDouglas K Rex MD Distinguished Professor of Medicine and Chancellorrsquos Professor presented current perspectives on screening surveillance diagnosis and treatment of Barrettrsquos esophagus

Barrettrsquos esophagus (BE) is character-ized by red (columnar) mucosa in the esophagus and described according to Praguersquos classification based on the following criteria (1) C length of the circumferential section and (2) M length of any circumferential section plus the length of any tongues Biop-sies will demonstrate goblet cells which are not seen in the normal stomach but are seen in the intestine

These cells define the intestinal meta-plasia

The risk of esophageal adenocarcinoma is associated with being a white male the presence of BE chronic gastrointestinal disease or obesity and a family history of esophageal carcinoma In fact 85 of the cases of BE are in white males The stages of BE are classified as simple Barrettrsquos (no dysplasia) Barrettrsquos with low-grade dysplasia Barrettrsquos with high-grade dysplasia (HGD) and adenocarci-noma The American College of Gastro-enterology has specific recommendations for the surveillance intervals for patients with BE6 Three studies that assessed the risk of cancer development in patients with HGD who were followed up for 8 7 and 5 years respectively suggest that 6 to 8 of these patients develop cancer7-9

Nodular disease in BE patients must be removed by endoscopic mucosal resection (EMR) which is an effec-tive therapy for nodules with HGD or intramucosal carcinoma and provides more accurate staging than endoscopic ultrasonography The best treatment for flat disease is radiofrequency ablation (RFA) Alternative therapies include cryotherapy photodynamic therapy and argon plasma coagulation or multipolar cautery

Esophagectomy is generally recognized to have greater morbidity and mortality than any elective operation performed in the United States A study assessed 30-day mortality in patients admitted to hospitals that performed from fewer than 2 esophagectomies per year to approxi-mately 2 to 6 esophagectomies per year10 The 30-day mortality rate decreased as the number of surgeries performed per year increased suggesting that the higher the volume of esophagectomies the better the results However factors such as the patientrsquos age and the existence of comorbidities will increase the mortality rate from esophagectomy

EMR is not recommended for excising long segments of BE because it is asso-ciated with distortion of anatomy for subsequent radiofrequency ablation stricture formation bleeding and perfo-ration EMR is an adequate therapy for BE if it fully removes the damaged lining If there is residual Barrettrsquos tissue after EMR then RFA should be used to complete ablation

Hepatocellular Carcinoma The Growing Disease Burden

Paul Y Kwo MD Professor of Medicine and Medical Director Liver Transplantation discussed key aspects of hepatocellular carci-noma from epidemiology to treatment

How Do We AchieveExcellence in Screening

Use high-quality colonoscopists - Should be able to quote ADR - Should see split-dose preparations - Should see consistent photographic

documentation of cecal intubation - Should see appropriate use of follow-up

exams

Switch from gFOBT to FIT - Avoid examining specimens from DRE


Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and is the third leading cause of cancer-related deaths Although HCC is associated with hepatitis B world-wide hepatitis C has driven the rapid rise in HCC (50-70 of all HCC cases) in the United States where the age-adjusted incidence of HCC has doubled from 1985 to 1998 Other risk factors in the United States include alcohol use nonalcoholic fatty liver disease inherited liver disease smoking and hemochromatosis

Two key mechanisms are implicated in the development of HCC liver cirrhosis following tissue damage (infectious or toxic damage) and mutations occur-ring in 1 or more oncogenes or tumor suppressor genes The mean doubling time for the majority of HCC tumors is 4 months11 and these tumors are biologically aggressive The prog-nosis of symptomatic patients is very poor particularly because 90 of these individuals have underlying cirrhosis Following intrahepatic metastases and vascular invasion HCC can spread to the lungs bones and adrenal glands

The first step in HCC screening is to iden-tify the individuals at risk that is to iden-tify individuals with liver cirrhosis Ultra-sonography every 6 months to 12 months with assessment of alpha-fetoprotein every 6 months is the current standard of care for screening high-risk patients (hepatitis B carriers and patients with nonndashhepatitis-B cirrhosis) similar to guidelines of the American Association for the Study of Liver Diseases Alpha-fetoprotein assessment alone is not sufficient unless imaging modalities are not available The common prac-tice at Indiana University is to perform magnetic resonance imaging (MRI) every 9 months or dual-phase helical CT or ultrasound every 6 months to 12 months if the body mass index is normal

HCC is diagnosed by dual-phase helical CT scan or MRI with intravenous contrast A retrospective analysis of 269 patients with cirrhosis and HCC showed HCC was diagnosed at stages 1 and 2 in 70 of patients in the group with standard-of-care surveillance 37 of patients with substandard surveillance and only 18 of

patients with no surveillance Moreover the ability to provide liver transplantation and the 3-year survival rate following diagnosis increased when the standard-of-care surveillance is followed12

The current treatment options for HCC include surgical resection liver transplan-tation transarterial chemoembolization or radioembolization (yttrium-90 [Y90] microspheres) stereotactic radiation radiofrequency ablation and sorafenib The 5-year survival rate for surgical resection is 60 to 70 and the tumor recurrence rate is 50 in 3 years13 Liver transplantation offers the best chance for cure in selected cases1415 Living donor transplantation may provide timely transplantation Radical (stereotactic radiation and radiofrequency ablation therapies are effective for small tumors before orthotopic liver transplanta-tion (OLT) Radioembolization (Y90) in nontransplant patients appears to improve survival Sorafenib conferred a survival benefit in unresectable HCC16 and is being studied in multiple patient populations with HCC

Breakthrough Papers on Lower Gastrointestinal Tract in 2011

Charles J Kahi MD MSc Associate Professor of Clinical Medicine and Chief Gastrointestinal Section Roudebush VA Medical Center Indianapolis reviewed

several key papers from 2011 on lower gastro-intestinal tract disease

Rifaximin therapy for patients with irritable bowel syndrome without constipation17 Patients with irritable bowel syndrome (IBS) may have altered intestinal microbiota and systemic antibiotics have been used with mixed results Rifaximin is a minimally absorbed broad-spectrum antibiotic that has shown efficacy for IBS in small-scale studies Two multi-center industry-supported random-ized controlled trials (TARGET 1 and TARGET 2) involved 1260 patients with IBS (Rome II criteria) without consti-pation who were randomized in a 11 ratio to rifaximin (550 mg by mouth 3 times daily) or placebo for 2 weeks The primary end point was the propor-tion of patients who reported adequate relief of IBS symptoms for at least 2 weeks of the first 4 weeks after treat-ment completion The secondary end point was relief of IBS-related bloating The primary and secondary end points were reached in 407 and 402 of patients respectively in the rifaximin arm compared with 317 and 303 in the placebo arm (P lt 001) The results indicated a durable response to rifax-imin over 3 months and a safety profile of rifaximin that is similar to placebo However a very high response rate was seen in the placebo arm

Prognosis of Patients With HCCPatient Survival

Therapy 1 Year 3 Years

No radical therapy 54 28

Surgical resection 81 44

Ethanol injection 82 38

Transplatation 84 74

Castells A et al Hepatology19931811211LlovetJMetalHepatology1998271572LlovetJMetalHepatology 19992962


Fidaxomicin versus vancomycin for Clostridium difficile infection18

Increasing disease severity and recur-rence rates have been observed in Clos-tridium difficile infection (CDI) which is usually treated with metronidazole or vancomycin Fidaxomicin is a new macrocyclic antibiotic with no cross-resistance with other antibiotics The present study was a noninferiority multicenter phase III randomized controlled trial of 629 adults random-ized in a 11 ratio to fidaxomicin (200 mg twice daily) or to vancomycin (125 mg 4 times daily) for 10 days The primary end point at 4-week follow-up was clinical cure defined as resolution of diarrhea and no need for additional CDI therapy The secondary end point was CDI recurrence within 4 weeks after therapy Clinical cure rates with fidaxomicin were noninferior to clinical cures rates with vancomycin (882 vs 858) The results showed that recur-rence rates were significantly lower in the fidaxomicin group (154 vs 253 P = 005) Lower recurrence rates were seen in patients with non-nucleosome assembly protein-1 strains (69 relative reduction) Fidaxomicin can be poten-tially advantageous in the treatment of CDI because a reduction in recurrence also likely decreases person-to-person transmission (ldquoglobal curerdquo) More-over fidaxomicin is bactericidal specifi-cally against C difficile but preserves normal anaerobic flora (less recurrence possibly less vancomycin-resistant enterococci) However its use may be precluded by the expense $2800 for a 10-day course

Use of aspirin or nonsteroidal anti-inflammatory drugs increases risk for diverticulitis and diverticular bleeding19 Case-control studies have suggested a higher prevalence of nonsteroidal anti-inflammatory drug (NSAID) use in patients with compli-cated diverticular disease (bleeding diverticulitis) This was a prospective study of a large cohort of men (N = 47210 aged 40-75 years) enrolled in the Health Professionals Follow-up Study Methods included supplemen-tary questionnaires and assessment of aspirin and nonaspirin NSAID use and diverticulitis or diverticular bleeding Bleeding risks for aspirin and NSAIDS were similar (hazard ratio = 17)

Regular use of aspirin and NSAIDs was associated with an increased risk of diverticulitis and diverticular bleeding These results have important clinical and public health implications given the prevalence of diverticulosis and NSAID use in the elderly Aspirin and NSAIDs should be used with caution in patients at risk of diverticular compli-cations

Breakthrough Papers in Hepatology in 2011

Marco A Lacerda MD Associate Professor of Clinical Medicine reviewed several papers from 2011 in hepatology with implications for clinical practice

High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis20 Patients with ulcerative colitis and primary sclerosing cholangitis (UCPSC) are at higher risk for colorectal neoplasia In this study patients with UCPSC who were previously enrolled in a trial of high-dose ursodeoxycholic acid (UDCA) were analyzed for the devel-opment of colorectal neoplasia Of the 56 patients enrolled in the previous study 25 were in a UDCA group and 31 were in a placebo group Surveil-lance colonoscopy and pathology (mean time = 44 years) indicated that 9 of the 25 (36) UDCA-treated patients developed neoplasia (1 cancer 1 high-grade 7 low-grade) Three of the 31 (97) patients in the placebo group developed neoplasia (1 cancer 1 high-grade 1 low-grade hazard ratio = 44 P = 02) This study demonstrated that long-term use of high-dose UDCA in patients with UCPSC is associated with increased risk of colorectal neoplasia

Early liver transplantation for severe alcoholic hepatitis21 This study analyzed the effect of early liver trans-plant (patients with lt 6-month sobriety) on 6-month survival of 26 patients with severe alcoholic hepatitis The patients had no prior episodes of alcoholic hepa-titis and had scores of 045 or higher according to the Lille model (which calculates scores ranging from 0 to 1 with a score of at least 045 indicating nonresponse to medical therapy and an

increased risk of death in the absence of transplantation) or rapid worsening of liver function despite medical therapy The results demonstrated that the 6-month survival of those who under-went early liver transplant was higher than that of 26 matched nonrandomized control patients (77 vs 23 P lt 001) However 3 patients resumed drinking posttransplantation The study showed that early liver transplantation can improve survival in patients with a first episode of severe alcoholic hepatitis not responding to medical therapy

Rifaximin treatment in hepatic encephalopathy22 A total of 299 patients who were in remission from recurrent hepatic encephalopathy (HE) resulting from chronic liver disease received either rifaximin at a dosage of 550 mg twice daily (140 patients) or placebo (159 patients) for 6 months The primary end point was the time to the first breakthrough of HE and the secondary end point was the time to the first hospital admission due to HE Rifaximin was superior to placebo in maintaining remission from HE and significantly reducing hospitalizations due to HE-related episodes No obvious cognitive deficits or impaired quality of life were observed after rifaximin treat-ment

Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease the St Francis Heart Study randomized clinical trial23 Nonalco-holic fatty acid liver disease (NAFLD) is defined as a spectrum from benign steatosis to necroinflammatory changes and fibrosis In this study 1005 patients were randomized to receive atorvastatin (20 mg) vitamin C (1 g) and vitamin E (1000 IU) or matching placebo as part of the St Francis Heart Study randomized clinical trial Follow-up was an average of 36 years CT scans of the patients were used to calculate liver to spleen ratios in 455 patients at baseline and at follow-up The study demonstrated that after 4 years of therapy atorvastatin plus vitamins C and E lowered the risk of moderate-to-severe hepatic steatosis by 70 in the 80 patients who had NAFLD at baseline Baseline triglyceride levels (odds ratio [OR] = 1003 P lt 001) and body mass index (OR = 010 P lt 001) were indepen-dent predictors of NAFLD


Breakthrough Papers in Upper Gastrointestinal Tract in 2011

Lee McHenry MD Professor of Medicine and Medical Director IU Spring Mill Medical Clinics Carmel Indiana examined breakthrough papers in upper gastrointes-tinal tract from 2011 including papers on Helicobacter pylori celiac disease and gastroesophageal reflux disease

Randomized study comparing levo-floxacin omeprazole nitazoxanide and doxycycline versus triple therapy for the eradication of Helicobacter pylori24 H pylori is a Class I carcinogen The current standard of care (proton pump inhibitors plus amoxicillin and cla-rithromycin) fails in 30 of patients mainly because of drug resistance to clar-ithromycin This study was a randomized prospective open-labeled trial of LOAD-7 (levofloxacin once daily omeprazole once daily nitazoxanide [antiprotozoal agent] twice daily and doxycycline once daily for 7 days) or LOAD-10 (the same regimen for 10 days) the combined efficacy of the LOAD therapies was compared with LAC therapy (lansoprazole amoxicillin and clarithromycin) The eradication rates of LOAD-7 and LOAD-10 were 889 and 90 respectively and the combined LOAD efficacy was 894 which was significantly higher than that of LAC therapy (733) These results are particularly robust considering that these efficacies were determined in the intention-to-treat population

A prospective study of duodenal bulb biopsy in newly diagnosed and established adult celiac disease25 The gold standard to diagnose celiac disease is biopsy of the more distal duodenum showing villous atrophy (VA) In this study the biopsy findings of the duodenal bulb and distal duodenum of patients with newly diagnosed and established celiac disease were compared with those of control patients The diagnosis was considered positive only when the Marsh stage 3 criteria were met (epithelial lymphocytes hyperplasia and partial VA) Interestingly patients with newly diagnosed celiac disease (9) and with established celiac disease (14) were more likely to have VA in the duodenal bulb alone than were control patients Hence this study is important because it would enable the diagnosis of an additional

10 to 15 of patients by performing a duodenal bulb biopsy in addition to distal duodenal biopsies Therefore duodenal bulb biopsy should be performed in addi-tion to distal duodenal biopsy in patients with suspected celiac disease

Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD the LOTUS randomized clinical trial26 This was a randomized multicenter parallel-group study of 554 patients with chronic gastroesophageal reflux disease (GERD) The remission rates of the laparoscopic 360-degree Nissen fundo-plication with posterior crural repair were compared with esomeprazole (20-40 mgd) At the 5-year follow-up the remission rate (the need for more than 40 mg of esomeprazole) was 93 in the medical arm and 85 in the surgical arm The 5-year remission rates in this study are higher than those in previous studies It appears from these results that we are losing some of the durability of the surgical repair However consid-ering the long-term side effects of proton pump inhibitors such as osteoporosis and pneumonia antireflux surgery may be an acceptable option in the future

Pregnancy outcome and risk of celiac disease in offspring a nationwide case-control study27 This was a population-based case-control study that evaluated the risk of celiac disease in newborns who were exposed to cesarean delivery (elective or emergency) and adverse fetal events (low Apgar score small for gesta-tional age low birth weight and preterm) A comparison of 11000 offspring with biopsy-verified celiac disease with 53000 age- and sex-matched control patients found a positive association between celiac disease and elective cesarean delivery Newborns who were small for gestational age had a 21 increased risk of celiac disease whereas other preg-nancy exposures did not increase the risk of future celiac disease The emergency cesarean did not increase the risk thus the bacterial flora of the newborn may play a role in the development of celiac disease

Intestinal Transplantation Definition Advantages and Risks

Richard Mangus MD Assistant Professor of Surgery described the advantages and risks

of intestinal transplantation and illustrated its cost benefit as compared with parenteral nutrition

Intestinal failure is defined as the inability of the intestinal tract to main-tain adequate nutritional status and fluidelectrolyte balance It results from a loss or absence of sufficient functional intestinal area Manage-ment approaches include medical or surgical alteration of the damaged area parenteral nutrition and intestinal transplantation Intestinal transplanta-tion has many advantages over other treatment options it replaces normal intestinal anatomy and continuity the patient is able to eat and drink it provides a chance for definitive cure of disease parenteral nutrition can be stopped which decreases infection risk and it leads to a reversal of liver injury However it is also associated with the risks of major surgery host rejection and life-long immunosuppression

An isolated intestinal transplant is indi-cated when there is intestinal failure in the absence of any other organ failure and when the normal function of liver stomach and pancreas are intact A modi-fied multivisceral transplant is performed when there is intestinal failure in the absence of liver failure and the liver func-tion is normal but there is dysfunction of the stomach and intestine with or without pancreatic dysfunction A multivisceral transplant is usually indicated in intestinal failure accompanied by liver failure with or without the dysfunction of stomach and pancreas Intestinal transplantation is also considered for certain nontraditional indications such as diffuse mesenteric thrombosis benignlow-grade malig-nant tumors involving the mesenteric root neuroendocrine tumors (carcinoid insulinoma others) desmoid tumors abdominal catastrophesfistulas radia-tion enteritis trauma and enteropathiesdysmotility disorders

For isolated and modified multivis-ceral transplants (liver excluded) the 1-year risk of rejection is 45 to 50 For multivisceral transplants (liver included) the 1-year risk of rejection is 15 The liver is known to be protective against rejection Additional complica-tions include graft versus host disease posttransplant lymphoproliferative


disorder disease recurrence and pseudo-obstruction that encompasses obstruction chronic rejection and narcotic addiction (chronic pain)

Between 2005 and 2007 28 centers world-wide reported to the worldwide database of all intestinal transplants that 389 intes-tinal transplants were performed on 377 patients In the United States 151 trans-plants were reported in 2010 (16 fewer than in 2009) There were 17 centers with at least 1 transplant and 6 centers with 10 or more intestinal transplants

Intestinal transplantation has been shown to be a cost-effective therapy and is superior to continued par-enteral nutrition in appropriately selected patients Costs for intestinal transplantation including the initial hospitalization for the transplant range from $200000 to $500000 There are frequent hospital readmis-sions posttransplant but these admis-sions decrease markedly after the second year The cost benefit of transplantation reaches parity with parenteral nutrition after 2 years to 3 years posttransplant and is more cost-effective thereafter

Viral Hepatitis Update

Paul Y Kwo MD Professor of Medicine and Medical Director Liver Transplantation described new developments in the treat-ment of hepatitis B and hepatitis C and gave practical clinical tips

Hepatitis BIn the Unites States there are approxi-mately 2 million people infected with hepatitis B virus (HBV) and the mode of transmission is usually sexual trans-mission or unsafe injections or transfu-sions The risk of vertical transmission of HBV infection is highest in neonates The current treatment options for HBV include interferon injections and 5 oral agents The preferred first-line therapy is entecavir-tenofovir (oral agents) Tenofovir is effective against lamivudine resistance but entecavir is not Without previous lamivudine treatment both tenofovir and entecavir have high rates of viral suppression with minimal resis-tance Lamivudine and telbivudine are second-line agents Interferon is used less frequently in the United States than

the oral agents Pregnant women with a viral load over 108 copies are candidates for lamivudine tenofovir or telbivu-dine HBV reactivation is common after chemotherapyimmunosuppression and can be fatal Screening for hepatitis B surface antigen and anti-HBc proteins is essential in such patients and long-term HBV prophylaxis should be considered Finally individuals with HBV DNA above 2000 IU and alanine aminotrans-ferase levels above the upper limit of normal are candidates for therapy

Hepatitis CThere are 170 million to 200 million carriers of the hepatitis C virus (HCV) worldwide with 3 million to 4 million carriers in the United States Currently 25 of the HCV patients have cirrhosis The greatest risk factors associated with acute HCV infec-tion are injection drug use (43) and other high-risk behaviors along with exposure to infected blood Two long-term follow-up studies of interferon treatment have demonstrated undetectable HCV RNA in 99 of patients after an average follow-up of 41 years and 56 years suggesting that HCV is curable

In the United States genotype 1 is the most common form of hepatitis C followed by genotypes 2 and 3 Recently it was reported that individuals with genotype 1 who were treated with pegin-

terferon (peg IFN) and ribavirin and were carrying the CC allele on the IL28B gene showed a very high cure rate of 75 to 80 with a short treatment duration28

The 2 new protease inhibitors boceprevir and telaprevir have been approved for genotype 1 HCV infection These are administered in combination with peg IFNribavirin and have improved the response rate to 70 For genotypes 2 and 3 the peg IFNribavirin therapy is the standard of care It is important to consider drug-drug interaction before administering these drugs because both strongly inhibit CYP3A45 and are partially metabolized by CYP3A45

Higher sustained virologic response rates have been reported in peg IFNribavirin plus telaprevirndashtreated patients (75) than in those treated with peg IFNribavirin alone (75 vs 44 P lt 0001)29 The side effects associated with telaprevir treatment are rash anemia drug-related eosinophilia nausea peri-anal symptoms and diarrhea Boceprevir plus peg IFNribavirin has been more effective for the treatment of patients coinfected with HCVHIV than peg IFNribavirin alone (61 vs 27)30 Both drugs are effective in nonresponders (patients not responding to interferon) Anemia caused by boceprevir treatment is manageable

Intestinal TransplantationOutcomes

Patient Survival

Age group 1 year 5 years

18 to 34 years 81 70

35 to 49 years 80 63

50 to 64 years 93 38

65+ years 100 NA

FromtheOrganProcurementandTransplantNetwork(US)2002-2007


Whatrsquos New in Pancreatic Disorders and Treatment

Evan L Fogel MD MSc Professor of Clinical Medicine reviewed the most current data related to pancreatic disorders and their treatment

The main clinical features of chronic pancreatitis include abdominal pain and exocrine and endocrine insuffi-ciency Pain management is achieved through medical endoscopic and surgical intervention The commonly used surgical procedures are Whipple Puestow Freyrsquos and Begerrsquos proce-dures However the procedure that is being used with increasing frequency is total pancreatectomy with auto-islet cell transplantation (TP-AIT) Patients undergoing surgery receive transplanta-tion of native islet cells to prevent the risk of diabetes which is directly related to the islet cell yield Most patients have less pain after surgery and 50 to 80 are narcotic independent at the 2-year to 4-year follow-up Quality of life for pediatric patients after TP-AIT was significantly improved in a single-center prospective study of 19 children (aged 5-18 years mean = 145) with chronic or acute recurrent pancreatitis31 The study concluded that the majority of patients can be weaned off narcotic medications after surgery and insulin independence (or minimal use) can be achieved in more than 60 of patients

Pancreatic divisum (PD) is a congenital abnormality of the pancreas with a worldwide incidence of 7 The vast majority of patients with PD are entirely asymptomatic In patients who are symptomatic minor papilla therapy which enlarges stenotic orifices either endoscopically or surgically improves symptoms in 75 to 80 of cases Mutational analysis of control patients and patients with unexplained pancre-atitis showed that the frequency of PD was no different in patients with idiopathic pancreatitis (5) alcoholic pancreatitis (7) and control patients (7) but PD frequency was higher in patients with the genetic mutations PRSS1 (16) SPINK1 (16) and CFTR (47) It was concluded that PD alone should no longer be considered an independent cause of pancreatitis rather it acts as a cofactor in patients

with genetic mutations32 However the study suffered from the following limitations the proportion of genetic mutations (PRSS1 SPINK1) in control populations is unknown magnetic resonance cholangiopancreatography is not the gold standard for diagnosis of PD and the coexistence of a genetic mutation with PD does not preclude other therapeutic options (ie minor papilla therapy)

Post-ERCP pancreatitis (PEP) is the most common major complication in 1 to 10 as high as 30 of patients under-going ERCP (endoscopic retrograde cholangiopancreatography) Reducing the pressure gradient across the pan-creatic sphincter with a pancreatic duct stent may lower the frequency of this complication33 Thus temporary small-diameter PD stents lower the frequency and severity of post-ERCP pancreatitis in high-risk patients and they are now considered standard care The efficacy of various pharmacologic agents for preven-tion of PEP has been studied Udenafil a phosphodiesterase type 5 inhibitor was not effective in the prevention of PEP34 However a meta-analysis supported the use of NSAIDs in the prevention of PEP35 In this study prophylactic rectal indo-methacin was also shown to significantly reduce the incidence and severity of PEP in high-risk patients

Evaluation and Treatment of Pelvic Floor Disorders

Diane M Settles MD Assistant Professor of Clinical Medicine gave a complete overview of pelvic floor disorders and an evaluation of available treatment options

The pelvic floor is a hammock made up of connective tissues muscles and neural structures Symptoms of pelvic floor disor-ders (PFDs) include urinary incontinence (UI) pelvic organ prolapse fecal incon-tinence (FI) and dyspareunia It is still a question whether dyssynergic defecation is a symptom of true pelvic floor dysfunction FI is the second most common reason for patients to be admitted to a nursing facility A survey of 1961 women found that greater than 23 of women had at least 1 PFD 15 had UI 9 had FI and 29 had pelvic organ prolapse However this may be an underrepresentation because women are often embarrassed to report problems of incontinence

Pregnancydelivery parity age obesity ethnicity smoking chronic pulmonary conditions and menopause have been linked to PFDs According to the National Health and Nutrition Examination Survey data PFDs are more common among women who have had at least 1 child In premeno-pausal women parous women have

What I Tell Patients RegardingTreatment of Hepatitis C

HCV can be cured in 75 of all cases Therapy is evolving about half of all genotype

1 individuals can be treated with 6 months of therapy

Genotype 23 still has sustained viral response rates of gt75 with peginterferonribavirin

IL-28 CC genotype will identify those who can be treated for shorter duration

Silymarin donrsquot bother


a higher prevalence of stress urinary incontinence and UI and in postmeno-pausal women parity has little effect on UI Sphincter defects are associated with parity however anal sphincter defects are most commonly associated with the first pregnancy36 A range of 7 to 60 of pregnant women expe-rience UI and 6 experience FI One mechanism of injury during preg-nancy and childbirth is neural injury that can occur as a result of operative delivery prolonged second stage of labor or high birth weight The second mechanism is anal sphincter disruption which is associated with gross and occult injuries role and risk of episiotomy maternal birth position and epidural use According to a Cochrane Review of 21 studies performed to assess the role of elective cesarean in preserving maternal pelvic floor function it was concluded that elective emergency cesarean surgery cannot be recommended for protecting anal continence

The evaluation of PFDs can be performed using different techniques A physical examination is composed of a detailed neurologic examination perianal inspection and a detailed rectal examination that should include the assessment of resting and squeezing tone and attempted defecation Mano-metric testing of anorectal abnormalities in patients with defecation disorders confirmed diagnosis in 90 of the cases provided new information in 80 of cases and influenced treatment in 84 of cases Anal endosonography for the assessment of the thickness and integ-rity of sphincters and pelvic magnetic resonance imaging for recognition of external anal sphincter atrophy are the other methods to evaluate PFDs

PFDs can be managed through lifestyle modifications medications Kegel exercises biofeedback surgery sacral nerve stimulation and artificial sphinc-ters Loperamide lomotil and codeine are the common medications used to reduce the frequency of incontinence Hormone replacement therapy showed a 65 improvement in symptoms and 25 of patients were asymptomatic after 6 months of treatment37 Biofeed-back has been shown to improve symptoms in 60 of the patients in

a randomized controlled trial of 171 patients38 Biofeedback is the main-stay of therapy in patients who fail to respond to supportive medication

Diagnostic Testing in Inflammatory Bowel Disease

Michael V Chiorean MD Associate Professor of Clinical Medicine Fellowship Program Director described the most current approaches to diagnostic testing for inflam-matory bowel disease including their relative advantages and disadvantages

Calprotectin and lactoferrin are the 2 fecal biomarkers commonly used in the diagnosis of inflammatory bowel disease (IBD) in clinical practice The advantages of these markers are that they are fairly sensitive and they provide a full bowel screen because signs of inflammation anywhere in the gastrointestinal tract will be reflected in the assays These markers can detect inflammation in patients without an elevated C-reactive protein level or an elevated sedimentation rate Assays are convenient because stool samples are routinely collected in IBD cases They are also relatively inexpensive compared with other diagnostic tests ($40 and $60 for insurance payers) The disadvantage of using these fecal biomarkers is their nonspecificity they may be elevated in patients using NSAIDs and those suffering from infec-tions or malignancy In a meta-analysis of pooled data from 30 studies including almost 6000 patients with established IBD the sensitivity of calprotectin (threshold = 50 mcgg - 100 mcgg) was found to be greater than 90 and the specificity was 80 to 9039 In a meta-analysis of 6 studies of adults and chil-dren with suspected IBD and a pretest probability of 40 the sensitivity and specificity of calprotectin were 93 and 96 respectively40 These data suggest that the use of calprotectin would prevent a large number of patients from undergoing further testing and delayed diagnosis would occur in only 6 of the patients

Anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) are the most extensively studied markers

for diagnosing IBD In a recent meta-analysis of 60 studies with almost 1000 patients the ASCA and p-ANCA status was evaluated in patients with IBD versus patients with functional bowel disease41 It was found that the sensitivity of a positive ASCA result with a nega-tive p-ANCA result was approximately 60 The specificity was not perfect (92) and in a population with a low pretest probability such as patients with nonspecific symptoms this would lead to a substantial number of false positive results p-ANCA seems to have a higher overall accuracy and if a patient is both ASCA-positive and p-ANCA-positive this provides some strength to the diag-nosis because the specificity dramati-cally increases However few patients with IBD are both ASCA-positive and p-ANCA-positive

In previous studies the correlation of calprotectin and lactoferrin with disease activity as measured by the endoscopic index has been shown to be similar and these 2 markers seem to be better than C-reactive protein in predicting disease activity In a study performed at Indiana University a good correlation of fecal calprotectin with endoscopic disease activity in patients with both UC and Crohnrsquos disease was established42

In summary fecal inflammatory markers (calprotectin and lactoferrin) are useful in IBD diagnosis because they are sensi-tive and inexpensive offer a full bowel screen and can detect inflammation in patients without elevated C-reactive protein levels However their nonspecificity is a disadvantage Serological markers (ASCA and p-ANCA) have modest specificity however their low sensitivity precludes their use in the diagnosis of IBD

Best Use of 5-Aminosalicylates Immunomodulatory Agents Probiotics Diet Alternative Therapies in IBDMonika Fischer MD Assistant Professor of Clinical Medicine reviewed the most current data on the treatment of IBD including changing recommendations related to the use of 5-aminosalicylates

5-aminosalicylates (5-ASAs) continue to be first-line therapy for ulcerative colitis


(UC) The American College of Gastro-enterology IBD Task Force has strongly recommended 5-ASAs for the induction of remission in UC and to prevent relapse in quiescent UC The recommendation is based on 11 high-quality randomized controlled trials and the optimum dose of mesalamine is 24 g or the equivalent for both indications Rare but serious side effects include interstitial nephritis pancreatitis pneumonitis pericarditis and hepatitis Up to 8 of patients are 5-ASA intolerant Once-daily dosing of 5-ASAs has been shown to achieve better compliance higher efficacy and better outcomes43 The combined approach of oral 5-ASAs plus topical 5-ASAs as first-line therapy is highly effective in mildly severe to moderately severe active UC The current recommendation suggests oral mesalamine plus topical mesalamine for inducing as well as for maintaining remission However 80 of patients favor oral treatment alone Thus patient preference highly affects drug adherence

Based on a meta-analysis of 3 random-ized controlled trials of mesalamine (4gd) 5-ASAs are no longer recom-mended for induction or maintenance of remission in Crohnrsquos disease Although the prevention of colitis-related cancer by 5-ASAs has been actively studied none of the previous studies have conclusively shown any impact of 5-ASAs on colitis-related cancer risk

The common immunomodulatory agents used in the treatment of UC are the thiopurine analogs azathioprine (AZA) and 6-mercaptopurine (6-MP) and methotrexate (MTX) AZA and 6-MP are recommended for maintenance but not for induction of remission of UC MTX is not recommended for UC induction or maintenance but the recommendation is based on only 2 small studies The efficacy rate of AZA in Crohnrsquos disease mainte-nance therapy after steroid (prednisolone) administration was 42 compared with 7 for placebo (P = 001)44 In the case of the addition of 6-MP treatment in children with active steroid-dependent Crohnrsquos disease the duration of steroid use was shorter (P lt 001) and the cumulative steroid dose required was lower (P lt 01) Moreover there was less relapse in the 6-MP group than in the placebo group (P = 007)45

Underdosing of thiopurine analogs is a form of undertreatment and dosages should be modified on the basis of thiopu-rine methyltransferase enzyme activity Regular monitoring for myelosuppression is essential during thiopurine treatment To achieve continuous remission thio-purines should probably be continued indefinitely withdrawal is associated with a high risk of relapse even after stable remission of several years

Evidence suggests that IBD is primarily caused by a dysregulated mucosal inflammatory response to intestinal bacteria in genetically susceptible indi-viduals The majority of currently used IBD therapies modulates the immune system Therapies that modulate the gut flora may prove to be quite successful in the future Dietary intake is related to the risk of developing IBD However there are no data to support diet as a form of treatment in Crohnrsquos disease and UC Probiotics have great therapeutic poten-tial in IBD management however the lack of evidence and the cost consider-ations have limited probiotics to adjuvant therapy only

Best Use of Biologic Agents Agent Selection Monitoring Dosing and When to StopDebra J Helper MD Associate Professor of Clinical Medicine and Medical Director Inflammatory Bowel Disease Center discussed new developments in the treatment of Crohnrsquos disease including recommenda-tions for when to adjust treatment with specific agents by stopping adjusting doses or switching agents

The current FDA-approved drugs for moderate-to-severe as well as refractory Crohnrsquos disease are the IgG antindashtumor necrosis factor monoclonal antibodies infliximab adalimumab certolizumab pegol and natalizumab

In terms of efficacy adalimumab and certolizumab pegol show remis-sion at weeks 20 to 30 compared with infliximab which shows remission at week 4 however the 3 agents appear to be basically equivalent in terms of their ability to induce remission Their response rates range from 40 to 70 The response and remission rates of

natalizumab for Crohnrsquos disease at 10 weeks are 56 and 37 respectively In terms of durability infliximab and adalimumab show a loss of response over time (13 and 203 per patient year respectively) All 4 agents are intravenous infusions or subcutaneous injections each with certain limita-tions All have similar safety profiles and are associated with risk of infec-tion demyelinating disease congestive heart failure hepatitis and lympho-proliferative disease Infliximab and adalimumab can cause infusion-site reactions and lupus-like reactions

The Study of Biologic and Immuno-modulator Naive Patients in Crohnrsquos Disease (SONIC) demonstrated that combination therapy of infliximab and azathioprine (25 mgkg) was superior to that of infliximab or azathioprine mono-therapy46 Another study showed that the administration of hydrocortisone before infliximab infusion in patients with Crohnrsquos disease decreases the risk of developing antibodies to infliximab47

A combined approach using infliximab methotrexate and sphincter-sparing surgery in patients with severe fistu-lizing Crohnrsquos disease was effective in achieving short-term response48 Cipro-floxacin has also been used effectively in combination with infliximab in the treat-ment of fistulizing Crohnrsquos disease with an improved outcome a response of 73 in the combination group versus 39 in the placebo group49

Disease activity before and after therapy with biologic agents can be monitored by various tests such as C-reactive protein sedimentation rate fecal calprotectin or lactoferrin endoscopy radiographic imaging and capsule imaging To monitor the biologic agent itself in case of an increase in symptoms parameters such as the trough levels and peak levels of infliximab as well as the human antichi-meric antibodyantibodies to infliximab levels can be measured There are no commercially available ways to monitor adalimumab or certolizumab pegol Evalu-ations for tuberculosis a complete blood count (at least once a year) and routine liver and kidney tests are common practice to monitor complications The exception is natalizumab which is associated with the complication of progressive multifocal leukoencephalopathy for which an anti-


body test for JC virus is available Based on previous studies specific information on dosing is available along with algorithms for dose adjustments and agent switching

The factors to be considered while stop-ping a biologic agent are reaction infec-tion malignancy neurologic symptoms worsened congestive heart failure skin lesions and loss of response

All antindashtumor necrosis factor agents are category B drugs except natalizumab which is a category C drug There has been no convincing evidence of adverse effects of biologic agents on the fetus to date It is recommended that infliximab be withheld from week 30 of pregnancy if possible and be resumed after delivery Overall an individualized therapy is required for best disease control during pregnancy

REFERENCES1 Kimura T Yamamoto E Yamano HO et al A novel pit pattern identi-fiestheprecursorofcolorectalcancerderivedfromsessileserratedadenoma Am J Gastroenterol2012107(3)460-469Epub2012Jan10

2 vanRossumLGvanRijnAFLaheijRJetalRandomcomparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population Gastroenterology2008135(1)82-90Epub2008Mar25

3 AhlquistDATaylorWRMahoneyDWetalThestoolDNAtest is more accurate than the plasma septin 9 test in detecting colorectal neoplasia Clin Gastroenterol Hepatol 201210(3)272-277

4 FroehlichFWietlisbachVGonversJJBurnandBVaderJPImpactof colonic cleansing on quality and diagnostic yield of colonoscopy the European Panel of Appropriateness of Gastrointestinal Endoscopy European multicenter study Gastrointest Endosc 200561(3)378-384

5 Aoun E Abdul-Baki H Azar C et al A randomized single-blind trial of split-dose PEG-electrolyte solution without dietary restriction compared with whole dose PEG-electrolyte solution with dietary restriction for colonoscopy preparation Gastroin-test Endosc200562(2)213-218

6 WangKKSamplinerREPracticeParametersCommitteeofthe American College of Gastroenterology Updated guidelines 2008forthediagnosissurveillanceandtherapyofBarrettrsquosesophagus Am J Gastroenterol2008103(3)788-797

7 ReidBJLevineDSLongtonGBlountPLRabinovitchPSPredictors of progression to cancer in Barrettrsquos esophagus baselinehistologyandflowcytometryidentifylow-andhigh-risk patient subsets Am J Gastroenterol200095(7)1669-1676

8 SchnellTGSontagSJChejfecGetalLong-termnonsurgicalmanagement of Barrettrsquos esophagus with high-grade dyspla-sia Gastroenterology2001120(7)1607-1619

9 ButtarNSWangKKSeboTJetalExtentofhigh-gradedysplasia in Barrettrsquos esophagus correlates with risk of adenocarcinoma Gastroenterology2001120(7)1630-1639

10BirkmeyerJDSiewersAEFinlaysonEVetalHospitalvolumeand surgical mortality in the United States N Engl J Med 2002346(15)1128-1137

11SheuJCSungJLChenDSetalGrowthrateofasymptom-atic hepatocellular carcinoma and its clinical implications Gastroenterology198589(2)259-266

12StravitzRTHeumanDMChandNetalSurveillanceforhepatocellular carcinoma in patients with cirrhosis improves

outcome Am J Med2008121(2)119-12613LlovetJMFusterJBruixJIntention-to-treatanalysisofsur-

gical treatment for early hepatocellular carcinoma resection versus transplantation Hepatology199930(6)1434-1440

14MazzaferroVRegaliaEDociRetalLivertransplantationforthe treatment of small hepatocellular carcinomas in patients with cirrhosis N Engl J Med1996334(11)693-699

15 Yao FY Bass NM Nikolai B et al Liver transplantation for hepatocel-lular carcinoma analysis of survival according to the intention-to-treat principle and dropout from the waiting list Liver Transpl 20028(10)873-883

16LlovetJRicciSMazzaferroVetalfortheSHARPInvestiga-tors Study Group Sorafenib improves survival in advanced hepatocellularcarcinoma(HCC)resultsofaphaseIIIrandomizedplacebo-controlledtrial(SHARPtrial)J Clin Oncol 200725(suppl)18SAbstractLBA1

17PimentelMLemboACheyWDetalRifaximintherapyforpatients with irritable bowel syndrome without constipation N Engl J Med2011364(1)22-32

18LouieTJMillerMAMullaneKMetalFidaxomicinversusvancomycin for Clostridium difficile infection N Engl J Med 2011364(5)422-431

19 Strate LL Liu YL Huang ES Giovannucci EL Chan AT Use of aspirinornonsteroidalanti-inflammatorydrugsincreasesriskfor diverticulitis and diverticular bleeding Gastroenterology 2011140(5)1427-1433

20EatonJESilveiraMGPardiDSetalHigh-doseursodeoxy-cholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis Am J Gastroenterol2011106(9)1638-1645

21MathurinPMorenoCSamuelDetalEarlylivertransplantationfor severe alcoholic hepatitis N Engl J Med2011365(19)1790-1800

22BassNMMullenKDSanyalAetalRifaximintreatmentinhepatic encephalopathy N Engl J Med2010362(12)1071-1081

23FosterTBudoffMJSaabSAhmadiNGordonCGuerciADAtorvastatinandantioxidantsforthetreatmentofnonalcoholic fatty liver disease the St Francis Heart Study randomized clinical trial Am J Gastroenterol2011106(1)71-77Epub2010Sep14

24BasuPPRayapudiKPacanaTShahNJKrishnaswamyNFlynnMArandomizedstudycomparinglevofloxacinomepra-zole nitazoxanide and doxycycline versus triple therapy for the eradication of Helicobacter pylori Am J Gastroenterol 2011106(11)1970-1975Epub2011Oct11

25EvansKEAzizICrossSSetalAprospectivestudyofduodenalbulb biopsy in newly diagnosed and established adult celiac disease Am J Gastroenterol2011106(10)1837-1842Epub2011May24

26GalmicheJPHatlebakkJAttwoodSetalfortheLOTUSTrialCollaboratorsLaparoscopicantirefluxsurgeryvsesome-prazoletreatmentforchronicGERDtheLOTUSrandomizedclinical trial JAMA2011305(19)1969-1977

27MaringrildKStephanssonOMontgomerySMurrayJALudvigs-sonJFPregnancyoutcomeandriskofceliacdiseaseinoffspring a nationwide case-control study Gastroenterology 2012142(1)39-45Epub2011Oct10

28GeDFellayJThompsonAJetalGeneticvariationinIL28Bpredicts hepatitis C treatment-induced viral clearance Nature2009461(7262)399-401

29JacobsonIMMcHutchisonJGDusheikoGetalTelaprevirincombinationwithpeginterferonalfa-2aandribaviriningenotype 1 HCV treatment-naiumlve patients Final results of phase3ADVANCEstudyHepatology201052(suppl4)427AAbstract211

30MallolasLPmolLRiveroAetalBoceprevirpluspeginter-feronribavirin for the treatment of HCVHIV co-infected pa-tientsendoftreatment(week48)interimresultsPresentedatEASL2012April202012BarcelonaSpainAbstract366

31BellinMDFreemanMLSchwarzenbergSJetalQualityoflife improves for pediatric patients after total pancreatec-tomy and islet autotransplant for chronic pancreatitis Clin Gastroenterol Hepatol20119(9)793-799Epub2011May5

32BertinCPelletierALVulliermeMPetalPancreasdivisumisnot a cause of pancreatitis by itself but acts as a partner of genetic mutations Am J Gastroenterol2012107(2)311-317Epub2011Dec13

33ChoudharyABechtoldMLArifMetalPancreaticstentsforprophylaxisagainstpost-ERCPpancreatitisameta-analysisand systematic review Gastrointest Endosc201173(2)275-282

34OhHCCheonYKChoYDetalUseofudenafilisnotassoci-atedwithareductioninpost-ERCPpancreatitisresultsofarandomized placebo-controlled multicenter trial Gastroin-test Endosc201174(3)556-562Epub2011Jul28

35ElmunzerBJWaljeeAKEltaGHetalAmeta-analysisofrectalNSAIDsinthepreventionofpost-ERCPpancreatitisGut200857(9)1262-1267Epub2008Mar28

36SultanAHKammMAHudsonCNThomasJMBartramCIAnal-sphincter disruption during vaginal delivery N Engl J Med19933291905-1911

37DonnellyVOrsquoConnellPROrsquoHerlihyCTheinfluenceofoestro-gen replacement on faecal incontinence in postmenopausal women Br J Obstet Gynaecol1997104(3)311-315

38NortonCChelvanayagamSWilson-BarnettJRedfernSKammMARandomizedcontrolledtrialofbiofeedbackforfecalinconti-nence Gastroenterology2003125(5)1320-1329

39vonRoonACKaramountzosLPurkayasthaSetalDiagnosticprecisionoffecalcalprotectinforinflammatoryboweldiseaseand colorectal malignancy Am J Gastroenterol2007102(4)803-813Epub2007Feb23

40vanRheenenPFVandeVijverEFidlerVFaecalcalprotectinforscreeningofpatientswithsuspectedinflammatoryboweldisease diagnostic meta-analysis BMJ2010341c3369

41ReeseGEConstantinidesVASimillisCetalDiagnosticpre-cision of anti-Saccharomyces cerevisiae antibodies and peri-nuclearantineutrophilcytoplasmicantibodiesininflammatorybowel disease Am J Gastroenterol2006101(10)2410-2422

42SaadAMChioreanMVHelperDJetalTheaccuracyoffecalcalprotectin for the diagnosis and assessment of disease activityininflammatoryboweldiseaseAmericanCollegeofGastroenterology2006Abstract

43DignassAUBokemeyerBAdamekHetalMesalamineonce daily is more effective than twice daily in patients with quiescent ulcerative colitis Clin Gastroenterol Hepatol 20097(7)762-769Epub2009Apr16

44CandySWrightJGerberMAdamsGGerigMGoodmanRAcontrolled double blind study of azathioprine in the manage-ment of Crohnrsquos disease Gut199537(5)674-678

45MarkowitzJGrancherKKohnNLesserMDaumFAmulti-centertrialof6-mercaptopurineandprednisoneinchildrenwith newly diagnosed Crohnrsquos disease Gastroenterology2000 119(4)895-902

46ColombelJFSandbornWJReinischWetalfortheSONICStudyGroupInfliximabazathioprineorcombinationtherapyfor Crohnrsquos disease N Engl J Med2010362(15)1383-1395

47FarrellRJAlsahliMJeenYTFalchukKRPeppercornMAMichetti P Intravenous hydrocortisone premedication reduces antibodiestoinfliximabinCrohnrsquosdiseasearandomizedcontrolled trial Gastroenterology2003124(4)917-924

48RoumeguegraverePBouchardDPigotFetalCombinedapproachwithinfliximabsurgeryandmethotrexateinseverefistulizinganoperineal Crohnrsquos disease results from a prospective study Inflamm Bowel Dis201117(1)69-76

49WestRLvanderWoudeCJHansenBEetalClinicalandendosonographiceffectofciprofloxacinonthetreatmentofperianalfistulaeinCrohnrsquosdiseasewithinfliximabadouble-blind placebo-controlled study Ailment Pharmacol Ther 200420(11-12)1329-1336

Readthisnewsletterandreceive20hoursofCMEcreditTo get your CME credit immediately simply log onto www2012GIHepUpdatecom totaketheposttestanddownloadyourcertificatecopy2012IndianaUniversityandHealthFocusIncAllrightsreserved


hood of extracolonic findings It is also not approved by Centers for Medicare amp Medicaid Services because of insuf-ficient data in the elderly and because it is less cost-effective than colonoscopy Capsule colonoscopy which requires extensive bowel preparation is yet another nonndashFDA-approved screening method with a sensitivity greater than 80 for polyps 6 mm and smaller and a specificity of less than 80

The adenoma detection rate (ADR) the primary measure of the quality of colo-noscopy varies greatly among gastro-enterologists the lowest ADR ranges from 7 to 155 and the highest ADR ranges from 327 to 44 Some of the factors that may underlie the variable detection rate are training (eg lesion recognition withdrawal technique and withdrawal time) personality visual gaze patterns and withdrawal time A prospective study demonstrated that adequate bowel preparation results in a detection rate of 294 for any adenoma and a detection rate of 64 for large adenomas (gt1 cm) when compared with inadequate bowel preparation which showed a detection rate of 239 for any adenoma and a detection rate of 43 for large adenomas (P lt 05)4 In bowel preparation split-dosing has been shown to provide more satisfactory results than traditional dosing5 Thus the components of good detection are a good bowel preparation adequate time and a sound technique

Barrettrsquos Esophagus Screening Surveillance Diagnosis and TreatmentDouglas K Rex MD Distinguished Professor of Medicine and Chancellorrsquos Professor presented current perspectives on screening surveillance diagnosis and treatment of Barrettrsquos esophagus

Barrettrsquos esophagus (BE) is character-ized by red (columnar) mucosa in the esophagus and described according to Praguersquos classification based on the following criteria (1) C length of the circumferential section and (2) M length of any circumferential section plus the length of any tongues Biop-sies will demonstrate goblet cells which are not seen in the normal stomach but are seen in the intestine

These cells define the intestinal meta-plasia

The risk of esophageal adenocarcinoma is associated with being a white male the presence of BE chronic gastrointestinal disease or obesity and a family history of esophageal carcinoma In fact 85 of the cases of BE are in white males The stages of BE are classified as simple Barrettrsquos (no dysplasia) Barrettrsquos with low-grade dysplasia Barrettrsquos with high-grade dysplasia (HGD) and adenocarci-noma The American College of Gastro-enterology has specific recommendations for the surveillance intervals for patients with BE6 Three studies that assessed the risk of cancer development in patients with HGD who were followed up for 8 7 and 5 years respectively suggest that 6 to 8 of these patients develop cancer7-9

Nodular disease in BE patients must be removed by endoscopic mucosal resection (EMR) which is an effec-tive therapy for nodules with HGD or intramucosal carcinoma and provides more accurate staging than endoscopic ultrasonography The best treatment for flat disease is radiofrequency ablation (RFA) Alternative therapies include cryotherapy photodynamic therapy and argon plasma coagulation or multipolar cautery

Esophagectomy is generally recognized to have greater morbidity and mortality than any elective operation performed in the United States A study assessed 30-day mortality in patients admitted to hospitals that performed from fewer than 2 esophagectomies per year to approxi-mately 2 to 6 esophagectomies per year10 The 30-day mortality rate decreased as the number of surgeries performed per year increased suggesting that the higher the volume of esophagectomies the better the results However factors such as the patientrsquos age and the existence of comorbidities will increase the mortality rate from esophagectomy

EMR is not recommended for excising long segments of BE because it is asso-ciated with distortion of anatomy for subsequent radiofrequency ablation stricture formation bleeding and perfo-ration EMR is an adequate therapy for BE if it fully removes the damaged lining If there is residual Barrettrsquos tissue after EMR then RFA should be used to complete ablation

Hepatocellular Carcinoma The Growing Disease Burden

Paul Y Kwo MD Professor of Medicine and Medical Director Liver Transplantation discussed key aspects of hepatocellular carci-noma from epidemiology to treatment

How Do We AchieveExcellence in Screening

Use high-quality colonoscopists - Should be able to quote ADR - Should see split-dose preparations - Should see consistent photographic

documentation of cecal intubation - Should see appropriate use of follow-up

exams

Switch from gFOBT to FIT - Avoid examining specimens from DRE



























































Patient Survival


18 to 34 years 81 70

35 to 49 years 80 63

50 to 64 years 93 38

65+ years 100 NA































































































































































Patient Survival


18 to 34 years 81 70

35 to 49 years 80 63

50 to 64 years 93 38

65+ years 100 NA





































































































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